Conversion to Radical Nephrectomy From Robotic Partial Nephrectomy Is Most Commonly Due to Anatomic and Oncologic Complexity.

PURPOSE: Partial nephrectomy is standard-of-care treatment for small renal masses. As utilization of partial nephrectomy increases and includes larger and complex tumors, the risk of conversion to radical nephrectomy likely increases. We evaluated incidence and reason for conversion to radical nephrectomy in patients scheduled for partial nephrectomy by surgeons participating in MUSIC (the Michigan Urologic Surgery Improvement Collaborative). MATERIALS AND METHODS: All patients in whom robotic partial nephrectomy was planned were stratified by completed procedure (robotic partial nephrectomy vs radical nephrectomy). Preoperative and intraoperative records were reviewed for preoperative assessment of difficulty and reason for conversion. Patient, tumor, pathologic, and practice variables were compared between cohorts. RESULTS: Of 650 patients scheduled for robotic partial nephrectomy, conversion to radical nephrectomy occurred in 27 (4.2%) patients. No conversions to open were reported. Preoperative documentation indicated a plan for possible conversion in 18 (67%) patients including partial with possible radical (n = 8), partial vs radical (n = 6), or likely radical nephrectomy (n = 4). Intraoperative documentation indicated that only 5 (19%) conversions were secondary to bleeding, with the remaining conversions due to tumor complexity and/or oncologic concerns. Patients undergoing conversion had larger (4.7 vs 2.8 cm, P < .001) and higher-complexity tumors (64% vs 6%, P < .001) with R.E.N.A.L. (for radius, exophytic/endophytic, nearness of tumor to collecting system, anterior/posterior, location relative to polar line) nephrometry score ≥ 10. The converted cases had a higher rate of ≥ pT3 (27% vs 8.4%, P = .008). CONCLUSIONS: There was a low rate of conversion from robotic partial to radical nephrectomy in the MUSIC-KIDNEY (Kidney mass: Identifying and Defining Necessary Evaluation and therapY) collaborative, and an even lower risk of conversion due to uncontrolled bleeding. Targeted review of each conversion identified appropriate decision-making based on oncologic risk in most cases.

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.

Conditional survival does not improve over time in metastatic castration-resistant prostate cancer patients undergoing docetaxel.

PURPOSE: To investigate the conditional overall survival (OS) of metastatic castration-resistant prostate cancer (mCRPC) patients receiving docetaxel chemotherapy. METHODS: We used deidentified patient-level data from the Prostate Cancer DREAM Challenge database and the control arm of the ENTHUSE 14 trial. We identified 2158 chemonaïve mCRPC patients undergoing docetaxel chemotherapy in the five randomized clinical trials. The 6-month conditional OS was calculated at times 0, 6, 12, 18, and 24 months from randomization. Survival curves of each group were compared using the log-rank test. Patients were then stratified into low- and high-risk groups based on the median predicted value of our recently published nomogram predicting OS in mCRPC patients. RESULTS: Nearly half (45%) of the study population was aged between 65 and 74 years. Median interquartile range prostate-specific antigen for the overall cohort was 83.2 (29.6-243) ng/mL, and 59% of patients had bone metastasis with or without lymph node involvement. The 6-month conditional survival rates at 0, 6, 12, 18, and 24 months for the entire cohort were 93% (95% confidence interval [CI]: 92-94), 82% (95% CI: 81-84), 76% (95% CI: 73-78), 75% (95% CI: 71-78), and 71% (95% CI: 65-76). These rates were, respectively, 96% (95% CI: 95-97), 92% (95% CI: 90-93), 84% (95% CI: 81-87), 81% (95% CI: 77-85), and 79% (95% CI: 72-84) in the low-risk group and 89% (95% CI: 87-91), 73% (95% CI: 70-76), 65% (95% CI: 60-69), 64% (95% CI: 58-70), and 58% (95% CI: 47-67) in the high-risk group. CONCLUSION: The conditional OS for patients undergoing docetaxel chemotherapy tends to plateau over time, with the main drop in conditional OS happening during the first year from initiating docetaxel treatment. That is the longer a patient survives, the more likely they are to survive further. This prognostic information could be a useful tool for a more accurate tailoring of both follow-up and therapies. PATIENT SUMMARY: In this report, we looked at the future survival in months of patients with metastatic castration resistant prostate cancer on chemotherapy who have already survived a certain period. We found that the longer time that a patient survives, the more likely they will continue to survive. We conclude that this information will help physicians tailor follow-ups and treatments for patients for a more accurate personalized medicine.

Convolutional Neural Network Quantification of Gleason Pattern 4 and Association With Biochemical Recurrence in Intermediate-Grade Prostate Tumors.

Differential classification of prostate cancer grade group (GG) 2 and 3 tumors remains challenging, likely because of the subjective quantification of the percentage of Gleason pattern 4 (%GP4). Artificial intelligence assessment of %GP4 may improve its accuracy and reproducibility and provide information for prognosis prediction. To investigate this potential, a convolutional neural network (CNN) model was trained to objectively identify and quantify Gleason pattern (GP) 3 and 4 areas, estimate %GP4, and assess whether CNN-predicted %GP4 is associated with biochemical recurrence (BCR) risk in intermediate-risk GG 2 and 3 tumors. The study was conducted in a radical prostatectomy cohort (1999-2012) of African American men from the Henry Ford Health System (Detroit, Michigan). A CNN model that could discriminate 4 tissue types (stroma, benign glands, GP3 glands, and GP4 glands) was developed using histopathologic images containing GG 1 (n = 45) and 4 (n = 20) tumor foci. The CNN model was applied to GG 2 (n = 153) and 3 (n = 62) tumors for %GP4 estimation, and Cox proportional hazard modeling was used to assess the association of %GP4 and BCR, accounting for other clinicopathologic features including GG. The CNN model achieved an overall accuracy of 86% in distinguishing the 4 tissue types. Furthermore, CNN-predicted %GP4 was significantly higher in GG 3 than in GG 2 tumors (P = 7.2 × 10-11). %GP4 was associated with an increased risk of BCR (adjusted hazard ratio, 1.09 per 10% increase in %GP4; P = .010) in GG 2 and 3 tumors. Within GG 2 tumors specifically, %GP4 was more strongly associated with BCR (adjusted hazard ratio, 1.12; P = .006). Our findings demonstrate the feasibility of CNN-predicted %GP4 estimation, which is associated with BCR risk. This objective approach could be added to the standard pathologic assessment for patients with GG 2 and 3 tumors and act as a surrogate for specialist genitourinary pathologist evaluation when such consultation is not available.

Initial Management of Indeterminate Renal Lesions in a Statewide Collaborative: A MUSIC-KIDNEY Analysis.

PURPOSE: Renal masses can be characterized as "indeterminate" due to lack of differentiating imaging characteristics. Optimal management of indeterminate renal lesions remains nebulous and poorly defined. We assess management of indeterminate renal lesions within the MUSIC-KIDNEY (Michigan Urological Surgery Improvement Collaborative-Kidney mass: Identifying and Defining Necessary Evaluation and therapY) collaborative. MATERIALS AND METHODS: Each renal mass is classified as suspicious, benign, or indeterminate based on radiologist and urologist assessment. Objectives were to assess initial management of indeterminate renal lesions and the impact of additional imaging and biopsy on characterization prior to treatment. RESULTS: Of 2,109 patients, 444 (21.1%) had indeterminate renal lesions on their initial imaging, which included CT without contrast (36.2%), CT with contrast (54.1%), and MRI (9.7%). Eighty-nine patients (20.0%) underwent additional imaging within 90 days, 8.3% (37/444) underwent renal mass biopsy, and 3.6% (16/444) had reimaging and renal mass biopsy. Additional imaging reclassified 58.1% (61/105) of indeterminate renal lesions as suspicious and 21.0% (22/105) as benign, with only 20.9% (22/105) remaining indeterminate. Renal mass biopsy yielded a definitive diagnosis for 87%. Treatment was performed for 149 indeterminate renal lesions (33.6%), including 117 without reimaging and 123 without renal mass biopsy. At surgery for indeterminate renal lesions, benign pathology was more common in patients who did not have repeat imaging (9.9%) than in those who did (6.7%); for ≤4 cm indeterminate renal lesions, these rates were 11.8% and 4.3%. CONCLUSIONS: About 33% of patients diagnosed with an indeterminate renal lesion underwent immediate treatment without subsequent imaging or renal mass biopsy, with a 10% rate of nonmalignant pathology. This highlights a quality improvement opportunity for patients with cT1 renal masses: confirmation that the lesion is suspicious for renal cell carcinoma based on high-quality, multiphase, cross-sectional imaging and/or histopathological features prior to surgery, even if obtaining subsequent follow-up imaging and/or renal mass biopsy is necessary. When performed, these steps lead to reclassification in 79% and 87% of indeterminate renal lesions, respectively.

Impact of preexisting opioid dependence on morbidity, length of stay, and inpatient cost of urological oncological surgery.

OBJECTIVES: To determine the incidence of preexisting opioid dependence in patients undergoing elective urological oncological surgery. In addition, to quantify the impact of preexisting opioid dependence on outcomes and cost of common urologic oncological procedures at a national level in the USA. METHODS: We used the National Inpatient Sample (NIS) to study 1,609,948 admissions for elective partial/radical nephrectomy, radical prostatectomy, and cystectomy procedures. Trends of preexisting opioid dependence were studied over 2003-2014. We use multivariable-adjusted analysis to compare opioid-dependent patients to those without opioid dependence (reference group) in terms of outcomes, namely major complications, length of stay (LOS), and total cost. RESULTS: The incidence of opioid dependence steadily increased from 0.6 per 1000 patients in 2003 to 2 per 1000 in 2014. Opioid-dependent patients had a significantly higher rate of major complications (18 vs 10%; p < 0.001) and longer LOS (4 days (IQR 2-7) vs 2 days (IQR 1-4); p < 0.001), when compared to the non-opioid-dependent counterparts. Opioid dependence also increased the overall cost by 48% (adjusted median cost $18,290 [IQR 12,549-27,715] vs. $12,383 [IQR 9225-17,494] in non-opioid-dependent, p < 0.001). Multivariable analysis confirmed the independent association of preexisting opioid dependence with major complications, length of stay in 4th quartile, and total cost in 4th quartile. CONCLUSIONS: The incidence of preexisting opioid dependence before elective urological oncology is increasing and is associated with adverse outcomes after surgery. There is a need to further understand the challenges associated with opioid dependence before surgery and identify and optimize these patients to improve outcomes.

A novel prognostic model predicting overall survival in patients with metastatic castration-resistant prostate cancer receiving standard chemotherapy: A multi-trial cohort analysis.

PURPOSE: Generalizable, updated, and easy-to-use prognostic models for patients with metastatic castration-resistant prostate cancer (mCRPC) are lacking. We developed a nomogram predicting the overall survival (OS) of mCRPC patients receiving standard chemotherapy using data from five randomized clinical trials (RCTs). METHODS: Patients enrolled in the control arm of five RCTs (ASCENT 2, VENICE, CELGENE/MAINSAIL, ENTHUSE 14, and ENTHUSE 33) were randomly split between training (n = 1636, 70%) and validation cohorts (n = 700, 30%). In the training cohort, Cox regression tested the prognostic significance of all available variables as a predictor of OS. Independent predictors of OS on multivariable analysis were used to construct a novel multivariable model (nomogram). The accuracy of this model was tested in the validation cohort using time-dependent area under the curve (tAUC) and calibration curves. RESULTS: Most of the patients were aged 65-74 years (44.5%) and the median (interquartile range) follow-up time was 13.9 (8.9-20.2) months. At multivariable analysis, the following were independent predictors of OS in mCRPC patients: sites of metastasis (visceral vs. bone metastasis, hazard ratio [HR]: 1.24), prostate-specific antigen (HR: 1.00), aspartate transaminase (HR: 1.01), alkaline phosphatase (HR: 1.00), body mass index (HR: 0.97), and hemoglobin (≥13 g/dl vs. <11 g/dl, HR: 0.41; all p < 0.05). A nomogram based on these variables was developed and showed favorable discrimination (tAUC at 12 and 24 months: 73% and 72%, respectively) and calibration characteristics on external validation. CONCLUSION: A new prognostic model to predict OS of patients with mCRPC undergoing first line chemotherapy was developed. This can help urologists/oncologists in counseling patients and might be useful to better stratify patients for future clinical trials.

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.

Management of patients who opt for radical prostatectomy during the coronavirus disease 2019 (COVID-19) pandemic: an international accelerated consensus statement.

OBJECTIVE: Coronavirus disease-19 (COVID-19) pandemic caused delays in definitive treatment of patients with prostate cancer. Beyond the immediate delay a backlog for future patients is expected. The objective of this work is to develop guidance on criteria for prioritisation of surgery and reconfiguring management pathways for patients with non-metastatic prostate cancer who opt for surgical treatment. A second aim was to identify the infection prevention and control (IPC) measures to achieve a low likelihood of coronavirus disease 2019 (COVID-19) hazard if radical prostatectomy (RP) was to be carried out during the outbreak and whilst the disease is endemic. METHODS: We conducted an accelerated consensus process and systematic review of the evidence on COVID-19 and reviewed international guidance on prostate cancer. These were presented to an international prostate cancer expert panel (n = 34) through an online meeting. The consensus process underwent three rounds of survey in total. Additions to the second- and third-round surveys were formulated based on the answers and comments from the previous rounds. The Consensus opinion was defined as ≥80% agreement and this was used to reconfigure the prostate cancer pathways. RESULTS: Evidence on the delayed management of patients with prostate cancer is scarce. There was 100% agreement that prostate cancer pathways should be reconfigured and measures developed to prevent nosocomial COVID-19 for patients treated surgically. Consensus was reached on prioritisation criteria of patients for surgery and management pathways for those who have delayed treatment. IPC measures to achieve a low likelihood of nosocomial COVID-19 were coined as 'COVID-19 cold' sites. CONCLUSION: Reconfiguring management pathways for patients with prostate cancer is recommended if significant delay (>3-6 months) in surgical management is unavoidable. The mapped pathways provide guidance for such patients. The IPC processes proposed provide a framework for providing RP within an environment with low COVID-19 risk during the outbreak or when the disease remains endemic. The broader concepts could be adapted to other indications beyond prostate cancer surgery.

COVID-19 Infection in Men on Testosterone Replacement Therapy.

BACKGROUND: Men who contract coronavirus disease 2019 (COVID-19) appear to have worse clinical outcomes compared with women which raises the possibility of androgen-dependent effects. AIM: We sought to determine if testosterone replacement therapy (TRT) is associated with worse clinical outcomes. METHODS: Through a retrospective chart review, we identified 32 men diagnosed with COVID-19 and on TRT. They were propensity score matched to 63 men diagnosed with COVID-19 and not on TRT. Data regarding comorbidities and endpoints such as hospital admission, intensive care unit admission, ventilator utilization, thromboembolic events, and death were extracted. Chi-square and Kruskal-Wallis tests examined differences in categorical and continuous variables, respectively. Logistic regression analysis tested the relationship between TRT status and the study endpoints. RESULTS: There were no statistically significant differences between the 2 groups, and TRT was not a predictor of any of the endpoints on multivariate analysis. CONCLUSION: These results suggest that TRT is not associated with a worse clinical outcome in men diagnosed with COVID-19. Rambhatla A, Bronkema CJ, Corsi N, et al. COVID-19 Infection in Men on Testosterone Replacement Therapy. J Sex Med 2021;18:215-218.

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.

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.

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.

Development of a Novel Scoring System Quantifies Opportunities to Reduce Surgery for Benign Renal Neoplasms: A Retrospective Quality Improvement Analysis within the MUSIC-KIDNEY Collaborative.

PURPOSE: Nonmalignant pathology has been reported in 15% to 20% of surgeries for cT1 renal masses. We seek to identify opportunities for improvement in avoiding surgery for nonmalignant pathology. MATERIALS AND METHODS: MUSIC-KIDNEY started collecting data in 2017. All patients with cT1 renal masses who had partial or radical nephrectomy for nonmalignant pathology were identified. Category for improvement (none-0, minor-1, moderate-2 or major-3) was independently assigned to each case by 5 experienced kidney surgeons. Specific strategies to decrease nonmalignant pathology were identified. RESULTS: Of 1,392 patients with cT1 renal masses 653 underwent surgery and 74 had nonmalignant pathology (11%). Of these, 23 (31%) cases were cT1b. Radical nephrectomy was performed in 17 (22.9%) patients for 5 cT1a and 12 cT1b lesions. Only 6 patients had a biopsy prior to surgery (5 oncocytoma, 1 unclassified renal cell carcinoma). Review identified 25 cases with minor (34%), 26 with moderate (35%) and 10 with major (14%) quality improvement opportunities. Overall 17% of cases had no quality improvement opportunities identified (12 partial nephrectomy, 1 radical nephrectomy). CONCLUSIONS: Review of patients with cT1 renal masses who underwent surgery for nonmalignant pathology revealed a significant number of cases in which this outcome may have been avoided. Approximately half of cases had moderate or major quality improvement opportunities, with radical nephrectomy for nonmalignant pathology being the most common reason. Our data indicate a lowest achievable and acceptable rate of nonmalignant pathology to be 1.9% and 5.4%, respectively. Avoiding interventions for nonmalignant pathology, particularly radical nephrectomy, is an important focus of quality improvement efforts. Strategies to decrease unnecessary interventions for nonmalignant pathology include greater use of repeat imaging, renal mass biopsy and surveillance.

Pathological staging of renal cell carcinoma: a review of 300 consecutive cases with emphasis on retrograde venous invasion.

AIMS: Pathological staging of renal cell carcinoma (RCC) can be challenging compared to other cancer types, as invasion often manifests as finger-like protrusions into vascular spaces or renal sinus tissue. Although prior studies have shown larger tumour size to be correlated highly with renal sinus invasion, prospective data on evaluating pathological stage are limited. We evaluated a large series reported by one urological pathologist. METHODS AND RESULTS: Three hundred consecutive specimens were reviewed. Tumours larger than 5 cm were routinely sampled extensively or grossly re-reviewed when no extrarenal extension was identified on initial examination. Apparent multifocal disease was assessed critically for intravascular spread. Retrograde venous invasion was reported in 15 of 300 (5%) cases, 13 of 15 of which were clear cell RCC. Of a total of 163 specimens with clear cell histology, only five of 34 (15%) tumours 7 cm or larger were reported as pT2, all of which had an explanatory comment indicating the absence of definitive extrarenal spread. In contrast, 15 of 20 (75%) pT2 tumours were non-clear cell histology (papillary, chromophobe and translocation-associated). Comparing pT3a or higher tumours, the median tumour size in cases with retrograde venous invasion was 8.0 cm, compared to 6.2 cm in cases without retrograde venous invasion (P = 0.005). CONCLUSIONS: Our findings support that retrograde venous invasion should be considered carefully before diagnosing multifocal clear cell RCC, which is rare in the sporadic setting. In the absence of vascular invasion, multifocal clear cell papillary RCC can be a mimic. pT2 occurs more frequently with non-clear cell histology (particularly papillary or chromophobe RCC).

Renal cell tumors with clear cell histology and intact VHL and chromosome 3p: a histological review of tumors from the Cancer Genome Atlas database.

Clear cell renal cell carcinoma is by far the most common form of kidney cancer; however, a number of histologically similar tumors are now recognized and considered distinct entities. The Cancer Genome Atlas published data set was queried (http://cbioportal.org) for clear cell renal cell carcinoma tumors lacking VHL gene mutation and chromosome 3p loss, for which whole-slide images were reviewed. Of the 418 tumors in the published Cancer Genome Atlas clear cell renal cell carcinoma database, 387 had VHL mutation, copy number loss for chromosome 3p, or both (93%). Of the remaining, 27/31 had whole-slide images for review. One had 3p loss based on karyotype but not sequencing, and three demonstrated VHL promoter hypermethylation. Nine could be reclassified as distinct or emerging entities: translocation renal cell carcinoma (n=3), TCEB1 mutant renal cell carcinoma (n=3), papillary renal cell carcinoma (n=2), and clear cell papillary renal cell carcinoma (n=1). Of the remaining, 6 had other clear cell renal cell carcinoma-associated gene alterations (PBRM1, SMARCA4, BAP1, SETD2), leaving 11 specimens, including 2 high-grade or sarcomatoid renal cell carcinomas and 2 with prominent fibromuscular stroma (not TCEB1 mutant). One of the remaining tumors exhibited gain of chromosome 7 but lacked histological features of papillary renal cell carcinoma. Two tumors previously reported to harbor TFE3 gene fusions also exhibited VHL mutation, chromosome 3p loss, and morphology indistinguishable from clear cell renal cell carcinoma, the significance of which is uncertain. In summary, almost all clear cell renal cell carcinomas harbor VHL mutation, 3p copy number loss, or both. Of tumors with clear cell histology that lack these alterations, a subset can now be reclassified as other entities. Further study will determine whether additional entities exist, based on distinct genetic pathways that may have implications for treatment.

Urinary fistula after robot-assisted partial nephrectomy: a multicentre analysis of 1 791 patients.

OBJECTIVE: To evaluate the incidence of and risk factors for a urine leak in a large multicentre, prospective database of robot-assisted partial nephrectomy (RPN). PATIENTS AND METHODS: A database of 1 791 RPN from five USA centres was reviewed for urine leak as a complication of RPN. Patient and tumour characteristics were compared between patients with and those without postoperative urine leaks. Fisher's exact test was used for qualitative variables and Wilcoxon sum-rank tests were used for quantitative variables. A review of the literature on PN and urine leak was conducted. RESULTS: Urine leak was noted in 14/1 791 (0.78%) patients who underwent RPN. The mean (sd) nephrometry score of the entire cohort was 7.2 (1.9), and 8.0 (1.9) in patients who developed urine leak. The median (range) postoperative day of presentation was 13 (3-32) days. Patients with urine leak presented in delayed fashion with fever (two of the 14 patients, 14%), gastrointestinal complaints (four patients, 29%), and pain (five patients, 36%). Eight of the 14 patients (57%) required admission, while eight (57%) and nine (64%) had a drain or stent placed, respectively. Drains and stents were removed after a median (range) of 8 (4-13) days and 21 (8-83) days, respectively. Variables associated with urine leak included tumour size (P = 0.021), hilar location (P = 0.025), operative time (P = 0.006), warm ischaemia time (P = 0.005), and pelvicalyceal repair (P = 0.018). Upon literature review, the historical incidence of urine leak ranged from 1.0% to 17.4% for open PN and 1.6-16.5% for laparoscopic PN. CONCLUSION: The incidence of urine leak after RPN is very low and may be predicted by some preoperative factors, affording better patient counselling of risks. The low urinary leak rate may be attributed to the enhanced visualisation and suturing technique that accompanies the robotic approach.

Intermediate-term cancer control outcomes in prostate cancer patients treated with robotic-assisted laparoscopic radical prostatectomy: a multi-institutional analysis.

PURPOSE: Cancer control outcomes following robot-assisted radical prostatectomy (RARP) for prostate cancer (PCa) remain inadequately addressed over intermediate-term (≥5-year) follow-up. We examined biochemical recurrence-free survival (BCRFS), clinical recurrence-free survival (CRFS), and cancer-specific survival (CSS) in a multi-institutional cohort of men undergoing RARP for localized PCa. MATERIALS AND METHODS: A total of 5670 PCa patients undergoing RARP ± pelvic lymph node dissection as primary treatment modality at three tertiary care centers between 2001 and 2010 were analyzed. BCRFS, CRFS, and CSS were estimated using the Kaplan-Meier method. Cox proportional hazards model tested their association with available preoperative and postoperative parameters. RESULTS: 43.6 and 15.1 % of patients had D'Amico intermediate- and high-risk disease, respectively. Over a mean (median) follow-up of 56 (50.4) months, 797 men had a BCR, 78 men had CR, and 32 men died of PCa. Actuarial BCRFS, CRFS, and CSS, respectively, were 83.3, 98.6, and 99.5 % at 5-year; 76.5, 97.5, and 98.7 % at 8-year; and 73.3, 96.7, and 98.4 % at 10-year follow-ups. Only 1.7 % of patients received any adjuvant treatment. Preoperative prostate-specific antigen (PSA) and biopsy Gleason score (GS) were independent clinical predictors of BCRFS, CRFS, and CSS, while postoperatively positive surgical margin, pathological GS, pathological stage, and lymph node invasion were significantly associated with BCR and CR (all p < 0.05). CONCLUSIONS: Cancer control outcomes of RARP appear comparable to those reported for open and laparoscopic RP in previous literature, despite low overall rate of adjuvant treatment. Disease severity and preoperative PSA may aid in risk prognostication and defining postoperative follow-up protocols.

An evaluation of the timing of surgical complications following nephrectomy: data from the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP).

PURPOSE: The rates of complications following radical/partial nephrectomy (RN/PN) are well known; however, the data regarding timing are opaque. Accordingly, we sought to assess the median time-to-event for 19 principal postoperative complications within 30 days following surgery. METHODS: Patients undergoing RN/PN were identified within the American College of Surgeons National Surgical Quality Improvement Program database (2005-2011). Primary endpoint was time-to-complication. Secondary endpoints included length-of-stay (LOS), re-intervention, re-admission and 30-day mortality. Multivariable regression models assessed the predictors for pre-/post-discharge complications and the effect of time-to-complication on secondary outcomes. RESULTS: Overall, 3820 patients underwent nephrectomy (RN = 63.6 %). The overall complication rate was 16.8 %, and the median LOS was 4 days. The majority of major complications (88.1 %), including bleeding/transfusion, renal, septic, deep venous thrombosis or pulmonary embolism, pulmonary, cardiac and neurologic, occurred prior to discharge. Conversely, the relatively minor complications, including wound and urinary tract infections, occurred predominantly post-discharge (70.7 %). The median time to major complications was 3 versus 13 days for minor complications. In multivariable analyses, age [odds ratio (OR) 1.02, p < 0.001], American Society of Anesthesiologists score ≥ 2 (p < 0.01) and PN (p < 0.001) were predictors of pre-discharge complications, while female gender (OR 1.67, p < 0.001), hypertension (OR 1.28, p = 0.007) and diabetes (OR 1.48, p < 0.001) were predictors of post-discharge complications. Creatinine ≥ 1.2 mg/dl and hematocrit < 30 increased (p < 0.01), whereas a minimally invasive approach decreased the odds (p < 0.05) for both pre-/post-discharge complications. For a given complication, time-to-complication did not affect the odds for mortality (p = 0.343) or re-intervention (p = 0.872). CONCLUSIONS: Approximately one in six patients suffers a complication following RN/PN; major complications tend to occur early with the majority occurring pre-discharge. Knowledge regarding the timing and risk factors for complications may facilitate improved patient-physician communication, both at admission and at discharge.