Role of cytoreductive radical prostatectomy in men with oligometastatic prostate cancer on molecular imaging.

PURPOSE OF REVIEW: The implementation of PET with prostate-specific membrane antigen (PSMA) tracer as primary staging tool occurred recently. Since its introduction, a novel category of patients emerged, with negative staging at conventional imaging, and positive molecular imaging. Local treatment in these patients might be associated with improved oncological outcomes when combined with systemic therapy. However, its impact on oligometastatic prostate cancer (omPCa) remains unknown. In this review, we aimed at investigating the role of cytoreductive radical prostatectomy (cRP) in oligometastatic disease at molecular imaging. RECENT FINDINGS: After comprehensive review of literature, two retrospective studies highlighted the feasibility, safety, and potential benefits of surgery in omPCA patients at molecular imaging. They showed that 72% of patients achieved PSA less than 0.01 ng/ml following cRP as part of a multimodal approach, 17% experienced radiographic progression, and 7% died at 27-month median follow-up. Moreover, complications postcRP after PSMA PET were modest, with a 40% rate of any adverse event, and 5% of grade more than 3. The 1-year urinary continence after cRP rate was 82%. The oncological, functional outcomes and the complication rate aligned with those observed in series of cRP after conventional imaging. SUMMARY: cRP is feasible, well tolerated, and effective in selected patients with omPCa at PSMA PET.

Not All Adverse Pathology Features Are Equal: Identifying Optimal Candidates for Adjuvant Radiotherapy Among Patients With Adverse Pathology at Radical Prostatectomy.

PURPOSE: Recent studies reported a potential benefit associated with adjuvant radiotherapy for patients with adverse pathology features of prostate cancer. We hypothesized that not all the patients with adverse features may benefit from adjuvant radiotherapy and, therefore, observation ± early salvage radiotherapy may still be considered in a subgroup of these patients. MATERIALS AND METHODS: Among 8,362 patients treated with radical prostatectomy at a single center between 1987 and 2020, 926 eligible patients with adverse pathology features (ie, grade group 4-5 with ≥pT3a stage and/or lymph node invasion) were identified. Cox models were used to assign a score to each feature. Patients were then stratified in low-, intermediate-, and high-risk groups, and interaction term analyses tested the impact of adjuvant radiotherapy for each risk subgroup after adjusting for inverse probability of treatment weighting. RESULTS: Overall, 538 (58%) vs 89 (10%) vs 299 (32%) patients received adjuvant radiotherapy vs early salvage radiotherapy vs observation. The 10-year overall survival rate was 90%. A significant interaction between adjuvant radiotherapy and high-risk group was recorded (HR 0.21, P = .04). After risk stratification and propensity-score weighting, survival analyses depicted comparable 10-year overall survival in low- and intermediate-risk patients treated with adjuvant radiotherapy or observation ± early salvage radiotherapy. Conversely, in high-risk patients, adjuvant radiotherapy was associated with significant improvement in 10-year overall survival compared to observation ± early salvage radiotherapy (76% vs 63%, P = .038). CONCLUSIONS: Among patients with adverse pathology features, we identified 3 subclassifications of risk. When testing the effect of adjuvant radiotherapy vs observation with or without early salvage radiotherapy on survival, only patients included in the high-risk group seemed to benefit from adjuvant radiotherapy.

Multiparametric magnetic resonance imaging of the prostate underestimates tumour volume of small visible lesions.

OBJECTIVE: To assess the relationship between the volume of the index lesion (IL) measured at multiparametric magnetic resonance imaging (mpMRI; MRIvol) and at radical prostatectomy (RPvol), stratifying it according to Prostate Imaging-Reporting and Data System (PI-RADS) score. PATIENTS AND METHODS: We identified 332 men with a positive mpMRI (single lesion with PI-RADS ≥3) who underwent systematic plus targeted biopsy and subsequent RP at two tertiary referral centres between 2013 and 2018. All mpMRIs were reviewed by experienced radiologists using PI-RADS scores. The study outcome was to assess the relationship between MRIvol (based on planimetry from MRI sequence best showing tumour) and RPvol (based on tumour involved area of each RP pathology slice). To achieve this endpoint, we performed a multivariable linear regression analysis (LRA) to predict RPvol using PI-RADS, prostate-specific antigen level, prostate volume, age, digital rectal examination, Gleason score at MRI-targeted biopsy, biopsy history and time from mpMRI to RP as covariates. Non-parametric locally estimated scatterplot smoothing (LOESS) function was used to graphically explore the relationship between MRIvol and RPvol, stratifying for PI-RADS score. RESULTS: Overall, 24%, 49% and 27% of men had visible PI-RADS 3, 4 and 5 lesions at mpMRI. The median (interquartile range [IQR]) MRIvol and RPvol were 0.67 (0.29-1.76) mL and 1.39 (0.58-4.23) mL. At LRA, MRIvol was significantly correlated with a RPvol underestimation (slope: 2.4, 95% confidence interval [CI] 0.1-46.3). The non-parametric LOESS analysis showed a non-linear relationship between MRIvol and RPvol. Significant underestimation was reported across all volumes with the highest differences between MRIvol and RPvol in the low volume range (<2 mL), where RPvol almost doubled MRIvol. A similar effect was observed across all PI-RADS scores subgroups. CONCLUSIONS: In the present study, mpMRI significantly underestimated the exact volume of the IL, especially for small visible lesions, regardless of PI-RADS score. This should be considered when planning tailored focal therapy approaches often delivered to men with smaller prostatic lesions.

The impact of race/ethnicity on upstaging and/or upgrading rates among intermediate risk prostate cancer patients treated with radical prostatectomy.

BACKGROUND: Race/ethnicity may predispose to less favorable prostate cancer characteristics in intermediate risk prostate cancer (IR PCa) patients. We tested this hypothesis in a subgroup of IR PCa patients treated with radical prostatectomy (RP). METHODS: We relied on the Surveillance, Epidemiology and End Results 2004-2016. The effect of race/ethnicity was tested in univariable and multivariable logistic regression analyses predicting upstaging (pT3+/pN1) and/or upgrading (Gleason Grade Group [GGG] 4-5) at RP. RESULTS: Of 20,391 IR PCa patients, 15,050 (73.8%) were Caucasian, 2857 (14.0%) African-American, 1632 (8.0%) Hispanic/Latino and 852 (4.2%) Asian. Asian patients exhibited highest age (64 year), highest PSA (6.8 ng/ml) and highest rate of GGG3 (31.9%). African-Americans exhibited the highest percentage of positive cores at biopsy (41.7%) and the highest proportion of NCCN unfavorable risk group membership (54.6%). Conversely, Caucasians exhibited the highest proportion of cT2 stage (35.6%). In univariable analyses, Hispanic/Latinos exhibited the highest rates of upstaging/upgrading among all race/ethnicities, in both favorable and unfavorable groups, followed by Asians, Caucasians and African-Americans in that order. In multivariable analyses, Hispanic/Latino race/ethnicity represented an independent predictor of higher upstaging and/or upgrading in favorable IR PCa (odds ratio [OR] 1.27, p < 0.01), while African-American race/ethnicity represented an independent predictor of lower upstaging and/or upgrading in unfavorable IR PCa (OR 0.79, p < 0.001). CONCLUSION: Race/ethnicity predisposes to differences in clinical, as well as in pathological characteristics in IR PCa patients. Specifically, even after full statistical adjustment, Hispanic/Latinos are at higher and African-Americans are at lower risk of upstaging and/or upgrading.

Radical cystectomy plus chemotherapy in patients with pure squamous cell bladder carcinoma: a population-based study.

PURPOSE: To test the effect of perioperative chemotherapy (CHT) on overall mortality (OM) and cancer-specific mortality (CSM) in patients with locally advanced or metastatic squamous cell carcinoma of the urinary bladder (SCC UB). METHODS: Within the Surveillance, Epidemiology and End Results database (1988-2016), we identified 1,018 SCC UB patients (664 T3-4aN0M0, 197 TanyN1-3M0 and 156 T4bN0-3 or M1), who underwent radical cystectomy with or without perioperative chemotherapy administration. Inverse probability of treatment-weighting (IPTW), Kaplan-Meier plots and Cox-regression models (CRMs) were used. RESULTS: CHT was administrated in 116 (17.5%) T3-4aN0M0, 77 (39.1%) TanyN1-3M0 and 47 (30.1%) T4bN0-3 or M1 patients. IPTW-adjusted 2-year cancer-specific survival (CSS) was 66.5 vs. 71.5% (p = 0.19), 60.9 vs. 29.5% (p < 0.001) and IPTW-adjusted 1-year CSS was 46.2 vs. 31.1% (p = 0.03) for CHT vs. no CHT administration in T3-4aN0M0, TanyN1-3M0 and T4bN0-3 or M1, respectively. In multivariable IPTW-adjusted CRMs, chemotherapy was an independent predictor of lower CSM in TanyN1-3M0 (HR 0.44) and in T4bN0-3 or M1 (HR 0.60), but not in T3-4aN0M0 (p = 0.6) patients. Virtually the same results were obtained on OM, as well as without IPTW-adjustment and after stratification according to age and gender. CONCLUSIONS: The use of perioperative CHT in patients with SCC UB confers survival benefit in the presence of T4b disease, lymph node or distant metastases. Conversely, patients with locally advanced disease but negative lymph node invasion do not benefit from its use. Pending higher quality data from prospective trials, these data should encourage the use of perioperative CHT in those high-risk patient groups.

Underestimation of Positron Emission Tomography/Computerized Tomography in Assessing Tumor Burden in Prostate Cancer Nodal Recurrence: Head-to-Head Comparison of 68Ga-PSMA and 11C-Choline in a Large, Multi-Institutional Series of Extended Salvage Lymph Node Dissections.

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

Contemporary conditional cancer-specific survival after radical nephroureterectomy in patients with nonmetastatic urothelial carcinoma of upper urinary tract.

BACKGROUND AND OBJECTIVES: To examine the effect of conditional survival on 5-year cancer-specific survival (CSS) probability after radical nephroureterectomy (RNU) in a contemporary cohort of patients with non-metastatic urothelial carcinoma of the upper urinary tract (UTUC). METHODS: Within the Surveillance, Epidemiology and End Results database (2004-2015), 6826 patients were identified. Conditional 5-year CSS estimates were assessed after event-free follow-up duration. Multivariable Cox regression (MCR) models predicted cancer-specific mortality (CSM) according to event-free follow-up length. RESULTS: Overall, 956 (14.0%) were T1 low grade(LG)N0 , 1305 (19.1%) T1 high grade(HG)N0 , 1215 (17.8%) T2 N0 , 2249 (32.9%) T3 N0 and 1101 (16.1%) T4 N0 /Tany N1-3 . From baseline, 93.4% to 94.2% in T1 LGN0 provided 5-year CSS and, respectively, 86.2% to 95.3% in T1 HGN0 , 77.5% to 87.8% in T2 N0 , 63.0% to 91.1% in T3 N0 , and 38.8% to 88.2% in T4 N0 /Tany N1-3 . In MCR models, relative to T1 LGN0 , T1 HGN0 (Hazard ratio [HR] 1.7), T2 N0 (HR 3.0), T3 N0 (HR: 5.2), and T4 N0 /Tany N1-3 (HR 11.9) were independent predictors of higher CSM. Conditional HRs decreased to levels equivalent to T1 LGN0 at 3 years vs 5 years of event-free survival for T1 HGN0 and all other groups, respectively. CONCLUSIONS: A direct relationship exists between event-free follow-up and survival probability after RNU. From a clinical perspective, such survival estimates may have particular importance during preoperative counseling.

The Impact of Experience on the Risk of Surgical Margins and Biochemical Recurrence after Robot-Assisted Radical Prostatectomy: A Learning Curve Study.

PURPOSE: Improved cancer control with increasing surgical experience (the learning curve) has been demonstrated for open and laparoscopic prostatectomy. We assessed the relationship between surgical experience and oncologic outcomes of robot-assisted radical prostatectomy. MATERIALS AND METHODS: We analyzed the records of 1,827 patients in whom prostate cancer was treated with robot-assisted radical prostatectomy. Surgical experience was coded as the total number of robotic prostatectomies performed by the surgeon before the patient operation. We evaluated the relationship of prior surgeon experience to the probability of positive margins and biochemical recurrence in regression models adjusting for stage, grade and prostate specific antigen. RESULTS: After adjusting for case mix, greater surgeon experience was associated with a lower probability of positive surgical margins (p = 0.035). The risk of positive margins decreased from 16.7% to 9.6% in patients treated by a surgeon with 10 and 250 prior procedures, respectively (risk difference 7.1%, 95% CI 1.7-12.2). In patients with nonorgan confined disease the predicted probability of positive margins was 38.4% in those treated by surgeons with 10 prior operations and 24.9% in those treated by surgeons with 250 prior operations (absolute risk reduction 13.5%, 95% CI -3.4-22.5). The relationship between surgical experience and the risk of biochemical recurrence after surgery was not significant (p = 0.8). CONCLUSIONS: Specific techniques used by experienced surgeons which are associated with improved margin rates need further research. The impact of experience on cancer control after robotic prostatectomy differed from that in the prior literature on open and laparoscopic radical prostatectomy, and should be investigated in larger multi-institutional studies.

The effect of androgen deprivation treatment on subsequent risk of bladder cancer diagnosis in male patients treated for prostate cancer.

INTRODUCTION: Bladder cancer (BCa) is three-to-four times more common in men than in women. To explain this gender gap, several theories have been proposed, including the impact of androgen hormones. The aim of this study was to investigate the differential impact of androgen deprivation therapy (ADT) on subsequent risk of developing BCa in men with prostate cancer (PCa). METHODS: A total of 196,914 patients diagnosed with histologically confirmed localized PCa between 2000 and 2009 were identified in the SEER-Medicare insurance program-linked database. Competing-risk regression analyses were performed to assess the risk of developing BCa adjusting for the risk of all-cause mortality. Univariable and multivariable competing-risk regression analyses were performed to test the effect of ADT on BCa incidence for each PCa treatment modality. RESULTS: Of the 196,914 individuals included in the study, 68,421 (34.7%) received ADT. Median (IQR) follow-up was 59 (29-95) months. Overall, a total of 2495 (1.3%) individuals developed BCa during follow-up. After stratification according to ADT, the 10-year cumulative incidence rate was 1.75% (95% CI 1.65-1.85). In the untreated group, the 10-year cumulative incidence rate was 1.99% (95% CI 1.83-2.15). In multivariable competing-risk regression, the use of ADT was not associated with BCa, after accounting for the risk of dying from any cause (p = 0.1). CONCLUSION: We failed to identify any impact of ADT on the risk of developing a subsequent BCa even after stratifying according to the type of treatment. Further studies are required to explain the gender gap in BCa incidence and outcomes.

Oncologic outcomes after robot-assisted versus open radical cystectomy: a systematic review and meta-analysis.

PURPOSE: The efficacy of RARC in oncologic outcomes compared ORC is controversial. We assess potential differences in oncologic outcomes between robot-assisted radical cystectomy (RARC) and open radical cystectomy (ORC). METHODS: We performed the literature search systematically according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement. A pooled meta-analysis was performed to assess the difference in oncologic outcomes between RARC and ORC, separately in randomized controlled trials (RCTs) and non-randomized studies (NRCTs). RESULTS: Five RCTs and 28 NRCTs were included in this systematic review and meta-analysis. There was no difference in the rate of overall positive surgical margin (PSM) in RCTs, while NRCTs showed a lower rate for RARC. There was no difference in the soft tissue PSM rate between RARC and ORC in both RCTs and NRCTs. There was no difference in the lymph node yield by standard and extended lymph node dissection between RARC and ORC in both RCTs and NRCTs. There was no significant difference in survival outcomes between RARC and ORC in both RCTs and NRCTs. CONCLUSIONS: Based on the current evidence, there is no difference in the rate of PSMs, lymph node yield, recurrence rate and location as well as short-term survival outcomes between RARC and ORC in RCTs. In NRCTs, only PSM rates were better for RARC compared to ORC, but this was likely due to selection and reporting bias which are inherent to retrospective study designs.

Impact of multiparametric MRI and MRI-targeted biopsy on pre-therapeutic risk assessment in prostate cancer patients candidate for radical prostatectomy.

PURPOSE: To assess the current status and future potential of multiparametric MRI (mpMRI) and MRI-targeted biopsy (MRI-TBx) on the pretherapeutic risk assessment in prostate cancer patients' candidates for radical prostatectomy. METHODS: A literature search of the MEDLINE/PubMed and Scopus database was performed. English-language original and review articles were analyzed and summarized after an interactive peer-review process of the panel. RESULTS: Pretherapeutic risk assessment tools should be based on target plus systematic biopsies, where the addition of systematic biopsy (TRUS-Bx) to the mpMRI-target cores is associated with a lower rate of upgrading at final pathology. The combination of mpMRI findings with clinical parameters outperforms models based on clinical parameters alone in the prediction of adverse pathological outcomes and oncological results. This is particularly true when a specialized radiologist is present. CONCLUSION: The combination of mpMRI findings and clinical parameters should be considered to improve patient stratification in the pretherapeutic risk assessment. There is an urgent need to develop or include MRI data and MRI-TBx findings in available preoperative risk tools. This will allow improving the pretherapeutic risk assessment, providing important additional information for patient-tailored treatment planning and optimizing outcomes.

Nomograms in urologic oncology, advantages and disadvantages.

PURPOSE OF REVIEW: To critically review the current literature regarding the recently published nomograms in urologic oncology and to examine the advantages and disadvantages of their application. RECENT FINDINGS: Several nomograms have been developed in the field of urologic oncology over the recent years, to improve clinical decision-making and patients counseling. In the current review, we examined 6 nomograms on prostate cancer, 9 nomograms on kidney cancer and 8 nomograms on bladder cancer that have been recently published. Most of the examined nomograms lack external validation and very few have investigated the clinical utility of any given model, as measured by its ability to improve clinical decision-making. Two studies relied on genomic classifiers and showed up to 6% improved accuracy compared with the models based only on clinical variables. However, these new tools were limited by elevated cost and scarce availability of these new biomarkers, which may represent barriers toward future use. SUMMARY: Several nomograms have been developed in these recent years in urologic oncology. All exhibited elevated accuracy, good calibration and promising decision analyses, when they were internally validated. However, external validations and assessment of clinical utility are needed before they can be incorporated into routine clinical practice.

Comparison of perioperative complications and health-related quality of life between robot-assisted and open radical cystectomy: A systematic review and meta-analysis.

To compare postoperative complications and health-related quality of life of patients undergoing robot-assisted radical cystectomy with those of patients undergoing open radical cystectomy. A systematic search was carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. A pooled meta-analysis was carried out to assess the differences between robot-assisted radical cystectomy and open radical cystectomy according to randomized and non-randomized comparative studies, respectively. We identified six randomized comparative studies and 31 non-randomized comparative studies. Most robot-assisted radical cystectomy patients were treated with extracorporeal urinary diversion. Robot-assisted radical cystectomy was associated with longer operative times, and lower blood loss and transfusion rates compared with open radical cystectomy in both randomized comparative studies and non-randomized comparative studies. There was no significant difference between robot-assisted radical cystectomy and open radical cystectomy in the rate of patients with any or major complications within 90 days both in randomized comparative studies and non-randomized comparative studies. Non-randomized comparative studies reported a lower rate of complications at 30 days, mortality at 90 days and length of stay for patients treated with robot-assisted radical cystectomy, which were not confirmed in randomized comparative studies. Additionally, there were no differences in postoperative quality of life score assessment at 3 and 6 months between robot-assisted radical cystectomy and open radical cystectomy. Robot-assisted radical cystectomy is associated with less blood loss and lower transfusion rates. There is no difference in complications, length of stay, mortality, and quality of life between robot-assisted radical cystectomy and open radical cystectomy. Data from non-randomized comparative studies favor perioperative outcomes in robot-assisted radical cystectomy patients, the failure to confirm in randomized comparative studies, likely due to bias in study design and reporting. Further randomized comparative studies comparing postoperative complications and quality of life between robot-assisted radical cystectomy with intracorporeal urinary diversion and open radical cystectomy are required to assess potential differences between these two surgical approaches.

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.

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.

Identifying candidates for super-extended staging pelvic lymph node dissection among patients with high-risk prostate cancer.

OBJECTIVES: To assess if the preoperative lymph node invasion (LNI) risk could be used to tailor the extent of pelvic lymph node dissection (PLND) according to individual profile in patients with prostate cancer (PCa) undergoing radical prostatectomy (RP), and to identify those who would benefit from the removal of the common iliac and pre-sacral nodes. PATIENTS AND METHODS: A total of 471 patients with high-risk PCa treated with RP and a super-extended PLND that included the removal of the pre-sacral and common iliac nodes between 2006 and 2016 were identified. The risk of LNI was calculated according to the Briganti nomogram. Multivariable logistic regression analyses assessed the association between LNI risk and involvement of the common iliac and pre-sacral regions. The risk of positive common iliac and pre-sacral nodes was plotted over the LNI risk using the LOWESS-smoothed fit curve. RESULTS: The median preoperative LNI risk was 25.5%. The median number of nodes removed was 23, and 171 (36.3%) patients had LNI. Overall, 61 (13.0%) and 28 patients (5.9%), respectively, had positive common iliac and pre-sacral nodes alone or in combination with other sites. The LNI risk was associated with the involvement of the common iliac and pre-sacral regions (all P < 0.001). The proportion of patients with positive common iliac and pre-sacral nodes progressively increased according to the LNI risk. The adoption of a 30% threshold would result in avoiding the removal of the common iliac and pre-sacral nodes in >60% cases, with a risk of missing LNI in these regions of <5%. CONCLUSIONS: Fewer than 5% of patients with an LNI risk of <30% harbour positive common iliac and pre-sacral nodes. A super-extended PLND that includes the dissection of these regions should be considered exclusively in patients with an LNI risk ≥30%.

How can we expand active surveillance criteria in patients with low- and intermediate-risk prostate cancer without increasing the risk of misclassification? Development of a novel risk calculator.

OBJECTIVE: To develop a novel tool to increase the number of patients with prostate cancer eligible for active surveillance (AS) without increasing the risk of unfavourable pathological features (i.e., misclassification) at radical prostatectomy (RP). PATIENTS AND METHODS: Overall, 16 049 patients with low- or intermediate-risk prostate cancer treated with RP were identified. Misclassification was defined as non-organ confined or grade group ≥3 disease at RP. The coefficients of a logistic regression model predicting misclassification were used to develop a risk score. We then performed a systematic analysis of different thresholds to discriminate between patients with or without unfavourable disease and we compared it to available AS criteria. RESULTS: Overall, 5289 (33.0%) patients had unfavourable disease. At multivariable analyses, PSA level, clinical stage, biopsy grade group, the number of positive cores, and PSA density were associated with the risk of unfavourable disease (all P < 0.001). The Prostate Cancer Research International: Active Surveillance (PRIAS) criteria were associated with a lower risk of misclassification (13%) compared to other criteria. Overall, 3303 (20.6%) patients were eligible according to the PRIAS protocol. The adoption of an 18% threshold according to the risk score increased the proportion of eligible patients from 20.6% to 29.4% without increasing the risk of misclassification as compared to the PRIAS criteria. CONCLUSIONS: The use of a novel risk score for AS selection would result in an absolute increase of 10% in the number of patients eligible for this approach without increasing the risk of misclassification.

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.

Assessing perioperative, functional and oncological outcomes of patients with imperative versus elective indications for robot-assisted partial nephrectomy: Results from a high-volume center.

OBJECTIVE: To determine the impact of imperative or elective indications on the perioperative, functional and oncological outcomes of patients undergoing robot-assisted partial nephrectomy. METHODS: Between June 2006 and September 2016, data of patients who underwent robot-assisted partial nephrectomy at the Onze-Lieve-Vrouwziekenhuis Hospital in Aalst, Belgium, were retrospectively reviewed from a prospectively collected database. Only patients with non-metastatic, clinical T1-T2 graded tumors were included. Perioperative, functional and oncological outcomes were recollected. A comparative analysis was carried out after dividing patients into two groups: those who underwent robot-assisted partial nephrectomy for an elective indication (group 1, n = 194), and for an imperative indication (group 2, n = 57) caused by a solitary kidney (n = 20), impaired renal function (n = 2) or both (n = 35). RESULTS: Patients in group 2 were older (74 vs 71 years, P < 0.001), and had a higher Charlson Comorbidity Index (P < 0.001) and American Society of Anesthesiologists score (P < 0.001). No differences were observed concerning laterality, sex, preoperative aspects and dimensions used for an anatomical score or clinical stage. Surgical outcomes considering estimated blood loss, surgical time, ischemia time and transfusion rate showed no significant difference between groups. The complication rate according to Clavien-Dindo showed no difference between groups (P = 0.6). No difference was found between groups with regard to percentage decrease of estimated glomerular filtration rate (7.4 vs 4.8%, P < 0.15). CONCLUSIONS: Robot-assisted partial nephrectomy can be safely and effectively carried out by experienced surgeons in a high-volume center with similar perioperative, functional and oncological outcomes for both elective or imperative indications.