Search

An optimal approach to magnetic resonance imaging fusion targeted prostate biopsy (PBx) remains unclear (number of cores, intercore distance, Gleason grading [GG] principle). The aim of this study was to develop a precise pixel-wise segmentation diagnostic artificial intelligence (AI) algorithm for tumor detection and GG as well as an algorithm for virtual prostate biopsy that are used together to systematically investigate and find an optimal approach to targeted PBx. Pixel-wise AI algorithms for tumor detection and GG were developed using a high-quality, manually annotated data set (slides n = 442) after fast-track annotation transfer into segmentation style. To this end, a virtual biopsy algorithm was developed that can perform random biopsies from tumor regions in whole-mount whole-slide images with predefined parameters. A cohort of 115 radical prostatectomy (RP) patient cases with clinically significant, magnetic resonance imaging-visible tumors (n = 121) was used for systematic studies of the optimal biopsy approach. Three expert genitourinary (GU) pathologists (Y.T., A.P., A.Q.) participated in the validation. The tumor detection algorithm (aware version sensitivity/specificity 0.99/0.90, balanced version 0.97/0.97) and GG algorithm (quadratic kappa range vs pathologists 0.77-0.78) perform on par with expert GU pathologists. In total, 65,340 virtual biopsies were performed to study different biopsy approaches with the following results: (1) 4 biopsy cores is the optimal number for a targeted PBx, (2) cumulative GG strategy is superior to using maximal Gleason score for single cores, (3) controlling for minimal intercore distance does not improve the predictive accuracy for the RP Gleason score, (4) using tertiary Gleason pattern principle (for AI tool) in cumulative GG strategy might allow better predictions of final RP Gleason score. The AI algorithm (based on cumulative GG strategy) predicted the RP Gleason score of the tumor better than 2 of the 3 expert GU pathologists. In this study, using an original approach of virtual prostate biopsy on the real cohort of patient cases, we find the optimal approach to the biopsy procedure and the subsequent GG of a targeted PBx. We publicly release 2 large data sets with associated expert pathologists' GG and our virtual biopsy algorithm., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: De novo oligometastatic prostate cancer (omPCa) on prostate-specific membrane antigen (PSMA) positron emission tomography (PET) is a new disease entity and its optimal management remains unknown., Objective: To analyze the outcomes of patients treated with cytoreductive radical prostatectomy (cRP) for omPCa on PSMA-PET., Design, Setting, and Participants: Overall, 116 patients treated with cRP at 13 European centers were identified. Oligometastatic PCa was defined as miM1a and/or miM1b with five or fewer osseous metastases and/or miM1c with three or fewer lung lesions on PSMA-PET., Intervention: Cytoreductive radical prostatectomy., Outcome Measurements and Statistical Analysis: Thirty-day complications according to Clavien-Dindo, continence rates, time to castration-resistant PCa (CRPC), and overall survival (OS) were analyzed., Results and Limitations: Overall, 95 (82%) patients had miM1b, 18 (16%) miM1a, and three (2.6%) miM1c omPCa. The median prebiopsy prostate-specific antigen was 14 ng/ml, and 102 (88%) men had biopsy grade group ≥3 PCa. The median number of metastases on PSMA-PET was 2; 38 (33%), 29 (25%), and 49 (42%) patients had one, two, and three or more distant positive lesions. A total of 70 (60%) men received neoadjuvant systemic therapy, and 37 (32%) underwent metastasis-directed therapy. Any and Clavien-Dindo grade ≥3 complications occurred in 36 (31%) and six (5%) patients, respectively. At a median follow-up of 27 mo, 19 (16%) patients developed CRPC and eight (7%) patients died. The 1-yr urinary continence rate was 82%. The 2-yr CRPC-free survival and OS were 85.8% (95% confidence interval [CI] 78.5-93.7%) and 98.9% (95% CI 96.8-100%), respectively. The limitations include retrospective design and short-term follow-up., Conclusions: Cytoreductive radical prostatectomy is a safe and feasible treatment option in patients with de novo omPCa on PSMA-PET. Despite overall favorable oncologic outcomes, some of these patients have a non-negligible risk of early progression and thus should be considered for multimodal therapy., Patient Summary: We found that patients treated at expert centers with surgery for prostate cancer, with a limited number of metastases detected using novel molecular imaging, have favorable short-term survival, functional results, and acceptable rates of complications., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Androgen deprivation in combination with novel hormonal agents, docetaxel or the combination of abiraterone/prednisone plus docetaxel or darolutamide plus docetaxel represent the standard therapeutic approach in metastatic hormone-sensitive prostate cancer (mHSPC). Patients with low-risk prostate cancer also benefit from additional radiation therapy or radical prostatectomy in terms of progression-free and overall survival. Despite favourable response rates, basically all patients will develop castration-resistant prostate cancer (CRPC) within 2.5 to 4 years. Systemic chemotherapy, second-line hormonal treatment or systemic application of radionuclides such as Radium-223 or 177Lu-PSMA represent salvage management options. As the new medical treatment options have led to an improved oncological outcome with significantly prolonged survival times, about 50% to 65% of patients will develop symptoms due to local progression of prostate cancer. The management of such symptomatic local progression will become more important in upcoming years, which means that all uro-oncologists need to be aware of the various surgical management options. If complications of the lower urogenital tract occur, for example repetitive gross haematuria with or without bladder clotting and with the necessity for red blood cell transfusions, subvesical obstruction, acute urinary retention or rectourethral or rectovesical fistulas, these may be managed by palliative surgery such as palliative TURP, radical cystectomy, radical cystoprostatectomy with urinary diversion, and pelvic exenteration. Symptomatic or asymptomatic obstruction of the upper urinary tract can be managed by endoluminal or percutaneous urinary diversion, ureteral reimplantation, ileal ureter replacement, or implantation of a Detour system. However, an individualised and risk-adapted treatment strategy needs to be developed for each single patient to achieve an optimal therapeutic outcome with improvement of both symptoms and quality of life. In specific clinical situations, best supportive care may be an adequate option., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Purpose: Isolated recurrence in remnants of the seminal vesicles (SV) after treatment of primary prostate cancer (PCa) has become a more frequent entity with the widespread use of more sensitive next-generation imaging modalities. Salvage vesiculectomy is hypothesized to be a worthwhile management option in these patients. The primary goal of this study is to describe the surgical technique of this new treatment option. Secondary outcomes are peri- and post-operative complications and early oncological outcomes., Methods: Retrospective multicenter study, including 108 patients with solitary recurrence in the SV treated between January 2009 and June 2022, was performed. Patients with local recurrences outside the SVs or with metastatic disease were excluded. Both SVs were resected using a robot-assisted or an open approach. In selected cases, a concomitant lymphadenectomy was performed., Results: Overall, 31 patients (29%) reported complications, all but one grade 1 to 3 on the Clavien-Dindo Scale. A median PSA decrease of 2.07 ng/ml (IQR: 0.80-4.33, p < 0.001), translating into a median PSA reduction of 92% (IQR: 59-98%) was observed. At a median follow-up of 14 months, freedom from secondary treatment was 54%. Lymphadenectomy had a significant influence on PSA reduction (p = 0.018)., Conclusion: Salvage vesiculectomy for PCa recurrence limited to the SV is a safe procedure with excellent PSA response and is a potential curative treatment in a subset of patients. A concomitant lymphadenectomy can best be performed in all patients that did not underwent one at primary treatment., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: 68 Ga-prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) is a recommended imaging modality for patients with recurrent prostate cancer (PCa). Its routine implementation before radical prostatectomy (RP) may allow avoiding undertreatment. We aimed to analyze the diagnostic accuracy of 68 Ga-PSMA-PET/CT for pelvic lymph node metastases in a large cohort of patients treated with RP and extended pelvic lymph node dissection (ePLND) for high-risk PCa., Methods: This is a retrospective analysis of an institutional database of patients who underwent 68 Ga-PSMA-PET/CT before RP and ePLND for high-risk PCa. The diagnostic estimates of 68 Ga-PSMA-PET/CT with 95% confidence intervals (CIs) for lymph node involvement were calculated., Results: We included 165 high-risk PCa patients. The median PSA value was 24.5 ng/mL (range: 6.7-185) and all the patients had biopsy Grade Group 4-5. In total, 46 (28%) of patients had clinical lymph node involvement at 68 Ga-PSMA-PET/CT. A mean number of resected lymph nodes per patient was 22 (range: 15-45) and 149 (4.2%) of all resected nodes were positive for lymph node metastasis at final pathology. The diagnostic estimates for the detection of pN+ disease at RP were as follows: sensitivity 63% (95% CI: 51-75), specificity 97% (95% CI: 91-99), positive predictive value 94% (95% CI: 82-99), and negative predictive value 79% (95% CI: 70-86). The total accuracy of PSMA-PET was 83% (95% CI: 76-88)., Conclusion: Our analyses support high specificity and positive predictive value of pretreatment 68 Ga-PSMA PET/CT for the detection of pelvic lymph node metastasis in patients treated with RP for high-risk PCa. While a positive finding should be considered as robust indicator for clinical decision-making, a negative result cannot reliably rule out the presence of lymph node involvement in high-risk PCa; there is a need for advanced risk stratification in those patients., (© 2023 The Authors. The Prostate published by Wiley Periodicals LLC.)

Background: Incontinence and sexual dysfunction are long-lasting side effects after surgical treatment (radical prostatectomy, RP) of prostate cancer (PC). For an informed treatment decision, physicians and patients should discuss expected impairments. Therefore, this paper firstly aims to develop and validate prognostic models that predict incontinence and sexual function of PC patients one year after RP and secondly to provide an online decision making tool., Methods: Observational cohorts of PC patients treated between July 2016 and March 2021 in Germany were used. Models to predict functional outcomes one year after RP measured by the EPIC-26 questionnaire were developed using lasso regression, 80-20 splitting of the data set and 10-fold cross validation. To assess performance, R2, RMSE, analysis of residuals and calibration-in-the-large were applied. Final models were externally temporally validated. Additionally, percentages of functional impairment (pad use for incontinence and firmness of erection for sexual score) per score decile were calculated to be used together with the prediction models., Results: For model development and internal as well as external validation, samples of 11 355 and 8 809 patients were analysed. Results from the internal validation (incontinence: R2 = 0.12, RMSE = 25.40, sexual function: R2 = 0.23, RMSE = 21.44) were comparable with those of the external validation. Residual analysis and calibration-in-the-large showed good results. The prediction tool is freely accessible: https://nora-tabea.shinyapps.io/EPIC-26-Prediction/., Conclusion: The final models showed appropriate predictive properties and can be used together with the calculated risks for specific functional impairments. Main strengths are the large study sample (> 20 000) and the inclusion of an external validation. The models incorporate meaningful and clinically available predictors ensuring an easy implementation. All predictions are displayed together with risks of frequent impairments such as pad use or erectile dysfunction such that the developed online tool provides a detailed and informative overview for clinicians as well as patients., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Breidenbach, Dieng, Kowalski, Sibert, Wesselmann are employees of the two institutions in charge of the certification system (Deutsche Krebsgesellschaft e.V. and OnkoZert GmbH). Darr reports support for attending meetings by Janssen and IPSEN outside the submitted work. Stolzenburg reports outside of the submitted work: speaker honoraria from Intuitive Surgical and Janssen, as well as payments for medical advice by Avatera medical and support for attending meeting by Janssen, stock options by Avatera medical and Intuitive surgical. Conrad reports outside the submitted work honoraria from Jannsen Cilag GmbH and medac GmbH as lecturer as well as from Photocure GmbH for manuscript writing. Harke reports outside the submitted work honoraria by Intuitive Surgical and Pajunk. Lümmen reports outside the submitted work payments from Janssen. Kaftan reports outside the submitted work honoraria from uromed for participation in educationals and support for attending the annual meeting of the Deutsche Kontinenz Gesellschaft. All other authors have nothing to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Sibert et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background/aim: It is not possible to differentiate prostate carcinomas sufficiently to ensure that every patient receives the right therapy. New molecular markers are needed. Our objective was to identify a complex consisting of vimentin variant 3 (VIM3), autophagy-related protein 7 (ATG7) and tumor protein p53 (TP53) in prostate cancer cells and its effect on microRNA (miR)-371a-3p., Materials and Methods: Prostate cancer cell lines (PC3, DU145, LNCaP) and the benign prostatic hyperplasia cell line BPH-1 were cultured in growth medium for 24 h, then stimulated with endothelin 1 (EDN1) (50 nM) and withaferin A (2 nM) for 24 h. Cell extracts were then analyzed by western blot. The localization of VIM3, ATG7 and TP53 in the nucleus was demonstrated with immunofluorescence staining and complex formation was demonstrated by immunoprecipitation. Cancer cell migration was analyzed with a scratch assay and agarose drop analysis. The binding of the complex to the promoter of pri-miR-371a-3p was analyzed with a non-radioactive electrophoretic mobility shift assay. VIM3 knockdown using small interfering RNA and quantitative real-time polymerase chain reaction for miR-371a-3p were performed., Results: The complex was present in the nucleus of prostate cancer cells and in the BPH-1 cell line. EDN1 increased the levels of the complex partners and cell migration, whereas withaferin A reduced the levels of the complex partners and migration. The complex bound to the promoter of pri-miR-371a-3p and might be involved in its transcription. Transfection with miR-371a-3p increased migration of prostate cancer cells. VIM3 knockdown reduced miR-371a-3p expression., Conclusion: The VIM3-ATG7-P53 complex, with its stimulatory effect on miR-371a-3p, may have the potential to be a marker for improved differentiation between prostate carcinomas, allowing tailored therapy., (Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: The outcome of radiotherapy (RT) for prostate cancer (PCA) depends on the delivered dose. While the evidence for dose-escalated RT up to 80 gray (Gy) is well established, there have been only few studies examining dose escalation above 80 Gy. We initiated the present study to assess the safety of dose escalation up to 84 Gy., Methods: In our retrospective analysis, we included patients who received dose-escalated RT for PCA at our institution between 2016 and 2021. We evaluated acute genitourinary (GU) and gastrointestinal (GI) toxicity as well as late GU and GI toxicity., Results: A total of 86 patients could be evaluated, of whom 24 patients had received 80 Gy and 62 patients 84 Gy (35 without pelvic and 27 with pelvic radiotherapy). Regarding acute toxicities, no > grade 2 adverse events occurred. Acute GU/GI toxicity of grade 2 occurred in 12.5%/12.5% of patients treated with 80 Gy, in 25.7%/14.3% of patients treated with 84 Gy to the prostate only, and in 51.9%/12.9% of patients treated with 84 Gy and the pelvis included. Late GU/GI toxicity of grade ≥ 2 occurred in 4.2%/8.3% of patients treated with 80 Gy, in 7.1%/3.6% of patients treated with 84 Gy prostate only, and in 18.2%/0% of patients treated with 84 Gy pelvis included (log-rank test p = 0.358)., Conclusion: We demonstrated that dose-escalated RT for PCA up to 84 Gy is feasible and safe without a significant increase in acute toxicity. Further follow-up is needed to assess late toxicity and survival., (© 2023. The Author(s).)

Background: Accurate staging and identification of optimal candidates for local salvage therapy, such as salvage radical prostatectomy (SRP), is necessary to ensure optimal care in patients with radiorecurrent prostate cancer (PCa). We aimed to analyze performance of magnetic resonance imaging (MRI) and prostate-specific membrane antigen (PSMA)-positron emission tomography (PET)/computed tomography (CT) for predicting pathologic nonorgan confined disease (pT3) and lymph node involvement (pN+) in patients treated with SRP for radiorecurrent PCa., Methods: We retrospectively reviewed the institutional database to identify patients who underwent MRI or 68 Ga-PSMA-PET/CT before SRP for radiorecurrent PCa. The diagnostic estimates of MRI and PSMA-PET/CT for pT3 and pN+, were calculated., Results: We identified 113 patients with radiorecurrent PCa who underwent preoperative MRI followed by SRP; 53 had preoperative 68 Ga-PSMA-PET/CT. For the detection of pT3 disease, the overall accuracy of MRI was 70% (95% confidence interval [CI] 61-78), sensitivity 40% (95% CI 26-55) and specificity 94% (95% CI 85-98); PSMA-PET/CT had slightly higher accuracy of 77% (95% CI 64-88), and higher sensitivity of 90% (95% CI 68-99), but lower specificity of 70% (95% CI 51-84). For pN+ disease, MRI had poor sensitivity of 14% (95% CI 3-36), specificity of 50 (95% CI 39-61) and total accuracy of 43% (95% CI 34-53); PSMA-PET/CT had an accuracy of 85% (95% CI 72-93), sensitivity of 27% (95% CI 6-61), and specificity of 100% (95% CI 92-100)., Conclusion: In patients with radiorecurrent PCa, both, MRI, and 68 Ga-PSMA PET/CT are valuable tools for the pre-SRP staging and should be integrated into the standard workup. For lymph node metastases, 68 Ga-PSMA PET/CT is a strong rule-in test with nearly perfect specificity; in contrast MRI had a low accuracy for lymph node metastases., (© 2022 The Authors. The Prostate published by Wiley Periodicals LLC.)

Purpose of Review: Local treatment in oligometastatic prostate cancer patients is associated with improved survival. Nevertheless, in term of surgery, cytoreductive radical prostatectomy has no level of evidence 1 and is an individual treatment approach. We reviewed the recent literature to highlight parameters for selecting patients for a surgical approach., Recent Findings: Retrospective data on oncologic outcome for cytoreductive prostatectomy are confirmed. We identified several parameters that help to select patients for surgery. Patients with a favorable prostate-specific antigen (PSA) decline after androgen deprivation therapy (ADT) have excellent oncologic long-term control. Circulating tumor cells (CTC's) are frequently analyzed in more advanced prostate cancer. In case of C-reactive protein (CRP) at least a longer interval to develop castration resistant prostate cancer (CRPC) is shown in case of low CTC count at time of surgery. Nutrition status analyzed as the hemoglobin, albumin, lymphocyte, and platelet (HALP)-score is of significant value in demonstrating an effect of CRP., Summary: From retrospective findings we have several clinical and basic science parameters to select patients for CRP. PSA at the time of surgery is the most frequently analyzed one, whereas CTC and HALP-score are promising tools to select patients that need to be validated., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Despite growing interest in metastasis-directed therapy (MDT) for prostate cancer (PCa), little is known regarding the feasibility and effectiveness of surgical metastasectomy for isolated lesions. We performed a narrative review of the available evidence supporting metastasectomy for M1b-c lesions in men diagnosed with oligometastatic or oligorecurrent PCa. The case series and case reports we identified indicate that surgical MDT is a safe and feasible treatment option for well-selected patients with a small number of PCa metastases diagnosed via molecular imaging. It is difficult to draw evidence-based conclusions regarding the survival benefit of metastasectomy; however, metastasectomy might lead to a prostate-specific antigen response and could potentially delay systemic therapy in patients with oligometastatic PCa. Prospective studies incorporating novel imaging are needed to better establish the role of metastasectomy for patients with metastatic PCa. PATIENT SUMMARY: We reviewed the evidence on surgical removal of prostate cancer lesions that have spread to the organs (eg, liver and lung) or bone, which are called metastases. Limited results show that this approach is feasible and has favorable outcomes in selected patients., (Copyright © 2022 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

(1) Background: Local therapy is highly promising in a multimodal approach strategy for patients with low-volume metastatic prostate cancer (mPCa). We aimed to systematically assess and summarize the safety, oncologic, and functional outcomes of cytoreductive prostatectomy (cRP) in mPCa. (2) Methods: Three databases were queried in September 2022 for publications that analyzed mPCa patients treated with cytoreductive prostatectomy without restrictions. The outcomes of interest were progression-free survival (PFS), cancer-specific survival (CSS), overall survival (OS), perioperative complication rates, and functional outcomes following cRP. (3) Results: Overall, 26 studies were included in this systematic review. Among eight population-based studies, cRP was associated with a reduced risk of CSS and OS compared with no local therapy (NLT) after adjusting for the effects of possible confounders. Furthermore, one population-based study showed that cRP reduced the risk of CSS even when compared with radiotherapy (RT) of the prostate after adjusting for the effects of possible confounders. In addition, one randomized controlled trial (RCT) demonstrated that local therapy (comprising 85% of cRP) significantly improved the prostate-specific antigen (PSA)-PFS and OS. Overall, cRP had acceptable perioperative complication rates and functional outcomes. (4) Conclusions: Mounting evidence suggests that cRP offers promising oncological and functional outcomes and technical feasibility and that it is associated with limited complications. Well-designed RCTs that limit selection bias in patients treated with cRP are warranted.

The mobilization and activation of natural killer (NK) cells have been proposed as key mechanisms promoting anti-oncogenic effects of physical exercise. Although mouse models have proven that physical exercise recruits NK cells to tumor tissue and inhibits tumor growth, this preclinical finding has not been transferred to the clinical setting yet. In this first-in-human study, we found that physical exercise mobilizes and redistributes NK cells, especially those with a cytotoxic phenotype, in line with preclinical models. However, physical exercise did not increase NK cell tumor infiltrates. Future studies should carefully distinguish between acute and chronic exercise modalities and should be encouraged to investigate more immune-responsive tumor entities.

Aim: The aim of our study was to address the prevalence of oligometastatic recurrent prostate cancer (PCa) on PSMA-PET and the associated practice of metastasis-directed therapy (MDT). Next, we aimed to determine a PSA threshold below which most patients had local and/or oligometastatic recurrence on PSMA-PET., Methods: One hundred and ten consecutive patients with biochemical recurrence (BCR) after radical prostatectomy (RP) ± radiation were referred for 68 Ga-PSMA-11 or 18 F-DCFPyL PET/CT. We correlated the location and number of PSMA-positive lesions against the treatment choice after imaging. Detection rates were stratified by PSA levels at the time of PET/CT. The study design was monocentric retrospective., Results: Thirty-four patients (30.9%) had a PSMA-negative scan, while 17 (15.5%) had local recurrence and 59 (53.6%) had metastatic recurrence on PSMA-PET. ROC analysis revealed a cut-off of ≤3 metastatic lesions on PSMA-PET for the steering of treatment decisions towards MDT rather than solely systemic therapy (AUC: 0.88). Defined as 3 or fewer metastatic lesions, oligometastatic recurrent PCa was found in up to 30% (33/110) of all patients. At PSA levels below 3.5 ng/ml, the rate of PSMA-positive disease that was locally confined or oligometastatic was 76% (45/59), dropping significantly to 29.4% (5/17) above this threshold (p<0.001) as polymetastatic findings became more frequent., Conclusion: The detection of ≤3 oligometastases on PSMA-PET encouraged the consecutive pursuit of MDT instead of systemic therapy alone. PSMA-PET predominantly captured patients at recurrence stages amenable to localized treatment when initiated at PSA levels below 3.5 ng/ml., Competing Interests: A.D. has applied for a patent on 18F-JK-PSMA-7. No other potential conflicts of interest relevant to this article exist., (Thieme. All rights reserved.)

Background: The optimal definition and prognostic significance of persistently elevated prostate-specific antigen (PSA) after salvage lymph node dissection (sLND) for node-only recurrent prostate cancer (PCa) remain unknown., Objective: To assess the definition and clinical implications of persistently elevated PSA after sLND for node-only recurrent PCa after radical prostatectomy., Design, Setting, and Participants: The study included 579 patients treated with sLND at 11 high-volume centers between 2000 and 2016., Outcome Measurements and Statistical Analysis: We assessed the linear relationship between the first PSA after sLND and death from PCa. Different definitions of PSA persistence were included in a multivariable model predicting cancer-specific mortality (CSM) after surgery to identify the best cutoff value. We investigated the association between PSA persistence and oncologic outcomes using multivariable regression models. Moreover, the effect of early androgen deprivation therapy (ADT) after sLND was tested according to PSA persistence status and estimated risk of CSM., Results and Limitations: We found an inverse relationship between the first PSA after sLND and the probability of cancer-specific survival. PSA persistence defined as first postoperative PSA ≥0.3 ng/ml provided the best discrimination accuracy (C index 0.757). According to this cutoff, 331 patients (57%) experienced PSA persistence. The median follow-up for survivors was 48 mo (interquartile range 27-74). After adjusting for confounders, men with persistently elevated PSA had higher risk of clinical recurrence (hazard ratio [HR] 1.61), overall mortality (HR 2.20), and CSM (HR 2.59; all p < 0.001) after sLND. Early ADT administration after sLND improved survival only for patients with PSA persistence after surgery (HR 0.49; p = 0.024). Similarly, when PSA persistence status was included in multivariable models accounting for pathologic features, early ADT use after sLND was beneficial only for patients with a predicted risk of CSM at 5 yr of >10%., Conclusions: PSA persistence after sLND independently predicts adverse prognosis, with the best discrimination accuracy for CSM provided by a definition of PSA ≥ 0.3 ng/ml. We showed that when stratifying patients by final pathology results and PSA persistence status, early ADT use after sLND was beneficial only for patients with PSA persistence or with a calculated 5-yr risk of CSM of >10%, which could be useful as we await results from ongoing prospective trials., Patient Summary: We found that for patients with prostate cancer who had lymph nodes removed after their cancer recurred, persistently elevated prostate-specific antigen (PSA) levels predict poorer prognosis. We showed that a PSA level of ≥0.3 ng/ml provides the best accuracy in identifying patients with worse prognosis. This may help to improve risk stratification after lymph node removal and allow physicians to optimize treatment strategies after surgery., (Copyright © 2021 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: The SelectMDx test is a promising biomarker that is developed based on detecting urinary messenger RNA in combination with clinical prostate cancer (PCa) risk factors. We aimed to compare SelectMDx and mpMRI as a diagnostic test in detecting PCa and high grade(HG)-PCa in men suspected to have PCa., Methods: According to PRISMA, a systematic search was performed using major web databases for studies published before September 30, 2021. Studies that compared sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of SelectMDx and/or mpMRI were included. The bivariate random model that plotted sensitivity, specificity, PPV, NPV, and likelihood ratio (LR) for PCa and HG-PCa detection was applied to compare SelectMDx, mpMRI, and combination strategies (both positive and one or both positive)., Results: Seven studies comprising 1328 patients who had undergone SelectMDx and mpMRI to detect PCa were included. Regarding PCa detection, SelectMDx had a pooled sensitivity of 81%, specificity of 69.8%, PPV of 64.7%, NPV of 85%, and LRs of +2.68 to -0.27, while mpMRI had a pooled sensitivity of 80.8%, specificity of 73.4%, PPV of 72.4%, NPV of 83.5%, and LRs of +3.03 to -0.26. The one or both positive strategy had the highest sensitivity (96.3%), NPV (95.7%), and the lowest -LR (0.06). While the both positive strategy had the highest specificity (80.9%), the PPV (76.5%) and +LR (3.68). In the scenario of PI-RADS 3 lesions not being biopsied in case of a negative SelectMDx (n = 44), unnecessary biopsies would be reduced by 42% (44/105) while the risk of missing HG-PCa would be 9% (4/44)., Conclusion: The performance of SelectMDx is comparable to that of mpMRI with regards to PCa and HG-PCa detection. In addition, this biomarker could help refine the clinical decision-making regarding the necessity of a biopsy in patients suspected to has been PCa., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Androgen deprivation therapy (ADT) has adverse effects on body composition, including muscle wasting and body fat accumulation, which may be attenuated by nutrition therapy. This systematic review summarises available evidence on the effects of dietary interventions on lean mass, fat mass and body mass index (BMI) in men treated with ADT for prostate cancer., Methods: MEDLINE, Embase, Web of Science and ClinicalTrials.org were searched from inception through December 2020. We included all controlled trials evaluating effects of supplementation or dietary interventions on body composition in men with prostate cancer receiving continuous ADT. Methodological quality of the studies was assessed using the Cochrane Collaboration's risk of bias tool. Meta-analysis was performed using a random effects model to calculate standardised mean differences between intervention and comparator groups. (PROSPERO; CRD42020185777)., Results: Eleven studies (n = 536 participants) were included. Seven studies investigated the effects of dietary advice interventions, e.g. individual or group counselling, and four studies included a nutritional supplement. Eight studies combined the dietary intervention with exercise. Nine studies reported sufficient data for inclusion in the meta-analysis. Dietary advice and supplementation interventions combined were not associated with significant changes in lean mass (0.05 kg; 95% CI: -0.17, 0.26; p = 0.674; n = 355), fat mass (-0.22 kg; 95% CI: -0.45, 0.01; p = 0.064; n = 336) or BMI (-0.16 kg*m -2 ; 95% CI: -0.37, 0.04; p = 0.121; n = 399). Dietary advice interventions alone were associated with a significant fat mass reduction (-0.29 kg; 95% CI: -0.54, -0.03; p = 0.028; n = 266)., Conclusions: Most studies were dietary advice interventions targeting caloric restriction, which showed the potential to reduce fat mass but did not increase lean mass in men treated with ADT. Future interventions should investigate whether a combination of dietary advice and protein supplementation with concomitant resistance exercise could counteract ADT-induced muscle wasting., (© 2021. The Author(s).)

Background: To demonstrate the feasibility of resecting isolated locally relapsing seminal vesicle remnants after primary radical prostatectomy and radiotherapy. Early oncologic outcomes and prognostic risk factors for relapse are demonstrated., Objectives and Methods: A total of 32 patients underwent open resection of locoregional prostate cancer recurrence in seminal vesicles, as documented on either MRI, 11C-choline, or 68Ga-PSMA PET/CT scans. Age, PSA-DT, PSA, and time to recurrence after primary treatment resection status were used in a uni- and multivariate Cox regression analysis for biochemical relapse after surgery., Results: Median patient age at time of salvage surgery was 70 (57-77) years. Median PSA and PSA-DT was 2.79 (0.4-61.54) ng/mL and 5.4 (1.6-20.1) months, respectively. Median surgical time and hospital stay was 132 (75-313) min and 5.5 (4-13) days, respectively. After a mean follow-up of 29 (2-92) months, 3 patients died at 8, 14, and 40 months after salvage surgery, and 6 (18.75%) patients remain without biochemical relapse and further treatment. Median progression-free survival was 12 (1-81) months. In the univariable Cox regression analysis, age at time of surgery, preoperative PSA, and the time from primary treatment to salvage surgery were identified as significant parameters for biochemical relapse. Only the interval from primary to salvage surgery was significant in the multivariate analysis with a hazard ratio of 1.008 (95% CI: 1.001-1.015, p = 0.018). In the entire cohort, 4 adjunctive surgeries (3 ureteroneocystostomies and 1 nephrectomy) were needed due to local progressive disease., Conclusion: Seminal vesicle resection is feasible with no significant intra- or postoperative complications. Almost all patients progressed to biochemical or systemic relapse. Salvage surgery must be seen as a preventive for local symptoms, in our experience most often postrenal ipsilateral obstruction., (© 2021 S. Karger AG, Basel.)

Purpose: To examine the predictive and prognostic value of preoperative Systemic Immune-inflammation Index (SII) in patients with radio-recurrent prostate cancer (PCa) treated with salvage radical prostatectomy (SRP)., Materials and Methods: This multicenter retrospective study included 214 patients with radio-recurrent PCa, treated with SRP between 2007 and 2015. SII was measured preoperatively (neutrophils × platelets/lymphocytes) and the cohort was stratified using optimal cut-off. Uni- and multivariable logistic and Cox regression analyses were performed to evaluate the predictive and prognostic value of SII as a preoperative biomarker., Results: A total of 81 patients had high preoperative SII (≥ 730). On multivariable logistic regression modeling, high SII was predictive for lymph node metastases (OR 3.32, 95% CI 1.45-7.90, p = 0.005), and non-organ confined disease (OR 2.55, 95% CI 1.33-4.97, p = 0.005). In preoperative regression analysis, high preoperative SII was an independent prognostic factor for cancer-specific survival (CSS; HR 10.7, 95% CI 1.12-103, p = 0.039) and overall survival (OS; HR 8.57, 95% CI 2.70-27.2, p < 0.001). Similarly, in postoperative multivariable models, SII was associated with worse CSS (HR 22.11, 95% CI 1.23-398.12, p = 0.036) and OS (HR 5.98, 95% CI 1.67-21.44, p = 0.006). Notably, the addition of SII to preoperative reference models improved the C-index for the prognosis of CSS (89.5 vs. 80.5) and OS (85.1 vs 77.1)., Conclusions: In radio-recurrent PCa patients, high SII was associated with adverse pathological features at SRP and survival after SRP. Preoperative SII could help identify patients who might benefit from novel imaging modalities, multimodal therapy or a closer posttreatment surveillance., (© 2021. The Author(s).)

Background: Serum albumin-to-globulin ratio (AGR) has been shown to be associated with poor prognosis in different malignancies. In this study we aimed to evaluate the predictive value of preoperative AGR for oncological outcomes in patients with radiation recurrent prostate cancer (PCa) treated with salvage radical prostatectomy (SRP)., Methods: A retrospective review of 214 consecutive patients with radiation recurrent PCa who underwent SRP at five referral centers. Levels of albumin and globulin were obtained before SRP and used to calculate the preoperative AGR level. The optimal cut off value of preoperative AGR was 1.4. Univariable and multivariable Cox regression analyses were performed., Results: Overall 89 (41.6%) patients had a low preoperative AGR. Low serum AGR was associated with biochemical recurrence (BCR) in univariable Cox regression analysis (HR 1.60, 95%CI 1.06-2.43, P=0.026). When adjusted for the effects of established preoperative and postoperative clinicopathologic confounders in different multivariable Cox regression models, this association did not retain its statistical significance. Moreover, preoperative AGR was not associated with metastasis free survival (P=0.21), overall survival (P=0.91) or cancer specific survival (P=0.61)., Conclusions: In patients with radiation recurrent PCa undergoing SRP, low preoperative AGR was associated with the risk of BCR only in univariable analysis. There was no association with metastasis or survival outcomes. Further studies are needed to evaluate this biomarker in the setting of primary PCa and to identify the patients most likely to benefit from a local therapy.

A valid treatment option for recurrence after definite radiotherapy (RT) for localized prostate cancer (PC) is salvage radical prostatectomy (SRP). However, data on SRP are scarce, possibly resulting in an underutilization. A systematic review was performed using MEDLINE (Pubmed), Embase, and Web of Science databases including studies published between January 1980 and April 2020. Overall, 23 English language articles including a total number of 2323 patients were selected according to PRISMA criteria. The overall median follow-up was 37.5 months (IQR 35.5-52.5). Biochemical-recurrence (BCR)-free probability ranged from 34% to 83% at five years, respectively, and from 31% to 37% at 10 years. Cancer specific survival (CSS) and overall survival (OS) ranged from 88.7% to 98% and 64% to 95% at five years and from 72% to 83% and 65% to 72% at 10 years, respectively. Positive surgical margins ranged from 14% to 45.8% and pathologic organ-confined disease was reported from 20% to 57%. The rate of pathologic > T2-disease ranged from 37% to 80% and pN1 disease differed between 0% to 78.4%. Pre-SRP PSA, pre-SRP Gleason Score (GS), pathologic stage after SRP, and pathologic lymph node involvement seemed to be the strongest prognostic factors for good outcomes. SRP provides accurate histopathological and functional outcomes, as well as durable cancer control. Careful patient counseling in a shared decision-making process is recommended.

Purpose: To report on long-term outcomes of patients treated with active surveillance (AS) for localized prostate cancer (PCa) in the daily routine setting., Methods: HAROW (2008-2013) was a non-interventional, health service research study about the management of localized PCa in the community setting, with 86% of the study centers being office-based urologists. A follow-up examination of all patients who opted for AS as primary treatment was carried out. Overall, cancer-specific, and metastasis-free survival, as well as discontinuation rates, were determined., Results: Of 329 patients, 62.9% had very-low- and 21.3% low-risk tumours. The median follow-up was 7.7 years (IQR 4.7-9.1). Twenty-eight patients (8.5%) died unrelated to PCa, of whom 19 were under AS or watchful waiting (WW). Additionally, seven patients (2.1%) developed metastasis. The estimated 10-year overall and metastasis-free survival was 86% (95% CI 81.7-90.3) and 97% (95% CI 94.6-99.3), respectively. One hundred eighty-seven patients (56.8%) discontinued AS changing to invasive treatment: 104 radical prostatectomies (RP), 55 radiotherapies (RT), and 28 hormonal treatments (HT). Another 50 patients switched to WW. Finally, 37.4% remained alive without invasive therapy (22.2% AS and 15.2% WW). Intervention-free survival differed between the risk groups: 47.8% in the very-low-, 33.8% in the low- and 34.6% in the intermediate-/high-risk-group (p = 0.008). On multivariable analysis, PSA-density ≥ 0.2 ng/ml 2 was significantly predictive for receiving invasive treatment (HR 2.55; p = 0.001)., Conclusion: Even in routine care, AS can be considered a safe treatment option. Our results might encourage office-based urologists regarding the implementation of AS and to counteract possible concerns against this treatment option., (© 2020. The Author(s).)

Purpose of Review: Salvage surgeries are rarely offered and performed in prostate cancer except for isolated lymph node metastases. Meanwhile, data are sufficient that salvage radical prostatectomy is recommended by the guidelines. In the following review, we focus on different treatment strategies comparing open and DaVinci laparoscopic approach with regard to functional and oncologic outcome. Of further interest are palliative surgeries., Recent Findings: Salvage radical prostatectomy is mainly performed in high volume centres. Data are increasing on minimal invasive surgery, although data on functional outcome are conflicting. As patients with prostate cancer have longer life expectancy even in metastasized disease, the possibility of developing symptomatic progression increases as well. We need to be aware that the confrontation with symptomatic prostate cancer patients will be more frequent in the future and that there are surgical approaches to palliate these patients sufficiently., Summary: Data on minimal invasive salvage radical prostatectomy are getting more valid and are an option in experienced centres. Salvage radical prostatectomy is a definitive curative option for the patients. To avoid local progression, palliative local surgeries need to be discussed with the patients., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: PSMA imaging is frequently used for monitoring of androgen deprivation therapy (ADT) in prostate cancer. In a previous study, [ 18 F]-JK-PSMA-7 exhibited favorable properties for tumor localization after biochemical recurrence. In this retrospective study, we evaluated the performance of [ 18 F]-JK-PSMA-7 under ADT., Procedures: We examined the performance of [ 18 F]-JK-PSMA-7 in 70 patients (first cohort) with increasing or detectable PSA values under ADT (PSA < 2 ng/ml for 21/70 patients). We further analyzed 58 independent patients with PSA levels < 2 ng/ml under ADT, who were imaged with [ 68 Ga]PSMA-11 or [ 18 F]DCFPyL (second cohort). Finally, we compared detection rates between [ 18 F]-JK-PSMA-7, [ 68 Ga]PSMA-11, and [ 18 F]DCFPyL., Results: In the first cohort, we detected [ 18 F]-JK-PSMA-7-positive lesions in 63/70 patients. In patients with PSA levels ≥ 2 ng/ml, the detection rate was 100 % (49/49). In patients with PSA < 2 ng/ml, the detection rate was significantly lower (66.7 %, 14/21, p = 9.7 × 10 -5 ) and dropped from 85.7 % (12/14, PSA levels between 0.3 and 2.0 ng/ml) to 28.6 % (2/7) for PSA levels < 0.3 ng/ml (p = 1.73 × 10 -2 ). In the second cohort (PSA < 2 ng/ml), the detection rate was 79.3 % (46/58) for [ 68 Ga]PSMA-11 or [ 18 F]DCFPyL. Again, the detection rate was significantly higher (p = 1.1 × 10 -2 ) for patients with PSA levels between 0.3 and 2.0 ng/ml (87.0 %, 40/46) relative to those with PSA levels < 0.3 ng/ml (50 %, 6/12). No significant difference was found between [ 18 F]-JK-PSMA-7 and [ 68 Ga]PSMA-11 or [ 18 F]DCFPyL in patients with PSA levels < 2 ng/ml (p = 0.4295)., Conclusion: [ 18 F]-JK-PSMA-7 PET showed a high detection rate in patients with PSA levels ≥ 0.3 ng/ml under ADT. The lower PSA threshold of 0.3 ng/ml for high detection rates was consistent across the three PSMA ligands. Thus, PSMA imaging is suitable for clinical follow-up of patients with increasing PSA levels under ADT.

Competing Interests: Der Autor gibt an, dass kein Interessenkonflikt besteht.

Context: Pelvic lymph node dissection (PLND) yields the most accurate staging in patients undergoing radical prostatectomy (RP) for prostate cancer (PCa), although it can be associated with morbidity., Objective: To systematically evaluate the impact of PLND extent on perioperative morbidity in patients undergoing RP. A new PLND-related complication assessment tool is proposed., Evidence Acquisition: A systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) was conducted. MEDLINE/PubMed, Scopus, Embase and Web of Science databases were searched to yield studies discussing perioperative complications following RP and PLND. The extent of PLND was classified according to the European Association of Urology PCa guidelines. Studies were categorized according to the extent of PLND. Intra- and postoperative complications were classified as "strongly," "likely," or "unlikely" related to PLND. Anatomical site of perioperative complications was recorded. A cumulative meta-analysis of comparative studies was conducted using Review Manager 5.3 (Cochrane Collaboration, Oxford, UK)., Evidence Synthesis: Our search generated 3645 papers, with 176 studies meeting the inclusion criteria. Details of 77 303 patients were analyzed. Of these studies, 84 (47.7%), combining data on 28 428 patients, described intraoperative complications as an outcome of interest. Overall, 534 (1.8%) patients reported one or more intraoperative complications. Postoperative complications were reported in 151 (85.7%) studies, combining data on 73 629 patients. Overall, 10 401 (14.1%) patients reported one or more postoperative complication. The most reported postoperative complication strongly related to PLND was lymphocele (90.6%). The pooled meta-analysis revealed that RP + limited PLND/standard PLND had a significantly decreased risk of experiencing any intraoperative complication (risk ratio [RR]: 0.55; p =  0.01) and postoperative complication strongly related to PLND (RR: 0.46; p =  <0.00001), particularly for lymphocele formation (RR: 0.52; p =  0.0003) and thromboembolic events (RR: 0.59; p =  0.008), when compared with extended/superextended PLND. The extent of PLND was confirmed to be an independent predictor of lymphocele formation (RR: 1.77; p <  0.00001)., Conclusions: The perioperative morbidity of PLND in patients undergoing RP and PLND for PCa significantly correlates with the extent of PLND. More standardized reporting of intra- and postoperative complications is needed to better estimate the direct impact of PLND extent on perioperative morbidity., Patient Summary: Pelvic lymph node dissection (PLND) is the most accurate method for staging in patients undergoing radical prostatectomy for prostate cancer, although it can be associated with complications. This study aims to systematically evaluate the impact of PLND extent on perioperative complications in these patients. We found that intra- and postoperative complications correlate significantly with the extent of PLND. A more rigorous assessment and thorough reporting of perioperative complications are recommended., (Copyright © 2021 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Purpose: Magnetic resonance imaging-guided transurethral ultrasound ablation uses directional thermal ultrasound under magnetic resonance imaging thermometry feedback control for prostatic ablation. We report 12-month outcomes from a prospective multicenter trial (TACT)., Materials and Methods: A total of 115 men with favorable to intermediate risk prostate cancer across 13 centers were treated with whole gland ablation sparing the urethra and apical sphincter. The co-primary 12-month endpoints were safety and efficacy., Results: In all, 72 (63%) had grade group 2 and 77 (67%) had NCCN® intermediate risk disease. Median treatment delivery time was 51 minutes with 98% (IQR 95-99) thermal coverage of target volume and spatial ablation precision of ±1.4 mm on magnetic resonance imaging thermometry. Grade 3 adverse events occurred in 9 (8%) men. The primary endpoint (U.S. Food and Drug Administration mandated) of prostate specific antigen reduction ≥75% was achieved in 110 of 115 (96%) with median prostate specific antigen reduction of 95% and nadir of 0.34 ng/ml. Median prostate volume decreased from 37 to 3 cc. Among 68 men with pretreatment grade group 2 disease, 52 (79%) were free of grade group 2 disease on 12-month biopsy. Of 111 men with 12-month biopsy data, 72 (65%) had no evidence of cancer. Erections (International Index of Erectile Function question 2 score 2 or greater) were maintained/regained in 69 of 92 (75%). Multivariate predictors of persistent grade group 2 at 12 months included intraprostatic calcifications at screening, suboptimal magnetic resonance imaging thermal coverage of target volume and a PI-RADS™ 3 or greater lesion at 12-month magnetic resonance imaging (p <0.05)., Conclusions: The TACT study of magnetic resonance imaging-guided transurethral ultrasound whole gland ablation in men with localized prostate cancer demonstrated effective tissue ablation and prostate specific antigen reduction with low rates of toxicity and residual disease.

Introduction: Although relapses after radiotherapy are common in prostate cancer (PCA) patients, those with a high risk for radioresistance cannot be identified prior to treatment yet. Therefore, this proof-of-concept study was performed to compare protein expression profiles of patients with radio-recurrent PCA to patients treated with primary radical prostatectomy separated by Gleason risk groups. We hypothesized that radio-recurrent PCA have a similar protein expression as high-risk Gleason PCA., Methods: Patient cohorts consisted of (i) 31 patients treated with salvage prostatectomy for locally recurrent PCA after primary radiotherapy and (ii) 94 patients treated with primary prostatectomy split into a Gleason high-risk (≥4 + 3; n = 42 [44.7%]) versus a low-risk group (≤3 + 4; n = 52 [55.3%]). Immunohistochemistry was performed using 15 antibodies with known association to radioresistance in PCA in vitro. ELISA was used for validation of selected markers in serum., Results: Androgen receptor (AR) was overexpressed in most radio-recurrent PCA (89.7%) and in most primary high-risk Gleason PCA (87.8%; p = 0.851), while only 67.3% of the low-risk group showed an expression (p = 0.017). Considering the highest Gleason pattern in primary PCA, aldo-keto reductase family 1 member C3 (AKR1C3) was most similarly expressed by patients with radio-recurrent PCA and patients with Gleason patterns 4 and 5 (p = 0.827 and p = 0.893) compared to Gleason pattern 3 (p = 0.20). These findings were supported by ELISA., Conclusion: This is the first study to evaluate protein markers in order to predict radioresistance in PCA. Our results point to AR and AKR1C3 as the most promising markers that might help stratify patients for radiotherapy., (© 2020 S. Karger AG, Basel.)

Purpose: For patients with prostate cancer, validated and reliable instruments are essential for measuring patient-reported outcomes. The aim of this study was to validate the German version of the widely established Expanded Prostate Cancer Index Composite with 26 items (EPIC-26)., Methods: A German translation of the original questionnaire was tested in 3094 patients with localized or locally advanced (any T, any N and M0) prostate cancer with treatment intent (including radical prostatectomy, brachytherapy, active surveillance, watchful waiting). They completed the EPIC-26 questionnaire before treatment. A total of 521 of them also completed a questionnaire 12 months afterward. Internal consistency, sensitivity to change, and construct validity were assessed., Results: The internal consistency of all domains was sufficient (Cronbach's alpha between 0.64 and 0.93). Item-to-scale correlation coefficients showed acceptable associations between items and their domain score (all > 0.30), with the lowest scores for "bloody stools" (r = 0.37) and "breast problems" (r = 0.32). Confirmatory and exploratory factor analysis confirmed the five-dimension structure of the EPIC-26 (comparative fit index 0.95)., Conclusions: Psychometric evaluation suggests that the German version of the EPIC-26 is a well-constructed instrument for measuring patient-reported health-related symptoms in patients with prostate cancer.

Background/aim: Vimentin3 (Vim3) was recently described as a tumour marker for the direct discrimination between benign and malignant kidney tumours. Here, we examined its expression in prostate cancer (PCa) cell lines and the regulation of its expression by endothelin receptors., Materials and Methods: Prostate cancer cell lines (PC3, DU145, LNCap) were incubated with endothelin 1 (ET-1), BQ123 [endothelin A receptor (ETAR) antagonist], BQ788 [endothelin B receptor (ETBR) antagonist], BQ123+ET-1, BQ788+ET-1 for 24 h and a scratch assay was performed. Cell extracts were analysed by western blotting and qRT-PCR., Results: ET-1 induced Vim3 overexpression. Blocking the ETBR in the different prostate cancer cell lines yielded a higher migration rate, whereby Vim3 expression was significantly increased., Conclusion: Vim3 concentration increases in cell lines without a functional ETBR and may be used as a marker for PCas where ETBR is frequently methylated., (Copyright© 2021, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: Different bone-modifying agents like bisphosphonates and receptor activator of nuclear factor-kappa B ligand (RANKL)-inhibitors are used as supportive treatment in men with prostate cancer and bone metastases to prevent skeletal-related events (SREs). SREs such as pathologic fractures, spinal cord compression, surgery and radiotherapy to the bone, and hypercalcemia lead to morbidity, a poor performance status, and impaired quality of life. Efficacy and acceptability of the bone-targeted therapy is therefore of high relevance. Until now recommendations in guidelines on which bone-modifying agents should be used are rare and inconsistent., Objectives: To assess the effects of bisphosphonates and RANKL-inhibitors as supportive treatment for prostate cancer patients with bone metastases and to generate a clinically meaningful treatment ranking according to their safety and efficacy using network meta-analysis., Search Methods: We identified studies by electronically searching the bibliographic databases Cochrane Controlled Register of Trials (CENTRAL), MEDLINE, and Embase until 23 March 2020. We searched the Cochrane Library and various trial registries and screened abstracts of conference proceedings and reference lists of identified trials., Selection Criteria: We included randomized controlled trials comparing different bisphosphonates and RANKL-inihibitors with each other or against no further treatment or placebo for men with prostate cancer and bone metastases. We included men with castration-restrictive and castration-sensitive prostate cancer and conducted subgroup analyses according to this criteria., Data Collection and Analysis: Two review authors independently extracted data and assessed the quality of trials. We defined proportion of participants with pain response and the adverse events renal impairment and osteonecrosis of the jaw (ONJ) as the primary outcomes. Secondary outcomes were SREs in total and each separately (see above), mortality, quality of life, and further adverse events such as grade 3 to 4 adverse events, hypocalcemia, fatigue, diarrhea, and nausea. We conducted network meta-analysis and generated treatment rankings for all outcomes, except quality of life due to insufficient reporting on this outcome. We compiled ranking plots to compare single outcomes of efficacy against outcomes of acceptability of the bone-modifying agents. We assessed the certainty of the evidence for the main outcomes using the GRADE approach., Main Results: Twenty-five trials fulfilled our inclusion criteria. Twenty-one trials could be considered in the quantitative analysis, of which six bisphosphonates (zoledronic acid, risedronate, pamidronate, alendronate, etidronate, or clodronate) were compared with each other, the RANKL-inhibitor denosumab, or no treatment/placebo. By conducting network meta-analysis we were able to compare all of these reported agents directly and/or indirectly within the network for each outcome. In the abstract only the comparisons of zoledronic acid and denosumab against the main comparator (no treatment/placebo) are described for outcomes that were predefined as most relevant and that also appear in the 'Summary of findings' table. Other results, as well as results of subgroup analyses regarding castration status of participants, are displayed in the Results section of the full text. Treatment with zoledronic acid probably neither reduces nor increases the proportion of participants with pain response when compared to no treatment/placebo (risk ratio (RR) 1.46, 95% confidence interval (CI) 0.93 to 2.32; per 1000 participants 121 more (19 less to 349 more); moderate-certainty evidence; network based on 4 trials including 1013 participants). For this outcome none of the trials reported results for the comparison with denosumab. The adverse event renal impairment probably occurs more often when treated with zoledronic acid compared to treatment/placebo (RR 1.63, 95% CI 1.08 to 2.45; per 1000 participants 78 more (10 more to 180 more); moderate-certainty evidence; network based on 6 trials including 1769 participants). Results for denosumab could not be included for this outcome, since zero events cannot be considered in the network meta-analysis, therefore it does not appear in the ranking. Treatment with denosumab results in increased occurrence of the adverse event ONJ (RR 3.45, 95% CI 1.06 to 11.24; per 1000 participants 30 more (1 more to 125 more); high-certainty evidence; 4 trials, 3006 participants) compared to no treatment/placebo. When comparing zoledronic acid to no treatment/placebo, the confidence intervals include the possibility of benefit or harm, therefore treatment with zoledronic acid probably neither reduces nor increases ONJ (RR 1.88, 95% CI 0.73 to 4.87; per 1000 participants 11 more (3 less to 47 more); moderate-certainty evidence; network based on 4 trials including 3006 participants). Compared to no treatment/placebo, treatment with zoledronic acid (RR 0.84, 95% CI 0.72 to 0.97) and denosumab (RR 0.72, 95% CI 0.54 to 0.96) may result in a reduction of the total number of SREs (per 1000 participants 75 fewer (131 fewer to 14 fewer) and 131 fewer (215 fewer to 19 fewer); both low-certainty evidence; 12 trials, 5240 participants). Treatment with zoledronic acid and denosumab likely neither reduces nor increases mortality when compared to no treatment/placebo (zoledronic acid RR 0.90, 95% CI 0.80 to 1.01; per 1000 participants 48 fewer (97 fewer to 5 more); denosumab RR 0.93, 95% CI 0.77 to 1.11; per 1000 participants 34 fewer (111 fewer to 54 more); both moderate-certainty evidence; 13 trials, 5494 participants). Due to insufficient reporting, no network meta-analysis was possible for the outcome quality of life. One study with 1904 participants comparing zoledronic acid and denosumab showed that more zoledronic acid-treated participants than denosumab-treated participants experienced a greater than or equal to five-point decrease in Functional Assessment of Cancer Therapy-General total scores over a range of 18 months (average relative difference = 6.8%, range -9.4% to 14.6%) or worsening of cancer-related quality of life., Authors' Conclusions: When considering bone-modifying agents as supportive treatment, one has to balance between efficacy and acceptability. Results suggest that Zoledronic acid likely increases both the proportion of participants with pain response, and the proportion of participants experiencing adverse events However, more trials with head-to-head comparisons including all potential agents are needed to draw the whole picture and proof the results of this analysis., (Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

The best surgical template for salvage pelvic lymph node dissection (sLND) in patients with nodal recurrence from prostate cancer (PCa) after radical prostatectomy (RP) is currently unknown. We analyzed data of 189 patients with a unilateral positive positron emission tomography (PET) scan of the pelvic lymph node areas, who were treated with bilateral pelvic sLND after RP at 11 high-volume centers. The primary endpoint was missed contralateral disease at final pathology, defined as lymph node positive for PCa in the side opposite to the positive spot(s) at the PET scan. Overall, 93 (49%) and 96 (51%) patients received a 11 C-choline and a 68 Ga prostate-specific membrane antigen (PSMA) PET scan, respectively, and 171 (90%) and 18 (10%) men had one and two positive spots, respectively. The rate of missed contralateral PCa was 18% (34/189), with the rates being 17% (29/171) and 28% (5/18) in men with one and two positive spots, respectively. While the rate of contralateral disease did not differ between 68 Ga-PSMA and 11 C-choline (29% and 27%, respectively) among men with two positive spots, the rate of contralateral PCa was only 6% with 68 Ga-PSMA versus 28% with 11 C-choline in patients with a single positive spot. This finding was confirmed at multivariable logistic regression analysis predicting missed disease at final pathology after accounting for confounders (odds ratio: 0.24; p =  0.001). However, in men with a single positive spot at 68 Ga-PSMA PET/computed tomography, the rate of single confirmed lymph node metastasis at final pathology was only 33%, suggesting the need for extended template even if unilateral dissection is performed. Awaiting confirmatory studies, patients diagnosed with a single positive spot at the 68 Ga-PSMA PET scan might be considered for unilateral extended pelvic sLND. PATIENT SUMMARY: We assessed the risk of missing contralateral disease in patients with a positron emission tomography (PET) scan suggestive of unilateral nodal recurrence from prostate cancer (PCa) after radical prostatectomy and who were treated with bilateral salvage lymph node dissection (sLND). Variability exists according to the number of positive spots and PET tracer, with the lowest rate of missed PCa in men diagnosed with a single positive spot at a 68 Ga prostate-specific membrane antigen PET scan (6%). If replicated, our data suggest that these patients might be considered for unilateral extended pelvic sLND., (Copyright © 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objective: To investigate the diagnostic performance of gallium-68 prostate-specific membrane antigen positron emission tomography/computed tomography ( 68 Ga-PSMA PET/CT) in patients with recurrent prostate cancer with regard to the presence of lymph node metastases (LNM) and local recurrences after primary radiotherapy., Patients and Methods: We retrospectively reviewed 142 patients following salvage radical prostatectomy (sRP), 50 of which had a 68 Ga-PSMA PET/CT performed as a preoperative staging module. Predictive clinical parameters were analysed in a multivariate Cox regression analysis. Sensitivity, specificity, positive (PPV) and negative predictive values (NPV) and the accuracy of 68 Ga-PSMA PET/CT were analysed with regard to LNM and local recurrence., Results: In all, 613 lymph nodes were resected in 40 patients and 23 lymph nodes had metastatic deposits in 14 patients. In all patients local recurrence could have been found with 68 Ga-PSMA PET/CT. Sensitivity, specificity, PPV and NPV and accuracy on a per lymph node basis were 34.78% (16.38-57.2%), 100% (99.38-100%), 100%, 97.52% (96.69-98.15%) and 97.55% (96.00-98.62%). For detecting local recurrence, the sensitivity and PPV were both 100% with an accuracy of 100% (92.89-100%)., Conclusion: 68 Ga-PSMA PET/CT should be the standard imaging in biochemical recurrent prostate cancer. With this imaging module one detects first local recurrence and can detect locoregional and distant metastases more precisely than standard CT and bone scan., (© 2020 The Authors BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Background/aim: Endothelin-1 (ET-1) is overexpressed in many types of cancer, inhibiting the release of the microRNA 15a (miR-15a) and inducing the production of Mxi-2. Our aim was to identify a molecular complex regulating p53 activity in prostate cancer (PCa)., Materials and Methods: DU145 cells were treated with ET-1, MAPK p38 inhibitor, Endothelin A receptor inhibitor (ETAR inhibitor) and Endothelin B receptor inhibitor (ETBR inhibitor). Extracts were analysed using Western Blot, immunoprecipitation and qRT-PCR. Furthermore, prostate cancer patient samples were analysed using qRT-PCR and ELISA., Results: The hypothesised molecular complex was identified, with miR-15a, microRNA 1285 (miR-1285) and Mxi-2 levels up-regulated in patients in relation to increasing aggressiveness of PCa., Conclusion: A complex composed of Argonaut 2 (Ago2)/Mxi-2/miR-1285 is involved in PCa. The expression of Mxi-2 correlates with increasing PCa aggressiveness and might be used as a non-invasive marker for the diagnosis and progression of PCa., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Objectives: To evaluate retrospectively the surgical, symptomatic and oncological outcomes of pelvic exenteration surgery (PES) in men with significant intrapelvic complications of locally advanced castration-sensitive (CSPC) and castration-resistant prostate cancer (CRPC)., Patients and Methods: A total of 103 patients with locally advanced progressive and symptomatic CSPC or CRPC underwent PES (radical cystoprostatectomy, n = 71 [68.9%]; radical prostatectomy with continent vesicostomy, n = 9 [8.7%]; total exenteration, n = 23 [22.3%]). All patients underwent local staging via magnetic resonance imaging, cystoscopy and rectoscopy. Systemic staging was carried out with chest, abdominal and pelvic computed tomography scans and bone scans. Peri-operative complications were assessed according to Clavien-Dindo classification. Symptom-free and overall survival were evaluated using the Kaplan-Meier method. Statistical tests were two-tailed with a P value <0.05 taken to indicate statistical significance., Results: After a median (range) follow-up of 36.5 (3-123) months, the symptom-free survival rate at 1 and 3 years was 89.2% (n = 89) and 64.1% (n = 66), respectively. The median symptom-free survival was 27.9 months. A total of 78.6% of the patients were symptom-free during their remaining lifetime. The overall survival rate at 1 and 3 years was 92.2% and 43.7%, respectively, and the median overall survival was 33.6 months. Clavien-Dindo grades 2, 3 and 4 complications developed in 31 (30.6%), 12 (11.6%) and eight patients (8.1%), respectively., Conclusion: Pelvic exenteration surgery is technically feasible in well-selected patients, resulting in symptom relief in >90% of patients, covering 80% of their remaining lifetime., (© 2020 The Authors BJU International © 2020 BJU International Published by John Wiley & Sons Ltd.)

Purpose: We compared the use of 11 C-choline and 68 Ga-prostate specific membrane antigen in men undergoing salvage lymph node dissection for nodal recurrent prostate cancer., Materials and Methods: The study included 641 patients who experienced prostate specific antigen rise and nodal recurrence after radical prostatectomy and underwent salvage lymph node dissection. Lymph node recurrence was documented by positron emission tomography/computerized tomography using 11 C-choline (407, 63%) or 68 Ga-PSMA ligand (234, 37%). The outcome was underestimation of tumor burden (difference between number of positive nodes on final pathology and number of positive spots at positron emission tomography/computerized tomography). Multivariable analysis tested the association between positron emission tomography/computerized tomography tracer ( 11 C-choline vs 68 Ga-PSMA) and tumor burden underestimation., Results: Overall the extent of tumor burden underestimation was significantly higher in the 11 C-choline group compared to the 68 Ga-PSMA group (p <0.0001), which was confirmed on multivariable analysis (p=0.028). Repeating these analyses according to prostate specific antigen, tumor burden underestimation was lower with 68 Ga-PSMA only when prostate specific antigen was 1.5 ng/ml or less. Conversely, the underestimation of the 2 tracers became similar when prostate specific antigen was greater than 1.5 ng/ml. Furthermore, we evaluated the risk of underestimation by number of positive spots on positron emission tomography/computerized tomography. The higher the number of positive spots the higher the underestimation of tumor burden regardless of the tracer used (p=0.2)., Conclusions: Positron emission tomography/computerized tomography significantly underestimates the burden of prostate cancer recurrence, regardless of the tracer used. 68 Ga-PSMA was associated with a lower rate of underestimation in patients with a prostate specific antigen below 1.5 ng/ml and a limited nodal tumor load. In all other men there was no benefit from 68 Ga-PSMA over 11 C-choline in assessing the extent of nodal recurrence.

Purpose of Review: The standard treatment in metastatic prostate cancer (mPCa) is systemic, based on androgen deprivation therapy recommended in different forms, alone or combined with abiraterone acetate or docetaxel. The aim of this review is to synthesize the available data from literature regarding the optimal treatment of the primary in patients diagnosed with metastatic prostate cancer., Recent Findings: Multimodal treatments offer the best chance for survival for these patients, but the optimal strategy lacks consensus. Using retrospective studies as an argument, recent articles sustain the clinical and oncological benefits of local therapies in hormone-naïve metastatic prostate cancer, represented by radical prostatectomy or radiotherapy. Through these procedures, local control of disease can be achieved, thus avoiding potential complications and further surgical interventions. Even if the current results are not evenly relevant, the treatment of the primary along with metastasis-directed therapy could improve survival and even cure-selected patients., Summary: This article emphasizes important aspects regarding a feasible management of mPCa, with possible impact on subsequent guidelines. The expected results from ongoing trials may provide another perspective in treatment of these cases.

18 F-prostate-specific membrane antigen (PSMA)-1007 is excreted mainly through the liver. We benchmarked the performance of 18 F-PSMA-1007 against 3 renally excreted PSMA tracers. Methods: Among 668 patients, we selected 27 in whom PET/CT results obtained with 68 Ga-PSMA-11, 18 F-DCFPyL (2-(3-(1-carboxy-5-[(6-[ 18 F]fluoro-pyridine-3-carbonyl)-amino]-pentyl)-ureido)-pentanedioic acid), or 18 F-JK-PSMA-7 (JK, Juelich-Koeln) were interpreted as equivocal or negative or as oligometastatic disease (PET-1). Within 3 wk, a second PET scan with 18 F-PSMA-1007 was performed (PET-2). The confidence in the interpretation of PSMA-positive locoregional findings was scored on a 5-point scale, first in routine diagnostics (reader 1) and then by an independent second evaluation (reader 2). Discordant PSMA-positive skeletal findings were examined by contrast-enhanced MRI. Results: For both readers, 18 F-PSMA-1007 facilitated the interpretability of 27 locoregional lesions. In PET-2, the clinical readout led to a significantly lower number of equivocal locoregional lesions ( P = 0.024), and reader 2 reported a significantly higher rate of suspected lesions that were falsely interpreted as probably benign in PET-1 ( P = 0.023). Exclusively in PET-2, we observed a total of 15 PSMA-positive spots in the bone marrow of 6 patients (22%). None of the 15 discordant spots had a morphologic correlate on the corresponding CT scan or on the subsequent MRI scan. Thus, 18 F-PSMA-1007 exhibits a significantly higher rate of unspecific medullary spots ( P = 0.0006). Conclusion: 18 F-PSMA-1007 may increase confidence in interpreting small locoregional lesions adjacent to the urinary tract but may decrease the interpretability of skeletal lesions., (© 2020 by the Society of Nuclear Medicine and Molecular Imaging.)

Background: Innovations in treatments, imaging, and molecular characterisation in advanced prostate cancer have improved outcomes, but there are still many aspects of management that lack high-level evidence to inform clinical practice. The Advanced Prostate Cancer Consensus Conference (APCCC) 2019 addressed some of these topics to supplement guidelines that are based on level 1 evidence., Objective: To present the results from the APCCC 2019., Design, Setting, and Participants: Similar to prior conferences, experts identified 10 important areas of controversy regarding the management of advanced prostate cancer: locally advanced disease, biochemical recurrence after local therapy, treating the primary tumour in the metastatic setting, metastatic hormone-sensitive/naïve prostate cancer, nonmetastatic castration-resistant prostate cancer, metastatic castration-resistant prostate cancer, bone health and bone metastases, molecular characterisation of tissue and blood, inter- and intrapatient heterogeneity, and adverse effects of hormonal therapy and their management. A panel of 72 international prostate cancer experts developed the programme and the consensus questions., Outcome Measurements and Statistical Analysis: The panel voted publicly but anonymously on 123 predefined questions, which were developed by both voting and nonvoting panel members prior to the conference following a modified Delphi process., Results and Limitations: Panellists voted based on their opinions rather than a standard literature review or formal meta-analysis. The answer options for the consensus questions had varying degrees of support by the panel, as reflected in this article and the detailed voting results reported in the Supplementary material., Conclusions: These voting results from a panel of prostate cancer experts can help clinicians and patients navigate controversial areas of advanced prostate management for which high-level evidence is sparse. However, diagnostic and treatment decisions should always be individualised based on patient-specific factors, such as disease extent and location, prior lines of therapy, comorbidities, and treatment preferences, together with current and emerging clinical evidence and logistic and economic constraints. Clinical trial enrolment for men with advanced prostate cancer should be strongly encouraged. Importantly, APCCC 2019 once again identified important questions that merit assessment in specifically designed trials., Patient Summary: The Advanced Prostate Cancer Consensus Conference provides a forum to discuss and debate current diagnostic and treatment options for patients with advanced prostate cancer. The conference, which has been held three times since 2015, aims to share the knowledge of world experts in prostate cancer management with health care providers worldwide. At the end of the conference, an expert panel discusses and votes on predefined consensus questions that target the most clinically relevant areas of advanced prostate cancer treatment. The results of the voting provide a practical guide to help clinicians discuss therapeutic options with patients as part of shared and multidisciplinary decision making., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

In preclinical trials, the recently developed tracer 2-methoxy- 18 F-DCFPyL ( 18 F-JK-prostate-specific membrane antigen [PSMA]-7) has shown favorable properties regarding clinical performance and radiochemical accessibility. The aim of this study was to evaluate the clinical utility of 18 F-JK-PSMA-7 for PET/CT imaging of patients with prostate cancer. Methods: In an Institutional Review Board-approved pilot study, the initial clinical utility of PET/CT imaging with 18 F-JK-PSMA-7 was directly compared with 68 Ga-PSMA-11 PET/CT in a group of 10 patients with prostate cancer. The 2 PSMA tracers were administered to each patient less than 3 wk apart. Next, we analyzed the data of 75 consecutive patients who had undergone clinical 18 F-JK-PSMA-7 PET/CT imaging for tumor localization of biochemical recurrence (BCR). Results: The pilot study in 10 patients who were examined with both PSMA tracers demonstrated that 18 F-JK-PSMA-7 was at least equivalent to 68 Ga-PSMA-11. All unequivocally 68 Ga-PSMA-11-positive lesions could be also detected using 18 F-JK-PSMA-7, and in 4 patients additional suspected PSMA-positive lesions were identified (1 patient changed from PSMA-negative to PSMA-positive). In patients with BCR (after prostatectomy or radiotherapy), the capacity of 18 F-JK-PSMA-7 PET/CT to detect at least one PSMA-positive lesion was 84.8%. The prostate-specific antigen (PSA)-stratified detection rate of 18 F-JK-PSMA-7 after prostatectomy varied among 54.5% (6/11 patients; PSA < 0.5 μg/L), 87.5% (14/16 patients; PSA 0.5-2 μg/L), and 90.9% (20/22 patients; PSA > 2 μg/L). Conclusion: The tracer 18 F-JK-PSMA-7 was found to be safe and clinically useful. We demonstrated that 18 F-JK-PSMA-7 was not inferior when directly compared with 68 Ga-PSMA-11 in a pilot study but indeed identified additional PSMA-avid suspected lesions in oligometastasized patients with BCR. In a subsequent analysis of a clinical cohort of BCR patients, 18 F-JK-PSMA-7 was useful in tumor localization. 18 F-JK-PSMA-7 is recommended for future prospective trials., (© 2020 by the Society of Nuclear Medicine and Molecular Imaging.)

Purpose of Review: Local treatment of the primary by either radical prostatectomy or radiation therapy is discussed controversially. The role of cytoreductive radical prostatectomy has been evaluated in few retrospective clinical studies but data of prospective randomized clinical phase-III trials are lacking. It is the purpose of this review to reflect the current knowledge on indication, functional and oncological outcomes of cytoreductive radical prostatectomy to objectively highlight what can be expected from this approach., Recent Findings: Cytoreductive radical prostatectomy (cRP) is associated with a long overall survival of more than 7 years and it is associated with a clinical progression-free survival of more than 6 years. When compared with nonsurgical approaches it becomes evident that about one-third of the patients will develop symptomatic local progression within 3 years whereas none of the surgically treated patients will experience such symptoms. cRP is associated with a low rate of significant complications and good functional outcome in well selected patients which do not differ from the results of a radical prostatectomy in treatment-naïve patients., Summary: Patients with low-volume/low-risk metastatic prostate cancer (mPCA), good response to neoadjuvant androgen deprivation therapy and a good Eastern Cooperative Onology Group performance status appear to be the best candidates for surgery. cRP might be an individualized treatment option in the multimodality management of mPCA. It is the purpose of the current to highlight the indication, surgical technique, treatment associated complications, functional and oncological outcome for cytoreductive radical prostatectomy.

Context: Whether focal therapy (FT) for prostate cancer (PC) jeopardizes outcomes from salvage treatments is a matter of debate still to be resolved., Objective: To review the literature on oncological and functional outcomes and complications for available treatment options for recurrent or residual PC after primary FT., Evidence Acquisition: We performed a nonsystematic search of PubMed for articles assessing relevant outcomes for salvage local treatment after FT failure using a manual search. When no evidence could be extracted for the FT domain, records dealing with recurrence after whole-gland ablation were considered., Evidence Synthesis: Four retrospective series assessed salvage treatments after FT failure evaluating cases of radical prostatectomy (RP) and repeat ablation (sample size from 12 to 22 patients). The quality of the studies was low, with a high risk of bias. Other options are radiation therapy (RT) and whole-gland or focal repeat ablations, although these have only been described after whole-gland ablation. With some exceptions, including sexual function for RP, overall complications and oncological and functional outcomes do seem to be acceptable and are not much worse than those in the primary setting. Important limitations include the low level of the evidence and the absence of standardized criteria for FT, salvage treatment, and FT failure., Conclusions: Current evidence shows acceptable outcomes for post-FT salvage options, although this is based on retrospective data. While it seems that FT has a minimal impact on salvage treatment results, prospective controlled studies are needed to confirm these preliminary data., Patient Summary: We performed a literature search to determine the treatment options available for prostate cancer after failure of focal therapy and their outcomes. Options include radical prostatectomy, repeat whole-gland ablation, focal ablation, and radiotherapy. Overall cancer control, impacts on urinary and sexual function, and complications seem slightly worse but not markedly different compared to primary treatments, but high-quality studies are awaited to confirm these findings., (Copyright © 2019 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Prostate cancer is the most common cancer in men. Its incidence increases with age. New treatment options have been introduced and there is a clear trend to more aggressive treatment in newly diagnosed metastatic disease. While prolonged survival of patients has been achieved, the new expensive drugs are associated with an increased burden on the healthcare system. Meanwhile, similarly to other tumour entities, there is a pool of different drugs available with comparable oncologic efficacy, but different side-effects. Effective diagnostic investigation and treatment decisions require additional factors, above and beyond clinical parameters, for a more individual treatment approach. In castration-resistant prostate cancer (CRPCA), there are promising molecular markers for treatment decisions. In metastatic disease, liquid biopsies and next generation sequencing of metastatic biopsies allow for genetic analysis. These will provide more insight into tumour dynamics and allow for patient selection. This review concentrates on molecular markers in CRPCA., Competing Interests: Der Autor gibt an, dass kein Interessenkonflikt besteht., (© Georg Thieme Verlag KG Stuttgart · New York.)

Context: Radiotherapy used for treating localized prostate cancer is effective at prolonging cancer-specific and overall survival. Still, acute and late pelvic toxicities are a concern, with gastrointestinal (GI) and genitourinary (GU) sequelae being most common as well as other pelvic complications., Objective: To present a critical review of the literature regarding the incidence and risk factors of pelvic toxicity following primary radiotherapy for prostate cancer and to provide a narrative review regarding its management., Evidence Acquisition: A collaborative narrative review of the literature from 2010 to present was conducted., Evidence Synthesis: Regardless of the modality used, the incidence of acute high-grade pelvic toxicity is low following conventionally fractionated external beam radiotherapy (EBRT). After moderate hypofractionation, the crude cumulative incidences for late grade 3 or higher (G3+) GI and GU complications are as high as 6% and 7%, respectively. After extreme hypofractionation, the 5-yr incidences of G2+ GU and GI toxicities are 3-9% and 0-4%, respectively. Following brachytherapy monotherapy, crude rates of late G3+ GU toxicity range from 6% to 8%, while late GI toxicity is rare. With combination therapy (EBRT and brachytherapy), the cumulative incidence of late GU toxicity is high, between 18% and 31%; however, the prevalence is lower at 4-14%. Whole pelvic radiotherapy remains a controversial treatment option as there is increased G3+ GI toxicity compared with prostate-only treatment, with no overall survival benefit. Proton beam therapy appears to have similar toxicity to photon therapies currently in use. With respect to specific complications, urinary obstruction and urethral stricture are the most common severe urinary toxicities. Rectal and urinary bleeding can be recurrent long-term toxicities. The risk of hip fracture is also increased following prostate radiotherapy. The literature is mixed on the risk of in-field secondary pelvic malignancies following prostate radiotherapy. Urinary and GI fistulas are rare complications. Management of these toxicities may require invasive treatment and reconstructive surgery for refractory and severe symptoms., Conclusions: There has been progress in the delivery of radiotherapy, enabling the administration of higher doses with minimal tradeoff in terms of slightly increased or equal toxicity. There is a need to focus future improvements in radiotherapy on sparing critical structures to reduce GU and GI morbidities. While complications such as fistulae, bone toxicity, and secondary malignancy are rare, there is a need for higher-quality studies assessing these outcomes and their management., Patient Summary: In this report, we review the literature regarding pelvic complications following modern primary prostate cancer radiotherapy and their management. Modern radiotherapy technologies have enabled the administration of higher doses with minimal increases in toxicity. Overall, high-grade long-term toxicity following prostate radiotherapy is uncommon. Management of late high-grade pelvic toxicities can be challenging, with patients often requiring invasive therapies for refractory cases., (Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.)