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.

Management of patients with advanced prostate cancer-metastatic and/or castration-resistant prostate cancer: Report of the Advanced Prostate Cancer Consensus Conference (APCCC) 2022.

BACKGROUND: Innovations in imaging and molecular characterisation together with novel treatment options have improved outcomes in advanced prostate cancer. However, we still lack high-level evidence in many areas relevant to making management decisions in daily clinical practise. The 2022 Advanced Prostate Cancer Consensus Conference (APCCC 2022) addressed some questions in these areas to supplement guidelines that mostly are based on level 1 evidence. OBJECTIVE: To present the voting results of the APCCC 2022. DESIGN, SETTING, AND PARTICIPANTS: The experts voted on controversial questions where high-level evidence is mostly lacking: locally advanced prostate cancer; biochemical recurrence after local treatment; metastatic hormone-sensitive, non-metastatic, and metastatic castration-resistant prostate cancer; oligometastatic prostate cancer; and managing side effects of hormonal therapy. A panel of 105 international prostate cancer experts voted on the consensus questions. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The panel voted on 198 pre-defined questions, which were developed by 117 voting and non-voting panel members prior to the conference following a modified Delphi process. A total of 116 questions on metastatic and/or castration-resistant prostate cancer are discussed in this manuscript. In 2022, the voting was done by a web-based survey because of COVID-19 restrictions. RESULTS AND LIMITATIONS: The voting reflects the expert opinion of these panellists and did not incorporate a standard literature review or formal meta-analysis. The answer options for the consensus questions received varying degrees of support from panellists, as reflected in this article and the detailed voting results are reported in the supplementary material. We report here on topics in metastatic, hormone-sensitive prostate cancer (mHSPC), non-metastatic, castration-resistant prostate cancer (nmCRPC), metastatic castration-resistant prostate cancer (mCRPC), and oligometastatic and oligoprogressive prostate cancer. CONCLUSIONS: These voting results in four specific areas from a panel of experts in advanced prostate cancer can help clinicians and patients navigate controversial areas of management for which high-level evidence is scant or conflicting and can help research funders and policy makers identify information gaps and consider what areas to explore further. However, diagnostic and treatment decisions always have to be individualised based on patient characteristics, including the extent and location of disease, prior treatment(s), co-morbidities, patient preferences, and treatment recommendations and should also incorporate current and emerging clinical evidence and logistic and economic factors. Enrolment in clinical trials is strongly encouraged. Importantly, APCCC 2022 once again identified important gaps where there is non-consensus and that merit evaluation in specifically designed trials. PATIENT SUMMARY: The Advanced Prostate Cancer Consensus Conference (APCCC) provides a forum to discuss and debate current diagnostic and treatment options for patients with advanced prostate cancer. The conference aims to share the knowledge of international experts in prostate cancer with healthcare providers worldwide. At each APCCC, an expert panel votes on pre-defined questions that target the most clinically relevant areas of advanced prostate cancer treatment for which there are gaps in knowledge. The results of the voting provide a practical guide to help clinicians discuss therapeutic options with patients and their relatives as part of shared and multidisciplinary decision-making. This report focuses on the advanced setting, covering metastatic hormone-sensitive prostate cancer and both non-metastatic and metastatic castration-resistant prostate cancer. TWITTER SUMMARY: Report of the results of APCCC 2022 for the following topics: mHSPC, nmCRPC, mCRPC, and oligometastatic prostate cancer. TAKE-HOME MESSAGE: At APCCC 2022, clinically important questions in the management of advanced prostate cancer management were identified and discussed, and experts voted on pre-defined consensus questions. The report of the results for metastatic and/or castration-resistant prostate cancer is summarised here.

Combining PSA and PET features to select candidates for salvage lymph node dissection in recurrent prostate cancer.

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 (<0.5 ng/ml), low (0.5-0.99 ng/ml), moderate (1-1.5 ng/ml) and high (>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 < 0.0001). There were 51 CRs after sLND. After adjusting for confounders, we found a significant, non-linear relationship between PSA level at sLND and the 12-month CR-free survival (p < 0.0001), with the highest probability of freedom from CR for patients who received sLND at PSA level ≥1 ng/ml. Conclusions: In case of PET-detected nodal recurrences amenable to sLND, salvage surgery was associated with the highest short-term oncologic outcomes when performed in men with PSA ≥ 1 ng/ml. Awaiting confirmatory data from prospective trials, these findings may help physicians to optimize the timing for 68Ga-PSMA PET in biochemical recurrent PCa.

Management of Patients with Advanced Prostate Cancer. Part I: Intermediate-/High-risk and Locally Advanced Disease, Biochemical Relapse, and Side Effects of Hormonal Treatment: Report of the Advanced Prostate Cancer Consensus Conference 2022.

BACKGROUND: Innovations in imaging and molecular characterisation and the evolution of new therapies have improved outcomes in advanced prostate cancer. Nonetheless, we continue to lack high-level evidence on a variety of clinical topics that greatly impact daily practice. To supplement evidence-based guidelines, the 2022 Advanced Prostate Cancer Consensus Conference (APCCC 2022) surveyed experts about key dilemmas in clinical management. OBJECTIVE: To present consensus voting results for select questions from APCCC 2022. DESIGN, SETTING, AND PARTICIPANTS: Before the conference, a panel of 117 international prostate cancer experts used a modified Delphi process to develop 198 multiple-choice consensus questions on (1) intermediate- and high-risk and locally advanced prostate cancer, (2) biochemical recurrence after local treatment, (3) side effects from hormonal therapies, (4) metastatic hormone-sensitive prostate cancer, (5) nonmetastatic castration-resistant prostate cancer, (6) metastatic castration-resistant prostate cancer, and (7) oligometastatic and oligoprogressive prostate cancer. Before the conference, these questions were administered via a web-based survey to the 105 physician panel members ("panellists") who directly engage in prostate cancer treatment decision-making. Herein, we present results for the 82 questions on topics 1-3. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Consensus was defined as ≥75% agreement, with strong consensus defined as ≥90% agreement. RESULTS AND LIMITATIONS: The voting results reveal varying degrees of consensus, as is discussed in this article and shown in the detailed results in the Supplementary material. The findings reflect the opinions of an international panel of experts and did not incorporate a formal literature review and meta-analysis. CONCLUSIONS: These voting results by a panel of international experts in advanced prostate cancer can help physicians and patients navigate controversial areas of clinical management for which high-level evidence is scant or conflicting. The findings can also help funders and policymakers prioritise areas for future research. Diagnostic and treatment decisions should always be individualised based on patient and cancer characteristics (disease extent and location, treatment history, comorbidities, and patient preferences) and should incorporate current and emerging clinical evidence, therapeutic guidelines, and logistic and economic factors. Enrolment in clinical trials is always strongly encouraged. Importantly, APCCC 2022 once again identified important gaps (areas of nonconsensus) that merit evaluation in specifically designed trials. PATIENT SUMMARY: The Advanced Prostate Cancer Consensus Conference (APCCC) provides a forum to discuss and debate current diagnostic and treatment options for patients with advanced prostate cancer. The conference aims to share the knowledge of international experts in prostate cancer with health care providers and patients worldwide. At each APCCC, a panel of physician experts vote in response to multiple-choice questions about their clinical opinions and approaches to managing advanced prostate cancer. This report presents voting results for the subset of questions pertaining to intermediate- and high-risk and locally advanced prostate cancer, biochemical relapse after definitive treatment, advanced (next-generation) imaging, and management of side effects caused by hormonal therapies. The results provide a practical guide to help clinicians and patients discuss treatment options as part of shared multidisciplinary decision-making. The findings may be especially useful when there is little or no high-level evidence to guide treatment decisions.

Impact of Early Dorsal Venous Complex Ligation on Urinary Continence Recovery after Robot-assisted Radical Prostatectomy: Results from a Phase 3 Randomized Controlled Trial.

BACKGROUND: Whether early ligation of the dorsal venous complex (DVC) might improve recovery of urinary continence (UC) after robot-assisted radical prostatectomy (RARP) has never been investigated in a prospective randomized study. OBJECTIVE: To assess whether early DVC ligation might affect UC recovery after RARP. INTERVENTION: DVC ligation (early vs standard). DESIGN, SETTING, AND PARTICIPANTS: A total of 312 patients with prostate cancer underwent primary RARP at a tertiary care institution. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was UC recovery at 1 and 4 mo after RARP. UC was defined as 0 pads/1 safety pad per day. All patients completed the International Prostate Symptom Score (IPSS) and International Consultation of Incontinence Questionnaire (ICIQ)-Short Form questionnaires. Secondary outcomes were early (≤4 mo) erectile function recovery, the positive surgical margin (PSM) rate, 30-d Clavien-Dindo complications, and biochemical recurrence rates. Quality of life was assessed using the EQ-5D-5L questionnaire. The association between treatment arm and UC recovery was also tested using multivariable regression models. RESULTS AND LIMITATIONS: After surgery, 23 patients withdrew their consent and 29 were lost to follow-up, leaving 261 patients available for per-protocol analyses. Of these, 32 patients (24%) in the experimental group and 37 (29%) in the control group used no pad/one safety pad at 1 mo after RARP, whereas 96 (72%) in the control group versus 83 (65%) in the control group were continent at 4-mo follow-up (both p = 0.3). Median ICIQ and IPSS scores did not differ between the groups at both time points. The results were confirmed on multivariable regression analyses. PSMs were observed for 32 patients (25%) in the experimental group versus 30 (22%) in the control group (p = 0.6). The incidence of postoperative complications (17% experimental vs 13% control) and the 1-yr biochemical recurrence-free survival did not differ between the groups. CONCLUSIONS: In this randomized clinical trial, we did not find evidence that early ligation of the DVC during RARP was associated with better UC recovery after surgery in comparison to the standard technique. Given its safety in terms of surgical margins and complications, this technique may be considered as an option for surgical dissection according to the physician's preference. PATIENT SUMMARY: Our trial showed that for patients undergoing robot-assisted surgical removal of the prostate, the timing of a specific step to control bleeding from a network of veins draining the prostate did not affect recovery of urinary continence after surgery. The results indicate that earlier control of these veins may be considered as an option according to the surgeon's preference.

Predicting the probability of pT3 or higher pathological stage at radical prostatectomy: COVID19-specific considerations.

Background: We 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. Methods: Within 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. Results: In 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%. Conclusion: The 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.

Recurrence pattern in localized RCC: results from a European multicenter database (RECUR).

INTRODUCTION: The impact of open versus minimally invasive surgery on recurrence pattern in the management of localized renal cell carcinoma (RCC) remains uncertain. We thus aimed to determine the impact of surgical approach on survival and recurrence pattern. MATERIAL AND METHODS: This is a multi-institutional, matched cohort study on patients with pT1-3aN0M0 RCC from the RECUR database. After propensity score matching between open and minimally invasive surgery, disease-free (DFS) survival and risk of first recurrence according to recurrence site, namely local recurrence, abdominal/retroperitoneal, thoracic/mediastinal or uncommon site metastases were investigated with Cox regression analysis. Overall (OS) and Cancer Specific Survival (CSS) were also assessed. RESULTS: After matching, 1,019 patients who underwent open and 1,019 who underwent minimally invasive surgery were included (of which 70 robot-assisted). At 5.2 years of median follow-up, 130 patients in open and 125 in minimally invasive group experienced disease progression. A higher risk of local recurrence (HR 2.06; 95% CI 1.18-3.58, P-value = 0.01) and uncommon site metastases (HR 1.09; 95% CI 1.01-1.16; P-value = .04) was found for minimally invasive surgery relative to open surgery, while no difference was found in terms of DFS (HR 0.83; 95% CI 0.64-1.06; P-value = .14). No differences were found in terms of OS and CSS. Main limitation is the retrospective nature of the study. CONCLUSIONS: The risk for local recurrence and uncommon site metastases was higher for minimally invasive surgery compared to open surgery, although no differences were found for OS, CSS, and DFS.

Predicting the Need for Biopsy to Detect Clinically Significant Prostate Cancer in Patients with a Magnetic Resonance Imaging-detected Prostate Imaging Reporting and Data System/Likert ≥3 Lesion: Development and Multinational External Validation of the Imperial Rapid Access to Prostate Imaging and Diagnosis Risk Score.

BACKGROUND: Although multiparametric magnetic resonance imaging (MRI) has high sensitivity, its lower specificity leads to a high prevalence of false-positive lesions requiring biopsy. OBJECTIVE: To develop and externally validate a scoring system for MRI-detected Prostate Imaging Reporting and Data System (PIRADS)/Likert ≥3 lesions containing clinically significant prostate cancer (csPCa). DESIGN, SETTING, AND PARTICIPANTS: The multicentre Rapid Access to Prostate Imaging and Diagnosis (RAPID) pathway included 1189 patients referred to urology due to elevated age-specific prostate-specific antigen (PSA) and/or abnormal digital rectal examination (DRE); April 27, 2017 to October 25, 2019. INTERVENTION: Visual-registration or image-fusion targeted and systematic transperineal biopsies for an MRI score of ≥4 or 3 + PSA density ≥0.12 ng/ml/ml. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Fourteen variables were used in multivariable logistic regression for Gleason ≥3 + 4 (primary) and Gleason ≥4 + 3, and PROMIS definition 1 (any ≥4 + 3 or ≥6 mm any grade; secondary). Nomograms were created and a decision curve analysis (DCA) was performed. Models with varying complexity were externally validated in 2374 patients from six international cohorts. RESULTS AND LIMITATIONS: The five-item Imperial RAPID risk score used age, PSA density, prior negative biopsy, prostate volume, and highest MRI score (corrected c-index for Gleason ≥3 + 4 of 0.82 and 0.80-0.86 externally). Incorporating family history, DRE, and Black ethnicity within the eight-item Imperial RAPID risk score provided similar outcomes. The DCA showed similar superiority of all models, with net benefit differences increasing in higher threshold probabilities. At 20%, 30%, and 40% of predicted Gleason ≥3 + 4 prostate cancer, the RAPID risk score was able to reduce, respectively, 11%, 21%, and 31% of biopsies against 1.8%, 6.2%, and 14% of missed csPCa (or 9.6%, 17%, and 26% of foregone biopsies, respectively). CONCLUSIONS: The Imperial RAPID risk score provides a standardised tool for the prediction of csPCa in patients with an MRI-detected PIRADS/Likert ≥3 lesion and can support the decision for prostate biopsy. PATIENT SUMMARY: In this multinational study, we developed a scoring system incorporating clinical and magnetic resonance imaging characteristics to predict which patients have prostate cancer requiring treatment and which patients can safely forego an invasive prostate biopsy. This model was validated in several other countries.

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.

Systematic Review of Active Surveillance for Clinically Localised Prostate Cancer to Develop Recommendations Regarding Inclusion of Intermediate-risk Disease, Biopsy Characteristics at Inclusion and Monitoring, and Surveillance Repeat Biopsy Strategy.

CONTEXT: There is uncertainty regarding the most appropriate criteria for recruitment, monitoring, and reclassification in active surveillance (AS) protocols for localised prostate cancer (PCa). OBJECTIVE: To perform a qualitative systematic review (SR) to issue recommendations regarding inclusion of intermediate-risk disease, biopsy characteristics at inclusion and monitoring, and repeat biopsy strategy. EVIDENCE ACQUISITION: A protocol-driven, Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA)-adhering SR incorporating AS protocols published from January 1990 to October 2020 was performed. The main outcomes were criteria for inclusion of intermediate-risk disease, monitoring, reclassification, and repeat biopsy strategies (per protocol and/or triggered). Clinical effectiveness data were not assessed. EVIDENCE SYNTHESIS: Of the 17 011 articles identified, 333 studies incorporating 375 AS protocols, recruiting 264 852 patients, were included. Only a minority of protocols included the use of magnetic resonance imaging (MRI) for recruitment (n = 17), follow-up (n = 47), and reclassification (n = 26). More than 50% of protocols included patients with intermediate or high-risk disease, whilst 44.1% of protocols excluded low-risk patients with more than three positive cores, and 39% of protocols excluded patients with core involvement (CI) >50% per core. Of the protocols, ≥80% mandated a confirmatory transrectal ultrasound biopsy; 72% (n = 189) of protocols mandated per-protocol repeat biopsies, with 20% performing this annually and 25% every 2 yr. Only 27 protocols (10.3%) mandated triggered biopsies, with 74% of these protocols defining progression or changes on MRI as triggers for repeat biopsy. CONCLUSIONS: For AS protocols in which the use of MRI is not mandatory or absent, we recommend the following: (1) AS can be considered in patients with low-volume International Society of Urological Pathology (ISUP) grade 2 (three or fewer positive cores and cancer involvement ≤50% CI per core) or another single element of intermediate-risk disease, and patients with ISUP 3 should be excluded; (2) per-protocol confirmatory prostate biopsies should be performed within 2 yr, and per-protocol surveillance repeat biopsies should be performed at least once every 3 yr for the first 10 yr; and (3) for patients with low-volume, low-risk disease at recruitment, if repeat systematic biopsies reveal more than three positive cores or maximum CI >50% per core, they should be monitored closely for evidence of adverse features (eg, upgrading); patients with ISUP 2 disease with increased core positivity and/or CI to similar thresholds should be reclassified. PATIENT SUMMARY: We examined the literature to issue new recommendations on active surveillance (AS) for managing localised prostate cancer. The recommendations include setting criteria for including men with more aggressive disease (intermediate-risk disease), setting thresholds for close monitoring of men with low-risk but more extensive disease, and determining when to perform repeat biopsies (within 2 yr and 3 yearly thereafter).

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.

Risk Stratification of Patients Candidate to Radical Prostatectomy Based on Clinical and Multiparametric Magnetic Resonance Imaging Parameters: Development and External Validation of Novel Risk Groups.

BACKGROUND: Despite the key importance of magnetic resonance imaging (MRI) parameters, risk classification systems for biochemical recurrence (BCR) in prostate cancer (PCa) patients treated with radical prostatectomy (RP) are still based on clinical variables alone. OBJECTIVE: We aimed at developing and validating a novel classification integrating clinical and radiological parameters. DESIGN, SETTING, AND PARTICIPANTS: A retrospective multicenter cohort study was conducted between 2014 and 2020 across seven academic international referral centers. A total of 2565 patients treated with RP for PCa were identified. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Early BCR was defined as two prostate-specific antigen (PSA) values of ≥0.2 ng/ml within 3 yr after RP. Kaplan-Meier and Cox regressions tested time and predictors of BCR. Development and validation cohorts were generated from the overall patient sample. A model predicting early BCR based on Cox-derived coefficients represented the basis for a nomogram that was validated externally. Predictors consisted of PSA, biopsy grade group, MRI stage, and the maximum diameter of lesion at MRI. Novel risk categories were then identified. The Harrel's concordance index (c-index) compared the accuracy of our risk stratification with the European Association of Urology (EAU), Cancer of the Prostate Risk Assessment (CAPRA), and International Staging Collaboration for Cancer of the Prostate (STAR-CAP) risk groups in predicting early BCR. RESULTS AND LIMITATIONS: Overall, 200 (8%), 1834 (71%), and 531 (21%) had low-, intermediate-, and high-risk disease according to the EAU risk groups. The 3-yr overall BCR-free survival rate was 84%. No differences were observed in the 3-yr BCR-free survival between EAU low- and intermediate-risk groups (88% vs 87%; p = 0.1). The novel nomogram depicted optimal discrimination at external validation (c-index 78%). Four new risk categories were identified based on the predictors included in the Cox-based nomogram. This new risk classification had higher accuracy in predicting early BCR (c-index 70%) than the EAU, CAPRA, and STAR-CAP risk classifications (c-index 64%, 63%, and 67%, respectively). CONCLUSIONS: We developed and externally validated four novel categories based on clinical and radiological parameters to predict early BCR. This novel classification exhibited higher accuracy than the available tools. PATIENT SUMMARY: Our novel and straightforward risk classification outperformed currently available preoperative risk tools and should, therefore, assist physicians in preoperative counseling of men candidate to radical treatment for prostate cancer.

Definition and Impact on Oncologic Outcomes of Persistently Elevated Prostate-specific Antigen After Salvage Lymph Node Dissection for Node-only Recurrent Prostate Cancer After Radical Prostatectomy: Clinical Implications for Multimodal Therapy.

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

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.

Patient- and Tumour-related Prognostic Factors for Urinary Incontinence After Radical Prostatectomy for Nonmetastatic Prostate Cancer: A Systematic Review and Meta-analysis.

CONTEXT: While urinary incontinence (UI) commonly occurs after radical prostatectomy (RP), it is unclear what factors increase the risk of UI development. OBJECTIVE: To perform a systematic review of patient- and tumour-related prognostic factors for post-RP UI. The primary outcome was UI within 3 mo after RP. Secondary outcomes included UI at 3-12 mo and ≥12 mo after RP. EVIDENCE ACQUISITION: Databases including Medline, EMBASE, and CENTRAL were searched between January 1990 and May 2020. All studies reporting patient- and tumour-related prognostic factors in univariable or multivariable analyses were included. Surgical factors were excluded. Risk of bias (RoB) and confounding assessments were performed using the Quality In Prognosis Studies (QUIPS) tool. Random-effects meta-analyses were performed for all prognostic factor, where possible. EVIDENCE SYNTHESIS: A total of 119 studies (5 randomised controlled trials, 24 prospective, 88 retrospective, and 2 case-control studies) with 131 379 patients were included. RoB was high for study participation and confounding; moderate to high for statistical analysis, study attrition, and prognostic factor measurement; and low for outcome measurements. Significant prognostic factors for postoperative UI within 3 mo after RP were age (odds ratio [OR] per yearly increase 1.04, 95% confidence interval [CI] 1.03-1.05), membranous urethral length (MUL; OR per 1-mm increase 0.81, 95% CI 0.74-0.88), prostate volume (PV; OR per 1-ml increase 1.005, 95% CI 1.000-1.011), and Charlson comorbidity index (CCI; OR 1.28, 95% CI 1.09-1.50). CONCLUSIONS: Increasing age, shorter MUL, greater PV, and higher CCI are independent prognostic factors for UI within 3 mo after RP, with all except CCI remaining prognostic at 3-12 mo. PATIENT SUMMARY: We reviewed the literature to identify patient and disease factors associated with urinary incontinence after surgery for prostate cancer. We found increasing age, larger prostate volume, shorter length of a section of the urethra (membranous urethra), and lower fitness were associated with worse urinary incontinence for the first 3 mo after surgery, with all except lower fitness remaining predictive at 3-12 mo.

Reducing the Risk of Postoperative Complications After Robot-assisted Radical Prostatectomy in Prostate Cancer Patients: Results of an Audit and Feedback Intervention Following the Implementation of Prospective Data Collection.

BACKGROUND: Prospective data collection for perioperative outcomes might increase awareness of surgical results obtained for patients with prostate cancer (PCa) undergoing robot-assisted radical prostatectomy (RARP). This would prompt the implementation of measures aimed at reducing the risk of adverse outcomes. OBJECTIVE: To assess the efficacy of an audit and feedback process aimed at identifying the most common complications after RARP and at implementing measures to improve outcomes. DESIGN, SETTING, AND PARTICIPANTS: Overall, 415 patients treated with RARP by a high-volume surgeon were included. Perioperative outcomes for 187 patients treated between September 2016 and December 2017 were prospectively collected at 30 d according to the European Association of Urology guideline recommendations (group 1). An audit and feedback process was implemented in January 2018 whereby the most common complication (anastomotic leak) was identified and measures aimed at improving outcomes (changes in the anastomotic technique) were implemented. The outcomes for group 1 were then compared to 228 patients treated after implementation of the modified surgical technique (group 2). SURGICAL PROCEDURE: A novel technique for posterior reconstruction and urethrovesical anastomosis was introduced. MEASUREMENTS: Perioperative outcomes included blood loss, operative time, length of stay, and 30-d postoperative complications. Logistic regression models tested the effect of the novel surgical technique on anastomotic leaks. RESULTS AND LIMITATIONS: Overall, 97 patients (23%) experienced postoperative complications at 30 d. The rate of anastomotic leaks was significantly lower in group 2 compared to group 1 (3.1% vs 9.6%; p < 0.01). Similarly, overall and Clavien-Dindo grade ≥2 complication rates were lower in group 2 versus group 1 (17% vs 31%, and 6% vs 20%; both p ≤ 0.001). In multivariable analyses, treatment after implementation of changes in the anastomotic technique independently predicted a lower risk of complications (odds ratio [OR] 0.58, 95% confidence interval [CI] 0.38-0.89) and of anastomotic leaks (OR 0.43, 95% CI 0.17-0.97). The lack of randomization represents the main limitation. CONCLUSIONS: Implementation of changes in the urethrovesical anastomosis technique arising from increased awareness of surgical outcomes reduced the risk of anastomotic leaks. These findings highlight the importance of audit and feedback processes using a standardized method for reporting surgical morbidity. PATIENT SUMMARY: Increased awareness of surgical outcomes prompted us to change our technique for connecting the bladder to the urethra during robot-assisted surgery to remove the prostate in patients with prostate cancer. These changes resulted in significant improvements in surgical outcomes.

Improving the stratification of intermediate risk prostate cancer.

BACKGROUND: Intermediate risk prostate cancer (IR PCa) may exhibit a wide array of phenotypes, from favorable to unfavorable. NCCN criteria help distinguishing between favorable versus unfavorable subgroups. We studied and attempted to improve this classification. METHODS: Within the SEER database 2010-2016, we identified 19,193 IR PCa patients treated with radical prostatectomy. A multivariable logistic regression model predicting unfavorable IR PCa was developed and externally validated, in addition to a head-to-head comparison with NCCN IR PCa stratification. RESULTS: Model development (development cohort N.=13,436: 3585 unfavorable versus 9851 favorable) rested on age, PSA, clinical T stage, biopsy Gleason Grade Group (GGG) and percentage of positive cores. All were independent predictors of unfavorable IR PCa. In external validation cohort (N.=5757: 1652 unfavorable versus 4105 favorable), NCCN stratification was 61.8% accurate in discriminating between favorable versus unfavorable, compared to 67.6% for nomogram, which exhibited excellent calibration, less pronounced departures from ideal prediction and greater net-benefit in decision curve analyses (DCA) than NCCN stratification. The optimal nomogram cutoff misclassified 312 of 1976 patients (15.8%) versus 598 of 2877 (20.8%) for NCCN stratification. Of NCCN misclassified patients, 90.0% harbored pT3-4 stages versus 84.6% of nomogram. CONCLUSIONS: The newly developed, externally validated nomogram discriminates better between favorable versus unfavorable IR PCa, according to overall accuracy, calibration, DCA, and actual numbers and stage distribution of misclassified patients.

Newly Diagnosed Oligometastatic Prostate Cancer: Current Controversies and Future Developments.

This report presents a 56-yr-old man in good general health status, newly diagnosed with a cT3b, cN1, cM1b, International Society of Urological Pathology grade group 3, low-volume (CHAARTED criteria), low-risk (LATITUDE criteria) metastatic prostate cancer. Staging was performed with conventional imaging: a computed tomography (CT) scan showed the presence of two enlarged lymph nodes on the left, close to the external iliac vessels. In addition, a suspicious 15-mm metastatic lesion was detected in the left pubic bone. This lesion was confirmed on the bone scan, without further metastatic lesions. In the context of a clinical trial, after an initial course of androgen deprivation therapy (ADT), the patient was treated with robot-assisted radical prostatectomy and extended pelvic lymph node dissection (histopathological examination: ypT3b pN1 R1). Postprostatectomy radiation therapy was delivered on prostatic bed (70Gy), pelvic lymph node area (54Gy), and pubic bone (51Gy). ADT was scheduled for a total period of 36 mo. Currently, the patient is still receiving ADT, which will be completed within 6 mo. The last prostate-specific antigen level was undetectable. The discussion is focused on the following three open questions: (1) Would molecular imaging (eg, prostate-specific membrane antigen positron emission tomography/CT) change the therapeutic approach to the patient? (2) Is there a role for local treatment in the metastatic setting? (iii) Should metastasis-directed therapy be considered for this patient? PATIENT SUMMARY: The optimal management of patients newly diagnosed with oligometastatic prostate cancer remains challenging. The fields of staging with modern imaging and therapy with novel treatment options are evolving rapidly. In particular, the role of a prostate-specific membrane antigen positron emission tomography/computed tomography scan for primary staging, the impact of a local treatment on the prostate, and the effect of direct therapies on the metastases represent important open questions in this intriguing field.