Intermediate-Term Oncological Outcome Assessment for Robotic Assisted Radical Prostatectomy Comparing Retzius Sparing to Standard Approach in a Randomized Control Cohort.

INTRODUCTION: Retzius sparing prostatectomy was promoted with the early continence result. The long-term oncological outcome is still unknown. In this study, we aimed to compare the Intermediate-term oncologic outcomes of these two approaches in patient's cohort who was treated as part of a randomized controlled trial. METHODS: A total of 120 patients were previously randomized equally to receive retzius sparing (RS-RARP) versus standard robotic assisted laparoscopic radical prostatectomy (S-RARP) between January 2015 to April 2016. Baseline, surgical, and pathological characteristics as well as oncologic outcomes were assessed. The analysis was done based on the treatment received. RESULT: Sixty-three patients underwent S-RARP while 57 patients underwent RS-RARP. There was no statistically significant difference in the baseline nor surgical characteristics. The median follow up was 71.24 (IQR 59.75 - 75.75). There were more pathological T3 diseases in RS-RARP. There was no significant difference in the positive margin status nor the biochemical recurrence rate among both groups. After S-RARP and RS-RARP, 6 and 10 patients had biochemical recurrence and the 5-years biochemical recurrence free survival were 91% and 85%, respectively. (p= 0.21) Conclusion: In this cohort, there was no difference in biochemical recurrence in the patients who received either technique. Further mutli-institutional studies with a larger sample size and longer follow up are required.

Admission Rates, Healthcare Utilization, and Inpatient Cost of Radiation Cystitis in the United States.

OBJECTIVE: To assess the incidence, cumulative healthcare burden, and financial impact of inpatient admissions for radiation cystitis (RC), while exploring practice differences in RC management between teaching and nonteaching hospitals. METHODS: We focused on 19,613 patients with a diagnosis of RC within the National Inpatient Sample (NIS) from 2008 to 2014. ICD-9 diagnosis and procedure codes were used. Complex-survey procedures were used to study the descriptive characteristics of RC patients and the procedures received during admission, stratified by hospital teaching status. Inflation-adjusted cost and cumulative annual cost were calculated for the study period. Multivariable logistic regression was used to study the impact of teaching status on the high total cost of admission. RESULTS: Median age was 76 (interquartile range 67-82) years. Most of the patients were males (73%; P < .001). 59,571 (61%) patients received at least one procedure, of which, 24,816 (25.5%) received more than one procedure. Median length of stay was 5days (interquartile range 2-9). Female patients and patients with a higher comorbidity score were more frequently treated at teaching hospitals. A higher proportion of patients received a procedure at a teaching hospital (64% vs 59%; P < .001). The inflation-adjusted cost was 9207 USD and was higher in teaching hospitals. The cumulative cost of inpatient treatment of RC was 63.5 million USD per year and 952.2 million USD over the study period. CONCLUSION: The incidence of RC-associated admissions is rising in the US. This disease is a major burden to US healthcare. The awareness of the inpatient economic burden and healthcare utilization associated with RC may have funding implications.

15-year biochemical failure, metastasis, salvage therapy, and cancer-specific and overall survival rates in men treated with robotic radical prostatectomy for PSA-screen detected prostate cancer.

BACKGROUND: An informed decision regarding a treatment option requires data on its long-term efficacy and side-effect profile. While the side-effects of robotic radical prostatectomy have been well-quantified, the data on its long-term efficacy are lacking. We here provide 15-year oncological outcomes of clinically-localized prostate cancer (CLPCa) patients treated with robot-assisted laparoscopic prostatectomy (RALP). METHODS: We treated 1,807 men with CLPCa with RALP between 2001 and 2005 and prospectively collected follow-up data through 2020. We examined the rates of biochemical failure (BCF), metastatic progression, secondary therapy use, PCa-specific mortality (PCSM), and overall survival (OS) using Kaplan-Meier and competing-risk cumulative incidence methods as appropriate. RESULTS: The median follow-up was 14.1 years. Six hundred eight and 312 men had D'Amico intermediate- and high-risk disease, respectively. Overall, the 15-year rates of BCF, metastasis, secondary therapy use, PCSM, and OS were 28.1%, 4.0%, 16.3%, 2.5%, and 82.1%, respectively. The rates of oncologic failure increased with increasing D'Amico (preoperative) and Diaz (postoperative) risk scores - BCF, metastasis, and PCSM rates in D'Amico low-, intermediate-, and high-risk groups at 15-years were 15.2%, 38.3%, and 44.1% [BCF], 1.1%, 4.1%, and 13.0% [metastasis], and 0.5%, 3.4%, and 6.6% [PCSM], respectively, and in Diaz risk groups 1, 2, 3, 4, and 5 were 5.5%, 20.6%, 41.8%, 66.9%, and 89.2% [BCF], 0%, 0.5%, 3.2%, 20.5%, and 60.0% [metastasis], and 0%, 0.8%, 0.6%, 13.5%, and 37.5% [PCSM], respectively. The OS rates in D'Amico low-to-high and Diaz 1-to-5 risk groups at 15-years were 85.9%, 78.6%, and 75.2%, and 89.4%, 83.2%, 80.6%, 67.2%, and 23.4%, respectively. CONCLUSIONS: Men diagnosed with clinically-localized prostate cancer in the contemporaneous PSA-screening era and treated with RALP achieve durable long-term oncological control. The data reported here (in a risk-stratified manner) represent the longest follow-up after robotic radical prostatectomy, and as such, should be of value when counseling patients regarding expected oncologic outcomes from RALP.

Analysis of Complications After Robot-Assisted Radical Cystectomy Between 2002-2021.

OBJECTIVE: To identify trends in complications following robot-assisted radical cystectomy (RARC) using a multi-institutional database, the International Robotic Cystectomy Consortium (IRCC). METHODS: A retrospective review of the IRCC database was performed (2976 patients, 26 institutions from 11 countries). Postoperative complications were categorized as overall or high grade (≥ Clavien Dindo III) and were further categorized based on type/organ site. Descriptive statistics was used to summarize the data. Multivariate analysis (MVA) was used to identify variables associated with overall and high-grade complications.  Cochran-Armitage trend test was used to describe the trend of complications over time. RESULTS: 1777 (60%) patients developed postoperative complications following RARC, 51% of complications occurred within 30 days of RARC, 19% between 30-90 days, and 30% after 90 days. 835 patients (28%) experienced high-grade complications. Infectious complications (25%) were the most prevalent, while bleeding (1%) was the least. The incidence of complications was stable between 2002-2021. Gastrointestinal and neurologic postoperative complications increased significantly (P < .01, for both) between 2005 and 2020 while thromboembolic (P = .03) and wound complications (P < .01) decreased. On MVA, BMI (OR 1.03, 95%CI 1.01-1.05, P < .01), prior abdominal surgery (OR 1.26, 95%CI 1.03-1.56, P = .03), receipt of neobladder (OR 1.52, 95%CI 1.17-1.99, P < .01), positive nodal disease (OR 1.33, 95%CI 1.05-1.70, P = .02), length of inpatient stay (OR 1.04, 95%CI 1.02-1.05, P < .01) and ICU admission (OR 1.67, 95%CI 1.36-2.06, P < .01) were associated with high-grade complications. CONCLUSION: Overall and high-grade complications after RARC remained stable between 2002-2021. GI and neurologic complications increased, while thromboembolic and wound complications decreased.

Time to second biochemical recurrence as a prognostic indicator in postprostatectomy patients who undergo salvage radiation therapy: An RTOG 9601 based post hoc analysis.

INTRODUCTION AND OBJECTIVE: The prognostic significance of a "second" biochemical recurrence (sBCR) after salvage radiation therapy (sRT) with/without hormonal therapy following primary radical prostatectomy in men with prostate cancer has not been examined. We hypothesized that a shorter time to sBCR will be associated with worse cancer control outcomes. METHODS: The RTOG 9601 study included 760 patients with tumor stage pT2/T3, pN0, who had either persistently elevated prostate-specific antigen (PSA) postradical prostatectomy or developed subsequent biochemical recurrence with PSA levels between 0.2 and 4.0 ng/ml. All patients received sRT (with or without 2 years of Bicalutamide) from 1998 to 2015. For our study, we focused on 421 patients who had sBCR after sRT-which was defined as a PSA increase of at least 0.3 ng/ml over the first nadir. Patients were divided into two categories: early sBCR (n = 210) and late sBCR (n = 211) using median time to sBCR (3.51 years). All patients who experienced sBCR received salvage hormonal therapy. Competing-risk analysis was used to examine the impact of early versus late sBCR on prostate cancer specific mortality (CSM), after accounting for available covariates. RESULTS: The majority of patients were age 60 years or older (75.8%), had pT3 disease (74.8%), and Gleason score 7 (75.2%). Overall, 13.8% had persistent PSA initially after surgery. At 10 years, starting at the time of sBCR, CSM rate was 31.3% in the early sBCR group versus 20.0% in the late sBCR group. In competing-risk analysis, time to sBCR was an independent predictor of CSM, where patients with early sBCR had 1.7-fold higher CSM risk (p = 0.026) than their counterparts with late sBCR. CONCLUSIONS: Time to sBCR after sRT (with or without concomitant Bicalutamide) is a significant predictor of CSM following initial radical prostatectomy. This information can be used to guide subsequent treatments, and to counsel patients.

Optimizing anti-androgen treatment use among men with pathologic lymph-node positive prostate cancer treated with radical prostatectomy: the importance of postoperative PSA kinetics.

BACKGROUND: Optimal postsurgical management of prostate cancer (PCa) patients with nodal metastasis at the time of radical prostatectomy remains unclear. We sought to examine the role of postoperative PSA kinetics and pathologic tumor characteristics in guiding additional hormonal therapy use in pN1 men. METHODS: In total, 297 pN1 PCa patients treated with radical prostatectomy and ePLND between 2002 and 2018 were identified within our prospectively maintained institutional cancer data-registry. Following surgery, these patients were managed with either immediate androgen deprivation therapy (iADT) or observation with deferred ADT (dADT). The former was defined as ADT given within ≤6 months of surgery and the latter as >6 months. The primary outcome was metastasis. Regression-tree analysis was used to stratify patients into novel risk-groups based on post-prostatectomy tumor characteristics and PSA kinetics and the corresponding metastasis risk. Multivariable Cox regression analyses tested the impact of iADT versus observation ± dADT on metastasis, cancer-specific mortality, and overall mortality within each risk-group separately. RESULTS: The median follow-up was 6.1 years (IQR 3.2-9.0). Regression-tree analysis stratified patients into 3 novel risk-groups (Harrell's C-index 0.79) based on PSA-nadir and time to biochemical failure: group 1 (low-risk) included patients with time to biochemical recurrence >6 months (n = 115), while groups 2 and 3 included patients with biochemical failure within ≤6 months with a postoperative PSA-nadir <1.05 ng/mL (group 2 [intermediate-risk], n = 125) or ≥1.05 ng/mL (group 3 [high-risk], n = 57), respectively. No other patient or tumor characteristics were significant for risk stratification. Within each risk-group, the 10-year metastasis-free survival rates with iADT versus observation ± dADT use were: group 1, 100% versus 95.4% (Log-rank p = 0.738), group 2, 80.6% versus 53.5% (Log-rank p = 0.016), and group 3, 41.5% versus 0% (Log-rank p = 0.015), respectively. Adjusted Cox regression analyses confirmed the benefit of iADT utilization in reducing metastasis in group 2 (p = 0.029) and group 3 (p = 0.008) patients, with no benefit for group 1 patients (p = 0.918). Similar results were noted for cancer-specific and overall mortality. CONCLUSIONS: Following radical prostatectomy, early postoperative PSA kinetics may provide valuable information for guiding the timing of ADT initiation-this may reduce over- and undertreatment of pN1 PCa men.

Anti-Androgen Therapy Overcomes the Time Delay in Initiation of Salvage Radiation Therapy and Rescues the Oncological Outcomes in Men with Recurrent Prostate Cancer After Radical Prostatectomy: A Post Hoc Analysis of the RTOG-9601 Trial Data.

BACKGROUND: It is unknown whether the addition of anti-androgen therapy (AAT) to late salvage radiation therapy (sRT) can lead to oncological outcomes equivalent to that of early sRT in men with recurrent prostate cancer (CaP) after surgery. METHODS: Data on 670 men who participated in the Radiation Therapy Oncology Group (RTOG)-9601 trial and who experienced biochemical recurrence were extracted using the National Clinical Trials Network (NCTN) data archive platform. Patients were stratified into four treatment groups: early sRT (pre-sRT prostate-specific antigen [PSA] < 0.7 ng/mL) and late sRT (pre-sRT PSA ≥ 0.7 ng/mL) with/without concomitant AAT, based on cut-offs reported in the original trial. Time-varying Cox proportional hazards and Fine-Gray competing-risk regression analyses assessed the adjusted hazards of overall mortality, CaP-specific mortality, and metastasis among the four treatment groups. RESULTS: At 15-years (median follow-up of 14.7 years), for patients treated with early sRT, early sRT with AAT, late sRT, and late sRT with AAT, the overall mortality, CaP-specific mortality, and metastasis rates were 22.9, 22.8, 40.1, and 22.9% (log-rank p = 0.0039), 12.1, 3.9, 22.7, and 8.0% (Gray's p = 0.0004), and 18.8, 14.6, 35.9, and 19.5% (Gray's p = 0.0004), respectively. Time-varying multivariable adjusted analysis demonstrated increased hazards of overall mortality in patients receiving delayed sRT versus early sRT (hazards ratio [HR] 1.49, 95% confidence interval [CI] 1.02-2.17); however, no difference remained after the addition of concomitant AAT to late sRT (HR 0.85, 95% CI 0.55-1.32, referent early sRT). Likewise, the hazards of cancer-specific mortality and metastatic progression were worse for late sRT when compared with early sRT, but were no different after the addition of AAT to late sRT. CONCLUSIONS: Poorer outcomes associated with late sRT in men with recurrent CaP may be rescued by delivery of concomitant AAT.

Relapses Rates and Patterns for Pathological T0 After Robot-Assisted Radical Cystectomy: Results From the International Robotic Cystectomy Consortium.

OBJECTIVES: To investigate the oncologic outcomes of pT0 after robot-assisted radical cystectomy (RARC). METHODS: A retrospective review of the International Robotic Cystectomy Consortium database was performed. Patients with pT0 after RARC were identified and analyzed. Data were reviewed for demographics and pathologic outcomes. Kaplan-Meier curves were used to depict recurrence-free survival (RFS), disease-specific survival (DSS), and overall survival (OS). Multivariate stepwise Cox regression models were used to identify variables associated with RFS and OS. RESULTS: Four hundred seventy-one patients (18%) with pT0 were identified. Median age was 68 years (interquartile range (IQR) 60-73), with a median follow up of 20 months (IQR 6-47). Thirty-seven percent received neoadjuvant chemotherapy and 5% had pN+ disease. Seven percent of patients experienced disease relapse; 3% had local and 5% had distant recurrence. Most common sites of local and distant recurrences were pelvis (1%) and lungs (2%). Five-year RFS, DSS, and OS were 88%, 93%, and 79%, respectively. Age (hazards ratio [HR] 1.05, 95% confidence interval [CI] 1.01-1.09, P = 0.02), pN+ve (HR 11.48, 95% CI 4.47-29.49, P < .01), and reoperations within 30 days (HR 5.53, 95% CI 2.08-14.64, P < .01) were associated with RFS. Chronic kidney disease (HR 3.24, 95% CI 1.45-7.23, P < .01), neoadjuvant chemotherapy (HR 0.41, 95% CI 0.18-0.92, P = .03), pN+ve (HR 4.37, 95% CI 1.46-13.06, P < .01), and reoperations within 30 days (HR 2.64, 95% CI, 1.08-6.43, P = .03) were associated with OS. CONCLUSIONS: Despite pT0 status at RARC, 5% had pN+ disease and 7% of patients relapsed. Node status was the variable strongest associated with RFS and OS in pT0.

High-intensity local treatment of clinical node-positive urothelial carcinoma of the bladder alongside systemic chemotherapy improves overall survival.

PURPOSE: Clinical node-positive urothelial carcinoma of the bladder (cN+UCaB) is a rapidly fatal disease with limited information on comparative-effectiveness of available treatment options. We sought to examine the impact of high-intensity vs. conservative local treatment (LT) regimens in management of these patients alongside systemic chemotherapy. MATERIALS AND METHODS: We identified 3,227 patients within the National Cancer Data Base who underwent multiagent systemic chemotherapy along with either high-intensity or conservative LT for primary cN+UCaB between 2004-2016. Patients who received no LT, TURBT alone, or <50 Gy radiation therapy to the bladder were included in the conservative group, while patients that received radical cystectomy with pelvic lymphadenectomy or ≥50 Gy radiation therapy with TURBT were included in the high-intensity group. Inverse probability of treatment weighting (IPTW) adjusted Kaplan-Meier and Cox regression analyses were used to assess overall survival (OS). Additionally, to assess whether the benefit of high-intensity LT differs by baseline mortality risk, we tested an interaction between 5-year predicted life-expectancy and the LT type. RESULTS: Overall, 784 (24.3%) and 2,443 (75.7%) cN+UCaB patients underwent high-intensity and conservative LT, respectively. IPTW-adjusted Kaplan-Meier analysis demonstrated OS to be significantly higher in the high-intensity group compared to the conservative group: 5-year OS 28.4% vs. 18.3%, respectively (Log-rank P<0.001). IPTW-adjusted multivariable Cox regression analysis confirmed the benefit of high-intensity LT in prolonging OS (HR 0.63, P<0.001). Interaction analysis showed that high-intensity LT approach was associated with longer OS in all patients regardless of their baseline 5-year life-expectancy (Pinteraction=0.79). CONCLUSION: Eligible patients with cN+UCaB should be considered for aggressive local treatment alongside multiagent systemic chemotherapy. Prospective trials are needed to validate these preliminary findings.

Impact of treatment modality on overall survival in localized ductal prostate adenocarcinoma: A national cancer database analysis.

PURPOSE: Ductal adenocarcinoma is considered a rare histological variant of prostate adenocarcinoma (PCa). Given the rarity of this subtype, optimal treatment strategies for men with nonmetastatic ductal PCa is largely unknown. We aimed to describe the impact of surgery, radiotherapy, systemic therapy, and observation on overall survival (OS) in men with nonmetastatic ductal PCa. MATERIALS AND METHODS: We selected 1,656 cases of nonmetastatic ductal PCa, diagnosed between 2004 and 2015, within the National Cancer Database. Covariates included age, race, Charlson comorbidity score, clinical T stage, clinical lymph node stage, serum prostate specific antigen (PSA), income, hospital type, insurance status, year of diagnosis, and location of residence. Cox regression analysis tested the impact of treatment (surgery, radiotherapy, systemic therapy, and observation) on OS. RESULTS: In men with nonmetastatic ductal PCa, median (interquartile range [IQR]) age and PSA were 67 (60-73) years and 6.2 (4.2-10.7) ng/ml, respectively. Advanced local stage (≥cT3a) was most frequently observed in patients initially treated with systemic therapy (34.8%), followed by those treated with radiotherapy (18.1%), surgery (7.1%) and observation (6.4%, P< 0.001). Serum PSA at presentation was highest in the systemic therapy cohort (median 16.0 ng/ml, IQR: 4.9-37.7), followed by the radiotherapy cohort (median 7.2 ng/ml, IQR: 4.1-12.2), observation cohort (median 7.0 ng/ml, IQR: 4.3-13.3) and surgery cohort (median 5.9 ng/ml, IQR: 4.3-9.2, P< 0.001). Multivariable analysis showed that in comparison to men treated surgically, OS was significantly lower for patients receiving radiotherapy (HR 2.2; 95% CI: 1.5-3.2), under observation (HR 4.6; 95% CI: 2.8-7.6) and receiving systemic therapy (HR 5.2; 95% CI: 3.0-9.1) as an initial course of treatment. CONCLUSIONS: While limited by its retrospective nature, our study shows that starting treatment with surgery is associated with more favorable long-term OS outcomes than radiotherapy, systemic therapy or observation.

A comparative propensity score-matched analysis of perioperative outcomes of intracorporeal vs extracorporeal urinary diversion after robot-assisted radical cystectomy: results from the International Robotic Cystectomy Consortium.

OBJECTIVE: To compare the perioperative outcomes of intracorporeal (ICUD) vs extracorporeal urinary diversion (ECUD) after robot-assisted radical cystectomy (RARC). PATIENTS AND METHODS: We retrospectively reviewed the prospectively maintained International Robotic Cystectomy Consortium (IRCC) database. A total of 972 patients from 28 institutions who underwent RARC were included. Propensity score matching was used to match patients based on age, gender, body mass index (BMI), American Society of Anesthesiologists Score (ASA) score, Charlson Comorbidity Index (CCI) score, prior radiation and abdominal surgery, receipt of neoadjuvant chemotherapy, and clinical staging. Matched cohorts were compared. Multivariate stepwise logistic and linear regression models were fit to evaluate variables associated with receiving ICUD, operating time, 90-day high-grade complications (Clavien-Dindo Classification Grade ≥III), and 90-day readmissions after RARC. RESULTS: Utilisation of ICUD increased from 0% in 2005 to 95% in 2018. The ICUD patients had more overall complications (66% vs 58%, P = 0.01) and readmissions (27% vs 17%, P = 0.01), but not high-grade complications (21% vs 24%, P = 0.22). A more recent RC era and ileal conduit diversion were associated with receiving an ICUD. Higher BMI, ASA score ≥3, and receiving a neobladder were associated with longer operating times. Shorter operating time was associated with male gender, older age, ICUD, and centres with a larger annual average RC volume. Longer intensive care unit stay was associated with 90-day high-grade complications. Higher CCI score, prior radiation therapy, neoadjuvant chemotherapy, and ICUD were associated with a higher risk of 90-day readmissions. CONCLUSIONS: Utilisation of ICUD has increased over the past decade. ICUD was associated with more overall complications and readmissions compared to ECUD, but not high-grade complications.

Ten-year disease progression and mortality rates in men who experience biochemical recurrence versus persistence after radical prostatectomy and undergo salvage radiation therapy: A post-hoc analysis of RTOG 9601 trial data.

PURPOSE: To compare local/metastatic disease progression and overall mortality rates in men with node-negative prostate cancer at radical prostatectomy (RP) that experience biochemical recurrence vs. persistence postoperatively and undergo salvage radiation therapy (sRT). MATERIALS AND METHODS: Data on 760 men who participated in the RTOG 9601 trial were extracted using the NCTN data archive platform. Patients were stratified into biochemical recurrence (nadir-PSA ≤0.4 ng/ml) or persistence (nadir-PSA >0.4 ng/ml) groups, based on the cut-off reported in the original trial. Inverse probability of treatment weighting (IPTW) methodology was utilized to minimize the baseline differences among groups. Competing-risk and Kaplan-Meier analyses estimated the impact of prostate-specific antigen (PSA) persistence vs. recurrence on local and metastatic disease progression and overall-mortality in the IPTW-adjusted model; a 2-sided P < 0.05 was considered significant. RESULTS: All patients received sRT, and about 50% of the patients in either group received concomitant antiandrogen therapy (P = 0.951). The median follow-up was 12 years. After IPTW, the 2 groups were well-matched with standardized mean differences ∼10%. In the IPTW-adjusted cohort, the 10-year local and metastatic disease occurrence rates were 3.2% vs. 1.4% (Gray's P = 0.0001) and 28.6% vs. 10.1% (Gray's P < 0.0001) in patients with persistent vs. recurrent PSA, respectively. Similarly, the 10-year overall-mortality rates were 24.9% vs. 11.9% (Log-rank P = 0.029), respectively. CONCLUSIONS: Patients with biochemical persistence after RP are approximately 2.5 times more likely to experience local/metastatic failure and death, compared to patients with biochemical recurrence after RP, despite equivalent sRT with/without antiandrogen therapy use. These data may facilitate patient counseling and shared treatment selection.

Clonal evaluation of prostate cancer molecular heterogeneity in biopsy samples by dual immunohistochemistry and dual RNA in situ hybridization.

Prostate cancer is frequently multifocal. Although there may be morphological variation, the genetic underpinnings of each tumor are not clearly understood. To assess the inter and intra tumor molecular heterogeneity in prostate biopsy samples, we developed a combined immunohistochemistry and RNA in situ hybridization method for the simultaneous evaluation of ERG, SPINK1, ETV1, and ETV4. Screening of 601 biopsy cores from 120 consecutive patients revealed multiple alterations in a mutually exclusive manner in 37% of patients, suggesting multifocal tumors with considerable genetic differences. Furthermore, the incidence of molecular heterogeneity was higher in African Americans patients compared with Caucasian American patients. About 47% of the biopsy cores with discontinuous tumor foci showed clonal differences with distinct molecular aberrations. ERG positivity occurred in low-grade cancer, whereas ETV4 expression was observed mostly in high-grade cancer. Further studies revealed correlation between the incidence of molecular markers and clinical and pathologic findings, suggesting potential implications for diagnostic pathology practice, such as defining dominant tumor nodules and discriminating juxtaposed but molecularly different tumors of different grade patterns.

The effect of multiplicity of PI-RADS 3 lesions on cancer detection rate of confirmatory targeted biopsy in patients diagnosed with prostate cancer and managed with active surveillance.

BACKGROUND AND OBJECTIVE: To determine the effect of multiplicity of prostate imaging reporting and data system assessment category 3 (PI-RADS 3) lesions on cancer detection rate (CDR) of confirmatory targeted biopsy of such lesion in patients diagnosed with prostate cancer and managed with active surveillance. METHODS: This study was conducted at a single academic institution. There were 91 men with ≥ 1 PI-RADS 3 lesion detected through magnetic resonance imaging (MRI) after systematic prostate biopsy in the course of management of patients diagnosed with prostate cancer with active surveillance. We compared the CDRs based on targeted biopsy of PI-RADS 3 lesions that occurred (1) as solitary lesions, (2) as 1 of multiple PI-RADS 3 only lesions, or (3) with ≥ 1 higher grade lesion. RESULTS: Median age was 65.0 years (interquartile range 59.5-70.0), median prostate specific antigen was 5.95 ng/ml (interquartile range 4.30-8.83), and median prostate specific antigen density was 0.161 ng/ml2 (0.071-0.194). Forty-three men had solitary PI-RADS 3 lesions, 22 had multiple PI-RADS 3 only lesions, and 26 had multiple lesions with ≥ 1 higher grade lesion. The overall CDR (Gleason score ≥ 3 + 3) based on confirmatory MRI targeted biopsy in a given PI-RADS 3 lesion in each group was 23%, 45%, and 54%, respectively (P = 0.0274). The CDRs for clinically significant disease (Gleason score ≥ 3 + 4) were 16%, 32%, and 35%, respectively (P = 0.1701). CONCLUSIONS: Coexisting lesions increase the CDR of confirmatory MRI targeted biopsy of PI-RADS 3 lesions in patients managed with active surveillance. Risk stratification algorithms for PI-RADS 3 lesion to guide biopsy and management decisions may consider including multiplicity of lesions.

Rare Histological Variants of Prostate Adenocarcinoma: A National Cancer Database Analysis.

PURPOSE: The American Joint Committee on Cancer recognizes 6 rare histological variants of prostate adenocarcinoma. We describe the contemporary presentation and overall survival of these rare variants. MATERIALS AND METHODS: We examined 1,345,618 patients who were diagnosed with prostate adenocarcinoma between 2004 and 2015 within the National Cancer Database. We focused on the variants mucinous, ductal, signet ring cell, adenosquamous, sarcomatoid and neuroendocrine. Characteristics at presentation for each variant were compared with nonvariant prostate adenocarcinoma. Cox regression was used to study the impact of histological variant on overall mortality. RESULTS: Few (0.38%) patients presented with rare variant prostate adenocarcinoma. All variants had higher clinical tumor stage at presentation than nonvariant (all p <0.001). Metastatic disease was most common with neuroendocrine (62.9%), followed by sarcomatoid (33.3%), adenosquamous (31.1%), signet ring cell (10.3%) and ductal (9.8%), compared to 4.2% in nonvariant (all p <0.001). Metastatic disease in mucinous (3.3%) was similar to nonvariant (p=0.2). Estimated 10-year overall survival was highest in mucinous (78.0%), followed by nonvariant (71.1%), signet ring cell (56.8%), ductal (56.3%), adenosquamous (20.5%), sarcomatoid (14.6%) and neuroendocrine (9.1%). At multivariable analysis, mortality was higher in ductal (HR 1.38, p <0.001), signet ring cell (HR 1.53, p <0.01), neuroendocrine (HR 5.72, p <0.001), sarcomatoid (HR 5.81, p <0.001) and adenosquamous (HR 9.34, p <0.001) as compared to nonvariant. CONCLUSIONS: Neuroendocrine, adenosquamous, sarcomatoid, signet ring cell and ductal variants more commonly present with metastases. All variants present with higher local stage than nonvariant. Neuroendocrine is associated with the worst and mucinous with the best overall survival.

Clonal evaluation of early onset prostate cancer by expression profiling of ERG, SPINK1, ETV1, and ETV4 on whole-mount radical prostatectomy tissue.

BACKGROUND: Expression profiles of erythroblast transformation-specific (ETS)-related gene fusions and serine protease inhibitor Kazal-type 1 (SPINK1) in early onset prostate cancer have not been thoroughly explored. METHODS: We retrieved 151 radical prostatectomy specimens from young men with prostate cancer (<55 years) and characterized the expression of ETS-related gene (ERG), SPINK1, ETS Variant 1 (ETV1), and ETV4 by dual immunohistochemistry and dual RNA in situ hybridization. Age, race, family history, preoperative prostate-specific antigen, biochemical recurrence, and pathological variables using whole-mount radical prostatectomy tissue were collected. RESULTS: A total of 313 tumor nodules from 151 men including 68 (45%) Caucasians and 61 (40%) African Americans were included in the analysis. Positive family history of prostate cancer was seen in 65 (43%) patients. Preoperative prostate-specific antigen ranged from 0.3 to 52.7 ng/mL (mean = 7.04). The follow-up period ranged from 1 to 123.7 months (mean = 30.3). Biochemical recurrence was encountered in 8 of 151 (5%). ERG overexpression was observed in 85 of 151 (56%) cases, followed by SPINK1 in 61 of 151 (40%), ETV1 in 9 of 149 (6%), and ETV4 in 4 of 141 (3%). There were 25 of 151 (17%) cases showing both ERG and SPINK1 overexpression within different regions of either the same tumor focus or different foci. Higher frequency of ERG overexpression was seen in younger patients (≤45 years old; 76% vs 49%, P = .002), Caucasian men (71% vs 41% P = .0007), organ-confined tumors (64% vs 33%, P = .0008), and tumors of Gleason Grade groups 1 and 2 (62% vs 26%, P = .009). SPINK1 overexpression was more in African American men (68% vs 26%, P = .00008), in tumors with high tumor volume (>20%) and with anterior located tumors. ETV1 and ETV4 demonstrated rare overexpression in these tumors, particularly in the higher-grade tumors. CONCLUSION: This study expands the knowledge of the clonal evolution of multifocal cancer in young patients and support differences in relation to racial background and genetics of prostate cancer.

Using video review to understand the technical variation of robot-assisted radical prostatectomy in a statewide surgical collaborative.

PURPOSE: Video assessment is an emerging tool for understanding surgical technique. Patient outcomes after robot-assisted radical prostatectomy (RARP) may be linked to technical aspects of the procedure. In an effort to refine surgical approaches and improve outcomes, we sought to understand technical variation for the key steps of RARP in a surgical collaborative. METHODS: The Michigan Urological Surgery Improvement Collaborative (MUSIC) is a statewide quality improvement collaborative with the aim of improving prostate cancer care. MUSIC surgeons were invited to submit representative complete videos of nerve-sparing RARP for blinded analysis. We also analyzed peri-operative outcomes from these surgeons in the registry. RESULTS: Surgical video data from 20 unique surgeons identified many variations in technique and time to complete different steps. Common to all surgeons was a transperitoneal approach and a running urethrovesical anastomosis. Prior to anastomosis, 25% surgeons undertook a posterior reconstruction and 30% employed urethral suspension. 65% surgeons approached the seminal vesicle anteriorly. For control of the dorsal vein complex, suture ligation was used in 60%, and vascular stapler was 15%. The majority (80%) of surgeons employed clips for managing pedicles. In examining patient outcomes for surgeons, peri-operative outcomes were not correlated with surgeon's operative time; however, surgeons with an EBL > 400 ml had significant difference among the five different techniques employed. CONCLUSIONS: Despite the worldwide popularity of RARP, the operation is still far from standardized. Correlating variation in technique with clinical outcomes may help provide objective data to support best practices with the goal to improve patient outcomes.