Predictive value of kallikrein forms and ß-microseminoprotein in blood from patients with evidence of detectable levels of PSA after radical prostatectomy.

PURPOSE: To determine whether ß-microseminoprotein or any of the kallikrein forms in blood-free, total or intact PSA or total hK2-predict metastasis in patients with evidence of detectable levels of PSA in blood after radical prostatectomy. METHOD: We determined marker concentrations in blood from 173 men treated with radical prostatectomy and evidence of detectable levels of PSA in the blood (PSA ≥ 0.05) after surgery between 2014 and 2015 and at least 1 year after any adjuvant therapy. We used Cox regression to determine whether any marker was associated with metastasis using both univariate and multivariable models that included standard clinical predictors. RESULTS: Overall, 42 patients had metastasis, with a median follow-up of 67 months among patients without an event. The levels of intact and free PSA and free-to-total PSA ratio were significantly associated with metastasis. Discrimination was highest for free PSA (c-index: 0.645) and free-to-total PSA ratio (0.625). Only free-to-total PSA ratio remained associated with overall metastasis (either regional or distant) after including standard clinical predictors (p = 0.025) and increased discrimination from 0.686 to 0.697. Similar results were found using distant metastasis as an outcome (p = 0.011; c-index increased from 0.658 to 0.723). CONCLUSION: Our results provide evidence that free-to-total PSA ratio can risk stratifying patients with evidence of detectable levels of PSA in blood after RP. Further research is warranted on the biology of prostate cancer markers in patients with evidence of detectable levels of PSA in blood after radical prostatectomy. Our findings on the free-to-total ratio for predicting adverse oncologic outcomes need to be validated in other cohorts.

The effect of the da Vinci® Vessel Sealer on robot-assisted laparoscopic prostatectomy complications.

The da Vinci® Vessel Sealer is a major contributor to the total cost of robot-assisted laparoscopic prostatectomy (RALP). We aimed to assess whether the use of the Vessel Sealer is associated with better surgical outcomes in a population of patients that underwent RALP with lymphadenectomy. We tested whether the use of the Vessel Sealer is associated with the development of lymphocele and/or other surgical outcomes. Most surgeons used the Vessel Sealer in almost all or almost no patients. Thus, to avoid the potential confounding variable of surgeon skill, we performed the initial analyses using data from a single surgeon who changed practice over time, and then using the entire population. Overall, the Vessel Sealer was used in 500 (36%) RALPs. Surgeon 1 performed 492 surgeries, and used the Vessel Sealer in 191 (39%). The Vessel Sealer was not associated with better surgical outcomes in patients operated on by Surgeon 1. The odds ratio for development of lymphocele was 1.95 (95% confidence interval [CI] 0.57-6.75). In the entire population, use of the sealer was significantly associated with a very small reduction of blood loss (22 cc, CI 13-30) but with a 32-min increase in the operating room time (CI 26-37). Use of the Vessel Sealer will have, at best, a very small effect on RALP outcomes that is of highly questionable relevance given its cost. In light of these results, the Vessel Sealer will only be used at our institution in the context of clinical trials.

Final Results of a Phase I Trial of WST-11 (TOOKAD Soluble) Vascular-targeted Photodynamic Therapy for Upper Tract Urothelial Carcinoma.

PURPOSE: Vascular-targeted photodynamic therapy with the intravascular photosensitizing agent padeliporfin (WST-11/TOOKAD-Soluble) has demonstrated therapeutic efficacy as an ablative treatment for localized cancer with potential adaptation for endoscopic management of upper tract urothelial carcinoma. This Phase I trial (NCT03617003) evaluated the safety of vascular-targeted photodynamic therapy with WST-11 in upper tract urothelial carcinoma. MATERIALS AND METHODS: Nineteen patients underwent up to 2 endoscopic vascular-targeted photodynamic therapy treatments, with follow-up for up to 6 months. Patients who had residual or recurrent upper tract urothelial carcinoma (any grade/size) failing prior endoscopic treatment or unable or unwilling to undergo surgical resection were eligible for inclusion. The primary endpoint was to identify the maximally tolerated dose of laser light fluence. A dose escalation model was employed, with increasing light fluence (100-200 mW/cm) using a modified continual reassessment method. The secondary endpoint was treatment efficacy, defined by absence of visible tumor and negative urine cytology 30 days posttreatment. RESULTS: Fourteen (74%) patients received the maximally tolerated dose of 200 mW/cm, 2 (11%) of whom experienced a dose-limiting toxicity. The initial 30-day treatment response rate was 94% (50% complete, 44% partial). Eight patients underwent a second treatment, with a final observed 68% complete response rate. Leading toxicities were flank pain (79%) and hematuria (84%), which were transient. No ureteral strictures associated with treatment were identified during follow-up. CONCLUSIONS: Vascular-targeted photodynamic therapy with WST-11 has an acceptable safety profile with strong potential as an effective, kidney-sparing endoscopic management option for upper tract urothelial carcinoma. The recently initiated multicenter Phase 3 ENLIGHTED trial (NCT04620239) is expected to provide further evidence on this therapy.

Multicenter Phase II Clinical Trial of Gemcitabine and Cisplatin as Neoadjuvant Chemotherapy for Patients With High-Grade Upper Tract Urothelial Carcinoma.

PURPOSE: Neoadjuvant chemotherapy (NAC) has proven survival benefits for patients with invasive urothelial carcinoma of the bladder, yet its role for upper tract urothelial carcinoma (UTUC) remains undefined. We conducted a multicenter, single-arm, phase II trial of NAC with gemcitabine and split-dose cisplatin (GC) for patients with high-risk UTUC before extirpative surgery to evaluate response, survival, and tolerability. METHODS: Eligible patients with defined criteria for high-risk localized UTUC received four cycles of split-dose GC before surgical resection and lymph node dissection. The primary study end point was rate of pathologic response (defined as < ypT2N0). Secondary end points included progression-free survival (PFS), overall survival (OS), and safety and tolerability. RESULTS: Among 57 patients evaluated, 36 (63%) demonstrated pathologic response (95% CI, 49 to 76). A complete pathologic response (ypT0N0) was noted in 11 patients (19%). Fifty-one patients (89%) tolerated at least three complete cycles of split-dose GC, 27 patients (47%) tolerated four complete cycles, and all patients proceeded to surgery. With a median follow up of 3.1 years, 2- and 5-year PFS rates were 89% (95% CI, 81 to 98) and 72% (95% CI, 59 to 87), while 2- and 5-year OS rates were 93% (95% CI, 86 to 100) and 79% (95% CI, 67 to 94), respectively. Pathologic complete and partial responses were associated with improved PFS and OS compared with nonresponders (≥ ypT2N any; 2-year PFS 100% and 95% v 76%, P < .001; 2-year OS 100% and 100% v 80%, P < .001). CONCLUSION: NAC with split-dose GC for high-risk UTUC is a well-tolerated, effective therapy demonstrating evidence of pathologic response that is associated with favorable survival outcomes. Given that these survival outcomes are superior to historical series, these data support the use of NAC as a standard of care for high-risk UTUC, and split-dose GC is a viable option for NAC.

Outcomes of Grade Group 2 and 3 Prostate Cancer on Initial Versus Confirmatory Biopsy: Implications for Active Surveillance.

BACKGROUND: Active surveillance (AS) is recommended as the preferred treatment for men with low-risk disease. In order to optimize risk stratification and exclude undiagnosed higher-grade disease, most AS protocols recommend a confirmatory biopsy. OBJECTIVE: We aimed to compare outcomes among men with grade group (GG) 2/3 prostate cancer on initial biopsy with those among men whose disease was initially GG1 but was upgraded to GG2/3 on confirmatory biopsy. DESIGN, SETTING, AND PARTICIPANTS: We reviewed patients undergoing radical prostatectomy (RP) in two cohorts: "immediate RP group," with GG2/3 cancer on diagnostic biopsy, and "AS group," with GG1 cancer on initial biopsy that was upgraded to GG2/3 on confirmatory biopsy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Probabilities of biochemical recurrence (BCR) and salvage therapy were determined using multivariable Cox regression models with risk adjustment. Risks of adverse pathology at RP were also compared using logistic regression. RESULTS AND LIMITATIONS: The immediate RP group comprised 4009 patients and the AS group comprised 321 patients. The AS group had lower adjusted rates of adverse pathology (27% vs 35%, p = 0.003). BCR rates were lower in the AS group, although this did not reach conventional significance (hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.50-1.06, p = 0.10) compared with the immediate RP group. Risk-adjusted 1- and 5-yr BCR rates were 4.6% (95% CI 3.0-6.5%) and 10.4% (95% CI 6.9-14%), respectively, for the AS group compared with 6.3% (95% CI 5.6-7.0%) and 20% (95% CI 19-22%), respectively, in the immediate RP group. A nonsignificant association was observed for salvage treatment-free survival favoring the AS group (HR 0.67, 95% CI 0.42, 1.06, p = 0.087). CONCLUSIONS: We found that men with GG1 cancer who were upgraded on confirmatory biopsy tend to have less aggressive disease than men with the same grade found at initial biopsy. These results must be confirmed in larger series before recommendations can be made regarding a more conservative approach in men with upgraded pathology on surveillance biopsy. PATIENT SUMMARY: We studied men with low-risk prostate cancer who were initially eligible for active surveillance but presented with more aggressive cancer on confirmatory biopsy. We found that outcomes for these men were better than the outcomes for those diagnosed initially with more serious cancer.

Estimating patient health in prostate cancer treatment counseling.

BACKGROUND: We assessed the concordance among urologists' judgment of health quartiles for patients with localized prostate cancer, and compared the life expectancy (LE) and ensuing treatment recommendations when following National Comprehensive Cancer Network (NCCN) guidelines based on actuarial life tables versus the Kent model, a validated LE prediction model. METHODS: NCCN suggests using actuarial life tables and relying on surgeon assessment of patient health to increase (for the best quartile) or decrease (for the worst quartile) LE by 50%. Eleven urologic surgeons allocated quartile of health and recommended treatments for ten patient vignettes. The 10-year survival probability was calculated using the Kent model and compared to the life-table estimate based on health quartile by surgeon consensus. RESULTS: Surgeon assessment agreed with the presumed true quartile of health based on a validated model in 41% of cases. For no case did three-quarters of surgeons assign health quartile correctly; in half of cases, <50% of surgeons assigned the correct quartile. The NCCN comorbidity-adjusted LE estimates underestimated risk of death in the best health quartile and overestimated risk of death in the worst health quartile, compared to the Kent model. Patients with LE > 10 years on NCCN estimation were recommended more frequently for surgery (81%) and those with ≤10 years estimated LE were more commonly recommended for radiation (57%) or observation (29%). CONCLUSIONS: A method based on physician-assessed health quartiles for LE estimation, as suggested by the NCCN guidelines, appears too crude to be used in the treatment counseling of men with localized prostate cancer, as compared to a validated prediction model, such as the Kent model.

Relationship Between Age, Comorbidity, and the Prevalence of Erectile Dysfunction.

BACKGROUND: Erectile dysfunction (ED) increases with age. Remarkably, the relationship between age and the risk of ED has only been described in crude categories, such as risk for men aged 50-59 yr, without taking comorbidities into account. OBJECTIVE: To understand how the risk of patient-reported ED varies according to age and comorbidity status. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study included a cohort of 17 250 patients with prostate cancer who completed the International Index of Erectile Function erectile function domain (IIEF-EF) questionnaire before any prostate treatment. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We created a logistic regression model to predict the probability of ED using age and comorbidities such as cardiovascular disease, diabetes, and hypertension as predictors. We used age as a nonlinear term to allow a curvilinear relationship between age and ED. RESULTS AND LIMITATIONS: The prevalence of patient-reported ED among men without any comorbidities increased from 10% to 79% from the age of 40 and 80 yr. The risk of ED increased sharply with comorbidity: the probability of ED for 50- and 75-yr-old individuals was 20% and 68% for healthy men, but 41% and 85% for those with hypertension, obesity, and diabetes. Men with several comorbidities have the same risk of ED as that of healthy men 15-25 yr older. Limitations include a healthier-than-average patient group and lack of information about some comorbidities and the severity of comorbidities. CONCLUSIONS: Our results allow us to better understand how the risk of ED changes with age and comorbidities. Further research should evaluate the impact of other risk factors not considered in the present study and should take risk factor severity into account. PATIENT SUMMARY: Our study shows how the probability of erectile dysfunction (ED) changes with increasing age, analyzed alone and when taking into account the presence of other risk factors for this condition (eg, diabetes, high blood pressure, and cardiovascular disease). Our results help in better understanding the probability of ED for men with and without comorbidities.

Predictors of Worsening Erectile Function in Men with Functional Erections Early After Radical Prostatectomy.

BACKGROUND: Prior studies suggest that men with good erectile function shortly after radical prostatectomy (RP) can subsequently have worsened erectile function. AIM: To determine the prevalence and predictors of early erectile function recovery post-RP and of worsening erectile function after initial erectile function recovery. METHODS: We retrospectively queried our institutional database. Men who underwent RP during 2008-2017 and who completed the International Index of Erectile Function erectile function domain both pre-RP and serially post-RP, constituted the population. Functional erections were defined as International Index of Erectile Function (IIEF)-6 erectile function domain scores ≥24. We analyzed factors predicting functional erections at 3 months post-RP as well as factors predicting a decrease in functional erections between 3 and 6 months, defined as ≥2-point drop in the erectile function domain. Multivariable logistic regression models were used to identify predictors of early erectile function recovery and also of subsequent decline. OUTCOMES: Erectile function recovery rates at 3 months post-RP and predictive factors; rates of erectile function decline between 3-6 months and associated predictors. RESULTS: Eligible patients comprised 1,655 men with median age of 62 (IQR 57, 67) years. Bilateral nerve-sparing (NS) surgery was performed in 71% of men, unilateral NS in 19%, and no NS in 10%. Of this population, 224 men (14%; 95% CI 12%, 15%) had functional erections at 3 months post-RP. On multivariable analysis, significant predictors of early erectile function recovery included: younger age (OR 0.93, P < .001), higher baseline erectile function domain score (OR 1.14, P < .001) and bilateral NS (OR 3.81, P = .002). The presence of diabetes (OR 0.43, P = .028) and a former smoking history (OR 0.63, P = .008; reference group: never smoker) was associated with the erectile dysfunction at 3 months post-RP. Of the men with early functional erections, 41% (95% CI 33%, 48%) had a ≥ 2-point decline in erectile function between 3 and 6 months. No factors were identified as predictors for this decline. CLINICAL IMPLICATIONS: Only a small proportion of men have functional erections at 3 months post-RP and a notable number of them will experience a decline in erectile function between 3 and 6 months. STRENGTHS AND LIMITATIONS: Strengths: large patient population and the use of validated questionnaire. LIMITATIONS: single-center retrospective study. CONCLUSION: A minority of men had functional erections 3 months post-RP, about half of whom had a decline in erectile function by month 6. We recommend appropriately counseling post-RP patients on the risk of such a decline in erectile function. Salter CA, Tin AL, Bernie HL, et al. Predictors of Worsening Erectile Function in Men with Functional Erections Early After Radical Prostatectomy. J Sex Med 2022;19:1790-1796.

Urethral Melanoma - Clinical, Pathological and Molecular Characteristics.

BACKGROUND: Mucosal melanoma involving the urethra is a rare disease with distinct clinical and molecular characteristics and poor outcomes. Our current knowledge is limited by the small number of reports regarding this disease. OBJECTIVE: To describe the clinical, pathological, and molecular characteristics of urethral melanoma. METHODS: We summarized the clinicopathologic data for 31 patients treated for urethral melanoma from 1986-2017 at our institution. Genomic data from our institutional sequencing platform MSK-IMPACT (n = 5) and gene-specific PCR data on BRAF, KIT, and/or NRAS (n = 8) were compared to genomic data of cutaneous melanomas (n = 143), vulvar/vaginal melanomas (n = 24), and primary non-melanoma urethral tumors (n = 5) from our institutional database. RESULTS: Twenty-three patients were diagnosed with localized disease, 7 had regional/nodal involvement and one had metastases. Initial treatment included surgery in 25 patients; seven had multimodal treatment. Median follow-up was 46 months (IQR 33-123). Estimated 5-year cancer-specific survival was 45%. No significant change in survival was observed based on a year of treatment.Primary urethral melanomas showed a higher frequency of TP53 mutations compared to cutaneous (80.0% vs. 18.2%, p = 0.006) and vulvar/vaginal melanomas (80.0 vs. 25.0%, p = 0.04). BRAF mutations were absent in urethral primaries (0% vs. 46% in cutaneous melanoma, p = 0.02). Tumor mutation burden was higher in cutaneous than urethral melanomas (p = 0.04). Urethral melanomas had a higher number of somatic alterations compared to non-melanoma urethral tumors (median 11 vs. 5, p = 0.03). CONCLUSIONS: Our findings support a unique mutational landscape of urethral melanoma compared to cutaneous melanoma. Survival remains poor and is unchanged over the time studied.

Uretero-enteric stricture outcomes: secondary analysis of a randomised controlled trial comparing open versus robot-assisted radical cystectomy.

OBJECTIVES: To analyse the risk of uretero-enteric anastomotic stricture in patients randomised to open (ORC) or robot-assisted radical cystectomy (RARC) with extracorporeal urinary diversion. PATIENTS AND METHODS: We included 118 patients randomised to RARC (n = 60) or ORC (n = 58) at a single, high-volume institution from March 2010 to April 2013. Urinary diversion was performed by experienced open surgeons. Stricture was defined as non-malignant obstruction on imaging, corroborated by clinical status, and requiring procedural intervention. The risk of stricture within 1 year was compared between groups using Fisher's exact test. RESULTS: In all, 58 and 60 patients were randomised to RARC and ORC, respectively. We identified five strictures, all in the ORC group. In patients with ≥1 year of follow-up, the increase in risk of stricture from open surgery was 9.3% (95% confidence interval 1.5%, 17%). Of the five strictures, three were managed endoscopically while two required open revision. There was no evidence that perioperative Grade 3-5 complications were associated with development of a stricture (P = 1) and no evidence of a difference in 24-month estimated glomerular filtration rate between arms (P = 0.15). CONCLUSIONS: In this study at a high-volume centre, RARC with extracorporeal urinary diversion achieved excellent ureteric anastomotic outcomes. Purported increased risk of stricture is not a reason to avoid RARC. Future research should examine the impact of different surgical techniques and operator experience on the risk of stricture, especially as more intracorporeal diversions are performed.

Oncologic Outcomes of Total Length Gleason Pattern 4 on Biopsy in Men with Grade Group 2 Prostate Cancer.

PURPOSE: Gleason Score 7 prostate cancer comprises a wide spectrum of disease risk, and precise substratification is paramount. Our group previously demonstrated that the total length of Gleason pattern (GP) 4 is a better predictor than %GP4 for adverse pathological outcomes at radical prostatectomy. We aimed to determine the association of GP4 length on prostate biopsy with post-prostatectomy oncologic outcomes. MATERIALS AND METHODS: We compared 4 GP4 quantification methods-including maximum %GP4 in any single core, overall %GP4, total length GP4 (mm) across all cores and length GP4 (mm) in the highest volume core-for prediction of biochemical recurrence-free survival after radical prostatectomy using multivariable Cox proportional hazards regression. RESULTS: A total of 457 men with grade group 2 prostate cancer on biopsy subsequently underwent radical prostatectomy. The 3-year biochemical recurrence-free survival probability was 85% (95% CI 81-88). On multivariable analysis, all 4 GP4 quantification methods were associated with biochemical recurrence-maximum %GP4 (HR=1.30; 95% CI 1.07-1.59; p=0.009), overall %GP4 (HR=1.61; 95% CI 1.21-2.15; p=0.001), total length GP4 (HR=2.48; 95% CI 1.36-4.52; p=0.003) and length GP4 in highest core (HR=1.32; 95% CI 1.11-1.57; p=0.001). However, we were unable to identify differences between methods of quantification with a relatively low event rate. CONCLUSIONS: These findings support further studies on GP4 quantification in addition to the ratio of GP3 and GP4 to classify prostate cancer risk. Research should also be conducted on whether GP4 quantification could provide a surrogate endpoint for disease progression for trials in active surveillance.

Feasibility of a geriatric comanagement (GERICO) pilot program for patients 75 and older undergoing radical cystectomy.

BACKGROUND: Retrospective studies have shown the beneficial impact of geriatric comanagement (GERICO) on perioperative outcomes of older adults with cancer. We prospectively assessed the feasibility of perioperative GERICO for older adults with bladder cancer undergoing radical cystectomy. METHODS: We conducted a pilot study wherein all patients 75 years and older undergoing radical cystectomy between October 2019 and November 2020 were referred to the Geriatric Service preoperatively. Feasibility was defined according to the percentage of patients who received preoperative evaluation by the Geriatrics Service, who were followed for more than 80% of their inpatient days and who had their surgery rescheduled for logistical reasons. Urology advanced practice provider (APP) satisfaction with the program was measured via an 11-item survey. RESULTS: Sixty-six eligible patients underwent radical cystectomy in the stated time frame; 59 (89%; 95% confidence interval [CI], 79-97%) were referred to the Geriatric Service for evaluation. The median age of patients who had geriatric comanagement was 79 years; 40 (68%) were male. Forty-one patients (69%) were visited on at least 80% of the days in which they were not in the intensive care unit. No surgeries were rescheduled for logistical reasons. Nine of the 12 urology APPs (75%) responded to the survey; all nine "somewhat" or "strongly" agreed with statements indicating satisfaction with the program. CONCLUSION: Despite the challenges of the COVID-19 pandemic, we showed that perioperative GERICO is feasible. Fully powered prospective randomized controlled trials should be conducted to assess GERICO's impact on perioperative outcomes of older adults with cancer.

Prevalence of High-Risk Prostate Cancer Metastasis to Cloquet's Ilioinguinal Lymph Node.

PURPOSE: Cloquet's node, located at the junction between the deep inguinal nodes and the external iliac chain, is easily accessible and commonly excised during pelvic lymph node dissection for prostate cancer. However, we hypothesize that Cloquet's node is not part of lymphatic metastatic spread of prostate cancer. MATERIALS AND METHODS: Between September 2016 and June 2019, 105 consecutive patients with high-risk prostate cancer (cT3a or Grade Group 4/5, or prostate specific antigen >20 ng/ml) underwent a laparoscopic radical prostatectomy and pelvic lymph node dissection. First, Cloquet's node was identified, retrieved and submitted separately to pathology as right and left Cloquet's node. Next, a pelvic lymph node dissection was completed including the external iliac, obturator fossa and hypogastric nodal packets. Each lymph node was cut into 3 mm slices which were separately embedded in paraffin, stained with hematoxylin and eosin, and examined microscopically. RESULTS: The final analysis included 95 patients. In this high-risk population, the median number of nodes removed was 22 (IQR 18-29); 39/95 patients (41%) had lymph node metastasis. The median number of Cloquet's nodes removed was 2 (IQR 2-3). Cloquet's node was negative in all but 1 patient (1.1%), who had very high-risk features and high metastatic burden in the lymph nodes. CONCLUSIONS: In high-risk prostate cancer, metastasis to the ilioinguinal node of Cloquet is rare. Given this low prevalence, Cloquet's node can be safely excluded from the pelvic lymph node dissection template.

The association between modifiable perioperative parameters and renal function after nephrectomy.

OBJECTIVE: To evaluate the association between intraoperative anaesthetic parameters, primarily intraoperative hypotension, and postoperative renal function in patients undergoing nephrectomy. PATIENTS AND METHODS: We reviewed data from 3240 consecutive patients who underwent nephrectomy between 2010 and 2018. Anaesthetic parameters evaluated included duration of hypotension, tachycardia, hypothermia, volatile anaesthetic use and mean arterial pressure in the post-anaesthesia care unit. Outcomes included acute kidney injury (AKI) and estimated glomerular filtration rate (eGFR) within the first year after nephrectomy. Associations between anaesthetic parameters and outcomes were evaluated with multivariable logistic regression and generalised estimating equation, respectively, adjusted for predictors of renal function after nephrectomy. RESULTS: Before nephrectomy, 677 (21%) patients had moderate-severe chronic kidney disease. A quarter of patients (n = 809) had postoperative AKI and 35% (n = 746) had Stage ≥3 chronic kidney disease 12-months after surgery. Only 12% of patients (n = 386) had >5 min of intraoperative hypotension. While not statistically significant, longer duration of intraoperative hypotension was associated with slightly higher rates of AKI (odds ratio [OR] per 10-min 1.14, 95% confidence interval [CI] 0.98, 1.32). Prolonged hypothermia was associated with increased rate of AKI (OR per 10-min 1.02, 95% CI 1.00, 1.04), and decreased eGFR (change in eGFR per 10-min -0.19, 95% CI -0.27, -0.12); however, these results have limited clinical significance. CONCLUSIONS: Under current practice, intraoperative anaesthetic parameters are tightly maintained, restricting the significance of their effect on postoperative renal function. Future studies should evaluate whether haemodynamic parameters during the early postoperative period, when they are monitored less frequently, are associated with renal functional outcome.

Somatic mutations as preoperative predictors of metastases in patients with localized clear cell renal cell carcinoma - An exploratory analysis.

OBJECTIVE: Recurrent genomic alterations in clear cell renal cell carcinoma (ccRCC) have been associated with treatment outcomes; however, current preoperative predictive models do not include known genetic predictors. We aimed to explore the value of common somatic mutations in the preoperative prediction of metastatic disease among patients treated for localized ccRCC. MATERIALS AND METHODS: After obtaining institutional review board approval, data of 254 patients with localized ccRCC treated between 2005 and 2015 who underwent genetic sequencing was collected. The mutation status of VHL, PBRM1, SETD2, BAP1 and KDM5C were evaluated in the nephrectomy tumor specimen, which served as a proxy for biopsy mutation status. The Raj et al. preoperative nomogram was used to predict the 12-year metastatic free probability (MFP). The study outcome was MFP; the relationship between MFP and mutation status was evaluated with Cox-regression models adjusting for the preoperative nomogram variables (age, gender, incidental presentation, lymphadenopathy, necrosis, and size). RESULTS: The study cohort included 188 males (74%) and 66 females (26%) with a median age of 58 years. VHL mutations were present in 152/254 patients (60%), PBRM1 in 91/254 (36%), SETD2 in 32/254 (13%), BAP1 in 19/254 (8%), and KDM5C in 19/254 (8%). Median follow-up for survivors was 8.1 years. Estimated 12-year MFP was 70% (95% CI: 63%-75%). On univariable analysis SETD2 (HR: 3.30), BAP1 (HR: 2.44) and PBRM1 (HR: 1.78) were significantly associated with a higher risk of metastases. After adjusting for known preoperative predictors in the existing nomogram, SETD2 mutations remained associated with a higher rate of metastases after nephrectomy (HR: 2.09, 95% CI: 1.19-3.67, P = 0.011). CONCLUSION: In the current exploratory analysis, SETD2 mutations were significant predictors of MFP among patients treated for localized ccRCC. Our findings support future studies evaluating genetic alterations in preoperative renal biopsy samples as potential predictors of treatment outcome.

Outcomes of Ureteroneocystostomy in Patients With Cancer.

OBJECTIVE: To determine the durability of ureteroneocystostomy as well as pre- or post-operative factors that may be associated with failure to provide appropriate renal drainage. METHODS: A total of 290 patients who underwent ureteral reimplantation to native bladder between 2003 and 2015 were identified. After excluding pediatric patients and those without any follow-up, 255 patients, 3 of whom had a subsequent contralateral reimplantation were included, for 258 observations. Kaplan-Meier method and univariate Cox models were used to assess whether factors such as radiation, prior abdominal surgery, age at re-implantation, gender and BMI are associated with re-implantation failure. RESULTS: Among 258 observations, there were 27 failures. Median follow-up time was 1.1 years from re-implantation surgery among patients without a failure.1 and 5-year ureteral re-implantation failure is 7% (95% CI 4%, 12%) and 22% (95% CI 15%, 33%), respectively. On univariate analysis, post-operative radiation was found to be strongly associated with poorer ureteral re-implantation survival (HR: 6.62; CI 2.40, 18.29; P = .0003) No significant association between re-implantation failure-free survival and age at reimplantation, gender, BMI, previous abdominal surgery, preoperative radiation and adjuvant radiation was noted (all P > .4). CONCLUSIONS: Ureteroneocystotomy in the malignant setting has reasonable success rates through five years. No preoperative factors were associated with re-implantation failure. While all patients need to be followed due to increasing rates of failure with time, patients receiving palliative or salvage radiation therapy appear to be more prone to failure requiring further intervention.

Open partial nephrectomy with kidney split: Effective surgical approach to resect completely endophytic tumors.

OBJECTIVES: To review perioperative, renal functional, and oncological outcomes of the kidney split technique in performing partial nephrectomy (PN) to resect completely endophytic renal tumors. METHODS: All consecutive patients who underwent open PN with kidney split between 2015 and 2019 at our institution were included. In this approach the kidney is incised along Brodel's line in an avascular plane to locate and then resect the endophytic tumor. Clinicopathologic data, perioperative metrics, complications, renal function, recurrence, and mortality were analyzed using descriptive statistics. RESULTS: Forty-two open PN with kidney split were performed in 40 patients. No patients required conversion to radical nephrectomy. Most tumors were pT1a renal cell carcinoma (76%), with no recurrences or deaths after a median follow-up of 15 months. All patients had tumors of moderate or high complexity by R.E.N.A.L. nephrometry score. Median cold ischemia time, operative time, estimated blood loss, and inpatient length-of-stay were 34 minutes, 152 minutes, 225 ml, and 2 days, respectively. No patients experienced any Clavien-Dindo grade 4 or 5 complications. Postoperative estimated glomerular filtration rate (eGFR) at last follow-up was >30 ml/min/1.73m2 in all but one patient, and no patients required dialysis. CONCLUSIONS: The kidney split represents an effective PN technique to resect complex, endophytic renal tumors. In our experience, this technique affords acceptable perioperative outcomes, preserved renal function, and no short-term recurrences or mortality events. Our series highlights the importance of adapting classical surgical techniques, using cold ischemia, and relying on preoperative and intraoperative ultrasonography to effectively guide this complex kidney-sparing operation.

The Clinicopathologic and Molecular Landscape of Clear Cell Papillary Renal Cell Carcinoma: Implications in Diagnosis and Management.

BACKGROUND: Clear cell papillary renal cell carcinoma (CCPRCC) is a recently described tumor entity. Several questions remain about its epidemiology, molecular features, and clinical behavior. OBJECTIVE: To comprehensively evaluate clinicopathologic and molecular features of CCPRCC, and compare it with more common kidney cancer subtypes. DESIGN, SETTING, AND PARTICIPANTS: We identified 89 CCPRCC patients and compared their clinicopathologic features with 1120 localized clear cell renal cell carcinoma (ccRCC) and 129 type 1 papillary renal cell carcinoma (pRCC) patients. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Nonparametric statistical testing was used to compare relevant features between tumor types. Overall, cancer-specific survival (CSS) and metastasis-free survival estimates were calculated from initial diagnosis using the Kaplan-Meier method. Patients with ipsilateral multifocal disease were explored further. A subset of CCPRCC tumors underwent genomic analysis and were compared with other RCC subtypes. RESULTS AND LIMITATIONS: A higher proportion of female (45% vs 32%) and African-American (19% vs 3%) patients were observed in the CCPRCC cohort than in the ccRCC and pRCC cohorts. CCPRCC tumors also had increased odds of presenting with additional ipsilateral masses (odds ratio [OR]: 4.41 [confidence interval {CI}: 2.34, 8.15], p < 0.001) and bilateral disease (OR: 4.80 [CI: 2.40, 9.59], p < 0.001) compared with ccRCC tumors. On molecular analysis, CCPRCC tumors showed fewer somatic aberrations and a greater degree of mitochondrial DNA depletion. In multifocal CCPRCC tumors, histologic concordance among the different renal cell carcinoma masses was estimated at 44% (7/16), and none of the individuals presenting exclusively with CCPRCC tumors developed metastatic disease after 5 yr. In contrast, multifocal tumors with CCPRCC and other nonconcordant histologies were more likely to experience adverse outcomes (CSS, log rank p = 0.034). CONCLUSIONS: CCPRCC is characterized by distinct molecular and epidemiologic features that could be used to refine current diagnostic approaches. Although their clinical course is generally indolent, multifocal CCPRCC tumors represent a unique diagnostic challenge. In this context, single-mass biopsies could miss concomitant aggressive disease, with a potential negative impact on patient outcomes. Furthermore, high discordance rates in multifocal CCPRCC tumors have important clinical implications in management. PATIENT SUMMARY: We explored the molecular and clinical features of clear cell papillary renal cell carcinoma (CCPRCC) relative to other kidney cancer subtypes. While CCPRCC generally conveys a good prognosis, additional caution should be taken when it is diagnosed using biopsy if multiple kidney masses are present.

Primary urethral cancer: treatment patterns and associated outcomes.

OBJECTIVES: To evaluate treatment patterns and associated outcomes of patients with urethral cancer. PATIENTS AND METHODS: After obtaining institutional review board approval we identified 165 patients treated for primary urethral cancer between 1956 and 2017. Treatment included monotherapy (surgery or radiation), dual therapy (surgery+radiation, surgery+chemotherapy, or chemotherapy+radiation) or triple therapy (surgery+radiation+chemotherapy). Rates of different treatments were described by treatment year. The association between treatment type and outcomes was evaluated with multivariable Cox regression models, adjusting for disease characteristics. RESULTS: The study cohort included 74 men and 91 women, with a median age of 61 years. Common histologies were squamous cell (36%), urothelial (27%) and adenocarcinoma (25%). At presentation, 72% of patients had invasive disease, 24% had nodal involvement, and 5% had metastases. Treatment included monotherapy (57%), dual therapy (21%), and triple therapy (10%). The use of monotherapy decreased over time, while rates of dual therapy remained consistent, and rates of triple therapy increased. The median follow-up was 4.7 years. Estimated 5-year local recurrence-free, disease-specific and overall survival were 51%, 48% and 41%, respectively. Monotherapy was associated with decreased local recurrence-free survival after adjusting for stage, histology, sex and year of treatment (P = 0.017). There was no evidence that treatment type was associated with distant recurrence, cancer-specific or overall survival. CONCLUSIONS: We found preliminary evidence that multimodal therapy, more commonly used in recent years, was of benefit in patients with primary urethral cancer. This finding should be confirmed in further studies involving multiple centres because of the low incidence of the disease.