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Purpose : To identify predictive factors for late rectal toxicity in prostate cancer patient who underwent intensitymodulated radiation therapy (IMRT). Methods : 415 prostate cancer patients who underwent IMRT between November 2008 and September 2019 were included. All patients underwent definitive radiation therapy with a total prescribed dose of 78 Gy, and 2 Gy per fraction. We analyzed the relationship between late rectal toxicity and the following factors : National Comprehensive Cancer Network (NCCN) risk classification, use of anticoagulants, radiation methods and various dose-volume histogram parameters. Results : Median follow-up period was 46 months (3-133). Grade ≥ 2 late rectal adverse events occurred in 8.0 ％ (n＝33). Univariate analysis revealed that NCCN high-risk group (P＝0.026) and low percentage of bladder wall volume irradictaed 70 Gy or more to total bladder wall volume (BW V70Gy％) were significantly associated with increased rate of Grade ≥ 2 late rectal toxicity (P＝0.026 and 0.036, respectively). Multivariate analysis showed that both of them were independently accociated with the rate of the toxicity (P＝0.016 and 0.033, respectively). Conclusion : NCCN high-risk group and low BW V70Gy％ might be predictive factors for Grade ≥ 2 late rectal toxicity., Article, 信州医学雑誌 71(3) : 159-165, (2023)

UNLABELLED: The global uptake of prostate cancer (PCa) active surveillance (AS) is steadily increasing. While prostate-specific antigen density (PSAD) is an important baseline predictor of PCa progression on AS, there is a scarcity of recommendations on its use in follow-up. In particular, the best way of measuring PSAD is unclear. One approach would be to use the baseline gland volume (BGV) as a denominator in all calculations throughout AS (nonadaptive PSAD, PSADNA), while another would be to remeasure gland volume at each new magnetic resonance imaging scan (adaptive PSAD, PSADA). In addition, little is known about the predictive value of serial PSAD in comparison to PSA. We applied a long short-term memory recurrent neural network to an AS cohort of 332 patients and found that serial PSADNA significantly outperformed both PSADA and PSA for follow-up prediction of PCa progression because of its high sensitivity. Importantly, while PSADNA was superior in patients with smaller glands (BGV ≤55 ml), serial PSA was better in men with larger prostates of >55 ml. PATIENT SUMMARY: Repeat measurements of prostate-specific antigen (PSA) and PSA density (PSAD) are the mainstay of active surveillance in prostate cancer. Our study suggests that in patients with a prostate gland of 55 ml or smaller, PSAD measurements are a better predictor of tumour progression, whereas men with a larger gland may benefit more from PSA monitoring.

The PROpel trial assessed the combination of olaparib+abiraterone acetate (AA) plus prednisone and androgen deprivation therapy (ADT) versus AA plus prednisone and ADT alone as first-line treatment for metastatic castration-resistant prostate cancer (mCPRP). To contextualize the progression free survival (PFS) benefit in PROpel, we performed a systematic review and quasi-individual patient data network meta-analysis on randomized controlled trials of first-line hormonal treatments for mCPRC. Meta-analysis was performed for the PROpel control arm and PREVAIL (enzalutamide) and COU-AA-302 (AA) treatment arms. Kaplan-Meier PFS curves were digitally reconstructed and differences in restricted mean survival time (ΔRMST) were computed. Combination therapy yielded longer PFS (24-mo ΔRMST 1.5 mo, 95% confidence interval 0.6-2.4) in comparison to novel hormonal treatments alone. However, the lack of mature overall survival data, higher complication rates, and higher health care costs are limitations of combination therapy. Ultimately, combining treatments, rather than molecularly targeted sequencing in cases of failure, might not be justified in unselected patients with mCRPC.Patient summaryA recent trial showed that for metastatic prostate cancer that does not respond to hormone treatment, combined therapy with two drugs (olaparib and abiraterone) may prolong survival free from cancer progression. We included these data in an analysis of three trials that confirmed a small benefit. This combination approach has higher complication rates and is more expensive, and longer-term results for overall survival are needed.

Antiresorptive agent-related osteonecrosis of the jaw (ARONJ) is a severe adverse event associated with use of bone resorption inhibitors (BRIs), such as zoledronic acid and denosumab. Based on the results of phase 3 clinical trials for BRIs, the frequency of ARONJ is reported to be 1 to 2%, but the actual frequency could be higher. We investigated 173 patients with prostate cancer with bone metastases who were treated either with zoledronic acid or denosumab at our hospital between July 2006 and June 2020. ARONJ occurred in 13 patients (8%); i.e., ten out of 159 patients (6%) who were treated with zoledronic acid, and three out of 14 patients (21%) who were treated with denosumab. Multivariate analysis showed that longer duration of BRI exposure and dental treatment before the initiation of BRI are associated with risk of ARONJ. ARONJ is associated with decreased mortality but the association is not significant. Generally, the occurrence of ARONJ may be underestimated; therefore, further studies are warranted to determine the actual frequency of ARONJ.

Prostate cancer (PCa) continues to be the second most common malignant tumour and the main cause of oncological death in men. Investigating endogenous volatile organic metabolites (VOMs) produced by various metabolic pathways is emerging as a novel, effective, and non-invasive source of information to establish the volatilomic biosignature of PCa. In this study, headspace solid-phase microextraction combined with gas chromatography–mass spectrometry (HS-SPME/GC-MS) was used to establish the urine volatilomic profile of PCa and identify VOMs that can discriminate between the two investigated groups. This non-invasive approach was applied to oncological patients (PCa group, n = 26) and cancer-free individuals (control group, n = 30), retrieving a total of 147 VOMs from various chemical families. This included terpenes, norisoprenoid, sesquiterpenes, phenolic, sulphur and furanic compounds, ketones, alcohols, esters, aldehydes, carboxylic acid, benzene and naphthalene derivatives, hydrocarbons, and heterocyclic hydrocarbons. The data matrix was subjected to multivariate analysis, namely partial least-squares discriminant analysis (PLS-DA). Accordingly, this analysis showed that the group under study presented different volatomic profiles and suggested potential PCa biomarkers. Nevertheless, a larger cohort of samples is required to boost the predictability and accuracy of the statistical models developed.

Background: Erectile dysfunction (ED) is common after prostate cancer treatment. It has been studied for conventional radiotherapy, but associations in the hypofractionated radiotherapy context are less clear. This study aimed to determine which factors are predicted for worsening ED after highly conformal, modestly hypofractionated radiotherapy to the prostate. Methods: Two hundred and twelve patients treated with 6000 cGy in twenty fractions across four centers were included in this study. Demographic, clinical, and dosimetry factors were then evaluated for post-treatment declines in erectile function using logistic regression and an explainable machine learning-based neural network. Results: 212 patients with a median follow-up of 3.6 years were evaluated. A total of 104 (49%) patients received androgen deprivation therapy. Prior to treatment, 52 (25%) patients were on ED medication. Mean doses to the penile bulb, penile crus, and penile shaft were 2490 (IQR: 1529–3656) cGy, 2095 (1306–3036) cGy, and 444 (313–650) cGy, respectively. Fifty-nine (28%) patients had a worsening of ED after treatment. On multivariable analysis, only the mean dose to the penile shaft [OR >345 vs. ≤345: 4.47 (1.43–13.99); p = 0.010] and pretreatment use of ED medication [OR yes vs. no: 12.5 (5.7–27.5; p < 0.001)] predicted for worsening ED. The neural network confirmed that the penile shaft mean dose and pre-treatment ED medication use are the most important factors in predicting ED. Conclusions: Pre-treatment ED and penile shaft dosimetry are important predictors for ED after hypofractionated radiotherapy for prostate cancer.

Prostate cancer is one of the most common causes of cancer mortality in the US and globally. Environmental factors such as diet and pesticides may play a role in modifying risk of prostate cancer among men. The existing literature has shown that “The Agricultural Health Study” population exhibits a higher incidence of prostate cancer (PCa) than the general population. Accordingly, I defined the specific aims of this dissertation as, 1. Describing the association between a balanced ratio of omega-6 to omega-3 fatty acids and any potential for effect modification by terbufos and fonofos; 2. Estimating the association between total fat and saturated fatty acids and prostate cancer; and 3. Evaluating the effect of polyunsaturated fatty acids and monounsaturated fatty acids on risk of prostate cancer., In this nested case control study, the effect sizes were estimated by multivariate logistic regression models including the potential confounding variables in the analysis. The results of this dissertation showed that lower ratios of omega-6/omega-3 fatty were associated with decreased risk of prostate cancer and that there was no evidence of effect modification by terbufos or fonofos. Our age-stratified analysis showed significant effect sizes for lower ratios of omega-6 to omega-3 fatty acids only for those who were younger (48-55 years old). For the other two aims of this study, I did not find any significant association between fatty acids and risk of prostate cancer. Furthermore, there was no significant interaction between terbufos/fonofos and total saturated fatty acids, polyunsaturated fatty acids and monounsaturated fatty acids. In conclusion, providing a balance between omega-6 and omega-3 fatty acids may decrease risk of prostate cancer in younger age groups.

Background: Many cancer survivors experience late effects after cancer. Comorbidity, health literacy, late effects, and help-seeking behavior may affect healthcare use and may differ among socioeconomic groups. We examined healthcare use among cancer survivors, compared with cancer-free individuals, and investigated educational differences in healthcare use among cancer survivors. Methods: A Danish cohort of 127,472 breast, prostate, lung, and colon cancer survivors from the national cancer databases, and 637,258 age- and sex-matched cancer-free individuals was established. Date of entry was 12 months after diagnosis/index date (for cancer-free individuals). Follow-up ended at death, emigration, new primary cancer, December 31st, 2018, or up to 10 years. Information about education and healthcare use, defined as the number of consultations with general practitioner (GP), private practicing specialists (PPS), hospital, and acute healthcare contacts 1–9 years after diagnosis/index date, was extracted from national registers. We used Poisson regression models to compare healthcare use between cancer survivors and cancer-free individuals, and to investigate the association between education and healthcare use among cancer survivors. Results: Cancer survivors had more GP, hospital, and acute healthcare contacts than cancer-free individuals, while the use of PPS were alike. One-to-four-year survivors with short compared to long education had more GP consultations (breast, rate ratios (RR) = 1.28, 95% CI = 1.25–1.30; prostate, RR = 1.14, 95% CI = 1.10–1.18; lung, RR = 1.18, 95% CI = 1.13–1.23; and colon cancer, RR = 1.17, 95% CI = 1.13–1.22) and acute contacts (breast, RR = 1.35, 95% CI = 1.26–1.45; prostate, RR = 1.26, 95% CI = 1.15–1.38; lung, RR = 1.24, 95% CI = 1.16–1.33; and colon cancer, RR = 1.35, 95% CI = 1.14–1.60), even after adjusting for comorbidity. One-to-four-year survivors with short compared to long education had less consultations with PPS, while no association was observed for hospital contacts. Conclusion: Cancer survivors used more healthcare than cancer-free individuals. Cancer survivors with short education had more GP and acute healthcare contacts than survivors with long education. To optimize healthcare use after cancer, we need to better understand survivors’ healthcare-seeking behaviors and their specific needs, especially among survivors with short education.

Prostate cancer (PCa) is the second most common cause of cancer death in American men. Metastatic castration-resistant prostate cancer (mCRPC) is the most lethal form of PCa and preferentially metastasizes to the bones through incompletely understood molecular mechanisms. Herein, we processed RNA sequencing data from patients with mCRPC (n = 60) and identified 14 gene clusters (modules) highly correlated with mCRPC bone metastasis. We used a novel combination of weighted gene co-expression network analysis (WGCNA) and upstream regulator and gene ontology analyses of clinically annotated transcriptomes to identify the genes. The cyan module (M14) had the strongest positive correlation (0.81, p = 4 × 10−15) with mCRPC bone metastasis. It was associated with two significant biological pathways through KEGG enrichment analysis (parathyroid hormone synthesis, secretion, and action and protein digestion and absorption). In particular, we identified 10 hub genes (ALPL, PHEX, RUNX2, ENPP1, PHOSPHO1, PTH1R, COL11A1, COL24A1, COL22A1, and COL13A1) using cytoHubba of Cytoscape. We also found high gene expression for collagen formation, degradation, absorption, cell-signaling peptides, and bone regulation processes through Gene Ontology (GO) enrichment analysis.

BACKGROUND: Guidelines suggest that active surveillance (AS) may be considered for select patients with favorable intermediate-risk (fIR) prostate cancer. OBJECTIVE: To compare the outcomes between fIR prostate cancer patients included by Gleason score (GS) or prostate-specific antigen (PSA). Most patients are classified with fIR disease due to either a 3 + 4 = 7 GS (fIR-GS) or a PSA level of 10–20 ng/ml (fIR-PSA). Previous research suggests that inclusion by GS 7 may be associated with worse outcomes. DESIGN, SETTING, AND PARTICIPANTS: We conducted a retrospective cohort study of US veterans diagnosed with fIR prostate cancer from 2001 to 2015. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We compared the incidence of metastatic disease, prostate cancer–specific mortality (PCSM), all-cause mortality (ACM), and receipt of definitive treatment between fIR-PSA and fIR-GS patients managed with AS. Outcomes were compared with those of a previously published cohort of patients with unfavorable intermediate-risk disease using cumulative incidence function and Gray’s test for statistical significance. RESULTS AND LIMITATIONS: The cohort included 663 men; 404 had fIR-GS (61%) and 249 fIR-PSA (39%). There was no evidence of difference in the incidence of metastatic disease (8.6% vs 5.8%, p = 0.77), receipt of definitive treatment (77.6% vs 81.5%, p = 0.43), PCSM (5.7% vs 2.5%, p = 0.274), and ACM (16.8% vs 19.1%, p = 0.14) between the fIR-PSA and fIR-GS groups at 10 yr. On multivariate regression, unfavorable intermediate-risk disease was associated with higher rates of metastatic disease, PCSM, and ACM. Limitations included varying surveillance protocols. CONCLUSIONS: There is no evidence of difference in oncological and survival outcomes between men with fIR-PSA and fIR-GS prostate cancer undergoing AS. Thus, presence of GS 7 disease alone should not exclude patients from consideration of AS. Shared decision-making should be utilized to optimize management for each patient. PATIENT SUMMARY: In this report, we compared the outcomes of men with favorable intermediate-risk prostate cancer in the Veterans Health Administration. We found no significant difference between survival and oncological outcomes.

We aimed to estimate the total health care costs attributable to prostate cancer (PCa) during care phases by age, cancer stage, tumor grade, and primary treatment in the first year in British Columbia (BC), Canada. Using linked administrative health data, we followed a cohort of men aged ≥ 50 years at diagnosis with PCa between 2010 and 2017 (Cohort 1) from the diagnosis date until the date of death, the last date of observation, or 31 December 2019. Patients who died from PCa after 1 January 2010, were selected for Cohort 2. PCa attributable costs were estimated by comparing costs in patients to matched controls. Cohort 1 (n = 22,672) had a mean age of 69.9 years (SD = 8.9) and a median follow-up time of 5.2 years. Cohort 2 included 6942 patients. Mean PCa attributable costs were the highest during the first year after diagnosis ($14,307.9 [95% CI: $13,970.0, $14,645.8]) and the year before death ($9959.7 [$8738.8, $11,181.0]). Primary treatment with radiation therapy had significantly higher costs each year after diagnosis than a radical prostatectomy or other surgeries in advanced-stage PCa. Androgen deprivation therapy (and/or chemotherapy) had the highest cost for high-grade and early-stage cancer during the three years after diagnosis. No treatment group had the lowest cost. Updated cost estimates could inform economic evaluations and decision-making.

Aldehyde dehydrogenase (ALDH) enzymes are involved in the growth and development of several tissues, including cancer cells. It has been reported that targeting the ALDH family, including the ALDH1A subfamily, enhances cancer treatment outcomes. Therefore, we aimed to investigate the cytotoxicity of ALDH1A3-affinic compounds that have been recently discovered by our group, on breast (MCF7 and MDA-MB-231) and prostate (PC-3) cancer cell lines. These compounds were investigated on the selected cell lines as single treatments and in combination with doxorubicin (DOX). Results showed that the combination treatment experiments of the selective ALDH1A3 inhibitors (compounds 15 and 16) at variable concentrations with DOX resulted in significant increases in the cytotoxic effect on the MCF7 cell line for compound 15, and to a lesser extent for compound 16 on the PC-3 cell line, compared to DOX alone. The activity of compounds 15 and 16 as single treatments on all cell lines was found to be non-cytotoxic. Therefore, our findings showed that the investigated compounds have a promising potential to target cancer cells, possibly via an ALDH-related pathway, and sensitize them to DOX treatment.

International audience; Background and Objectives: Some medications require specific medical procedures in the weeks before their start. Such procedures may meet the definition of instrumental variables (IVs). We examined how they may influence treatment effect estimation in propensity score (PS)-adjusted comparative studies, and how to remedy. Study Design and Setting: Different covariate assessment periods (CAPs) did and did not include the month preceding treatment start were used to compute PS in the French claims database (Syt eme National des Donn ees de Sant e-SNDS), and 1:1 match patients with metastatic castration resistant prostate cancer initiating abiraterone acetate or docetaxel. The 36-month survival was assessed. Results: Among 1, 213 docetaxel and 2, 442 abiraterone initiators, the PS distribution resulting from the CAP [-12; 0 months] distinctly separated populations (c 5 0.93; 273 matched pairs). The CAPs [-12;-1 months] identified 765 pairs (c 5 0.81). Strong docetaxel treatment predictors during the month before treatment start were implantable delivery systems (1% vs. 59%), which fulfilled IV conditions. The 36-month survival was not meaningfully different under the [-12; 0 months] CAP but differed by 10% points (38% vs. 28%) after excluding month À1. Conclusion: In the setting of highly predictive pretreatment procedures, excluding the immediate pre-exposure time from the CAP will reduce the risk of including potential IVs in PS models and may reduce bias.

Refereed/Peer-reviewed Objectives: To study how handling missing data on M stage in a clinical cancer register affects estimates of incidence of metastatic prostate cancer. Study Design and Setting: Estimates of age-standardized incidence of metastatic prostate cancer were obtained by the use of data in a population-based clinical cancer register in Sweden and using four methods for imputation of missing M stage. Adjusted survival was used to compare men with known and imputed M stage. Results: The proportion of men with missing M stage was high (66%) and varied according to the risk group and over calendar time. The estimated incidence of metastatic disease varied depending on imputation method, with all methods indicating a decreasing incidence over time. A combination of deterministic imputation (DI) and multiple imputation (MI) produced adjusted survival curves for men with imputed M stage that best resembled the survival for men with known M stage. Conclusions: Plausible estimates of incidence of metastatic prostate cancer in clinical cancer registers can be obtained by the use of a combination of DI of missing M stage and MI.

Prostate cancer (PCa) is the second most common malignancy in men, and the fifth leading cause of death worldwide. Mesenchymal stromal/stem cells (MSC) have been identified in PCa, although contradictory effects in malignant transformation and tumor progression have been described. Since umbilical cord (UC) MSC and cord blood serum (CBS) are rich in numerous growth and anti-inflammatory factors, UC-MSC secretome and CBS are able to modulate tumor cell proliferation and survival as well as immunity and angiogenesis. In the present study, we address this relationship and investigate the influence of UC-MSC secretome and CBS on two human PCa cell lines (PC3 and LNCaP) and a normal epithelial prostate cell line (HPEpiC). Our results disclosed that upon exposure to UC-MSC-conditioned medium or CBS, both PC3 and LNCaP cells exhibited reduced viability, proliferation, and motility while non-malignant epithelial prostate cells were unaffected. These findings were corroborated by expression analysis of AKT/PI3K signaling pathway, p53 and interleukin genes. UC-MSC and CBS factors decreased the expression of growth-stimulating AKT and PI3K effectors and simultaneously up-regulated the expression of tumor-suppressor p53. Moreover, a more anti-inflammatory expression profile was found in both malignant PCa cell lines. Altogether, these results shed light into possible mechanisms by which UC-MSC and CBS reduce PCa progression, further reinforcing their potential use as novel therapeutic agents in PCa. Graphical abstract

Over the past decade, abiraterone and enzalutamide have largely replaced ketoconazole as oral treatments for castration-resistant prostate cancer (CRPC). We investigated the differential adoption of abiraterone and enzalutamide across facilities in a national healthcare system to understand the impact a facility has on the receipt of these novel therapies. Using data from the VA Corporate Data Warehouse, we identified a cohort of men with CRPC who received the most common first-line therapies: abiraterone, enzalutamide, docetaxel, or ketoconazole between 2010 and 2017. We described variability in the adoption of abiraterone and enzalutamide across facilities by time period (2010-2013 or 2014-2017). We categorized facilities depending on the timing of adoption of abiraterone and enzalutamide relative to other facilities and described facility characteristics associated with early and late adoption. We identified 4998 men treated with ketoconazole, docetaxel, abiraterone, or enzalutamide as first-line CRPC therapy between 2010 and 2017 at 125 national facilities. When limiting the cohort to oral therapies, most patients treated earlier in the study period (2010-2013) received ketoconazole. A dramatic shift was seen by the second half of the study period (2014-2017) with most men treated with first-line abiraterone (61%). Despite this shift and a new standard of care, some facilities persisted in the widespread use of ketoconazole in the later period, so-called late adopting facilities. After multivariable adjustment, patients who received treatment at a late adopting facility were more likely receiving care at a lower complexity, rural facility, with less urology and hematology/oncology workforce (all p

Contains fulltext : 291601.pdf (Publisher’s version ) (Closed access) This case-based discussion describes a 65-year-old man newly diagnosed with International Society of Urological Pathology (ISUP) grade 2 prostate cancer (PCa). According to the European Association of Urology classification system, the patient harbors an intermediate-risk cancer. In step-by step discussion, we elaborate guideline-based treatment modalities for intermediate-risk PCa focused on debating active surveillance versus active treatment. Thereby, we discuss the importance of patient characteristics, including age, hereditary factors, life expectancy and comorbidity status, findings of multiparametric magnetic resonance imaging, as well as prostate-specific antigen (PSA) density and PSA kinetics, in predicting the clinical course of the disease. In addition, we focus on cribriform pathology as a predictor of adverse outcomes and critically discuss its relevance in patient management. Lastly, we outline genomic stratification in ISUP 2 cancer as a future tool to predict PCa aggressiveness. PATIENT SUMMARY: Based on current guidelines, patients with intermediate-risk prostate cancer are treated actively or can alternatively undergo an active surveillance approach when favorable risk factors are present. One major issue is to discriminate between patients who benefit from an active therapy approach and those who benefit from a deferred treatment. Therefore, reliable biomarkers and early predictors of disease progression are needed urgently.

PSMA-PET/CT for imaging prostate cancer (PC) has spread worldwide since its clinical introduction in 2011. The majority of experiences have been collected for PSMA-PET-imaging of recurrent PC. Data for primary staging of high-risk PC are highly promising. Meanwhile, a plethora of PSMA-ligands are available for clinical use (e.g. 68Ga-PSMA-11, 68GaPSMA-I&T, 68Ga-PSMA-617, 18F-DCFBC, 18F-DCFPyL, 18F-PSMA-1007, 18F-rhPSMA-7 and 18F-JK-PSMA-7). However, an official approval is available only for 68Ga-PSMA-11 (approved by the US FDA in 2020) and 18F-DCFPyL (approved by the US FDA in 2021). Recommendations for acquisition times vary from 1-2h p.i. It has been shown that for the majority of tumour lesions, the contrast in PSMAPET/CT increases with time. Therefore, additional late imaging can help to clarify unclear findings. PSMA-PET/CT should be performed prior to commencing an androgen deprivation therapy (ADT) since (long term) ADT reduces the visibility of PC lesions. Following injection of PSMA-ligands, hydration and forced diuresis are recommended for PSMA-ligands with primarily excretion via the kidneys in order to increase the visibility of tumour lesions adjacent to the urinary bladder. PSMA-ligands are physiologically taken up in multiple normal organs. For some 18F-labelled PSMA-ligands, presence of unspecific focal bone uptake has been reported. When using these tracers, focal bone uptake without CT-correlate should be interpreted with great caution. Besides prostate cancer, practically all solid tumors express PSMA in their neovasculature thereby taking up PSMA-ligands, although usually at a lower extent compared to PC. Also multiple benign lesions and inflammatory processes (e.g. lymph nodes) take up PSMA-ligands, also usually at lower extent compared to PC.

Any effective screening program must satisfy 2 criteria: 1) the test must identify clinically significant disease earlier than its clinical presentation, and 2) a treatment must be available that will alter the natural history of the disease. The controversy surrounding PSA testing that has raged since 1991 centers on these 2 points. Screening and treatment trials published during the past 3 decades have provided critical insights into our understanding of the natural history of PSA identified cancers and the impact of treatment. This in turn raises questions concerning the mechanism of prostate cancer mortality reduction. This essay reflects on the mechanisms of disease progression and the implications for future screening and treatment efforts.

Currently available data from long-running single- and multi-center active surveillance (AS) studies show that AS has excellent cancer-specific survival rates. For AS to be effective the ‘right’ patients should be selected for which up until 5-to-10 years ago systematic prostate biopsies were used. Because the systematic prostate strategy relies on sampling efficiency for the detection of prostate cancer (PCa), it is subject to sampling error. Due to this sampling error, many of the Gleason 3+3 PCas that were included on AS in the early days and were classified as low-risk, may in fact have had a higher Gleason score. Subsequently, AS-criteria were more strict to overcome or limit the number of men missing the potential window of curability in case their tumor would be reclassified. Five to ten years ago the prostate biopsy landscape changed drastically by the addition of magnetic resonance imaging (MRI) into the diagnostic PCa-care pathway, which has by now trickled down into the EAU guidelines. At the moment, the EAU guidelines recommend performing a (multi-parametric) MRI before prostate biopsy and combine systematic and targeted prostate biopsy when the MRI is positive (i.e. PIRADS ≥3). So because of the introduction of the MRI into the diagnostic PCa-care pathway, literature is showing that more Gleason 3+4 PCas are being diagnosed. But can it not be that the inclusion of MRI into the diagnostic PCa-care pathway causes risk inflation, resulting in men earlier eligible for AS, now being labelled ineligible for AS? Would it not be possible to include these current Gleason 3+4 PCas on AS? The authors hypothesize that the improved accuracy that comes with the introduction of MRI into the diagnostic PCa-care pathway permits to widen both the AS-inclusion and follow-up criteria. Maintaining our inclusion criteria for AS from the systematic biopsy era will unnecessarily and undesirably expose patients to the increased risk of overtreatment. The evidence behind the addition of MRI-targeted biopsies to systematic biopsies calls upon the re-evaluation of the AS inclusion criteria and research from one-size-fits-all protocols used so far, into the direction of more dynamic and individual risk-based AS-approaches.

Low-value testing and treatment contribute to billions of dollars in waste to the United States health care system annually. High frequency, low-cost testing, including prostate-specific antigen (PSA) testing, is a major contributor to this inefficient health care delivery. Despite decreasing mortality of prostate cancer over the last few decades, the reputation of prostate specific antigen (PSA) for prostate cancer screening has fluctuated over the last decade due to lack of clarity of the benefits of screening and high risk for overtreatment. The value of PSA could be improved by efficient implementation of smarter testing strategies that reduce the harms and increase the benefits.

INTRODUCTION: Clinically significant prostate cancer (csCaP) with Gleason ≥3 + 4 is found in 10% negative prebiopsy multiparametric (mp) MRI cases and varies widely for equivocal mpMRI cases. The objective of this study was to investigate long-term outcomes of patients with negative and equivocal mpMRIs and to develop a predictive score for csCaP risk stratification in this group. PATIENTS AND METHODS: Patients who underwent an upfront mpMRI between May 2015 and March 2018 with an MRI score Likert 1 to 3 were included in the study. Patients had either a CaP diagnosis at MRI-targeted biopsy or were not diagnosed and attended follow-up in the community. Outcomes were analysed through the Kaplan-Meier estimator and Cox Model. Regression coefficients of significant variables were used to develop a Risk of significant Cancer of the Prostate score (RosCaP). RESULTS: At first assessment 281/469 patients had mpMRI only and 188/469 mpMRI and biopsy, 26 csCaP were found at biopsy, including 10/26 in Likert 3 patients. 12/371 patients discharged without CaP after first assessment were diagnosed with csCaP during a median of 34.2 months' follow-up, 11/12 diagnosis occurred in patients omitting initial biopsy. csCaP diagnosis-free survival was 95.7% in the MRI group and 99.1% in the biopsy group. From these outcomes, a continuous RosCaP score was developed: RosCaP = 0.083 x Age - 0.202 x (1/PSA Density) + 0.786 (if Likert 3), and 4 risk classes were proposed. Limitations include retrospective design and absence of external validation. CONCLUSION: Age, PSA Density and MRI Likert score were significantly associated to the risk of csCaP and utilised to devise the novel RosCap predictive score focused to support risk assessment in patients with negative or equivocal mpMRI results.

Focal therapy of prostate cancer (PCa) is currently of great interest, but a metric of success. other than biopsy, is not yet available. In a patient with a repeatedly negative MRI and negative systematic biopsies, a scan employing the radioisotope 68Ga-PSMA-11 PET/CT identified a PSMA-avid hotspot in the prostate. PSMA-guided biopsy confirmed the diagnosis of a clinically-significant PCa. Following ablation of the lesion with high-intensity focused ultrasound (HIFU), the PSMA-avid lesion disappeared and targeted biopsy confirmed a fibrotic scar with no residual cancer. PSMA imaging may have a role in guiding diagnosis, focal ablation, and follow-up of men with PCa.

We present two 85-year-old men, with a similar history of prostate cancer treated more than 10 years ago with radiotherapy, who were in remission, but sought medical care at a time, due to alarm sign and symptoms. Case 2 resulted in a locally advanced secondary radiation-induced sarcoma of the penile base. Case 1 suffered from a round, 2 cm soft-tissue lesion with spiculated borders at the ureterovesical junction responsible for ipsilateral iliac vein compression and urinary obstruction without proven biochemical prostate cancer relapse, raising concerns about recurrence or secondary tumour. Both patients followed an oncological geriatric assessment and were ‘vulnerable’ at their presentation. Hence, we describe the effort to perform medical care adequacy regarding patient’s frailty and the anatomic locations within the prior radiation field. In case 2, we got a pathological diagnose and followed sequential multimodal treatments without success. But in case 1, minimal intervention resulted in improvement.

In our hospital, 553 patients with clinically localized prostate cancer underwent low-dose-rate (LDR) brachytherapy between March 2007 and December 2019. The patients were stratified based on the following prognosis according to the D'Amico risk classification criteria: low-risk and intermediate-risk groups (PSA ＜10, ≦T2a, GS : 3＋4 (≦30%)) were treated with LDR brachytherapy without supplemental extra beam radiotherapy (EBRT), while some patients in the high- and intermediate-risk groups were treated with LDR and supplemental EBRT. The 5- and 10-year overall survival rates were 94.8 and 85.5%, disease-specific survival rates were 99.8 and 97.7%, and biochemical recurrence-free survival rates were 95.7 and 90.7%. By risk stratification, the 5- and 10-year biochemical recurrence-free survival rates were 98.0 and 98.0% (low risk), 96.1 and 89.6% (intermediate risk), and 90.6 and 77.3% (high risk). The LDR outcome was generally good, but, 32 recurrence cases were observed. In the recurrent group, 9 patients did not undergo the recommended therapeutic strategy and 26 patients did not undergo preoperative magnetic resonance imaging.

A 70-year-old-man was referred with urination pain and pyuria. Prostate specific antigen was 10.6 ng/ml, and urine culture was Escherichia coli. The abdominal ultrasonography showed irregular low echo at the right lobe of prostate. Prostate magnetic resonance imaging (MRI) showed an extracapsular infiltrated prostate tumor in the right lobe. Levofloxacin was administered and prostate biopsy was performed. The pathological examination revealed that the prostate tissue was filled with inflammatory cells and had lost its glandular duct structure. The patient was diagnosed with malacoplakia of the prostate. Four months after prostate biopsy, prostate MRI imaging showed disappearance of the extracapsular infiltration in right peripheral zone., この論文の要旨は第250回日本泌尿器科学会関西地方会において発表した．

Purpose: To investigate if imaging biomarkers derived from 3-Tesla dual-tracer [(18)F]fluoromethylcholine (FMC) and [68Ga]Ga-PSMAHBED-CC conjugate 11 (PSMA)-positron emission tomography can adequately predict clinically significant prostate cancer (csPC). Methods: We assessed 77 biopsy-proven PC patients who underwent 3T dual-tracer PET/mpMRI followed by radical prostatectomy (RP) between 2014 and 2017. We performed a retrospective lesion-based analysis of all cancer foci and compared it to whole-mount histopathology of the RP specimen. The primary aim was to investigate the pretherapeutic role of the imaging biomarkers FMC- and PSMA-maximum standardized uptake values (SUVmax) for the prediction of csPC and to compare it to the mpMRI-methods and PI-RADS score. Results: Overall, we identified 104 cancer foci, 69 were clinically significant (66.3%) and 35 were clinically insignificant (33.7%). We found that the combined FMC+PSMA SUVmax were the only significant parameters (p < 0.001 and p = 0.049) for the prediction of csPC. ROC analysis showed an AUC for the prediction of csPC of 0.695 for PI-RADS scoring (95% CI 0.591 to 0.786), 0.792 for FMC SUVmax (95% CI 0.696 to 0.869), 0.852 for FMC+PSMA SUVmax (95% CI 0.764 to 0.917), and 0.852 for the multivariable CHAID model (95% CI 0.763 to 0.916). Comparing the AUCs, we found that FMC+PSMA SUVmax and the multivariable model were significantly more accurate for the prediction of csPC compared to PI-RADS scoring (p = 0.0123, p = 0.0253, respectively). Conclusions: Combined FMC+PSMA SUVmax seems to be a reliable parameter for the prediction of csPC and might overcome the limitations of PI-RADS scoring. Further prospective studies are necessary to confirm these promising preliminary results.

In the quest for the development of accurate, reliable, and cost-effective biosensing technology for early diagnostics of prostate cancer, we describe here an electrochemical biosensor combining a simple transducing method of differential pulse voltammetry (DPV) with an RNA-based aptamer labelled with a methylene blue redox group acting as a highly specific bioreceptor to the prostate cancer biomarker PCA3. A series of DPV measurements on screen-printed gold electrodes is functionalised with a redox-labelled aptamer in solutions (either buffer or synthetic urine) containing PCA3 in a wide range of concentrations from 0.1 picomolar (pM) to 10 nanomolar (nM). In these measurements, the current peak values correlate with the concentration of PCA3 and yield a low detection limit (LDL) of 0.1 pM. Furthermore, the binding kinetics study revealed the high affinity of the aptamer to the target PCA3 with the affinity constants KD of about 3.0 × 10−8 molar. In addition, the AFM study showed the increase in the molecular layer roughness caused by the binding of PCA3, which is a large RNA molecular fragment.

BackgroundThe aim of this study is to examine the dosimetric influence of endorectal balloons (ERB) in rectal sparing in prostate cancer patients with implanted hydrogel rectum spacers treated with dose escalated/hypofractionated intensity modulated proton beam therapy (IMPT). MethodsTen patients with localised prostate cancer included in the ProRegPros study and treated at our centre were invastigated in this study. All patients underwent a placement of hydrogel rectum spacers before planning. Two planning CTs (with and without 120 cm3 fluid-filled ERB) were acquired for each patient. Dose prescription was set according to the used simultaneous integrated boost strategy with 72 Gray (Gy)/2.4 Gy/5 x weekly to prostate+1 cm of the seminal vesicle, and 60 Gy/2 Gy/5 x weekly to prostate+2 cm of the seminal vesicle. Planning with two lateral-opposed IMPT beams was performed in both CTs. Rectal dosimetry values including dose-volume statistics and normal tissue complication probability (NTCP) in both plans were compared (non-ERB plans vs. ERB plans).ResultsFor ERB plans compared to non-ERB, the reductions were 8.51 ± 5.25 Gy (RBE) (p= 0.000) and 15.76 ± 11.11Gy (P= 0.001) for the mean and the median rectal dose, respectively. No significant reductions in rectal volumes receiving high dose levels were found. The use of ERB resulted in significant reduction in rectal volume receiving 50 Gy (RBE), 40 Gy (RBE), 30 Gy (RBE), 20 Gy (RBE), and 10 Gy (RBE) with P values of 0.034, 0.008, 0.003, 0.001, and 0.001, respectively. For the anterior rectum, no differences between ERB and non-ERB plans were observed. For the posterior rectum, ERB reduced rectal volumes received 30 Gy (RBE), 20 Gy (RBE), and 10 Gy (RBE) with P values of 0.019, 0.003, and 0.001, respectively. No significant reductions in mean or median rectal toxicity (Late rectal bleeding ≥2, necrosis/stenosis, and Late rectal toxicity ≥ 3) were observed when using the ERB according to NTCP models.ConclusionThe ERB reduced rectal volumes exposed to intermediate/low dose levels. However, no significant reduction in rectal volumes receiving high/intermediate doses could be observed. No benefit but also no disadvantage of the ERB for late rectal toxicity was found according to available NTCP models.

Castration-resistant prostate cancer (CRPC) is the main driving force of mortality in prostate cancer patients. Among the parameters contributing to the progression of CRPC and treatment failure, elevation of the steroidogenic enzyme AKR1C3 and androgen receptor variant 7 (AR-V7) are frequently reported. The AKR1C3/AR-V7 complex has been recognized as a major driver for drug resistance in advanced prostate cancer. Herein we report that the level of AKR1C3 is reciprocally regulated by the full-length androgen receptor (AR-FL) through binding to the distal enhancer region of the AKR1C3 gene. A novel function of PTUPB in AKR1C3 inhibition was discovered and PTUPB showed more effectiveness than indomethacin and celecoxib in suppressing AKR1C3 activity and CRPC cell growth. PTUPB synergizes with enzalutamide treatment in tumor suppression and gene signature regulation. Combination treatments with PTUPB and enzalutamide provide benefits by blocking AR/AR-V7 signaling, which inhibits the growth of castration relapsed VCaP xenograft tumors and patient derived xenograft organoids. Targeting of the ARK1C3/AR/AR-V7 axis with PTUPB and enzalutamide may overcome drug resistance to AR signaling inhibitors in advanced prostate cancer.

BackgroundMultiparametric magnetic resonance imaging (mpMRI) improves detection of clinically significant prostate cancer (csPCa), but the subjective Prostate Imaging Reporting and Data System (PI-RADS) system and quantitative apparent diffusion coefficient (ADC) are inconsistent. Restriction spectrum imaging (RSI) is an advanced diffusion-weighted MRI technique that yields a quantitative imaging biomarker for csPCa called the RSI restriction score (RSIrs).ObjectiveTo evaluate RSIrs for automated patient-level detection of csPCa.Design setting and participantsWe retrospectively studied all patients (n=151) who underwent 3 T mpMRI and RSI (a 2-min sequence on a clinical scanner) for suspected prostate cancer at University of California San Diego during 2017-2019 and had prostate biopsy within 180 d of MRI.InterventionWe calculated the maximum RSIrs and minimum ADC within the prostate, and obtained PI-RADS v2.1 from medical records.Outcome measurements and statistical analysisWe compared the performance of RSIrs, ADC, and PI-RADS for the detection of csPCa (grade group ≥2) on the best available histopathology (biopsy or prostatectomy) using the area under the curve (AUC) with two-tailed α=0.05. We also explored whether the combination of PI-RADS and RSIrs might be superior to PI-RADS alone and performed subset analyses within the peripheral and transition zones.Results and limitationsAUC values for ADC, RSIrs, and PI-RADS were 0.48 (95% confidence interval: 0.39, 0.58), 0.78 (0.70, 0.85), and 0.77 (0.70, 0.84), respectively. RSIrs and PI-RADS were each superior to ADC for patient-level detection of csPCa (p&nbsp

Background: Diagnosis of prostatic diseases is via a prostate biopsy and subsequent histology. So, a prostate biopsy should be carried out to get a histological diagnosis when indicated. Materials and Methods: This is a five-year retrospective study conducted at the University of Port Harcourt Teaching Hospital. Ethical approval for the study was sought and gotten from the hospital’s ethical committee. The information gotten included history, duration of symptoms, examination findings, age of the patient, Gleason grade and histological diagnosis. The data from the folders were collected and evaluated. Frequencies, percentages, the mean and standard deviation were used to summarize the data as appropriate. Results: The age range was from 45 to 96 years with a mean age of 68.10 ± 9.11 years. A hundred and fifty patients had prostate cancer. The commonest grade of cancer was the Gleason grade 5 (46.67%). No statistically significant relationship between Gleason grade and age. Conclusion: The mean age of patients in this study was 68.10 ± 9.11. Over 50% of patients biopsied had prostate cancer, and 46.67% had a high-grade disease. Health awareness campaigns and screening programs in Africa to make people aware of prostatic diseases. Earlier presentation to the hospital when symptomatic will lead to better treatment.

International audience; Objective > Despite an increasing number of therapeutic indications, there are no specific recommendations regarding the management of PARP inhibitors other than what is specified in the SmPC of each substance. A Delphi French consensus was conducted to establish practical guidelines to meet the needs identified by healthcare professionals and patients. Method > Following the Delphi method, statements to optimize PARP inhibitor management were drafted by a multidisciplinary Steering Committee made up of 17 experts. These statements were submitted to the independent and anonymous vote of clinicians involved in treating patients on PARP inhibitors. Results > This article presents 52 statements on the following topics: initiation and treatment; management of adverse events (hematological effects, gastrointestinal effects, renal effects, pulmonary effects, cutaneous effects, hypertension, insomnia, fatigue, dizziness); special popu-lations and situations; communication with the patient; adherence. Forty-nine statements obtained voter consensus after 3 voting rounds. A hematologist and a nephrologist supplemented this task by drafting an expert opinion on the risk of occurrence of secondary leukemia and nephrological toxicity. Conclusions > This paper is the first Delphi consensus on the practical management of PARP inhibitors. The pragmatic recommendations resulting from this paper should make it possible to manage the side effects of PARP inhibitors better and thus prevent early treatment discontinua-tion and improve patient adherence by preserving quality of life.

Focal therapy has emerged as an interesting option for localized low- to intermediate-risk prostate cancer (PCa). Targeted microwave ablation (TMA) is a novel FT modality involving targeted delivery of microwave energy under multiparametric magnetic resonance imaging (MRI)/ultrasound guidance.To describe the step-by-step procedure for TMA and report early functional outcomes.This was an experimental phase 1-2 trial in 11 patients diagnosed with a single, MRI-visible PCa lesion of up to 12 mm, scored as International Society of Urological Pathology grade group (GG) 1 or 2.Transperineal TMA under MRI/ultrasound image fusion guidance.We recorded patient and PCa features; intraoperative and postoperative parameters; pain (Visual Analog Scale [VAS]) and adverse events (Common Terminology Criteria for Adverse Events v5.0); and prostate-specific antigen (PSA), International Prostate Symptom Score (IPSS) and International Index of Erectile Function (IIEF-5) scores at 1 wk and 1, 3, and 6 mo.The median patient age was 67 yr (interquartile range [IQR] 18). Median PSA was 5.4 ng/ml (IQR 1.8), median prostate volume was 51 cmTMA is safe, feasible, and well tolerated in patients with low- to intermediate-risk PCa. Oncological outcomes are still awaited.Targeted microwave therapy is safe and feasible for selected patients with low- to intermediate-risk prostate cancer. The procedure is well tolerated and does not require a urinary catheter after the procedure. Cancer control outcomes are still awaited.

Background: The aim of this study was to investigate the feasibility of ultrahypofractionated radiotherapy to the prostate bed in patients with biochemical and/or clinical relapse following radical prostatectomy who were enrolled in the prospective, observational, multicentric POPART trial (NCT04831970). Methods: Patients with post-radical prostatectomy PSA levels of ≥0.1–2.0 ng/mL and/or local relapse at PSMA PET/CT or multiparametric MRI were treated with Linac-based SBRT on the prostate bed up to a total dose of 32.5 Gy in five fractions every other day (EQD21.5 = 74.2 Gy). Maximum acute toxicity was assessed using the Common Terminology Criteria for Adverse Events version 5 scale. International Consultation on Incontinence Questionnaire—Short Form (ICIQ-SF) and Prostate Cancer Index Composite for Clinical Practice (EPIC-CP) scores were assessed at baseline and during the follow-up. Results: From April 2021 to June 2022, thirty men with a median age of 72 years (range 55–82) were enrolled in three centers. The median PSA level before RT was 0.30 ng/mL (range 0.18–1.89 ng/mL). At 3 months post-treatment, no GI or ≥2 GU side effects were reported; three patients (10%) experienced Grade 1 GU toxicity. No changes in ICIQ-SF or in the urinary domains of EPIC-CP were observed, while a transient worsening was registered in the bowel domain. At the same time point, all but two patients, who progressed distantly, were found to be biochemically controlled with a median post-treatment PSA level of 0.07 ng/mL (range 0–0.48 ng/mL). Conclusions: Our preliminary findings show that SBRT can be safely extended to the postoperative setting, without an increase in short-term toxicity or a significant decline in QoL. Long-term results are needed to confirm this strategy.

We evaluated the clinical course of patients with localized prostate cancer in whom long-term successful androgen deprivation therapy (ADT) was ceased. Study subjects were 24 patients with stage B prostate cancer who were initially treated with ADT for a median duration of 93 months. The median age at the cessation of ADT was 84 years. The median nadir serum prostate specific antigen (PSA) level was 0.022 ng/ml. The median duration of follow-up from the cessation of ADT was 31 months. During follow-up, five patients showed PSA elevation of ≥2 ng/ml from the nadir. Serum testosterone level was tested in 20 patients, and five showed testosterone recovery ≥0.5 ng/ml. Seven patients died from diseases other than prostate cancer, but there were no deaths caused by prostate cancer. This study demonstrated that long-term successful ADT for localized prostate cancer could be ceased with adequate follow-up evaluation.

To test the hypothesis of an association between the American Society of Anesthesiologists (ASA) physical status classification system and the risk of 90-days postoperative complications after robot-assisted radical prostatectomy (RARP), graded using the Clavien-Dindo classification system (CDS). In a period ranging from January 2013 to October 2020, 1143 patients were evaluated. ASA classification was computed by trained anesthesiologists. Postoperative complications at 90 days after RARP were grouped as greater than one (CDS between 2 and 4a) versus up to one (CDS between 0 and 1). The risk association was computed using logistic regression models. According to ASA physical status classification system, patients were distributed as follows: 102 (8.9%) ASA 1, 934 (81.7%) ASA 2, and 107 (9.4%) ASA 3. Overall, 90-days postoperative complications occurred in 277 (24.2%) cases, of which 137 (12%) were graded as CDS 1 vs. 105 (9.2%) CDS 2 vs. 17 (1.5%) CDS 3a vs. 15 (1.3%) CDS 3b vs. 3 (0.3%) CDS 4a. ASA 2 and 3 patient categories were more likely to have 90-days postoperative complications CDS 1 (12.5% and 16.8%, respectively) compared to ASA 1 patients (4.9%). The risk association was stronger for ASA 3 (odds ratio, [OR]: 4.085; 95%CI: 1.457-11.455; p = 0.007) than for ASA 2 (OR: 2.907; 95%CI: 1.106-7.285; p = 0.023) patient categories. After adjustment for clinical, pathological, and perioperative covariates, including pelvic lymph node dissection (performed vs. not performed), either ASA 2 or 3 categories remained independent predictors of 90-days postoperative complications CDS 1. The risk of 90-days postoperative complications CDS 1 after RARP increased as the ASA physical status deteriorated independently by performing or not an extended pelvic lymph node dissection. In the ASA 3 patients category, RARP should be performed at tertiary referral centers to safely manage the risk of postoperative complications.

Purpose To analyse the Health-Related Quality of Life (HRQoL) at diagnosis of patients with prostate cancer (PCa) according to tumour extension and urinary symptomatology and to explore factors associated with HRQoL. Methods 408 Controls and 463 PCa cases were included. Eligibility criteria were a new diagnosis of PCa (cases), 40–80 years of age, and residence in the participating hospitals’ coverage area for ≥ 6 months before recruitment. HRQoL was evaluated using the 12-Item Short-Form Health Survey, Mental (MCS) and Physical Component Summaries (PCS), and urinary symptoms with the International Prostate Symptom Score. HRQoL scores for all PCa cases, according to tumour extension and urinary symptoms, were compared with controls. In addition, information about lifestyles and comorbidities was collected and its association with low HRQoL (lower scores) were explored using logistic regression models. Results Overall cases had similar PCS score, but lower MCS score than controls. The lowest standardised scores for both PCS and MCS were reached by cases with severe urinary symptoms and a metastatic tumour [mean (SD); PCS: 41.9 (11.5), MCS: 42.3 (10.3)]. Having “below” PCS and MCS scores was associated with the presence of three or more comorbidities in the cases [aOR = 2.86 (1.19–6.84) for PCS and aOR = 3.58 (1.37–9.31) for MCS] and with severe urinary symptomatology [aOR = 4.71 (1.84–12.08) for PCS and aOR = 7.63 (2.70–21.58) for MCS]. Conclusion The mental dimension of HRQoL at diagnosis of patients with PCa was lower than in controls, especially for cases with severe urinary symptoms and a metastatic tumour. Comorbidities and urinary symptoms were variables associated with the HRQoL of PCa cases.

Summary: In patients with non-metastatic prostate cancer, treated with radiation therapy and androgen deprivation therapy for 3 years and DMAB on average for 5 years, BMD was in the normal or osteopenic range. Discontinuation of DMAB led to a bone loss of 2–5%. In men with osteopenia, the bone loss was prevented by zoledronate. Purpose: Patients with prostate cancer receiving androgen deprivation therapy (ADT) are treated with denosumab (DMAB) to prevent fractures and preserve bone mass. We wanted to investigate the change in BMD in men with non-metastatic prostate cancer discontinuing DMAB. Methods: We conducted a retrospective cohort study based on medical records from patients referred to the Department of Endocrinology from the Department of Urology, Aarhus University Hospital between June 1, 2018, and June 1, 2021. We retrieved information on biochemistry and DXA performed 0–6 months after the last DMAB injection and a second DXA performed approximately 12 months after the first. In case of a BMD T-score ≤ − 1 at the lumbar spine or total hip at the first DXA, the patients were treated with zoledronate. The primary endpoint was change in lumbar spine BMD. Results: We included 50 patients with non-metastatic prostate cancer. The mean DMAB treatment duration was 5 ± 0.1 years. Among the patients treated with zoledronate (n = 9), BMD was maintained at the spine and femoral neck after a mean of 16 months. We found a significant decrease in BMD; − 4.9 ± 4.2%, − 1.9 ± 3.5%, and − 2.4 ± 3.6% at the spine, total hip, and femoral neck between the first and second DXA in the patients not treated with zoledronate (n = 24) (p ≤ 0.01 for all). One patient who did not receive ZOL sustained multiple fragility vertebral fractures after DMAB discontinuation. Conclusion: In men with non-metastatic prostate cancer, discontinuation of DMAB after stopping ADT led to an average bone loss of 2–5%. Zoledronate prevented bone loss in men with osteopenia.

Objective: To analyze the perioperative outcomes of neoadjuvant hormone therapy (NHT) before laparoscopic and robot-assisted surgery for localized high-risk prostate cancer in a Chinese cohort. Methods: The clinical data of 385 patients with localized high-risk prostate cancer who underwent radical prostatectomy (RP) in our hospital from January 2019 to June 2021 were analyzed retrospectively, including 168 patients with preoperative NHT and 217 patients with simple surgery. Clinical characteristics were compared in the above two groups, the laparoscopic RP (LRP) cohort (n = 234) and the robot-assisted laparoscopic radical prostatectomy (RALP) cohort (n = 151), respectively. Results: In the overall cohort, compared with the control group, the NHT group had a shorter operative time, less blood loss, a lower positive surgical margin rate, and a higher proportion of Gleason score (GS) downgrading after the operation (p < 0.05). However, there was no significant difference in hospitalization time, biochemical recurrence, urine leakage, urinary continence, or prostate-specific antigen (PSA) progression-free survival (p > 0.05). In the LRP cohort, it was found that the NHT group also had shorter operative time, less blood loss, lower positive surgical margin rate, a higher proportion of GS downgrading after the operation, and faster recovery of urinary control than the control group (p < 0.05). There was no marked difference in hospitalization time, biochemical recurrence, urinary leakage, or PSA progression-free survival. However, in the RALP cohort, the NHT group had a significant difference in the GS downgrading after the operation compared with the control group (p < 0.05). In the overall cohort, multiple analyses showed that initial PSA level, GS at biopsy, clinical T stage, lymph node invasion, use of NHT, and surgical methods were significantly associated with positive surgical margin (p < 0.05) while NHT did not account for biochemical recurrence (p > 0.05). Conclusions: NHT can lower the difficulty of surgery, reduce positive surgical margin rate, and help recovery in short-term urinary control in patients with high-risk prostate cancer after LRP. However, we do not have evidence on the benefit of NHT in high-risk PCa patients treated with RALP. For these patients, surgery can be performed as early as possible.

Background: The introduction of novel hormonal agents (NHAs) such as abiraterone acetate (ABI) and enzalutamide (ENZ) for metastatic castration-resistant prostate cancer (mCRPC) was an important milestone given their survival benefits, tolerability, and ease of administration relative to taxane chemotherapies. This descriptive study sought to describe the utilization trends of ABI and ENZ in patients with mCRPC in the early years after their approval in the province of Quebec in Canada. Methods: A retrospective population-based cohort was extracted from Quebec public healthcare administrative databases. The cohort included first-time users of NHAs (ABI or ENZ) from 2011 to 2016. The primary analyses aimed to describe the overall temporal trends (2011–2016) of NHA initiators by chemotherapy status (chemotherapy-naïve versus post-chemotherapy), and prescribing specialty (medical oncology versus urology versus others). Results: The cohort comprised 2183 patients, with 1562 (72%) in the chemotherapy-naïve group and 621 (28%) in the post-chemotherapy group. While the majority of patients were post-chemotherapy NHA initiators in 2012, this proportion decreased over time and accounted for only 13% of NHA initiators by the end of 2016. Medical oncologists were the most frequent prescribers of NHAs (upwards of 60%) throughout 2012 but fell to 45% by the end of 2016. Conversely, the proportion of prescriptions by urologists increased from 22% in 2012 to 42% in 2016. Conclusion: Over time, there was an increasing proportion of (1) patients who initiated NHAs without prior chemotherapy treatment, (2) NHA prescribing by urologists, and (3) ENZ users. Taken together, this implies that the introduction of NHAs has altered the management of mCRPC and urologists quickly adopted NHAs into their practice.

Nowadays, there is still no consensus on the most accurate PET radiopharmaceutical to early detect prostate cancer (PCa) relapse. A tailored radiotracer choice based on a specific patient’s profile could ensure prompt disease detection and an improvement in patients management. We aimed to compare the [18F]fluciclovine and [18F]fluorocholine PET/CT detection rate (DR) in PCa patients restaged for early biochemical recurrence (BCR), according to clinical and biochemical features. A cohort of 138 PCa patients with early BCR (mean age: 71 y, range: 50–87 y) were homogeneously randomized 1:1 to a [18F]fluciclovine or a [18F]fluorocholine PET/CT group. The respective PET/CT DR, according to per-patient and per-region analysis, and the impact of the biochemical, clinical, and histological parameters, were compared. The PSA cut-off values predictive of a positive scan were also calculated. Overall, the [18F]fluciclovine PET/CT DR was 64%, significantly higher than the [18F]fluorocholine PET/CT DR of 35% (p = 0.001). Similarly, in the per-region analysis, the [18F]fluciclovine PET/CT DR was 51% in the prostate region, significantly higher compared to 15% of [18F]fluorocholine (p < 0.0001). Furthermore, a statistically significant higher DR in per-patient and per-region (prostate/prostate bed) analysis was observed in the [18F]fluciclovine group for 0.5–1 ng/mL (p = 0.018, p = 0.049) and >1 ng/mL (p = 0.040, p < 0.0001) PSA values. A PSA of 0.45 ng/mL for [18F]fluciclovine and of 0.94 ng/mL for [18F]fluorocholine was identified as the optimal cut-off value in predicting a positive PET/CT scan. Our results demonstrated a better [18F]fluciclovine PET/CT DR compared to [18F]fluorocholine for restaging PCa patients in early BCR, particularly in the detection of locoregional recurrence. The significantly higher [18F]fluciclovine DR for low PSA values (PSA < 1 ng/mL) supports its use in this setting of patients.

Tumoral uptake of large-size nanoparticles is mediated by the enhanced permeability and retention (EPR) effect, with variable accumulation and heterogenous tumor tissue penetration depending on the tumor phenotype. The performance of nanocarriers via specific targeting has the potential to improve imaging contrast and therapeutic efficacy in vivo with increased deep tissue penetration. To address this hypothesis, we designed and synthesized prostate cancer-targeting starPEG nanocarriers (40 kDa, 15 nm), [89Zr]PEG-(DFB)3(ACUPA)1 and [89Zr]PEG-(DFB)1(ACUPA)3, with one or three prostate-specific membrane antigen (PSMA)-targeting ACUPA ligands. The in vitro PSMA binding affinity and in vivo pharmacokinetics of the targeted nanocarriers were compared with a nontargeted starPEG, [89Zr]PEG-(DFB)4, in PSMA+ PC3-Pip and PSMA- PC3-Flu cells, and xenografts. Increasing the number of ACUPA ligands improved the in vitro binding affinity of PEG-derived polymers to PC3-Pip cells. While both PSMA-targeted nanocarriers significantly improved tissue penetration in PC3-Pip tumors, the multivalent [89Zr]PEG-(DFB)1(ACUPA)3 showed a remarkably higher PC3-Pip/blood ratio and background clearance. In contrast, the nontargeted [89Zr]PEG-(DFB)4 showed low EPR-mediated accumulation with poor tumor tissue penetration. Overall, ACUPA conjugated targeted starPEGs significantly improve tumor retention with deep tumor tissue penetration in low EPR PC3-Pip xenografts. These data suggest that PSMA targeting with multivalent ACUPA ligands may be a generally applicable strategy to increase nanocarrier delivery to prostate cancer. These targeted multivalent nanocarriers with high tumor binding and low healthy tissue retention could be employed in imaging and therapeutic applications.

Este artículo se encuentra disponible en la siguiente URL: https://www.sciencedirect.com/science/article/pii/S0167814022044991?via%3Dihub En este artículo de investigación también participan:Gianluca Ingrosso, Filippo Alongi, Shafak Aluwini, Stefano Arcangeli, Pierre Blanchard, Felipe Couñago, Gilles Créhange, Piet Dirix, Alfonso Gomez Iturriaga, Matthias Guckenberger, David Pasquier, Paul Sargos, Marta Scorsetti, Stéphane Supiot, Alison C. Tree, Almudena Zapatero, Jennifer Le Guevelou, Piet Ost y Claus Belka. Background and purpose: Oligometastatic prostate cancer is a new and emerging treatment field with only few prospective randomized studies published so far. Despite the lack of strong level I evidence, metastasis-directed therapies (MDT) are widely used in clinical practice, mainly based on retrospective and small phase 2 studies and with a large difference across centers. Pending results of ongoing prospective randomized trials, there is a clear need for more consistent treatment indications and radiotherapy practices. Material and methods: A European Society for Radiotherapy and Oncology (ESTRO) Guidelines Committee consisting of radiation oncologists’ experts in prostate cancer was asked to answer a dedicated questionnaire, including 41 questions on the main controversial issues with regard to oligometastatic prostate cancer. Results: The panel achieved consensus on patient selection and routine use of prostate-specific membrane antigen positron emission tomography (PSMA PET) imaging as preferred staging and restaging imaging. MDT strategies are recommended in the de novo oligometastatic, oligorecurrent and oligoprogressive disease setting for nodal, bone and visceral metastases. Radiation therapy doses, volumes and techniques were discussed and commented. Conclusion: These recommendations have the purpose of providing standardization and consensus to optimize the radiotherapy treatment of oligometastatic prostate cancer until mature results of randomized trials are available.

Incidental prostate cancer (IPCa) is encountered in 10% of surgical procedures for benign prostatic obstruction (BPO). Identification of patients with underlying detrimental prostate cancer is paramount for tailored treatment decision-making, but guideline recommendations for this setting are lacking.To highlight clinical and histological characteristics related to BPO surgery that may predict IPCa with unfavorable pathology.We included men with IPCa who underwent radical prostatectomy (RP) in the short term after IPCa diagnosis. Two cohorts were built according to final pathology for the RP specimen: unfavorable pathology (International Society of Urological Pathology [ISUP] grade group [GG] ≥3 and/or ≥pT3a and/or pN1) versus favorable pathology.We performed multivariate regression analysis for the endpoint, which was unfavorable pathology for the RP specimen. Using the model estimates for prostate-specific antigen (PSA), ISUP GG, age, and prostate volume, we established a model for estimating the risk of unfavorable histopathology.Overall, 112 patients were included in the final assessment. On multivariate analysis, PSA (odds ratio [OR] 1.083, 95% confidence interval [CI] 1.003-1.170; p = 0.042), ISUP GG for the specimen from BPO surgery (OR 3.090; 95% CI 1.129-8.457; p = 0.028), and age (OR 1.121, 95% CI 1.026-1.225; p = 0.012) were independent predictors for unfavorable histopathology. On receiver operating characteristic analysis, the area under the curve was 0.751. A novel calculator was developed to predict adverse pathology for men with IPCa. The study is limited by its retrospective design.For men with IPCa, PSA before surgery for BPO, ISUP GG, and age are independent predictors of unfavorable disease. Our results might improve preoperative risk assessment for patient counseling.We developed a novel calculator to estimate the risk of underlying detrimental disease in men diagnosed with prostate cancer at surgery for benign prostatic obstruction.

Background: Accurate monitoring following focal treatment of prostate cancer (PCa) is paramount for timely salvage treatment or retreatment. Objective: To evaluate the diagnostic accuracy of multiparametric magnetic resonance imaging (mpMRI) to detect residual PCa in the short-term follow-up of focal treatment with irreversible electroporation (IRE) using transperineal or transrectal template ± targeted biopsies. Design, setting, and participants: A retrospective international multicenter study of men with biopsy-proven PCa, treated with focal IRE, and followed by mpMRI (index-test) and template biopsies (reference-test) between February 2013 and January 2021, was conducted. Outcome measurements and statistical analysis: Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of mpMRI were calculated for in- and outfield residual disease based on two definitions of significant PCa: University College London (UCL) 1—International Society of Urological Pathology (ISUP) ≥3 or ISUP ≥1 with maximum cancer core length (MCCL) ≥6 mm, and UCL2—ISUP ≥2 or ISUP ≥1 with MCCL ≥4 mm. Results and limitations: A total of 303 patients from five focal therapy centers were treated with primary IRE. The final analysis was performed on 217 men (median age 67, median prostate-specific antigen 6.2, 81% ISUP 2/3) who underwent both mpMRI and template biopsies. Multiparametric MRI missed 38/57 (67%) positive biopsy locations (UCL1) in 22 patients. Sensitivity, specificity, PPV, and NPV of mpMRI to detect whole gland residual disease (UCL1) were 43.6% (95% confidence interval [CI]: 28–59), 80.9% (95% CI: 75–86), 33.3% (95% CI: 21–47), and 86.7% (95% CI: 81–91), respectively. Based on UCL2, sensitivity, specificity, PPV, and NPV were 35.8% (95% CI: 25–48), 82.0% (95% CI: 75–88), 47.1% (95% CI: 34–61), and 74.1% (95% CI: 67–80), respectively. Limitations are the retrospective nature and short follow-up. Conclusions: The diagnostic accuracy of mpMRI to detect residual clinically significant PCa following IRE was low. Follow-up template biopsies should be performed, regardless of mpMRI results. Patient summary: We investigated the accuracy of magnetic resonance imaging (MRI) to detect residual prostate cancer after treatment with irreversible electroporation. The accuracy of MRI is insufficient, and we emphasize the importance of confirmatory prostate biopsies.

Background After radical prostatectomy (RP), depending on stage, up to 40% of patients with prostate cancer (PCa) will experience biochemical failure (BF). Despite salvage therapy, approximately one-third of these patients will need permanent hormone therapy (pHT) and are at risk of progression to castration-resistant PCa (CRPC). Prognostic markers herald the need for neoadjuvant, adjuvant, or multimodal treatment. Objective To evaluate the added value of blood LRG1 in predicting treatment failure in patients who have undergone radical prostatectomy (RP). Design, setting, and participants We quantified LRG1 in serum or plasma sampled before radical prostatectomy from patients from the Martini-Klinik (Martini; n = 423), the Danish CuPCa cohort (CuPCa; n = 182), and Oslo University Hospital (OUH; n = 145). Outcome measurements and statistical analysis The endpoints were BF, pHT, and CRPC. The association between LRG1 and survival outcomes was evaluated using Kaplan-Meier estimation and Cox proportional-hazards modeling. The added predictive value of LRG1 in nested models was estimated using the concordance index, time-dependent area under the receiver operating characteristic curve, and decision curve analysis. Results and limitations In multivariable Cox models using preoperative characteristics, LRG1 was associated with an estimated lower risk of BF in the Martini cohort (adjusted hazard ratio [aHR] 0.68, 95% confidence interval [CI] 0.52–0.90) and in the CuPCa cohort (aHR 0.47, 95% CI 0.30–0.73). Using preoperative prognostic variables, our data showed that doubling of LRG1 was also associated with a lower risk of pHT receipt in the CuPCa cohort (aHR 0.43, 95% CI 0.20–0.93) and of CRPC development in the OUH cohort (aHR 0.32, 95% CI 0.15–0.69). Similar aHR values were observed using either preoperative or postoperative variables for all endpoints. Conclusions PCa patients with high blood LRG1 are at lower risk of BF, pHT receipt, and progression to CRPC. Since LRG1 adds value to established prognostic models, new prognostic factor combinations including LRG1 should be considered in future studies. Patient summary We measured concentrations of the blood-based protein LRG1 before surgery for prostate cancer. Patients with high LRG1 levels had better disease-free survival, suggesting that LRG1 can help in predicting prognosis.

The objective of this study was to evaluate the safety and feasibility of (99m)Tc-based prostate-specific membrane antigen (PSMA) robot-assisted–radioguided surgery to aid or improve the intraoperative detection of lymph node metastases during primary robot-assisted radical prostatectomy (RARP) for prostate cancer (PCa). Methods: Men with primary high-risk PCa (≥ cT3a, International Society of Urological Pathology (ISUP) grade group ≥ 3 or prostate-specific antigen of ≥ 15 ng/mL) with potential lymph node metastasis (Briganti nomogram risk > 10% or on preoperative imaging) were enrolled in the study. Patients underwent staging (68)Ga-PSMA PET/CT scanning. Preoperatively, a (99m)Tc-labeled PSMA ligand ((99m)Tc PSMA I&S; 500 MBq) was administered followed by SPECT/CT. A RARP including extended pelvic lymph node dissection was performed, with intraoperative tracing of PSMA-avid tissues using a prototype DROP-IN γ-probe. Resected specimens were also measured ex vivo. Histopathologic concordance with probe findings was evaluated. A radiotracer count of ≥ 1.5 times the background reference (in vivo), and ≥ 10 (absolute count) in the ex vivo setting, was considered positive. Results: Twelve patients were included (median age, 68 y, and prostate-specific antigen, 9.15 ng/mL). Most of the patients harbored ISUP 5 PCa (75%) and had avid lymph nodes on preoperative PSMA PET (64%). The DROP-IN probe aided resection of PSMA-avid (out-of-template) lymph nodes and residual disease at the prostate bed. Eleven metastatic lymph nodes were identified by the probe that were not observed on preoperative (68)Ga-PSMA PET/CT. Of the 74 extraprostatic tissue specimens that were resected, 22 (29.7%) contained PCa. The sensitivity, specificity, positive predictive value, and negative predictive value of inpatient use of the γ-probe were 76% (95% CI, 53%–92%), 69% (95% CI, 55%–81%), 50%, and 88%, respectively. Ex vivo, the diagnostic accuracy was superior: 76% (95% CI, 53%–92%), 96% (95% CI, 87%–99%), 89%, and 91%, respectively, for sensitivity, specificity, positive predictive value, and negative predictive value. Of the missed lymph nodes in vivo (n = 5) and ex vivo (n = 5), 90% were micrometastasis (≤3 mm). No complications greater than Clavien–Dindo Grade I occurred. Conclusion: Robot-assisted (99m)Tc-based PSMA-radioguided surgery is feasible and safe in the primary setting, optimizing the detection of nodal metastases at the time of RARP and extended pelvic lymph node dissection. Further improvement of the detector technology may optimize the capabilities of robot-assisted (99m)Tc-based PSMA-radioguided surgery.