Anesthetic Technique (Spinal vs. General Anesthesia) in Holmium Laser Enucleation of the Prostate: Retrospective Analysis of Procedural and Functional Outcomes among 1,159 Patients.

OBJECTIVE: The aim of the study was to compare procedural efficacy, early and late functional outcomes in holmium laser enucleation of the prostate (HoLEP) under spinal anesthesia (SA) versus general anesthesia (GA). METHODS: We retrospectively reviewed patients undergoing HoLEP at our institution between 2012 and 2017. Standard pre-, peri-, and postoperative characteristics were compared according to anesthetic technique. Multivariable logistic regression analyses (MVAs) were employed to study the impact of SA on procedural efficacy and postoperative complications. RESULTS: Our study cohort consisted of 1,159 patients, of whom 374 (32%) underwent HoLEP under SA. While a medical history of any anticoagulation/antiplatelet therapy except low-dose acetylsalicylic acid was significantly more common among patients undergoing GA (16% vs. 10%, p = 0.001), no other significant differences in preoperative characteristics were noted including age, body mass index, American Society of Anesthesiologists Classification (ASA), prostate size, or International Prostate Symptom Score (IPSS), and quality of life scores. Patients under SA exhibited shorter times of enucleation 42 min (interquartile range [IQR]:27-59 vs. 45 min [IQR: 31-68], p = 0.002), and combined time of enucleation/morcellation/coagulation (57 min [IQR: 38-85] vs. 64 min [IQR: 43-93], p = 0.002), as well as fewer complications (Clavien-Dindo ≥3) (12 [3.2%] vs. 55 [7%], p = 0.013). These associations were confirmed in MVA. Patients did not differ significantly with regard to early micturition including post-void residual volume and maximum flow-rate improvement. At a median follow-up of 33 months (IQR: 32-44), patients with SA had a lower IPSS score (median 3 [IQR: 1-6] vs. 4 [IQR: 2-7], p = 0.039). However, no significant differences were observed with respect to any urinary incontinence, urge symptoms, and postoperative pain. CONCLUSION: In this large retrospective series, HoLEP under SA was a safe and efficacious procedure with comparable early and long-term functional outcomes.

Combined systematic versus stand-alone multiparametric MRI-guided targeted fusion biopsy: nomogram prediction of non-organ-confined prostate cancer.

OBJECTIVE: Based on unfavorable oncological and functional outcomes of non-organ-confined (NOC) prostate cancer (PCa), defined as ≥ pT3, pN1 or both, we aimed to develop a NOC prediction tool based on multiparametric MRI-guided targeted fusion biopsy (TBx). MATERIALS AND METHODS: Analyses were restricted to 594 patients with simultaneous PCa detection at systematic biopsy (SBx), TBx and subsequent radical prostatectomy (RP) at our institution. Development (n = 396; cohort 1) and validation cohorts (n = 198; cohort 2) were used to develop and validate the NOC nomogram. A head-to-head comparison was performed between stand-alone TBx model and combined TBx/SBx model. Second validation was performed in patients with positive TBx, but negative SBx (n = 193; cohort 3). RESULTS: The most parsimonious TBx model included three independent predictors of NOC: pretreatment PSA (OR 1.05 95% CI: 1.01-1.08), highest TBx-detected Gleason pattern (3 + 3 [REF] vs. ≥ 4 + 5; OR 9.3 95% CI 3.8-22) and presence of TBx-detected perineural invasion (OR 2.2 95% CI: 1.3-3.6). The combined TBx/SBx model had the same predictors. For the stand-alone TBx and combined TBx/SBx model, external validation yielded accuracy of 76.5% (95% CI: 69.3-83.1) and 76.6% (95% CI: 69.4-83.6) within cohort 2. The external validation of the stand-alone TBx model yielded 72.4% (95% CI: 65.0-79.6) accuracy within cohort 3. CONCLUSION: Our stand-alone TBx-based nomogram can identify PCa patients at the risk of NOC, using three simple variables, with the similar accuracy as the TBx/SBx-based model. It is non-inferior to combined TBx/SBx-based model and performs with sufficient accuracy in specific patients with positive TBx, but negative SBx.

Tumor characteristics, oncological and functional outcomes after radical prostatectomy in very young men ≤ 45 years of age.

PURPOSE: Age is an important prognostic factor for functional and oncological outcomes after radical prostatectomy (RP). Considering the long life-expectancy of young patients (≤ 45 years), it remains important to examine their outcomes. METHODS: Of 16.049 patients who underwent RP between 01/2006 and 12/2014 at the Martini-Klinik Prostate Cancer Center, 119 (0.7%) were ≤ 45. Known prognosticators were compared according to patient age at RP (categorical as ≤ 45, > 45 and ≤ 65, > 65 years). Kaplan-Meier plots and Cox-regressions analyzed oncological outcomes [biochemical recurrence (BCR)-free survival and metastasis-free survival (MFS)]. Logistic regressions were used for functional outcome. Urinary continence (UC) was defined as the use of 0 or 1 safety pad/day and potency as an IIEF-5 score of ≥ 18. RESULTS: Compared to their older counterparts, patients ≤ 45 years had more favorable tumor characteristics. Of all patients aged ≤ 45 years, 89% underwent bilateral and 9.3% unilateral nerve-sparing procedure. Five year BCR-free survival and MFS were 80.2% and 98.7% for patients ≤ 45 years, 72.8% and 95.0% for patients > 45 and ≤ 65 years and 70.5% and 94.9% for patients > 65 years. For the same groups, 1-year UC-rates were 97.4%, 89.4%, and 84.7% while 1.3%, 8.2%, and 11.6% used 1-2 pads/24 h. At 1-year, 75.6%, 58.6%, and 45.3% of preoperatively potent patients who underwent bilateral nerve-sparing were considered potent. Younger age was an independent predictor of favorable functional outcome also in multivariable analysis. CONCLUSIONS: Patients aged ≤ 45 years had more favorable tumor characteristics and oncological outcomes. Moreover, younger patients should be counseled about the excellent postoperative continence and potency rates.

Impact of positive surgical margin length and Gleason grade at the margin on biochemical recurrence in patients with organ-confined prostate cancer.

BACKGROUND: Positive surgical margins (PSMs) represent a poor prognostic factor at radical prostatectomy (RP). To investigate the impact of PSM, its length, the focality, and the PSM Gleason, on biochemical recurrence (BCR) in organ-confined RP patients. METHODS: Within a high-volume center database, we identified patients who harbored organ-confined (pathologic stage T2 disease) prostate cancer (PCa) at RP (2010-2016). Kaplan-Meier analyses and multivariable Cox regression models were used to test the effect of the PSM on the BCR risk. RESULTS: Overall, 8770 patients were identified. Of those, 6.6% (n = 579) harbored PSM. BCR-free survival at 72 months after RP was 77.7% vs 89.0% for patients with vs without PSM (P < .001). BCR-free survival rates at 72 months were 77.4% vs 73.6% (P = .1) for unifocal vs multifocal PSM, 77.2% vs 71.8% (P = .03) for Gleason pattern 3 vs ≥4 at the margin and 88.4% vs 66.3% (P < .001) for <3 vs ≥3 mm length of margin. In multivariable Cox models PSM was an independent predictor for BCR (hazard ratio [HR] = 2.40, P < .001). However, in subgroups with PSM, only ≥3 mm PSM represented an independent predictor (HR = 1.93, P = .04), while focality and Gleason at the margin were no significant predictors. CONCLUSION: PSM represents an independent predictor for BCR in organ-confined PCa at RP. Moreover, Gleason ≥4 at the margin and ≥3 mm PSM length were associated with worse BCR-free survival. Closer surveillance of patients with organ-confined PCa at RP and PSM can help to identify those who qualify for early salvage radiotherapy.

Inverse stage migration patterns in North American patients undergoing local prostate cancer treatment: a contemporary population-based update in light of the 2012 USPSTF recommendations.

PURPOSE: Recent studies demonstrated ongoing inverse stage migration in prostate cancer (PCa) patients towards more advanced and unfavorable tumors. The USPSTF grade D recommendation may impact this trend in North American patients. We assessed contemporary stage migration and treatment trends in a large North American cohort diagnosed with PCa 2009-2014. METHODS: Time-trend analyses were performed in patients within the Surveillance, Epidemiology, and End Results database, with complete data of clinical tumor stage, biopsy Gleason score, and validated PSA values, resulting in 211,645 assessable patients. Patients were stratified according to their different treatment methods [radical prostatectomy (RP), radiotherapy (RT), and no local treatment (NLT)] and according to clinical and pathological risk stratification (D'Amico and CAPRA-S score). RESULTS: Over time, proportions of D'Amico low-risk (LR) decreased, with an increase in intermediate-to-high-risk (IR/HR) patients. These trends were more distinct in men ≥ 70 years. NLT proportions increased, most notably in D'Amico LR and/or older patients. Conversely, RP proportions remained stable in younger HR and increased in older HR patients. Similar patterns were demonstrated in the RP-treated subgroup: D'Amico HR, pT3, and/or lymph-node invasion or CAPRA-S HR proportions increased from 23.5 to 30.8, 24.3 to 32.9, and 10.7 to 16.3% (each p ≤ 0.015). CONCLUSIONS: Inverse stage migration with increase of unfavorable PCa continues in most contemporary North American patients. However, a paradigm shift to treat LR patients with less invasive methods (NLT) was demonstrated. Contrary, HR patients increasingly undergo LT. Future studies with long-term follow-up might answer if inverse stage migration vs. treatment trends translate into different PCa metastases/mortality rates vs. proposed NLT benefits, particularly related to USPSTF-recommended reduced PSA screening.

Long-term cancer control outcomes in patients with biochemical recurrence and the impact of time from radical prostatectomy to biochemical recurrence.

BACKGROUND: Rates of metastatic progression (MP) and prostate cancer mortality (PCSM) are variable after biochemical recurrence (BCR) in patients who underwent radical prostatectomy (RP). To describe long-term oncological outcomes of BCR patients and to analyze risk factors for further outcomes in these men with a special focus on RP-BCR time. METHODS: We retrospectively analyzed the data of 5509 RP patients treated between 1992 and 2006. Of those, we included 1321 patients who experienced BCR (PSA level ≥0.2 ng/mL) and did not receive any neoadjuvant or adjuvant therapy. Kaplan-Meier and time dependent Cox regression models were used. RESULTS: Median follow-up was 121 months. MP was recorded in 177 (13.4%), PCSM in 126 (9.5%), and overall mortality (OM) in 264 (20.0%) patients. Patients with MP had worse tumor characteristics such as higher Gleason Scores (GS), rapid PSA doubling-time (DT), and shorter RP-BCR time intervals. MP-free, PCSM-free, and overall survival rates were significantly worse in patients with RP-BCR time of <12 months versus patients with 12-35.9 or ≥36 months (P ≤ 0.001). Besides higher GS and rapid PSA-DT, RP-BCR time independently predicted MP, PCSM, and OM in multivariable regression analyses. Relative to the intermediate and longest RP-BCR time interval, the shortest interval (<12) carried the highest risk for all three endpoints. CONCLUSIONS: Only a small proportion of BCR patients proceed to MP or PCSM. Besides higher GS and rapid PSA-DT a shorter RP-BCR interval (<12 months) heralds the most aggressive phenotype for progression to all three examined endpoints: MP, PCSM, and OM.

Extent of lymph node dissection improves survival in prostate cancer patients treated with radical prostatectomy without lymph node invasion.

PURPOSE: To assess the effect of pelvic lymph node dissection (PLND) extent on cancer-specific mortality (CSM) in prostate cancer (PCa) patients without lymph node invasion (LNI) treated with radical prostatectomy (RP). METHODS: Within the Surveillance, Epidemiology, and End results (SEER) database (2004-2014), we identified patients with D'Amico intermediate- or high-risk characteristics who underwent RP with PLND, without evidence of LNI. First, multivariable logistic regression models tested for predictors of more extensive PLND, defined as removed lymph node count (NRN) ≥75th percentile. Second, Kaplan-Meier analyses and multivariable Cox regression models tested the effect of NRN ≥75th percentile on CSM. Finally, survival analyses were repeated using continuously coded NRN. RESULTS: In 28 147 RP and PLND patients without LNI, 67.3% versus 32.7% exhibited D'Amico intermediate- or high-risk characteristics. The median NRN was 6 (IQR 3-10), the 75th percentile defined patients with NRN ≥11. Patients with NRN ≥11 had higher rate of cT2/3 stage (29.8 vs 26.1%), GS ≥8 (25.7 vs 22.4%), and respectively more frequently exhibited D'Amico high-risk characteristics (34.6 vs 32.1%). In multivariable logistic regression models predicting the probability of more extensive PLND (NRN ≥11), higher biopsy GS, higher cT stage, higher PSA, more recent year of diagnosis, and younger age at diagnosis represented independent predictors. At 72 months after RP, CSM-free rates were 99.5 versus 98.1% for NRN ≥11 and NRN ≤10, respectively and resulted in a HR of 0.50 (P = 0.01), after adjustment for all covariates. Similarly, continuously coded NRN achieved independent predictor status (HR: 0.955, P = 0.01), where each additional removed lymph node reduced CSM risk by 4.5%. CONCLUSION: More extensive PLND at RP provides improved staging information and consequently is associated with lower CSM in D'Amico intermediate- and high-risk PCa patients without evidence of LNI. Hence, more extensive PLND should be recommended in such individuals.

Survival benefit of local versus no local treatment for metastatic prostate cancer-Impact of baseline PSA and metastatic substages.

BACKGROUND: To test whether local treatment (LT), namely radical prostatectomy (RP) or brachytherapy (BT) still confers a survival benefit versus no local treatment (NLT), when adjusted for baseline PSA (bPSA). To further examine whether the effect of LT might be modulated according to bPSA and M1 substages. METHODS: Of 13 906 mPCa patients within the SEER (2004-2014), 375 underwent RP, 175 BT, and 13 356 NLT. Multivariable competing risks regression (MVA CRR) analyses after 1:2 propensity score matching assessed the impact of LT versus NLT on cancer specific mortality (CSM). Interaction analyses tested the association between treatment type and bPSA within different M1 substages. RESULTS: MVA CRR analyses revealed lower CSM rates for LT (RP [HR: 0.55, CI: 0.44-0.70, P < 0.001] and BT [HR: 0.63, CI: 0.49-0.83, P < 0.001]) compared to NLT. A significant interaction existed between bPSA and treatment type, in M1b patients only. Here, LT conferred a survival benefit when bPSA was <60 ng/mL with maximum benefit when bPSA was <40 ng/mL. No survival benefit existed for M1b patients above the 60 ng/mL bPSA threshold and for M1c patients, regardless of bPSA. For M1a patients, LT conferred a survival benefit compared to NLT. However, dose-response according to bPSA could not be tested, due to insufficient sample size. CONCLUSIONS: Our observations provide new insight regarding the pivotal effect of bPSA and M1 substages on CSM, when LT is contemplated. While M1a patients benefited from LT, the survival benefit was modulated by bPSA in M1b patients and no survival benefit existed in M1c patients.

The impact of lymph node dissection and positive lymph nodes on cancer-specific mortality in contemporary pT2-3 non-metastatic renal cell carcinoma treated with radical nephrectomy.

OBJECTIVE: To assess the effect of lymph node dissection (LND), number of removed nodes (NRN), and number of positive nodes (NPN), on cancer-specific mortality (CSM) in contemporary vs historical patients with pT2-3 Nany M0 renal cell carcinoma (RCC) treated with radical nephrectomy (RN). PATIENTS AND METHODS: Within the Surveillance, Epidemiology, and End Results database (2001-2013), we identified patients with non-metastatic pT2-3 Nany RCC who underwent RN with or without LND. Kaplan-Meier analyses and multivariable Cox regression models with propensity score weighting for inverse probability of treatment were used. RESULTS: Of 25 357 patients, 24.8% underwent LND (2001-2007: 3 167 patients vs 2008-2013: 3 133 patients). The median NRN was 3 (interquartile range [IQR]: 1-7). Positive nodes were identified in 17.1%: 9.3% of pT2 and 21.6% of pT3 patients, who underwent LND. The median NPN was 2 (IQR: 1-3). In multivariable models, LND did not decrease CSM (hazard ratio [HR] 1.29; P < 0.001). LND extent, defined as NRN, did not decrease CSM (HR 0.94; P = 0.3). Finally, multivariable models testing the effect of NPN showed increased CSM in pT3 but not in pT2 patients (HR 1.29 and 1.58, P = 0.02 and P = 0.1, respectively). NRN exerted a protective effect on CSM in patients with positive nodes (HR 0.98; P = 0.007). CONCLUSION: In contemporary and historical patients LND or its extent do not protect from CSM. However, the NPN increases the rate of CSM in pT3 patients. Consequently, LND and its extent appear to have little if any therapeutic value in pT2-3 Nany M0 patients, besides its prognostic impact. High-risk non-metastatic patients may represent a target population for a multi-institutional prospective trial.

First North American validation and head-to-head comparison of four preoperative nomograms for prediction of lymph node invasion before radical prostatectomy.

OBJECTIVES: To perform a head-to-head comparison of four nomograms; namely, the Cagiannos, the 2012-Briganti, the Godoy and the online-Memorial Sloan Kettering Cancer Center (MSKCC), for prediction of lymph node invasion (LNI) in a North American population. PATIENTS AND METHODS: A total of 19 775 patients with clinically localized prostate cancer (PCa) who had undergone radical prostatectomy and pelvic lymph node dissection (PLND) were identified within the Surveillance Epidemiology and End Results (SEER) database. All four nomograms were tested using Heagerty's concordance index (C-index), calibration plots and decision curve analysis (DCA). In addition, we examined specific nomogram-derived thresholds to compare the number of avoided PLNDs and missed LNI-positive cases. RESULTS: All nomograms were found to have highly comparable C-index values: the Cagiannos, 78.6%; the Godoy, 78.2%; the 2012-Briganti, 79.8%; and the MSKCC, 79.9%. The Cagiannos nomogram showed the best calibration, followed by the 2012-Briganti, the Godoy and the online-MSKCC. In DCA, the 2012-Briganti and the Cagiannos, in that order, provided the best results, followed by the Godoy and the online-MSKCC models. For each nomogram, the threshold associated with ≤10% missed LNI cases avoided 8 693 (46.6%), 8 652 (46.4%), 8 461 (45.4%) and 8 590 (46.1%) PLNDs, respectively, with the use of the Cagiannos (2.6% threshold), the online-MSKCC (4.3% threshold), the Godoy (3.6% threshold) and the 2012-Briganti (4.6% threshold) nomograms. CONCLUSION: The Cagiannos and the 2012-Briganti nomograms exhibited the best calibrations and DCA results. Conversely, C-index values and ability to avoid unnecessary PLNDs were virtually the same for all four nomograms examined.

Postoperative complications of contemporary open and robot-assisted laparoscopic radical prostatectomy using standardised reporting systems.

OBJECTIVES: To analyse time trends and contemporary rates of postoperative complications after radical prostatectomy (RP) and to compare the complication profile of open RP (ORP) and robot-assisted laparoscopic RP (RALP) using standardised reporting systems. PATIENTS AND METHODS: Retrospective analysis of 13 924 RP patients in a single institution (2005-2015). Complications were collected during hospital stay and via standardised questionnaire 3 months after, and grouped into eight schemes. Since 2013, the revised Clavien-Dindo classification was used (n = 4 379). Annual incidence rates of different complications were graphically displayed. Multivariable logistic regression analyses compared complications between ORP and RALP after inverse probability of treatment weighting (IPTW). RESULTS: After the introduction of standardised classification systems, complication rates have increased with a contemporary rate of 20.6% (2013-2015). While minor Clavien-Dindo grades represented the majority (I: 10.6%; II: 7.9%), severe complications (Grades IV-V) were rare (<1%). In logistic regression analyses after IPTW, RALP was associated with less blood loss, shorter catheterisation time, and lower risk of Clavien-Dindo Grade II and III complications. CONCLUSION: Our results emphasise the importance of standardised reporting systems for quality control and comparison across approaches or institutions. Contemporary complication rates in a high-volume centre remain low and are most frequently minor Clavien-Dindo grades. RALP had a slightly better complication profile compared to ORP.

The impact of time to catheter removal on short-, intermediate- and long-term urinary continence after radical prostatectomy.

PURPOSE: To assess the impact of prolonged catheterization time on 1-week (short-term), 3-month (intermediate-term) and 1-year (long-term) UC. METHODS: Between 2008 and 2015, 6918 men underwent RP by four high-volume surgeons. Exclusion criteria were baseline urinary incontinence (UI) and radiotherapy prior or within 12 months after RP. For the remaining 4111 patients, data on short-, intermediate- and long-term UC were available for 3989, 2490 and 1967 patients, respectively. UC was defined as the use of zero or 1-safety pad/24 h. Time to catheter removal was categorized into ≤ 7, 8-14 and ≥ 15 days. To assess the impact of catheterization time on short-, intermediate- and long-term UI, uni- and multivariable logistic regression analyses adjusted for age, BMI, prostate volume, pathological tumor stage, Charlson comorbidity index and nerve-sparing technique were performed. RESULTS: Post-RP UC rates at 1 week for catheterization of ≤ 7, 8-14 and ≥ 15 days were 31.2, 27.4 and 18.0%. For the same groups, 3-month and 1-year UC rates were 82.7, 79.2 and 74.1% as well as 90.8, 91.6 and 88.2%, respectively. In multivariate logistic regressions, longer catheterization time was associated with worse short- and intermediate UI (OR 15 days: 2.19 and 1.54; p = ≤ 0.001 and p = 0.04). This difference dissipated at 1 year after RP (p > 0.05). CONCLUSIONS: While longer catheterization is associated with worse short- and intermediate-term UC, it has no adverse impact on long-term UC.

Validation of the current eligibility criteria for focal therapy in men with localized prostate cancer and the role of MRI.

PURPOSE: To validate current eligibility criteria for focal therapy (FT) in prostate cancer men undergoing radical prostatectomy (RP) and to assess the role of magnetic resonance imaging (MRI). METHODS: Retrospective analysis of 217 RP patients (2009-2016) with preoperative MRI (almost all in external institutions) and fulfillment of different FT eligibility criteria: unilateral tumor, clinical tumor stage ≤ cT2a, prostate volume ≤ 60 mL and either biopsy Gleason 3 + 3 or ≤ 3 + 4 and PSA ≤ 10 or ≤ 15 ng/mL. Multivariable logistic regression analyses (MVA) assessed the role of MRI to predict the presence of significant contralateral tumor or extracapsular extension (ECE), including seminal vesicle invasion. To quantify model accuracy, Receiver Operating Characteristics-derived area under the curve (AUC) was used. RESULTS: Of 217 patients fulfilling widest biopsy criteria and 113 fulfilling additional MRI criteria, 64 (29.7%) and 37 (32.7%) remained eligible for FT according to histopathological results. In MVA, fulfillment of MRI criteria reached independent predictor status for prediction of contralateral tumor but not for ECE. Addition of MRI resulted in AUC gain (57.5-64.6%). Sensitivity, specificity, PPV and NPV for MRI to predict contralateral tumor were: 41.8, 71.6, 70.9 and 42.6%, respectively. Virtually the same results were recorded for Gleason 3 + 3 and/or PSA ≤ 10 ng/mL. CONCLUSIONS: Patient eligibility criteria for FT using biopsy criteria remained insufficient with respect to contralateral tumor disease. Although, MRI improves accuracy, it cannot safely exclude or minimize chance of significant cancer on contralateral prostate side. To date, stricter eligibility criteria are needed to provide more diagnostic reliability.

Radical prostatectomy or radiotherapy reduce prostate cancer mortality in elderly patients: a population-based propensity score adjusted analysis.

PURPOSE: Contemporary data regarding the effect of local treatment (LT) vs. non-local treatment (NLT) on cancer-specific mortality (CSM) in elderly men with localized prostate cancer (PCa) are lacking. Hence, we evaluated CSM rates in a large population-based cohort of men with cT1-T2 PCa according to treatment type. METHODS: Within the SEER database (2004-2014), we identified 44,381 men ≥ 75 years with cT1-T2 PCa. Radical prostatectomy and radiotherapy patients were matched and the resulting cohort (LT) was subsequently matched with NLT patients. Cumulative incidence and competing risks regression (CRR) tested CSM according to treatment type. Analyses were repeated after Gleason grade group (GGG) stratification: I (3 + 3), II (3 + 4), III (4 + 3), IV (8), and V (9-10). RESULTS: Overall, 4715 (50.0%) and 4715 (50.0%) men, respectively, underwent NLT and LT. Five and 7-year CSM rates for, respectively, NLT vs. LT patients were 3.0 and 5.4% vs. 1.5 and 2.1% for GGG II, 4.5 and 7.2% vs. 2.5 and 2.8% for GGG III, 7.1 and 10.0% vs. 3.5 and 5.1% for GGG IV, and 20.0 and 26.5% vs. 5.4 and 9.3% for GGG V patients. Separate multivariable CRR also showed higher CSM rates in NLT patients with GGG II [hazard ratio (HR) 3.3], GGG III (HR 2.6), GGG IV (HR 2.4) and GGG V (HR 2.6), but not in GGG I patients (p = 0.5). CONCLUSIONS: Despite advanced age, LT provides clinically meaningful and statistically significant benefit relative to NLT. Such benefit was exclusively applied to GGG II to V but not to GGG I patients.

Effect of pathological high-risk features on cancer-specific mortality in non-metastatic clear cell renal cell carcinoma: a tool for optimizing patient selection for adjuvant therapy.

PURPOSE: Adjuvant therapies for non-metastatic renal cell carcinoma (nmRCC) are being tested to improve outcomes in patients with high-risk (hR) nmRCC. The objective of the current study is to test the ability of three hR features to identify patients who are at the highest risk of cancer-specific mortality (CSM) after partial or radical nephrectomy. METHODS: Within the Surveillance Epidemiology and End Results (SEER) database (1988-2013), we identified 23,632 nm "clear cell" RCC partial or radical nephrectomy patients with hR features: Fuhrman grade (FG) 3 or 4 or pathological classifications T3a or T3b or lymph node invasion (LNI), or combination of these. Kaplan-Meier analyses (KM) and multivariable Cox's regression models (CRM) evaluated the effect of hR features on CSM. RESULTS: Overall 11,568 (48.9%) patients harbored FG3-4, 5575 (23.6%) pT3a/b, 140 (0.6%) LNI, 5366 (22.7%) FG3-4 and pT3a/b, 183 (0.8%) LNI and pT3a/b, 203 (0.9%) LNI and FG3-4 and 597 (2.5%) LNI, FG3-4 and pT3a/b. Median CSM-free survival was 51, 58 and 22 months for LNI and pT3a/b, for LNI and FG3-4 and for LNI, FG3-4 and pT3a/b and was not reached for the other groups. These results remained unchanged in multivariable CRMs, where all hR features represented independent predictors. CONCLUSIONS: Individuals with combination of LNI with FG3-4 or pT3a/b and patients with all three hR features are at highest risk of CSM. In consequence, these patients may represent ideal candidates for adjuvant therapy either in clinical practice or future prospective trials.

Does surgical delay for radical prostatectomy affect biochemical recurrence? A retrospective analysis from a Canadian cohort.

AIM: We sought to explore the impact of surgical wait time (SWT) to robot-assisted radical prostatectomy (RARP) on biochemical recurrence (BCR). METHOD: Retrospective review of a prospectively collected database between 2006 and 2015 was conducted on all RARP cases. SWT was defined as period from prostate biopsy to surgery. Primary outcome was the impact on BCR, which was defined as two consecutive PSA ≥ 0.2 ng/dl, or salvage external beam radiation therapy and/or salvage androgen deprivation therapy. Patients were stratified according to D'Amico risk categories. Univariable analysis (UVA) and multivariable analyses (MVA) with a Cox proportional hazards regression model were used to evaluate the effect of SWT and other predictive factors on BCR, in each D'Amico risk group and on the overall collective sample. RESULTS: Patients eligible for analysis were 619. Mean SWT was 153, 169, 150, and 125 days, for overall, low-, intermediate-, and high-risk patients, respectively. Multivariate analysis on the overall cohort did not show a significant relation between SWT and BCR. On subgroup analysis of D'Amico risk group, SWT was positively correlated to BCR for high-risk group (p = 0.001). On threshold analysis, cut-off was found to be 90 days. SWT did not significantly affect BCR on UVA and MVA in the low- and intermediate-risk groups. CONCLUSION: Increased delay to surgery could affect the BCR, as there was a positive association in high-risk group. Further studies with longer follow-up are necessary to assess the impact of wait time on BCR, cancer specific survival and overall survival.

Up regulation of the steroid hormone synthesis regulator HSD3B2 is linked to early PSA recurrence in prostate cancer.

HSD3B2 plays a crucial role in steroid hormone biosynthesis and is thus of particular interest in hormone dependent tumors such as prostate cancer. To clarify the clinical relevance of HSD3B2 expression in prostate cancer, we analyzed HSD3B2 protein expression by immunohistochemistry on our preexisting tissue microarray with 12.247 annotated cancers. Compared with normal tissue cytoplasmic HSD3B2 staining was stronger in prostate cancers. In 9371 interpretable cancers, HSD3B2 expression was found in 95.5% of cancers and was considered weak in 29.9%, moderate in 40.7% and strong in 24.9%. HSD3B2 up regulation was linked to advanced pathological tumor stage (pT), high Gleason grade, elevated preoperative PSA levels (p < 0.0001 each), lymph node metastasis (p = 0.0019), accelerated cell proliferation (p < 0.0001), androgen receptor (AR) expression (p < 0.0001), and early biochemical recurrence (p < 0.0001). HSD3B2 up regulation was only marginally more frequent in ERG positive (98%) than in ERG negative cancers (94%; p < 0.0001) and was strongly linked to deletions of 5q and 6q (p < 0.0001 each). Multivariate analyses showed that the prognostic impact of HSD3B2 expression was independent of established preoperative, but not of postoperative prognostic parameters. In summary, the results of our study demonstrate that HSD3B2 is strongly up regulated in a fraction of prostate cancers that are characterized by increased AR signaling, adverse tumor phenotype and early biochemical recurrence.

Local treatment for metastatic prostate cancer: A systematic review.

The potential oncological benefit for radical treatment in the setting of oligometastatic prostate cancer has been under investigation and is frequently discussed. We carried out a systematic review of English language articles using the Medline database (January 2000 to May 2017) to identify studies reporting local treatment in men with metastatic prostate cancer at diagnosis. Primary end-points were oncological outcomes, such as cancer-specific and overall mortality. Secondary end-points were non-oncological outcomes, such as complications, operating room time, blood loss or length of hospital stay. Two independent authors reviewed and extracted all search results. Overall, 18 studies reporting on local treatment in metastatic prostate cancer patients were identified (14 original articles, three brief correspondences and one letter to the editor). All of them were retrospective; one partly included prospective data. All studies addressed oncological outcomes, 16 compared local treatment with no-local treatment and 14 adjusted for confounders using multivariable regression models. All but one study concluded a survival benefit for local treatment in the metastatic setting. Due to heterogeneity of available data, a representative meta-analysis could not be carried out. Five studies reported non-oncological outcomes. Although local treatment in metastatic prostate cancer appears to be feasible, its oncological effect remains unclear due to high susceptibility of available studies to significant selection bias.

Population-Based Validation of the 2014 ISUP Gleason Grade Groups in Patients Treated With Radical Prostatectomy, Brachytherapy, External Beam Radiation, or no Local Treatment.

BACKGROUND: To test discriminant ability of the 2014 ISUP Gleason grade groups (GGG) for prediction of prostate cancer specific mortality (PCSM) after radical prostatectomy (RP), brachytherapy (BT), external beam radiation (EBRT) or no local treatment (NLT) relative to traditional Gleason grading (TGG). METHODS: In the Surveillance, Epidemiology, and End Results (SEER)-database (2004-2009), 2,42,531 non-metastatic prostate cancer (PCa) patients were identified, who underwent local treatment (RP, BT, EBRT only) or NLT. Follow-up endpoint was PCSM. Biopsy and/or pathological Gleason score (GS) were categorized as TGG ≤6, 7, 8-10 or GGG: I (≤6), II (3 + 4), III (4 + 3), IV (8), and V (9-10). Kaplan-Meier plots, multivariable Cox regression analyses and receiver operating characteristics (ROC) area under the curve analyses (AUC) were used. RESULTS: Median follow-up was 76 months (IQR: 59-94). For the four examined treatment modalities, all five GGG strata and all three TGG strata independently predicted PCSM. GGG yielded 1.5-fold or greater HR differences between GGG II and GGG III, and twofold or greater HR differences between GGG IV and GGG V. Relative to TGG, GGG added 0.4-1.1% to AUC. CONCLUSIONS: This large population-based cohort study confirms the added discriminant properties of the novel GGG strata and confirms a modest gain in predictive accuracy. Prostate 77: 686-693, 2017. © 2017 Wiley Periodicals, Inc.

Oncologic and Functional Outcomes after Radical Prostatectomy for High or Very High Risk Prostate Cancer: European Validation of the Current NCCN® Guideline.

PURPOSE: We validated the current NCCN (National Comprehensive Cancer Network®) classification of very high risk patients, and compared the pathological, functional and oncologic outcomes between surgically treated high risk and very high risk patients. MATERIALS AND METHODS: We retrospectively analyzed 4,041 patients stratified into high risk or very high risk groups who underwent radical prostatectomy between 1992 and 2016. Kaplan-Meier as well as multivariable logistic and Cox regression analyses were used to compare outcomes between the groups. RESULTS: After radical prostatectomy the rate of adverse pathological features was higher in 1,369 very high risk vs 2,672 high risk cases. Functional outcomes were similar between the groups, with 1-year continence and potency rates of 81.0% and 43.6% in the very high risk compared to 81.9% and 45.2% in the high risk group, respectively (p = 0.7 and p = 0.9). In a subset of 1,835 patients who underwent radical prostatectomy between 1992 and 2011 (median followup 58.8 months, IQR 36.5-84.6), those with very high risk disease had significantly worse 5 and 8-year biochemical recurrence-free survival, metastatic progression-free survival, prostate cancer specific mortality-free survival and overall survival rates compared to those with high risk disease. CONCLUSIONS: Despite the relatively poor prognosis of patients with high risk prostate cancer, radical prostatectomy results in favorable 5 and 8-year metastatic progression-free survival, prostate cancer specific mortality-free survival and overall survival rates. Relative to high risk cases, their very high risk counterparts have significantly worse pathological and oncologic outcomes, and more frequently require additional therapies. These observations validate the stratification between high risk and very high risk in European patients with prostate cancer. Interestingly, very high risk patients treated with radical prostatectomy did not have a worse functional outcome than their high risk counterparts.