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Background and objective: In patients with oligorecurrent prostate cancer (PCa), prostate-specific membrane antigen–targeted radioguided surgery (PSMA-RGS) prolongs treatment-free survival. Data on patient-reported outcome measures (PROMs) are lacking. Methods: A retrospective assessment of validated PROMs (12-item Short Form Health Survey [SF-12], 26-item Expanded Prostate Index Composite, and Decision Regret Scale [DRS]) was performed before and after PSMA-RGS for oligorecurrent PCa. Mixed models were used. Key findings and limitations: A total of 373 patients were analyzed at a median (interquartile range [IQR]) age of 66 (61, 70) yr and prostate-specific antigen of 0.8 (0.4, 1.5) ng/ml. Six months after PSMA-RGS, the median (IQR) scores for the PROMs were as follows: SF-12 physical 54 (49, 56), SF-12 mental 53 (43, 56), urinary incontinence 86 (52, 100), urinary irritation 94 (88, 100), sexual 27 (9, 57), hormonal 90 (79, 100), and bowel 96 (83, 100). Only the sexual score decreased in a significant fashion from baseline over time (median [IQR], 17 [8,38]) after 3 yr vs 37 [13, 63] at baseline, p = 0.01). The decision regret remained low (median [IQR] DRS at 1 yr: 5 [0, 20]). More than 90% of the patients reported that PSMA-RGS was the correct decision after 1 yr. Conclusions and clinical Implications: We recorded no significant decrease in quality of life or any functional status domain, except sexual. While decision regret was low, sexual functioning might deteriorate further. Patient summary: No significant deterioration in health-related quality of life was reported after removing early prostate cancer metastases. Very few patients expressed remorse about their decision for salvage surgery.

International Society of Urological Pathology grade group 1 (GG 1) prostate cancer (PCa) is generally considered insignificant, with recent suggestions that it should even be considered as “noncancerous”. We evaluated outcomes for patients with GG 1 PCa on biopsy (bGG 1) and high-risk features (prostate-specific antigen [PSA] >20 ng/ml and/or cT3–4 stage) to challenge the hypothesis that every case of bGG 1 PCa has a benign disease course. We used the multi-institutional EMPaCT database, which includes data for 9508 patients with high-risk PCa undergoing surgery. We included patients with bGG 1 PCa (n = 848) in our analysis and divided them into three groups according to PSA >20 ng/ml, cT3–4 stage, or both. The estimated 10-yr cancer-specific survival (CSS) rate was 96% in the overall population, 88% in the group with both PSA >20 ng/ml and cT3–4 stage, 97% in the group with PSA >20 ng/ml alone, and 98% in the group with cT3–4 stage alone. Similar CSS outcomes were found in subgroups with GG 1 PCa on pathology (n = 502) and with GG 1 on biopsy diagnosed after 2005 (n = 253). Study limitations include the lack of magnetic resonance imaging (MRI) staging and MRI-targeted biopsies. In conclusion, patients with GG 1 and either PSA >20 ng/ml or cT3–4 stage have a low risk of dying from their cancer after surgery. However, patients with GG 1 PCa and both PSA >20 ng/ml and cT3–4 stage are at higher risk of cancer-specific mortality and active treatment should be discussed for this subgroup. Patient summary: We assessed outcomes for patients diagnosed with low-grade prostate cancer on biopsy who also had one or two factors associated with high risk disease. Men with both of those risk factors had a higher risk of dying from their prostate cancer. Active treatment should be discussed for this subgroup of patients.

Background and objective: With approval of novel systemic therapies within the past decade for metastatic hormone-sensitive (mHSPC) and castration-resistant (mCRPC) prostate cancer, patients may receive several therapy lines. However, the use of these treatments is under an ongoing change. We investigated contemporary treatment trends and progression-free (PFS) and overall (OS) survival of different therapy lines. Methods: Relying on our institutional tertiary-care database, we identified mHSPC and mCRPC patients. The main outcome consisted of treatment changes (estimated annual percentage change [EAPC]) within the past decade, as well as PFS and OS for different mHSPC and mCRPC treatment lines. Key findings and limitations: In 1098 metastatic patients, the median age was 70 yr with a median of two systemic therapy lines. For first-line mCRPC between 2013 and 2023, androgen deprivation monotherapy (ADT) monotherapy usage decreased significantly from 31% to 0% (EAPC −38.3%, p

Abstract Fascaplysin is a red cytotoxic pigment with anticancer properties isolated from the marine sponge Fascaplysinopsis sp. Recently, structure–activity relationship analysis reported by our group suggested that selective cytotoxicity of fascaplysin derivatives towards tumor cells negatively correlates with their ability to intercalate into DNA. To validate this hypothesis, we synthesized 6- and 7-tert-butylfascaplysins which reveal mitigated DNA-intercalating properties. These derivatives were found to be strongly cytotoxic to drug-resistant human prostate cancer cells, albeit did not demonstrate improved selectivity towards cancer cells when compared to fascaplysin. At the same time, kinome analysis suggested an activation of CHK1/ATR axis in cancer cells shortly after the drug exposure. Further experiments revealed induction of replication stress that is eventually converted to the toxic DNA double-strand breaks, resulting in caspase-independent apoptosis-like cell death. Our observations highlight new DNA-targeting effect of some fascaplysin derivatives and indicate more complex structure–activity relationships within the fascaplysin family, suggesting that cytotoxicity and selectivity of these alkaloids are influenced by multiple factors. Furthermore, combination with clinically-approved inhibitors of ATR/CHK1 as well as testing in tumors particularly sensitive to the DNA damage should be considered in further studies.

Abstract Malignancy grading of prostate cancer (PCa) is fundamental for risk stratification, patient counseling, and treatment decision-making. Deep learning has shown potential to improve the expert consensus for tumor grading, which relies on the Gleason score/grade grouping. However, the core problem of interobserver variability for the Gleason grading system remains unresolved. We developed a novel grading system for PCa and utilized artificial intelligence (AI) and multi-institutional international datasets from 2647 PCa patients treated with radical prostatectomy with a long follow-up of ≥10 years for biochemical recurrence and cancer-specific death. Through survival analyses, we evaluated the novel grading system and showed that AI could develop a tumor grading system with four risk groups independent from and superior to the current five grade groups. Moreover, AI could develop a scoring system that reflects the risk of castration resistant PCa in men who have experienced biochemical recurrence. Thus, AI has the potential to develop an effective grading system for PCa interpretable by human experts.

Objective: To examine the perioperative impact of factor V Leiden mutation on thromboembolic events' risk in radical prostatectomy (RP) patients. With an incidence of about 5%, factor V Leiden mutation is the most common hereditary hypercoagulability among Caucasians and rarer in Asia. The increased risk of thromboembolic events is three- to seven-fold in heterozygous and to 80-fold in homozygous patients. Methods: Within our prospectively collected database, we analysed 33 006 prostate cancer patients treated with RP between December 2001 and December 2020. Of those, patients with factor V Leiden mutation were identified. All patients received individualised recommendation of haemostaseologists for perioperative anticoagulation. Thromboembolic complications (deep vein thrombosis and pulmonary embolism) were assessed during hospital stay, as well as according to patient reported outcomes within the first 3 months after RP. Results: Overall, 85 (0.3%) patients with known factor V Leiden mutation were identified. Median age was 65 (interquartile range: 61–68) years. There was at least one thrombosis in 53 (62.4%) patients and 31 (36.5%) patients had at least one embolic event in their medical history before RP. Within all 85 patients with factor V Leiden mutation, we experienced no thromboembolic complications within the first 3 months after surgery. Conclusion: In our cohort of patients with factor V Leiden mutation, no thromboembolic events were observed after RP with an individualised perioperative coagulation management concept. This may reassure patients with this hereditary condition who are counselled for RP.

Abstract Objective To evaluate the relationship between pre‐operative PSA value, 68Ga‐prostate‐specific‐membrane‐antigen (PSMA) PET performance and oncologic outcomes after salvage lymph node dissection (sLND) for biochemical recurrent prostate cancer (PCa). Patients and methods The study included 164 patients diagnosed with ≤2 pelvic lymph‐node recurrence(s) of PCa documented on 68Ga‐PSMA PET scan and treated with pelvic ± retroperitoneal sLND at 11 high‐volume centres between 2012 and 2019. Pathologic findings were correlated to PSA values at time of sLND, categorized in early (1.5 ng/ml). Clinical recurrence (CR)‐free survival after sLND was calculated using multivariable analyses and plotted over pre‐operative PSA value. Results Median [interquartile range (IQR)] PSA at sLND was 1.1 (0.6, 2.0) ng/ml, and 131 (80%) patients had one positive spot at PET scan. All patients received pelvic sLND, whereas 91 (55%) men received also retroperitoneal dissection. Median (IQR) number of node removed was 15 (6, 28). The rate of positive pathology increased as a function of pre‐operative PSA value, with highest rates for patients with pre‐operative PSA > 1.5 ng/ml (pelvic‐only sLNDs: 84%; pelvic + retroperitoneal sLNDs: 90%). After sLND, PSA ≤ 0.3 ng/ml was detected in 67 (41%) men. On multivariable analyses, pre‐operative PSA was associated with PSA response (p

Objective The aim of this study was to evaluate the prognostic impact of concomitant prostate cancer (PCa) of the cancer-specific mortality (CSM) in the aging patient’s papulation with bladder cancer (BCa) treated with radical cystoprostatectomy (RCP). Materials and Methods Within the SEER database (2004–2015), 1468 patients were treated with RCP for BCa harboring histopathological PCa findings. To account for other cause mortality (OCM), multivariable competing risk regression (CRR) tested for potential BCa-CSM differences according to PCa characteristics risk factors predicting CSM Results CRR analysis revealed that only following BCa characteristics, as high pathological tumor stages(Ta/Tis/T1 [REF.] vs. T2; HR 2.03, 95% CI: 1.16-3.57, p = 0.014 vs. T3; HR 4.32, 95% CI: 2.45-7.61, p

Abstract. Background. The National Comprehensive Cancer Network (NCCN) guidelines recommend pelvic lymph node dissection (PLND) in NCCN high- and intermediate-risk prostate cancer patients. We tested for PLND nonadherence (no-PLND) rates within the Surveillance Epidemiology and End Results (2010–2015). Materials and methods. We identified all radical prostatectomy patients who fulfilled the NCCN PLND guideline criteria (n = 23,495). Nonadherence rates to PLND were tabulated and further stratified according to NCCN risk subgroups, race/ethnicity, geographic distribution, and year of diagnosis. Results. Overall, the no-PLND rate was 26%; it was 41%, 25%, and 11% in the NCCN intermediate favorable, intermediate unfavorable, and high-risk prostate cancer patients, respectively (p < 0.001). Over time, the no-PLND rates declined in the overall cohort and within each NCCN risk subgroup. Georgia exhibited the highest no-PLND rate (49%), whereas New Jersey exhibited the lowest (15%). Finally, no-PLND race/ethnicity differences were recorded only in the NCCN intermediate unfavorable subgroup, where Asians exhibited the lowest no-PLND rate (20%) versus African Americans (27%) versus Whites (26%) versus Hispanic-Latinos (25%). Conclusions. The lowest no-PLND rates were recorded in the NCCN high-risk patients followed by NCCN intermediate unfavorable and favorable risk in that order. Our findings suggest that unexpectedly elevated differences in no-PLND rates warrant further examination. In all the NCCN risk subgroups, the no-PLND rates decreased over time.

Background: Survival data regarding cytoreductive nephrectomy (CN) in metastatic renal cell carcinoma (mRCC) patients according to the type and extent of tumor-associated vascular thrombus are scarce. Objective: To test for survival differences in mRCC patients treated with CN according to the type and extent of tumor-associated vascular thrombus. Design, setting, and participants: Within Surveillance, Epidemiology, and End Results Research Plus (2004–2017), we identified CN mRCC patients with renal vein (pT3a-TT) versus infradiaphragmatic inferior vena cava (IVC; pT3b) versus supradiaphragmatic IVC tumor thrombus/IVC invasion (pT3c). Outcome measurements and statistical analysis: Overall survival (OS) was addressed in Kaplan-Meier and Cox regression analyses, in addition to 3-mo landmark analyses. Results and limitations: Of 2170 mRCC patients, 1880 (87%), 204 (9%), and 86 (4%) harbored pT3a-TT, pT3b, and pT3c, respectively. The respective median OS periods were 21, 23, and 12 mo (p

Abstract Spongian diterpenes are a group of marine natural compounds possessing various biological activities. However, their anticancer activity is still poorly studied and understood. We isolated six spongian diterpenes from the marine sponge Spongionella sp., including one new spongionellol A and five previously known molecules. The structures were elucidated using a detailed analysis MS and NMR spectra as well as by comparison with previously reported data. Two of them, namely, spongionellol A and 15,16-dideoxy-15α,17β-dihydroxy-15,17-oxidospongian-16-carboxylate-15,17-diacetate exhibited high activity and selectivity in human prostate cancer cells, including cells resistant to hormonal therapy and docetaxel. The mechanism of action has been identified as caspase-dependent apoptosis. Remarkably, both compounds were able to suppress expression of androgen receptor (AR) and AR-splice variant 7, as well as AR-dependent signaling. The isolated diterpenes effectively inhibited drug efflux mediated by multidrug-resistance protein 1 (MDR1; p-glycoprotein). Of note, a synergistic effect of the compounds with docetaxel, a substrate of p-glycoprotein, suggests resensitization of p-glycoprotein overexpressing cells to standard chemotherapy. In conclusion, the isolated spongian diterpenes possess high activity and selectivity towards prostate cancer cells combined with the ability to inhibit one of the main drug-resistance mechanism. This makes them promising candidates for combinational anticancer therapy.

Background: Up- and/or downgrading rates in single intermediate-risk positive biopsy core are unknown. Methods: We identified single intermediate-risk (Gleason grade group (GGG) 2/GGG3) positive biopsy core prostate cancer patients (≤ cT2c and PSA ≤ 20 ng/mL) within the Surveillance, Epidemiology, and End Results (SEER) database (2010–2015). Subsequently, separate uni- and multivariable logistic regression models tested for independent predictors of up- and downgrading. Results: Of 1,328 assessable patients with single core positive intermediate-risk prostate cancer at biopsy, 972 (73%) harbored GGG2 versus 356 (27%) harbored GGG3. Median PSA (5.5 vs 5.7; p = 0.3), median age (62 vs 63 years; p = 0.07) and cT1-stage (77 vs 75%; p = 0.3) did not differ between GGG2 and GGG3 patients. Of individuals with single GGG2 positive biopsy core, 191 (20%) showed downgrading to GGG1 versus 35 (4%) upgrading to GGG4 or GGG5 at RP. Of individuals with single GGG3 positive biopsy core, 36 (10%) showed downgrading to GGG1 versus 42 (12%) significant upgrading to GGG4 or GGG5 at RP. In multivariable logistic regression models, elevated PSA (10–20 ng/mL) was an independent predictor of upgrading to GGG4/GGG5 in single GGG3 positive biopsy core patients (OR:2.89; 95%-CI: 1.31–6.11; p = 0.007). Conclusion: In single GGG2 positive biopsy core patients, downgrading was four times more often recorded compared to upgrading. Conversely, in single GGG3 positive biopsy core patients, up- and downgrading rates were comparable and should be expected in one out of ten patients.

Objective: Cytoreductive radical prostatectomy (cRP) has been proposed as local treatment option in metastatic hormone-sensitive prostate cancer (mHSPC) to prevent local complications and potentially improve oncological outcomes. In this study, we examined the feasibility of a multimodal concept with primary chemohormonal therapy followed by cRP and analyzed prostate size reduction under systemic treatment, postoperative complication rates, as well as early postoperative continence. Methods: In this retrospective study, 38 patients with mHSPC underwent cRP after primary chemohormonal therapy (3-monthly luteinising hormone-releasing hormone-analogue + six cycles 3-weekly docetaxel 75 mg/m2) at two centers between September 2015 and December 2018. Results: Overall, 10 (26%) patients had high volume and 28 (74%) patients had low volume disease at diagnosis, according to CHAARTED definition. Median prostate-specific antigen (PSA) decreased from 65 ng/mL (interquartile range [IQR] 35.0–124.5 ng/mL) pre-chemotherapy to 1 ng/mL (IQR 0.3–1.7 ng/mL) post-chemotherapy. Prostate gland volume was significantly reduced by a median of 50% (IQR 29%–56%) under chemohormonal therapy (p = 0.003). Postoperative histopathology showed seminal vesicle invasion in 33 (87%) patients and negative surgical margins in 17 (45%) patients. Severe complications (Grade 3 according to Clavien-Dindo) were observed in 4 (11%) patients within 30 days. Continence was reached in 87% of patients after 1 month and in 92% of patients after 6 months. Median time to castration-resistance from begin of chemohormonal therapy was 41.1 months and from cRP was 35.9 months. Postoperative PSA-nadir ≤1 ng/mL versus >1 ng/mL was a significant predictor of time to castration-resistance after cRP (median not reached versus 5.3 months; p

Promising oncological results have been reported for salvage lymph node dissection (SLND) with prostate-specific membrane antigen–radioguided surgery (PSMA-RGS) in patients with prostate cancer (PCa) recurrence. We performed a proof-of-principle study assessing circulating tumour cells (CTCs) as a prognostic marker in patients undergoing SLND. Twenty consecutive patients with recurrent PCa treated with PSMA-RGS during April–July 2019 for PSMA-positive LNs were evaluated. Preoperative CTC counts were assessed using the US Food and Drug Administration–approved CellSearch system. Biochemical recurrence (BCR)-free survival (BFS) and therapy-free survival (TFS) were evaluated using the Kaplan-Meier method. Overall, three patients (15%) were CTC-positive. Postoperatively, CTC-positive patients had more pathologically positive LNs (median 8 vs 2) without a difference in overall LN count. During median follow-up of 10.1 mo, 14 patients experienced BCR and five received further therapy. In Kaplan-Meier analyses, median BFS was 1.4 versus 4.3 mo and median TFS was 10.3 mo versus not reached for CTC-positive versus CTC-negative patients. The main limitations are the small number of patients, the retrospective design, and short follow-up. Our pilot study suggests that CTC-positive patients seem to have worse pathological and short-term oncological outcomes. Therefore, further validation of this biomarker for treatment decision-making before local salvage therapy could be of value. Patient summary: We looked at outcomes for lymph node dissection in patients with recurrence of prostate cancer. We found that outcomes appear to be worse when circulating tumour cells (CTCs) can be measured in the blood preoperatively. We conclude that detection of CTCs indicates spread of tumour cells via the blood, which may limit the benefit of lymph node dissection. Thus, CTCs should be investigated in further studies as a potential marker to help in selecting patients who could benefit from lymph node dissection if their prostate cancer recurs.

Background: To determine the correlation between urine loss in PAD-test after catheter removal, and early urinary continence (UC) in RP treated patients. Methods: Urine loss was measured by using a standardized, validated PAD-test within 24 h after removal of the transurethral catheter, and was grouped as a loss of 50 g of urine, respectively. Early UC (median: 3 months) was defined as the usage of no or one safety-pad. Uni- and multivariable logistic regression models tested the correlation between PAD-test results and early UC. Covariates consisted of age, BMI, nerve-sparing approach, prostate volume, and extraprostatic extension of tumor. Results: From 01/2018 to 03/2021, 100 patients undergoing RP with data available for a PAD-test and early UC were retrospectively identified. Ultimately, 24%, 47%, 15%, and 14% of patients had a loss of urine 50 g in PAD-test, respectively. Additionally, 59% of patients reported to be continent. In multivariable logistic regression models, urine loss in PAD-test predicted early UC (OR: 0.21 vs. 0.09 vs. 0.03; for urine loss 1–10 g vs. 11–50 g vs. >50 g, Ref: p < 0.05). Conclusions: Urine loss after catheter removal strongly correlated with early continence as well as a severity in urinary incontinence.

BackgroundWe tested whether a model identifying prostate cancer (PCa) patients at risk of pT3-4/pN1 can be developed for use during COVID19 pandemic, in order to guarantee appropriate treatment to patients harboring advanced disease patients without compromising sustainability of care delivery.MethodsWithin the Surveillance, Epidemiology and End Results database 2010-2016, we identified 27,529 patients with localized PCa and treated with radical prostatectomy. A multivariable logistic regression model predicting presence of pT3-4/pN1 disease was fitted within a development cohort (n=13,977, 50.8%). Subsequently, external validation (n=13,552, 49.2%) and head-to-head comparison with NCCN risk group stratification was performed.ResultsIn model development, age, PSA, biopsy Gleason Grade Group (GGG) and percentage of positive biopsy cores were independent predictors of pT3-4/pN1 stage. In external validation, prediction of pT3-4/pN1 with novel nomogram was 74% accurate versus 68% for NCCN risk group stratification. Nomogram achieved better calibration and showed net-benefit over NCCN risk group stratification in decision curve analyses. The use of nomogram cut-off of 49% resulted in pT3-4/pN1 rate of 65%, instead of the average 35%.ConclusionThe newly developed, externally validated nomogram predicts presence of pT3-4/pN1 better than NCCN risk group stratification and allows to focus radical prostatectomy treatment on individuals at highest risk of pT3-4/pN1.

Probably, patients with de novo (synchronous) and recurrent (metachronous) oligometastatic hormone-sensitive prostate cancer have different oncologic outcomes. Thus, we are challenged with different scenarios in clinical practice, where different treatment options may apply. In the last years, several prospective studies have focused on the treatment of patients with de novo oligometastatic hormone-sensitive prostate cancer. Not only the addition of systemic therapeutic treatments, such as chemotherapy with docetaxel, abiraterone, enzalutamide, and apalutamide, next to androgen deprivation therapy, demonstrated to improve outcomes in these patients but also local therapy of the primary has been demonstrated to improve outcomes of low-volume metastatic disease. Next to radiotherapy, also radical prostatectomy has been reported as a feasible and safe treatment option. Additional metastasis-directed therapy in de novo metastatic disease is currently examined by four trials. In the recurrent metastatic setting, less data are available, and it remains uncertain if patients can be treated in the same way as synchronous oligometastatic disease. Metastasis-directed therapy has demonstrated to prolong outcomes, while data on survival are still missing.

Background: To test the value of immunohistochemistry (IHC) staining in prostate biopsies for changes in biopsy results and its impact on treatment decision-making. Methods: Between January 2017–June 2020, all patients undergoing prostate biopsies were identified and evaluated regarding additional IHC staining for diagnostic purpose. Final pathologic results after radical prostatectomy (RP) were analyzed regarding the effect of IHC at biopsy. Results: Of 606 biopsies, 350 (58.7%) received additional IHC staining. Of those, prostate cancer (PCa) was found in 208 patients (59.4%); while in 142 patients (40.6%), PCa could be ruled out through IHC. IHC patients harbored significantly more often Gleason 6 in biopsy (p < 0.01) and less suspicious baseline characteristics than patients without IHC. Of 185 patients with positive IHC and PCa detection, IHC led to a change in biopsy results in 81 (43.8%) patients. Of these patients with changes in biopsy results due to IHC, 42 (51.9%) underwent RP with 59.5% harboring ≥pT3 and/or Gleason 7–10. Conclusions: Patients with IHC stains had less suspicious characteristics than patients without IHC. Moreover, in patients with positive IHC and PCa detection, a change in biopsy results was observed in >40%. Patients with changes in biopsy results partly underwent RP, in which 60% harbored significant PCa.

BackgroundTo test the effect of race/ethnicity on cancer-specific mortality (CSM) after salvage radical prostatectomy (SRP).Material and methodsWe relied on the Surveillance, Epidemiology and End Results database (SEER, 2004–2016) to identify SRP patients of all race/ethnicity background. Univariate and multivariate Cox regression models addressed CSM according to race/ethnicity.ResultsOf 426 assessable SRP patients, Caucasians accounted for 299 (69.9%) vs. 68 (15.9%) African-Americans vs. 39 (9.1%) Hispanics vs. 20 (4.7%) Asians. At diagnosis, African-Americans (64 years) were younger than Caucasians (66 years), but not younger than Hispanics (66 years) and Asians (67 years). PSA at diagnosis was significantly higher in African-Americans (13.2 ng/ml), Hispanics (13.0 ng/ml), and Asians (12.2 ng/ml) than in Caucasians (7.8 ng/ml, p = 0.01). Moreover, the distribution of African-Americans (10.3%–36.6%) and Hispanics (0%–15.8%) varied according to SEER region. The 10-year CSM was 46.5% in African-Americans vs. 22.4% in Caucasians vs. 15.4% in Hispanics vs. 15.0% in Asians. After multivariate adjustment (for age, clinical T stage, lymph node dissection status), African-American race/ethnicity was an independent predictor of higher CSM (HR: 2.2, p < 0.01), but not Hispanic or Asian race/ethnicity. The independent effect of African-American race/ethnicity did not persist after further adjustment for PSA.ConclusionAfrican-Americans treated with SRP are at higher risk of CSM than other racial/ethnic groups and also exhibited the highest baseline PSA. The independent effect of African-American race/ethnicity on higher CSM no longer applies after PSA adjustment since higher PSA represents a distinguishing feature in African-American patients.

BackgroundStructured implementation of robot-assisted surgery in the field of medical education is lacking. We assessed students' interest in robot-assisted surgery and tested if the implementation of a hands-on robotic course into the curriculum could increase the interest to join a surgical discipline in general and especially in female students, since women are clearly underrepresented in surgical disciplines.MethodsAfter a prostate cancer focused seminar, 100 students were 1:1 randomized into two groups. Group B: Baseline characteristics and professional interest were assessed prior and after a hands-on robotic course, using a da Vinci® console with simulator (da Vinci® Surgical training, Intuitive Surgical Inc., USA). Group A served as post-interventional consistency control group, received the questionnaire only once after the hands-on training.ResultsThe male to female ratio of students was 54% and 46%. The interest to turn into urology/surgery, categorized as yes”, “no”, “maybe” changed from 18 to 16%, 36 to 30% and 46 to 54% respectively after the hands-on robotic course (p

Abstract Background Delayed neurocognitive recovery (DNCR) is a common and serious complication after radical prostatectomy. We hypothesized that patients with DNCR in the early postoperative period would report reduced health-related quality of life (HRQoL) and more cognitive failures 12 months after surgery, compared with patients without DNCR. Methods We performed a 12-month follow-up on 367 patients who had been enrolled in a prospective observational trial to study the incidence of DNCR after radical prostatectomy. Patients were screened for preoperative cognitive impairment and depression. We defined DNCR as a decline in cognitive function between days 3 and 5 after surgery, compared with baseline assessments. We evaluated HRQoL and cognitive failures 12 months after surgery with the 36-item Short Form Health Survey and the Cognitive Failures Questionnaire. General linear models were used to analyze associations of DNCR with HRQoL and cognitive failures. Results Delayed neurocognitive recovery in the early postoperative period was significantly associated with self-reported cognitive failures (B for no DNCR = − 0.411 [95% CI: − 0.798;0.024], p = 0.038), but not with physical (B = 0.082 [95% CI: − 0.021;0.186], p = 0.118) or mental HRQoL (B = − 0.044 [95% CI: − 0.149;0.062], p = 0.417) 12 months after surgery. Preoperative depression screening scores were significantly associated with self-reported cognitive failures and both physical and mental HRQoL 12 months after surgery. Conclusions Delayed neurocognitive recovery in the early period after radical prostatectomy has a long-term impact on patients’ daily lives by impairing memory, attention, action, and perception. Therefore, prevention of DNCR must be a priority for physicians and researchers. Consequent preoperative screening for depressive symptoms may facilitate early psycho-oncological intervention to improve postoperative HRQoL. Trials registration DRKS00010014 , date of registration: 21.03.2016, retrospectively registered.

Objective: Anoctamin 7 (ANO7) is a calcium2+-dependent chloride ion channel protein. Its expression is restricted to prostate epithelial cells. The exact function is unknown. This study aimed to analyze ANO7 expression and its clinical significance in prostate cancer (PCa). Methods: ANO7 expression was assessed by immunohistochemistry in 17,747 clinical PCa specimens. Results: ANO7 was strongly expressed in normal prostate glandular cells but often less abundant in cancer cells. ANO7 staining was interpretable in 13,594 cancer tissues and considered strong in 34.4%, moderate in 48.7%, weak in 9.3%, and negative in 7.6%. Reduced staining was tightly linked to adverse tumor features [high classical and quantitative Gleason grade, lymph node metastasis, advanced tumor stage, high Ki67 labeling index, positive surgical margin, and early biochemical recurrence (P < 0.0001 each)]. The univariate Cox hazard ratio for prostate-specific antigen (PSA) recurrence after prostatectomy in patients with negative vs. strong ANO7 expression was 2.98 (95% confidence interval 2.61–3.38). The prognostic impact was independent of established pre- or postoperatively available parameters (P < 0.0001). Analysis of annotated molecular data showed that low ANO7 expression was linked to TMPRSS2:ERG fusions (P < 0.0001), elevated androgen receptor expression (P < 0.0001), as well as presence of 9 of 11 chromosomal deletions (P < 0.05 each). A particularly strong association of low ANO7 expression with phosphatase and tensin homolog (PTEN) deletion may indicate a functional relationship with the PTEN/AKT pathway. Conclusions: These data identify reduced ANO7 protein expression as a strong and independent predictor of poor prognosis in PCa. ANO7 measurement, either alone or in combination, might provide clinically useful prognostic information in PCa.

Abstract Background Epithelial splicing regulatory protein 1 (ESRP1) and 2 (ESRP2) regulate alternative splicing events of various pre-mRNAs. Some of these targets play a role in cancer-associated processes, including cytoskeleton reorganization and DNA-repair processes. This study was undertaken to estimate the impact of ESRP1 and ESRP2 alterations on prostate cancer patient prognosis. Methods A tissue microarray made from 17,747 individual cancer samples with comprehensive, pathological, clinical and molecular data was analyzed by immunohistochemistry for ESRP1 and ESRP2. Results Nuclear staining for ESRP1 was seen in 38.6% (36.0% low, 2.6% high) of 12,140 interpretable cancers and in 41.9% (36.4% low, 5.3% high) of 12,962 interpretable cancers for ESRP2. Nuclear protein expression was linked to advanced tumor stage, high Gleason score, presence of lymph node metastasis, early biochemical recurrence, and ERG-positive cancers (p

Aim and Objectives: We aimed to test the impact of age on long-term urinary continence (≥12 months) in patients undergoing robotic-assisted radical prostatectomy. Methods and Materials: We relied on an institutional tertiary-care database to identify the patients who underwent robotic-assisted radical prostatectomy between January 2014 and January 2021. Patients were divided into three age groups: age group one (≤60 years), age group two (61–69 years) and age group three (≥70 years). Multivariable logistic regression models tested the differences between the age groups in the analyses addressing long-term urinary continence after robotic-assisted radical prostatectomy. Results: Of the 201 prostate cancer patients treated with robotic-assisted radical prostatectomy, 49 (24%) were assigned to age group one (≤60 years), 93 (46%) to age group two (61–69 years) and 59 (29%) to age group three (≥70 years). The three age groups differed according to long-term urinary continence: 90% vs. 84% vs. 69% for, respectively, age group one vs. two vs. three (p = 0.018). In the multivariable logistic regression, age group one (Odds Ratio (OR) 4.73, 95% CI 1.44–18.65, p = 0.015) and 2 (OR 2.94; 95% CI 1.23–7.29; p = 0.017) were independent predictors for urinary continence, compared to age group three. Conclusion: Younger age, especially ≤60 years, was associated with better urinary continence after robotic-assisted radical prostatectomy. This observation is important at the point of patient education and should be discussed in informed consent.

We aimed to externally validate the SEER-based nomogram used to predict downgrading in biopsied high-risk prostate cancer patients treated with radical prostatectomy (RP) in a contemporary European tertiary-care-hospital cohort. We relied on an institutional tertiary-care database to identify biopsied high-risk prostate cancer patients in the National Comprehensive Cancer Network (NCCN) who underwent RP between January 2014 and December 2022. The model’s downgrading performance was evaluated using accuracy and calibration. The net benefit of the nomogram was tested with decision-curve analyses. Overall, 241 biopsied high-risk prostate cancer patients were identified. In total, 51% were downgraded at RP. Moreover, of the 99 patients with a biopsy Gleason pattern of 5, 43% were significantly downgraded to RP Gleason pattern ≤ 4 + 4. The nomogram predicted the downgrading with 72% accuracy. A high level of agreement between the predicted and observed downgrading rates was observed. In the prediction of significant downgrading from a biopsy Gleason pattern of 5 to a RP Gleason pattern ≤ 4 + 4, the accuracy was 71%. Deviations from the ideal predictions were noted for predicted probabilities between 30% and 50%, where the nomogram overestimated the observed rate of significant downgrading. This external validation of the SEER-based nomogram confirmed its ability to predict the downgrading of biopsy high-risk prostate cancer patients and its accurate use for patient counseling in high-volume RP centers.

ContextMeticulous knowledge about the anatomy of the prostate and surrounding tissue represents a crucial and mandatory requirement during radical prostatectomy for reliable oncological and excellent replicable, functional outcomes. Since its introduction two decades ago, robotic-assisted laparoscopic radical prostatectomy (RALP) has evolved to become the predominant surgical approach in many industrialized countries.ObjectiveTo provide and highlight currently available literature regarding prostate anatomy and to help in improving oncological and functional outcomes in RALP.Methods/Evidence AcquiringPubMed database was searched using the following keywords: “robotic-assisted radical prostatectomy,” “anatomy,” “neurovascular bundle,” “nerve,” “periprostatic fascia,” “pelvis,” “sphincter,” “urethra,” “urinary incontinence,” and “erectile dysfunction.” Relevant articles and book chapters were critically reviewed and if eligible, they were included in this review.ResultsNew evidence in regards to prostatic anatomy and surgical approaches in RALP has been reported in recent years. Besides detailed anatomical studies investigating the meticulous structure of the fascial structures surrounding the prostate and neurovascular bundle preservation, debate about the optimal RALP approach is still ongoing, inspired by recent publications presenting promising functional outcomes following modifications in surgical approaches.ConclusionsThis review provides a detailed overview of the current knowledge of prostate anatomy, its surrounding tissue, and its influence on key surgical step development for RALP.

Five new β-resorcylic acid derivatives, 14-hydroxyasperentin B (1), β-resoantarctines A-C (3, 5, 6) and 8-dehydro-β-resoantarctine A (4), together with known 14-hydroxyasperentin (5′-hydroxyasperentin) (2), were isolated from the ethyl acetate extract of the fungus Penicillium antarcticum KMM 4685 associated with the brown alga Sargassum miyabei. The structures of the compounds were elucidated by spectroscopic analyses and modified Mosher’s method, and the biogenetic pathways for compounds 3–6 were proposed. For the very first time, the relative configuration of the C-14 center of a known compound 2 was assigned via analyses of magnitudes of the vicinal coupling constants. The new metabolites 3–6 were biogenically related to resorcylic acid lactones (RALs); however, they did not possess lactonized macrolide elements in their structures. Compounds 3, 4 and 5 exhibited moderate cytotoxic activity in LNCaP, DU145 and 22Rv1 human prostate cancer cells. Moreover, these metabolites could inhibit the activity of p-glycoprotein at their noncytotoxic concentrations and consequently synergize with docetaxel in p-glycoprotein-overexpressing drug-resistant cancer cells.

Marine fungi serve as a valuable source for new bioactive molecules bearing various biological activities. In this study, we report on the isolation of a new indole diketopiperazine alkaloid deoxy-14,15-dehydroisoaustamide (1) from the marine-derived fungus Penicillium dimorphosporum KMM 4689 associated with a soft coral. The structure of this metabolite, including its absolute configuration, was determined by HR-MS, 1D and 2D NMR as well as CD data. Compound 1 is a very first deoxyisoaustamide alkaloid possessing two double bonds in the proline ring. The isolated compound was noncytotoxic to a panel of human normal and cancer cell lines up to 100 µM. At the same time, compound 1 resensitized prostate cancer 22Rv1 cells to androgen receptor (AR) blocker enzalutamide. The mechanism of this phenomenon was identified as specific drug-induced degradation of androgen receptor transcription variant V7 (AR-V7), which also resulted in general suppression of AR signaling. Our data suggest that the isolated alkaloid is a promising candidate for combinational therapy of castration resistant prostate cancer, including drug-resistant subtypes.

IntroductionRandomized clinical trials demonstrated improved overall survival in chemotherapy exposed metastatic prostate cancer patients. However, real-world data validating this effect with large scale epidemiological data sets are scarce and might not agree with trials. We tested this hypothesis.Materials and MethodsWe identified de novo metastatic prostate cancer patients within the Surveillance, Epidemiology, and End Results (SEER) database (2014-2015). Kaplan-Meier plots and Cox regression models tested for overall survival differences between chemotherapy-exposed patients vs chemotherapy-naïve patients. All analyses were repeated in propensity-score matched cohorts. Additionally, landmark analyses were applied to account for potential immortal time bias.ResultsOverall, 4295 de novo metastatic prostate cancer patients were identified. Of those, 905 (21.1%) patients received chemotherapy vs 3390 (78.9%) did not. Median overall survival was not reached at 30 months follow-up. Chemotherapy-exposed patients exhibited significantly better overall survival (61.6 vs 54.3%, multivariable HR:0.82, CI: 0.72-0.96, p=0.01) at 30 months compared to their chemotherapy-naïve counterparts. These findings were confirmed in propensity score matched analyses (multivariable HR: 0.77, CI:0.66-0.90, p

BackgroundThis study aims to test the effect of the 10 most common nonurological primary cancers (skin, rectal, colon, lymphoma, leukemia, pancreas, stomach, esophagus, liver, lung) on overall mortality (OM) after secondary prostate cancer (PCa).Material and MethodsWithin the Surveillance, Epidemiology, and End Results (SEER) database, patients with 10 most common primary cancers and concomitant secondary PCa (diagnosed 2004–2016) were identified and were matched in 1:4 fashion (age, year at diagnosis, race/ethnicity, treatment type, TNM stage) with primary PCa controls. OM was compared between secondary and primary PCa patients and was stratified according to primary cancer type, as well as according to time interval between primary cancer vs. secondary PCa diagnoses.ResultsWe identified 24,848 secondary PCa patients (skin, n = 3,871; rectal, n = 798; colon, n = 3,665; lymphoma, n = 2,583; leukemia, n = 1,102; pancreatic, n = 118; stomach, n = 361; esophagus, n = 219; liver, n = 160; lung, n = 1,328) vs. 531,732 primary PCa patients. Secondary PCa characteristics were less favorable than those of primary PCa patients (PSA and grade), and smaller proportions of secondary PCa patients received active treatment. After 1:4 matching, all secondary PCa exhibited worse OM than primary PCa patients. Finally, subgroup analyses showed that the survival disadvantage of secondary PCa patients decreased with longer time interval since primary cancer diagnosis and subsequent secondary PCa.ConclusionPatients with secondary PCa are diagnosed with less favorable PSA and grade. Even after matching for PCa characteristics, secondary PCa patients still exhibit worse survival. However, the survival disadvantage is attenuated, when secondary PCa diagnosis is made after longer time interval, since primary cancer diagnosis.

Abstract Background TFAP2D is a transcription factor important for modulating gene expression in embryogenesis. Its expression and prognostic role in prostate cancer has not been evaluated. Methods Therefore, a tissue microarray containing 17,747 prostate cancer specimens with associated pathological, clinical, and molecular data was analyzed by immunohistochemistry to assess the role of TFAP2D. Results TFAP2D expression was typically increased in prostate cancer as compared to adjacent non-neoplastic glands. TFAP2D staining was considered negative in 24.3% and positive in 75.7% of 13,545 interpretable cancers. TFAP2D staining was significantly linked to advanced tumor stage, high classical and quantitative Gleason grade, lymph node metastasis, and a positive surgical margin (p ≤ 0.0045). TFAP2D positivity was more common in ERG fusion positive (88.7%) than in ERG negative cancers (66.8%; p

Abstract The role of subcellular survivin compartmentalization in the biology and prognosis of prostate cancer is unclear. We therefore investigated subcellular localization of survivin in more than 3000 prostate cancer patients by quantitative immunohistochemistry and performed transcriptomics of 250 prostate cancer patients and healthy donors using publicly available datasets. Survivin (BIRC5) gene expression was increased in primary prostate cancers and metastases, but did not differ in recurrent vs non-recurrent prostate cancers. Survivin immunohistochemistry (IHC) staining was limited exclusively to the nucleus in 900 prostate cancers (40.0%), and accompanied by various levels of cytoplasmic positivity in 1338 tumors (59.4%). 0.5% of prostate cancers did not express survivin. Nuclear and cytoplasmic survivin staining intensities were strongly associated with each other, pT category, and higher Gleason scores. Cytoplasmic but not nuclear survivin staining correlated with high tumor cell proliferation in prostate cancers. Strong cytoplasmic survivin staining, but not nuclear staining predicted an unfavorable outcome in univariate analyses. Multivariate Cox regression analysis showed that survivin is not an independent prognostic marker. In conclusion, we provide evidence that survivin expression is increased in prostate cancers, especially in metastatic disease, resulting in higher aggressiveness and tumor progression. In addition, subcellular compartmentalization is an important aspect of survivin cancer biology, as only cytoplasmic, but not nuclear survivin accumulation is linked to biological aggressiveness and prognosis of prostate cancers.

Abstract Survivin is an inhibitor of apoptosis. Aberrant survivin expression occurs in malignant tumors and has often been linked to unfavorable patient outcome. Here we analyzed 12 432 prostate cancers by immunohistochemistry. Survivin immunostaining was regularly expressed at high levels in normal prostate epithelium but expression was often reduced in prostate cancers. Among 9492 evaluable prostate cancers, 9% expressed survivin strongly, 19% moderately, 28% weakly, and 44% lacked it. Loss of cytoplasmic survivin was seen in advanced tumor stage, higher Gleason score, preoperative PSA levels, and Ki‐67 labeling index, and associated with earlier PSA recurrence (P

The chromatin‐organizing factor CCCTC‐binding factor (CTCF) is involved in transcriptional regulation, DNA‐loop formation, and telomere maintenance. To evaluate the clinical impact of CTCF in prostate cancer, we analyzed CTCF expression by immunohistochemistry on a tissue microarray containing 17 747 prostate cancers. Normal prostate tissue showed negative to low CTCF expression, while in prostate cancers, CTCF expression was seen in 7726 of our 12 555 (61.5%) tumors and was considered low in 44.6% and high in 17% of cancers. Particularly, high CTCF expression was significantly associated with the presence of the transmembrane protease, serine 2:ETS‐related gene fusion: Only 10% of ERG‐negative cancers, but 30% of ERG‐positive cancers had high‐level CTCF expression (P

Abstract Background Protein tyrosine phosphatase non-receptor 12 (PTPN12) is ubiquitously tyrosine phosphatase with tumor suppressive properties. Methods PTPN12 expression was analyzed by immunohistochemistry on a tissue microarray with 13,660 clinical prostate cancer specimens. Results PTPN12 staining was typically absent or weak in normal prostatic epithelium but seen in the majority of cancers, where staining was considered weak in 26.5%, moderate in 39.9%, and strong in 4.7%. High PTPN12 staining was associated with high pT category, high classical and quantitative Gleason grade, lymph node metastasis, positive surgical margin, high Ki67 labeling index and early prostate specific antigen recurrence (p

Dysregulation of S100A8 is described in many different human tumor types, but its role in prostate cancer is unknown. To evaluate the clinical relevance of S100A8 expression in prostate cancer, a tissue microarray containing 13,665 tumors was analyzed by immunohistochemistry. Cytoplasmic S100A8 staining was compared to prostate cancer phenotype, patient prognosis and molecular features including TMPRSS2:ERG fusion status and deletions of PTEN, 3p, 5q and 6q. S100A8 immunostaining was typically seen in normal prostate tissue but lost in 60% of 9786 interpretable prostate cancers. In the remaining tumors, S100A8 was considered weak in 17.9%, moderate in 17.8% and strong in 5.4% of cases. Loss of S100A8 expression was linked to advanced tumor stage, high Gleason grade, positive nodal status, positive surgical margin and high preoperative PSA (P

Objective Prostate secretory protein of 94 amino acids (PSP94) is a target gene of the EZH2 transcriptional repressor and is often downregulated in prostate cancer; however, its prognostic value is disputed.Methods Immunohistochemical analysis of a tissue microarray of 12, 432 prostate cancer specimens was performed to evaluate PSP94 expression. Correlation of PSP94 expression with tumor phenotype, patient prognosis, TMPRSS2:ERG fusion status, EZH2 expression and PTEN deletion was studied.Results PSP94 expression was increased in benign prostatic hyperplasia; however, it was downregulated in 48% and negative in 42% of the 9, 881 interpretable prostate cancer specimens. The loss of PSP94 expression was inversely correlated to EZH2 expression (P < 0.0001) and largely unrelated to the ERG status, but strongly correlated with high Gleason grade, advanced tumor stage, and nodal metastasis (P P < 0.0001) and from 40% in Gleason 3+3 = 6 to 46% in Gleason 4+3 = 7 and 60% in Gleason ≥4+4 = 8 (P < 0.0001). Loss of PSP94 was linked to early prostate-specific antigen recurrence, but with little absolute effect (P < 0.0001). However, it provided additional prognostic impact in cancer specimens with PTEN deletion. Loss of PSP94 deteriorated prognosis of cancer patients with PTEN deletion by more than 10% (P < 0.0001). The combination of PTEN deletion and PSP94 loss provided independent prognostic information that was observed in several subgroups defined by classical and quantitative Gleason grade.Conclusions The results of our study suggest that combined PSP94/PTEN analysis can be potentially used in the clinical prognosis of prostate cancer.

Abstract Background SNW1 is a nuclear receptor co-activator involved in splicing and transcription control, including androgen receptor signaling. Overexpression of SNW1 has been linked to adverse prognosis in different cancer types, but studies on the role of SNW1 in prostate cancer are lacking. Methods Using immunohistochemistry, we analyzed SNW1 expression in 10,310 prostate cancers in a tissue microarray (TMA) with attached clinical and molecular data. Results The comparison with normal prostate tissue revealed an up regulation of SNW1 in a subset of cancer samples. SNW1 staining was considered weak in 31.5%, moderate in 37.7% and strong in 14% of cancers. Strong SNW1 expression was markedly more frequent in prostate cancers harboring the TMPRSS2:ERG fusion (24%) than in ERG negative cancers (7%, p

Two new guanidine alkaloids, batzelladines O (1) and P (2), were isolated from the deep-water marine sponge Monanchora pulchra. The structures of these metabolites were determined by NMR spectroscopy, mass spectrometry, and ECD. The isolated compounds exhibited cytotoxic activity in human prostate cancer cells PC3, PC3-DR, and 22Rv1 at low micromolar concentrations and inhibited colony formation and survival of the cancer cells. Batzelladines O (1) and P (2) induced apoptosis, which was detected by Western blotting as caspase-3 and PARP cleavage. Additionally, induction of pro-survival autophagy indicated as upregulation of LC3B-II and suppression of mTOR was observed in the treated cells. In line with this, the combination with autophagy inhibitor 3-methyladenine synergistically increased the cytotoxic activity of batzelladines O (1) and P (2). Both compounds were equally active in docetaxel-sensitive and docetaxel-resistant prostate cancer cells, despite exhibiting a slight p-glycoprotein substrate-like activity. In combination with docetaxel, an additive effect was observed. In conclusion, the isolated new guanidine alkaloids are promising drug candidates for the treatment of taxane-resistant prostate cancer.

Results of three randomized clinical trials (RCTs) comparing adjuvant radiotherapy (ART) and early salvage radiotherapy (eSRT) of prostate carcinoma and a subsequent meta-analysis of the individual patient data from these RCTs were recently published. The results suggest that early eSRT is as effective and potentially less toxic than ART. Therefore, eSRT should be considered the standard of care. However, due to limitations in the RCTs, ART remains a valid treatment option in patients with the combination of high-risk features such as Gleason Score (GS) 8–10, positive surgical margins (R1) and pathological T-stage 3 or 4 (pT3/4). This article provides a critical appraisal of the RCTs and the rationale for recommendations adopted in the current national guidelines regarding patients with high-risk features after radical prostatectomy (RP): ART should be offered in case of pT3/pT4 and R1 and Gleason Score 8–10; ART can be offered in case of pT3/pT4 and R0 and Gleason Score 8–10 as well as in case of multifocal R1 (including pT2) and Gleason Score 8–10. In any case, the alternative treatment option of eSRT in case of rising PSA should be discussed with the patient.

N-methylpretrichodermamide B (NB) is a biologically active epidithiodiketopiperazine isolated from several strains of the algae-derived fungus Penicillium sp. Recently, we reported the first data on its activity in human cancer cells lines in vitro. Here, we investigated the activity, selectivity, and mechanism of action of NB in human prostate cancer cell lines, including drug-resistant subtypes. NB did not reveal cross-resistance to docetaxel in the PC3-DR cell line model and was highly active in hormone-independent 22Rv1 cells. NB-induced cell death was stipulated by externalization of phosphatidylserine and activation of caspase-3. Moreover, inhibition of caspase activity by z-VAD(OMe)-fmk did not affect NB cytotoxicity, suggesting a caspase-independent cell death induced by NB. The compound has a moderate p-glycoprotein (p-gp) substrate-like affinity and can simultaneously inhibit p-gp at nanomolar concentrations. Therefore, NB resensitized p-gp-overexpressing PC3-DR cells to docetaxel. A kinome profiling of the NB-treated cells revealed, among other things, an induction of mitogen-activated protein kinases JNK1/2 and p38. Further functional analysis confirmed an activation of both kinases and indicated a prosurvival role of this biological event in the cellular response to the treatment. Overall, NB holds promising anticancer potential and further structure–activity relationship studies and structural optimization are needed in order to improve its biological properties.

Introduction and Objectives: Knowledge about the significance of sarcopenia (muscle loss) in prostate cancer (PCa) patients is limited. The aim of this study was to determine the influence of skeletal muscle index (SMI) on early functional and pathological outcome in patients undergoing radical prostatectomy (RP).Materials and Methods: One hundred randomly chosen patients who received RP between November 2016 and April 2017 at Martini-Klinik (Hamburg, Germany) were retrospectively assessed. SMI (skeletal muscle mass cross-sectional area at L3/m2) was measured by preoperative staging computed tomography scans at L3 level. Cox regression analysis was applied to determine the impact of SMI on post-operative outcome. Follow-up was 12 months. Continence was defined as no more than one safety pad per day.Results: Mean age of the cohort was 63.6 years. Mean SMI was 54.06 cm2/m2 (range, 40.65–74.58 cm2/m2). Of the patients, 41.4% had pT2, 28.7% had pT3a, and 29.9% had pT3b or pT4 PCa. SMI revealed to be without significant correlation on tumor stage. Follow-up data of 55 patients were available for early functional outcome analysis. SMI showed no significant influence on erectile function in multivariable Cox regression analysis. In multivariable Cox regression analysis, SMI turned out to have no influence on continence rates 6 weeks after surgery.Conclusion: The present study shows that patients undergoing RP have a wide range of SMI. Unlike in other urological malignancies, there was no significant impact of SMI on early functional outcome and pathological outcome. A larger cohort is needed to confirm these results.

Abstract Background Microtubule-associated protein Tau (MAPT) overexpression has been linked to poor prognosis and decreased response to taxane-based therapies in several cancer types, but its relevance in prostate cancer is unknown. Methods In this study, MAPT expression was analyzed by immunohistochemistry on a tissue microarray containing 17,747 prostate cancers. Results MAPT was absent in normal prostate epithelial cells but detectable in 1004 (8.2%) of 12,313 interpretable cancers. Its expression was associated with advanced tumor stage, high Gleason grade, positive lymph nodes, and early biochemical recurrence (p

Abstract Background Prostate Stem Cell Antigen (PSCA) is frequently expressed in prostate cancer but its exact function is unclear. Methods To clarify contradictory findings on the prognostic role of PSCA expression, a tissue microarray containing 13,665 prostate cancers was analyzed by immunohistochemistry. Results PSCA staining was absent in normal epithelial and stromal cells of the prostate. Membranous and cytoplasmic PSCA staining was seen in 53.7% of 9642 interpretable tumors. Staining was weak in 22.4%, moderate in 24.5% and strong in 6.8% of tumors. PSCA expression was associated with favorable pathological and clinical tumor features: Early pathological tumor stage (p

Background: To test the impact of urethral sphincter length (USL) and anatomic variants of prostatic apex (Lee-type classification) in preoperative multiparametric magnet resonance imaging (mpMRI) on mid-term continence in prostate cancer patients treated with radical prostatectomy (RP). Methods: We relied on an institutional tertiary-care database to identify patients who underwent RP between 03/2018 and 12/2019 with preoperative mpMRI and data available on mid-term (>6 months post-surgery) urinary continence, defined as usage 0/1 (-safety) pad/24 h. Univariable and multivariable logistic regression models were fitted to test for predictor status of USL and prostatic apex variants, defined in mpMRI measurements. Results: Of 68 eligible patients, rate of mid-term urinary continence was 81% (n = 55). Median coronal (15.1 vs. 12.5 mm) and sagittal (15.4 vs. 11.1 mm) USL were longer in patients reporting urinary continence in mid-term follow-up (both p < 0.01). No difference was recorded for prostatic apex variants distribution (Lee-type) between continent vs. incontinent patients (p = 0.4). In separate multivariable logistic regression models, coronal (odds ratio (OR): 1.35) and sagittal (OR: 1.67) USL, but not Lee-type, were independent predictors for mid-term continence. Conclusion: USL, but not apex anatomy, in preoperative mpMRI was associated with higher rates of urinary continence at mid-term follow-up.

Marine alkaloid fascaplysin and its derivatives are known to exhibit promising anticancer properties in vitro and in vivo. However, toxicity of these molecules to non-cancer cells was identified as a main limitation for their clinical use. Here, for the very first time, we synthesized a library of fascaplysin derivatives covering all possible substituent introduction sites, i.e., cycles A, C and E of the 12H-pyrido[1-2-a:3,4-b’]diindole system. Their selectivity towards human prostate cancer versus non-cancer cells, as well as the effects on cellular metabolism, membrane integrity, cell cycle progression, apoptosis induction and their ability to intercalate into DNA were investigated. A pronounced selectivity for cancer cells was observed for the family of di- and trisubstituted halogen derivatives (modification of cycles A and E), while a modification of cycle C resulted in a stronger activity in therapy-resistant PC-3 cells. Among others, 3,10-dibromofascaplysin exhibited the highest selectivity, presumably due to the cytostatic effects executed via the targeting of cellular metabolism. Moreover, an introduction of radical substituents at C-9, C-10 or C-10 plus C-3 resulted in a notable reduction in DNA intercalating activity and improved selectivity. Taken together, our research contributes to understanding the structure–activity relationships of fascaplysin alkaloids and defines further directions of the structural optimization.