Utility of Pelvic CT for Surveillance of T2-T4 Renal Cell Carcinoma After Nephrectomy With Curative Intent.

OBJECTIVE: The purpose of this study was to determine whether routine pelvic imaging is necessary during postoperative surveillance of pathologic T2-T4 renal cell carcinoma after nephrectomy for curative intent. MATERIALS AND METHODS: A retrospective single-institution cohort study with 603 subjects undergoing partial or radical nephrectomy of T2-T4 renal cell carcinoma with curative intent was conducted from January 1, 2000, through December 31, 2015. Clinical and imaging (CT or MRI) follow-up findings were evaluated in a prospectively maintained registry to determine the timing and location of recurrent and metastatic disease. The primary outcome was the proportion of subjects with positive or equivocal findings in the pelvis and negative findings in the chest and abdomen. Binomial CIs were calculated and compared with a prespecified minimum detection threshold of 5%. RESULTS: The T category distribution was as follows: T2 (28.9% [174/603]), T3 (70.3% [424/603]), and T4 (0.8% [5/603]). Most (81.8% [493/603]) of the patients underwent radical nephrectomy, and 27.0% (163/603) had recurrence or metastasis (mean time to first recurrence, 600 ± 695 days). Pelvic imaging findings were negative in 97.0% (585/603) of cases. Four subjects (0.7% [95% CI, 0.2-1.7%]) had isolated positive findings in the pelvis (p < 0.0001 vs the 5% threshold). Two (0.3% overall [95% CI, 0.04-1.1%]) of these positive findings were in subjects who did not have symptoms. CONCLUSION: Routine pelvic imaging of patients undergoing surveillance for asymptomatic T2-T4 renal cell carcinoma after nephrectomy performed with curative intent has minimal value and probably should not be performed.

Effect of Intravesical Instillation of Gemcitabine vs Saline Immediately Following Resection of Suspected Low-Grade Non-Muscle-Invasive Bladder Cancer on Tumor Recurrence: SWOG S0337 Randomized Clinical Trial.

Importance: Low-grade non-muscle-invasive urothelial cancer frequently recurs after excision by transurethral resection of bladder tumor (TURBT). Objective: To determine whether immediate post-TURBT intravesical instillation of gemcitabine reduces recurrence of suspected low-grade non-muscle-invasive urothelial cancer compared with saline. Design, Setting, and Participants: Randomized double-blind clinical trial conducted at 23 US centers. Patients with suspected low-grade non-muscle-invasive urothelial cancer based on cystoscopic appearance without any high-grade or without more than 2 low-grade urothelial cancer episodes within 18 months before index TURBT were enrolled between January 23, 2008, and August 14, 2012, and followed up every 3 months with cystoscopy and cytology for 2 years and then semiannually for 2 years. Patients were monitored for tumor recurrence, progression to muscle invasion, survival, and toxic effects. The final date of follow-up was August 14, 2016. Interventions: Participants were randomly assigned to receive intravesical instillation of gemcitabine (2 g in 100 mL of saline) (n = 201) or saline (100 mL) (n = 205) for 1 hour immediately following TURBT. Main Outcomes and Measures: The primary outcome was time to recurrence of cancer. Secondary end points were time to muscle invasion and death due to any cause. Results: Among 406 randomized eligible patients (median age, 66 years; 84.7% men), 383 completed the trial. In the intention-to-treat analysis, 67 of 201 patients (4-year estimate, 35%) in the gemcitabine group and 91 of 205 patients (4-year estimate, 47%) in the saline group had cancer recurrence within 4.0 years (hazard ratio, 0.66; 95% CI, 0.48-0.90; P<.001 by 1-sided log-rank test for time to recurrence). Among the 215 patients with low-grade non-muscle-invasive urothelial cancer who underwent TURBT and drug instillation, 34 of 102 patients (4-year estimate, 34%) in the gemcitabine group and 59 of 113 patients (4-year estimate, 54%) in the saline group had cancer recurrence (hazard ratio, 0.53; 95% CI, 0.35-0.81; P = .001 by 1-sided log-rank test for time to recurrence). Fifteen patients had tumors that progressed to muscle invasion (5 in the gemcitabine group and 10 in the saline group; P = .22 by 1-sided log-rank test) and 42 died of any cause (17 in the gemcitabine group and 25 in the saline group; P = .12 by 1-sided log-rank test). There were no grade 4 or 5 adverse events and no significant differences in adverse events of grade 3 or lower. Conclusions and Relevance: Among patients with suspected low-grade non-muscle-invasive urothelial cancer, immediate postresection intravesical instillation of gemcitabine, compared with instillation of saline, significantly reduced the risk of recurrence over a median of 4.0 years. These findings support using this therapy, but further research is needed to compare gemcitabine with other intravesical agents. Trial Registration: clinicaltrials.gov Identifier: NCT00445601.

Age, Gender and R.E.N.A.L. Nephrometry Score do not Improve the Accuracy of a Risk Stratification Algorithm Based on Biopsy and Mass Size for Assigning Surveillance versus Treatment of Renal Tumors.

PURPOSE: A previously published risk stratification algorithm based on renal mass biopsy and radiographic mass size was useful to designate surveillance vs the need for immediate treatment of small renal masses. Nonetheless, there were some incorrect assignments, most notably when renal mass biopsy indicated low risk malignancy but final pathology revealed high risk malignancy. We studied other factors that might improve the accuracy of this algorithm. MATERIALS AND METHODS: For 202 clinically localized small renal masses in a total of 200 patients with available R.E.N.A.L. (radius, exophytic/endophytic, nearness of tumor to collecting system or sinus, anterior/posterior, hilar tumor touching main renal artery or vein and location relative to polar lines) nephrometry score, preoperative renal mass biopsy and final pathology we assessed the accuracy of management assignment (surveillance vs treatment) based on the previously published risk stratification algorithm as confirmed by final pathology. Logistic regression was used to determine whether other factors (age, gender, R.E.N.A.L. score, R.E.N.A.L. score components and nomograms based on R.E.N.A.L. score) could improve assignment. RESULTS: Of the 202 small renal masses 53 (26%) were assigned to surveillance and 149 (74%) were assigned to treatment by the risk stratification algorithm. Of the 53 lesions assigned to surveillance 25 (47%) had benign/favorable renal mass biopsy histology while in 28 (53%) intermediate renal mass biopsy histology showed a mass size less than 2 cm. Nine of these 53 masses (17%) were incorrectly assigned to surveillance in that final pathology indicated the need for treatment (ie intermediate histology and a mass greater than 2 cm or unfavorable histology). Final pathology confirmed a correct assignment in all 149 masses assigned to treatment. None of the additional parameters assessed improved assignment with statistical significance. CONCLUSIONS: Age, gender, R.E.N.A.L. nephrometry score, R.E.N.A.L. score components and nomograms or combinations of these factors do not improve the predictive performance of a small renal mass management risk stratification algorithm based on renal mass biopsy and radiographic mass size.

Patient-Reported Convalescence and Quality of Life Recovery: A Comparison of Open and Robotic-Assisted Radical Cystectomy.

Background Robotic-assisted radical cystectomy (RARC) is gaining traction as a surgical approach, but there are limited data on patient-reported outcomes for this technique compared to open radical cystectomy (ORC). Objective To compare health-related quality of life (HRQoL) and short-term convalescence among bladder cancer patients who underwent ORC and RARC. Methods Review of a single-institution bladder cancer database was conducted. Baseline and postoperative HRQoL was evaluated using the Bladder Cancer Index (BCI) for 324 patients who had ORC (n = 267) or RARC (n = 57) between 2008 and 2012. The BCI assesses function and bother in urinary, bowel, and sexual domains. Among 87 distinct patients (ORC n = 67, RARC n = 20), we also evaluated short-term postoperative convalescence using the Convalescence and Recovery Evaluation (CARE) questionnaire. Our primary outcomes were HRQoL within 12 months and short-term convalescence within 6 weeks following cystectomy. We fit generalized estimating equation regression models to estimate longitudinal changes in BCI scores within domains, and CARE domain score differences were tested with Wilcoxon rank-sum tests. Results Clinical characteristics and baseline BCI/CARE scores were similar between the 2 groups (all P > .05). Within 1 year after surgery, recovery of HRQoL across all BCI domains was comparable, with scores nearly returning to baseline at 1 year for all patients. CARE scores at 4 weeks revealed that patients treated with ORC had better pain (29.1 vs 20.0, P = .02) domain scores compared to RARC. These differences abated by week 6. Conclusions HRQoL recovery and short-term convalescence were similar in this cohort following ORC and RARC.

Prostate capsule sparing versus nerve sparing radical cystectomy for bladder cancer: results of a randomized, controlled trial.

PURPOSE: Prostate capsule sparing and nerve sparing cystectomies are alternative procedures for bladder cancer that may decrease morbidity while achieving cancer control. However, to our knowledge the comparative effectiveness of these approaches has not been established. We evaluated functional and oncologic outcomes in patients undergoing these procedures. MATERIALS AND METHODS: We performed a single institution trial in patients with bladder cancer in whom transurethral prostatic urethral biopsy and transrectal prostate biopsy were negative. Men were randomized to prostate capsule sparing or nerve sparing cystectomy with neobladder creation and stratified by Sexual Health Inventory for Men score (greater than 21 vs 21 or less). Our primary end point was 12-month overall urinary function as measured by Bladder Cancer Index. Secondary end points included sexual function, cancer control and complications. RESULTS: A total of 40 patients were enrolled in the study with 20 patients in each arm. Urinary function at 12 months decreased by 13 and 28 points in the prostate capsule and nerve sparing groups, respectively (p = 0.10). Sexual function followed a similar pattern (p = 0.06). There was no difference in recurrence-free, metastasis-free or overall survival (each p >0.05). The rate of incidentally detected prostate cancer was similar (p = 0.15). CONCLUSIONS: Our study provides a randomized comparison of prostate capsule sparing and nerve sparing cystectomy techniques. We found no difference in functional or oncologic outcomes between the 2 approaches, although our study was underpowered due to a lack of patient accrual.

Sharpening the focus on causes and timing of readmission after radical cystectomy for bladder cancer.

BACKGROUND: Readmissions after radical cystectomy are common, burdensome, and poorly understood. For these reasons, the authors conducted a population-based study that focused on the causes of and time to readmission after radical cystectomy. METHODS: Using Surveillance, Epidemiology, and End Results-Medicare data, at total of 1782 patients who underwent radical cystectomy from 2003 through 2009 were identified. A piecewise exponential model was used to examine reasons for readmission as well as patient and clinical factors associated with the timing of readmission. RESULTS: One in 4 patients (25.5%) were readmitted within 30 days of discharge after radical cystectomy. Compared with patients without readmission, those readmitted were similar with regard to age, sex, and race. Readmitted patients had more complications (33.8% vs 13.9%; P< .001) and were more likely to have been discharged to skilled nursing facilities from their index admission (P< .001). The average time to readmission and subsequent length of stay were 11.5 days and 6.7 days, respectively. The majority of readmissions (67.4%) occurred within 2 weeks of discharge, 66.8% had emergency department charges, and 25.9% involved intensive care unit use. Although the spectrum of reasons for readmission varied over the 4 weeks after discharge, the most common included infection (51.4%), failure to thrive (36.3%), and urinary (33.2%) and gastrointestinal (23.1%) etiologies; 95.8% of patients had ≥ 1 of these diagnosis groups present at the time of readmission. CONCLUSIONS: Readmissions after radical cystectomy are common and time-dependent. Interventions to prevent and reduce the readmission burden after cystectomy likely need to focus on the first 2 weeks after discharge, take into consideration the spectrum of reasons for readmission, and target high-risk individuals.

Population level assessment of hospital based outcomes following laparoscopic versus open partial nephrectomy during the adoption of minimally invasive surgery.

PURPOSE: The comparative outcomes of laparoscopic and open partial nephrectomy remain incompletely defined. Therefore, we used population based data to examine resource use and short-term outcomes among patients with kidney cancer treated with laparoscopic vs open partial nephrectomy. MATERIALS AND METHODS: Using linked SEER (Surveillance, Epidemiology, and End Results)-Medicare data we identified patients with kidney cancer treated with laparoscopic or open partial nephrectomy from 2000 through 2007. We then used Medicare claims to identify several postoperative outcomes including intensive care unit care, length of stay, rehospitalizations, operative mortality and postoperative complications. We fit multivariate logistic regression models to estimate the association between each outcome and surgical approach (ie laparoscopic partial nephrectomy vs open partial nephrectomy), adjusting for patient and tumor characteristics. RESULTS: We identified 651 (28%) and 1,670 (72%) patients treated with laparoscopic partial nephrectomy and open partial nephrectomy, respectively. Compared to those who underwent open partial nephrectomy, patients treated with laparoscopic partial nephrectomy had a 34% lower probability of requiring intensive care unit time (20.0% vs 30.2%, p <0.001) and shorter median length of stay (3 vs 5 days, p <0.001), with no differences observed in the likelihood of rehospitalization or operative mortality. While the frequency of postoperative complications was similar (35.5% vs 36.1%, p = 0.829), patients treated with laparoscopic partial nephrectomy had a nearly twofold greater probability of genitourinary complications and postoperative hemorrhage (p <0.001). CONCLUSIONS: At a population level the patients with kidney cancer treated with laparoscopic partial nephrectomy experienced a shorter and less intense hospitalization, supporting the benefits of laparoscopy. However, the greater likelihood of procedure related complications highlights the need for continued efforts aimed at ensuring the safe adoption and application of this advanced surgical technique.

Open surgical partial nephrectomy for upper tract urothelial carcinoma.

We aimed to determine the ability of partial nephrectomy to prevent end-stage renal disease and tumor recurrence or progression in patients with upper tract urothelial carcinoma. Retrospectively, eight patients undergoing partial nephrectomy for upper tract urothelial carcinoma were identified and their medical records reviewed. All patients had imperative indications for nephron sparing, and diagnosis of upper tract urothelial carcinoma not adequately amenable to endoscopic management. Although three patients suffered acute tubular necrosis, only one required postoperative hemodialysis. During the follow-up period 25% (2/8) developed end-stage renal disease, including the one patient who had received postoperative hemodialysis. Recurrences occurred in five of seven patients with adequate oncological surveillance. Recurrences were successfully treated endoscopically in 80% (4/5) patients, and one patient had metastases. Of the eight patients, four have died. Death occurred 4 months, 1 year, 1.2 years and 3.5 years after partial nephrectomy. Of these patients, one succumbed to metastatic disease; the exact cause of death is unknown in the other three, but there was no documentation of metastatic cancer. The mean duration of follow up in the remaining four patients, all without evidence of metastatic urothelial cancer, is 71 months (range 22-108 months). In summary, partial nephrectomy for upper tract urothelial carcinoma in patients with imperative indications averts end-stage renal disease in most patients, and appears to be associated with acceptable disease-specific survival. Partial nephrectomy is a sparingly used option in patients with upper tract urothelial carcinoma refractory to endoscopic management who have imperative indications for nephron sparing.

Hybrid Oncocytic Tumors (HOTs) in Birt-Hogg-Dubé Syndrome Patients-A Tale of Two Cities: Sequencing Analysis Reveals Dual Lineage Markers Capturing the 2 Cellular Populations of HOT.

Birt-Hogg-Dubé (BHD) syndrome is associated with an increased risk of multifocal renal tumors, including hybrid oncocytic tumor (HOT) and chromophobe renal cell carcinoma (chRCC). HOT exhibits heterogenous histologic features overlapping with chRCC and benign renal oncocytoma, posing challenges in diagnosis of HOT and renal tumor entities resembling HOT. In this study, we performed integrative analysis of bulk and single-cell RNA sequencing data from renal tumors and normal kidney tissues, and nominated candidate biomarkers of HOT, L1CAM, and LINC01187 , which are also lineage-specific markers labeling the principal cell and intercalated cell lineages of the distal nephron, respectively. Our findings indicate the principal cell lineage marker L1CAM and intercalated cell lineage marker LINC01187 to be expressed mutually exclusively in a unique checkered pattern in BHD-associated HOTs, and these 2 lineage markers collectively capture the 2 distinct tumor epithelial populations seen to co-exist morphologically in HOTs. We further confirmed that the unique checkered expression pattern of L1CAM and LINC01187 distinguished HOT from chRCC, renal oncocytoma, and other major and rare renal cell carcinoma subtypes. We also characterized the histopathologic features and immunophenotypic features of oncocytosis in the background kidney of patients with BHD, as well as the intertumor and intratumor heterogeneity seen within HOT. We suggest that L1CAM and LINC01187 can serve as stand-alone diagnostic markers or as a panel for the diagnosis of HOT. These lineage markers will inform future studies on the evolution and interaction between the 2 transcriptionally distinct tumor epithelial populations in such tumors.

Integrative Drug Screening and Multiomic Characterization of Patient-derived Bladder Cancer Organoids Reveal Novel Molecular Correlates of Gemcitabine Response.

BACKGROUND AND OBJECTIVE: Predicting response to therapy for each patient's tumor is critical to improving long-term outcomes for muscle-invasive bladder cancer. This study aims to establish ex vivo bladder cancer patient-derived organoid (PDO) models that are representative of patients' tumors and determine the potential efficacy of standard of care and curated experimental therapies. METHODS: Tumor material was collected prospectively from consented bladder cancer patients to generate short-term PDO models, which were screened against a panel of clinically relevant drugs in ex vivo three-dimensional culture. Multiomic profiling was utilized to validate the PDO models, establish the molecular characteristics of each tumor, and identify potential biomarkers of drug response. Gene expression (GEX) patterns between paired primary tissue and PDO samples were assessed using Spearman's rank correlation coefficients. Molecular correlates of therapy response were identified using Pearson correlation coefficients and Kruskal-Wallis tests with Dunn's post hoc pairwise comparison testing. KEY FINDINGS AND LIMITATIONS: A total of 106 tumors were collected from 97 patients, with 65 samples yielding sufficient material for complete multiomic molecular characterization and PDO screening with six to 32 drugs/combinations. Short-term PDOs faithfully represent the tumor molecular characteristics, maintain diverse cell types, and avoid shifts in GEX-based subtyping that accompany long-term PDO cultures. Utilizing an integrative approach, novel correlations between ex vivo drug responses and genomic alterations, GEX, and protein expression were identified, including a multiomic signature of gemcitabine response. The positive predictive value of ex vivo drug responses and the novel multiomic gemcitabine response signature need to be validated in future studies. CONCLUSIONS AND CLINICAL IMPLICATIONS: Short-term PDO cultures retain the molecular characteristics of tumor tissue and avoid shifts in expression-based subtyping that have plagued long-term cultures. Integration of multiomic profiling and ex vivo drug screening data identifies potential predictive biomarkers, including a novel signature of gemcitabine response. PATIENT SUMMARY: Better models are needed to predict patient response to therapy in bladder cancer. We developed a platform that uses short-term culture to best mimic each patient's tumor and assess potential sensitivity to therapeutics.

Accuracy of determining small renal mass management with risk stratified biopsies: confirmation by final pathology.

PURPOSE: We assess the accuracy of a biopsy directed treatment algorithm in correctly assigning active surveillance vs treatment in patients with small renal masses by comparing biopsy results with final surgical pathology. MATERIALS AND METHODS: From 1999 to 2011, 151 patients with small renal masses 4 cm or smaller underwent biopsy and subsequent surgical excision. Biopsy revealed cell type and grade in 133 patients, allowing the hypothetical assignment of surveillance vs treatment using an algorithm incorporating small renal mass size and histological risk group. We compared the biopsy directed management recommendation with the ideal management as defined by final surgical pathology. RESULTS: Biopsy called for surveillance of 36 small renal masses and treatment of 97 small renal masses. Final pathology showed 11 patients initially assigned to surveillance should have been assigned to treatment (8.3% of all patients, 31% of those recommended for surveillance), whereas no patients moved from treatment to surveillance. Agreement between biopsy and final pathology was 92%. Using management based on final pathology as the reference standard, biopsy had a negative predictive value of 0.69 and positive predictive value 1.0 for determining management. Of the 11 misclassified cases, 7 had a biopsy indicating grade 1 clear cell renal cancer which was upgraded to grade 2 (5) or grade 3 (2). After modifying the histological risk group assignment to account for undergrading of clear cell renal cancer, agreement improved to 97%, with a negative predictive value of 0.86 and a positive predictive value of 1.0. CONCLUSIONS: Our results suggest that compared to final pathology, biopsy of small renal masses accurately informs an algorithm incorporating size and histological risk group that directs the management of small renal masses.

Association of RENAL nephrometry score with outcomes of minimally invasive partial nephrectomy.

OBJECTIVE: To evaluate the predictive value of the Radius, Exophytic, Nearness, Anterior, Location nephrometry scoring system and to investigate the influence of its individual components on perioperative outcomes of minimally invasive partial nephrectomy. METHODS: Consecutive laparoscopic partial nephrectomy (n = 189) and robotic partial nephrectomy (n = 109) cases from 2007 through 2011 were retrospectively reviewed from our prospectively maintained database. Urological surgeons assigned nephrometry scores, excluding cases without images available for review. The association of nephrometry score categories and individual components of the score to perioperative outcomes were assessed. RESULTS: No differences were observed in preoperative characteristics of low (n = 135), intermediate (n = 155) and high (n = 8) nephrometry groups. Higher nephrometry score was associated with an increased length of stay, estimated blood loss and warm ischemia time. Higher nephrometry scores were also associated with a greater proportion of major complications (P < 0.001). Distance to the renal sinus had the greatest impact on perioperative outcomes including operative and ischemic times, estimated blood loss, complications and length of stay. CONCLUSIONS: The Radius, Exophytic, Nearness, Anterior, Location nephrometry score has value as a predictive tool for perioperative outcomes of minimally invasive partial nephrectomy. Distance to the renal sinus seems to have the greatest association with outcomes. Using these findings, clinicians will be better able to counsel patients regarding anticipated perioperative outcomes of minimally invasive partial nephrectomy.

Characterization of Intercalated Cell Markers KIT and LINC01187 in Chromophobe Renal Cell Carcinoma and Other Renal Neoplasms.

Introduction. Chromophobe renal cell carcinoma (chromophobe RCC) is the third major subcategory of renal tumors after clear cell RCC and papillary RCC, accounting for approximately 5% of all RCC subtypes. Other oncocytic neoplasms seen commonly in surgical pathology practice include the eosinophilic variant of chromophobe RCC, renal oncocytoma, and low-grade oncocytic unclassified RCC. Methods. In our recent next-generation sequencing based study, we nominated a lineage-specific novel biomarker LINC01187 (long intergenic non-protein coding RNA 1187) which was found to be enriched in chromophobe RCC. Like KIT (cluster of differentiation 117; CD117), a clinically utilized chromophobe RCC related biomarker, LINC01187 is expressed in intercalated cells of the nephron. In this follow-up study, we performed KIT immunohistochemistry and LINC01187 RNA in situ hybridization (RNA-ISH) on a cohort of chromophobe RCC and other renal neoplasms, characterized the expression patterns, and quantified the expression signals of the two biomarkers in both primary and metastatic settings. Results. LINC01187, in comparison to KIT, exhibits stronger and more uniform expression within tumors while maintaining temporal and spatial consistency. LINC01187 also is devoid of intra-tumoral heterogeneous expression pattern, a phenomenon commonly noted with KIT. Conclusions. LINC01187 expression can augment the currently utilized KIT assay and help facilitate easy microscopic analyses in routine surgical pathology practice.

Postoperative complications and long-term survival among patients treated surgically for renal cell carcinoma.

PURPOSE: In addition to their acute implications, adverse events after oncological surgery may have late or long-term consequences for patient outcomes. We assessed the relationship between postoperative complications and long-term survival among patients treated surgically for kidney cancer. MATERIALS AND METHODS: Using Surveillance, Epidemiology and End Results-Medicare data we identified patients with kidney cancer treated surgically from 1995 through 2005. After excluding from analysis those who died during the index hospitalization or within 30 days of surgery we compared overall survival for patients with or without a postoperative complication. We then fit multivariate Cox proportional hazard models to estimate the association between complications and long-term survival, adjusting for patient characteristics, cancer severity and surgical approach. RESULTS: We identified 4,687 (37%) and 7,931 patients (63%) with and without a postoperative complication, respectively. During a median followup of 32 months (range 1 to 132) 3,425 patients (27.1%) died of any cause. Patients with at least 1 postoperative complication had lower unadjusted 5-year survival (59.9% vs 69.5%, p <0.001). On multivariate analyses the occurrence of a complication was also associated with significantly worse long-term survival (HR 1.24, 95% CI 1.16-1.33). This relationship was consistent with time, across surgical approaches and among patients with various specific complications, including acute renal failure, cardiac and neurological events, postoperative infection and sepsis. CONCLUSIONS: The occurrence of a postoperative complication is associated with decreased long-term survival after surgery for kidney cancer. Clarification of the cascade of events underlying this relationship may lead to new strategies to improve outcomes among cancer survivors.

A matched comparison of perioperative outcomes of a single laparoscopic surgeon versus a multisurgeon robot-assisted cohort for partial nephrectomy.

PURPOSE: Minimally invasive nephron sparing surgery is gaining popularity for small renal masses. Few groups have evaluated robot-assisted partial nephrectomy compared to other approaches using comparable patient populations. We present a matched pair analysis of a heterogeneous group of surgeons who performed robot-assisted partial nephrectomy and a single experienced laparoscopic surgeon who performed conventional laparoscopic partial nephrectomy. Perioperative outcomes and complications were compared. MATERIALS AND METHODS: All 249 conventional laparoscopic and robot-assisted partial nephrectomy cases from January 2007 to June 2010 were reviewed from our prospectively maintained institutional database. Groups were matched 1:1 (108 matched pairs) by R.E.N.A.L. (radius, exophytic/endophytic properties, nearness of tumor to collecting system or sinus, anterior/posterior, location relative to polar lines) nephrometry score, transperitoneal vs retroperitoneal approach, patient age and hilar nature of the tumor. Statistical analysis was done to compare operative outcomes and complications. RESULTS: Matched analysis revealed that nephrometry score, age, gender, tumor side and American Society of Anesthesia physical status classification were similar. Operative time favored conventional laparoscopic partial nephrectomy. During the study period robot-assisted partial nephrectomy showed significant improvements in estimated blood loss and warm ischemia time compared to those of the experienced conventional laparoscopic group. Postoperative complication rates, and complication distributions by Clavien classification and type were similar for conventional laparoscopic and robot-assisted partial nephrectomy (41.7% and 35.0%, respectively). CONCLUSIONS: Robot-assisted partial nephrectomy has a noticeable but rapid learning curve. After it is overcome the robotic procedure results in perioperative outcomes similar to those achieved with conventional laparoscopic partial nephrectomy done by an experienced surgeon. Robot-assisted partial nephrectomy likely improves surgeon and patient accessibility to minimally invasive nephron sparing surgery.

Long-term survival following partial vs radical nephrectomy among older patients with early-stage kidney cancer.

CONTEXT: Although partial nephrectomy is the preferred treatment for many patients with early-stage kidney cancer, recent clinical trial data, which demonstrate better survival for patients treated with radical nephrectomy, have generated new uncertainty regarding the comparative effectiveness of these treatment options. OBJECTIVE: To compare long-term survival after partial vs radical nephrectomy among a population-based patient cohort whose treatment reflects contemporary surgical practice. DESIGN, SETTING, AND PATIENTS: We performed a retrospective cohort study of Medicare beneficiaries with clinical stage T1a kidney cancer treated with partial or radical nephrectomy from 1992 through 2007. Using an instrumental variable approach to account for measured and unmeasured differences between treatment groups, we fit a 2-stage residual inclusion model to estimate the treatment effect of partial nephrectomy on long-term survival. MAIN OUTCOME MEASURES: Overall and kidney cancer-specific survival. RESULTS: Among 7138 Medicare beneficiaries with early-stage kidney cancer, we identified 1925 patients (27.0%) treated with partial nephrectomy and 5213 patients (73.0%) treated with radical nephrectomy. During a median follow-up of 62 months, 487 (25.3%) and 2164 (41.5%) patients died following partial or radical nephrectomy, respectively. Kidney cancer was the cause of death for 37 patients (1.9%) treated with partial nephrectomy, and 222 patients (4.3%) treated with radical nephrectomy. Patients treated with partial nephrectomy had a significantly lower risk of death (hazard ratio [HR], 0.54; 95% CI, 0.34-0.85). This corresponded with a predicted survival increase with partial nephrectomy of 5.6 (95% CI, 1.9-9.3), 11.8 (95% CI, 3.9-19.7), and 15.5 (95% CI, 5.0-26.0) percentage points at 2, 5, and 8 years posttreatment (P < .001). No difference was noted in kidney cancer-specific survival (HR, 0.82; 95% CI, 0.19-3.49). CONCLUSION: Among Medicare beneficiaries with early-stage kidney cancer who were candidates for either surgery, treatment with partial rather than radical nephrectomy was associated with improved survival.

TERT Promoter Mutations in Keratinizing and Nonkeratinizing Squamous Metaplasia of the Urinary Tract.

We identified urothelial tract biopsy and resection specimens with keratinizing squamous metaplasia (KSM), nonkeratinizing squamous metaplasia (NKSM), and urothelial and squamous carcinomas over a 20-yr period, focusing on cases with neurogenic lower urinary tract dysfunction (NLUTD) and/or those with spatial or temporal variation in sampling. TERT promoter mutations as assessed via allele-specific polymerase chain reaction were surprisingly common in our testing cohort, identified not only in 15 (94%) invasive cancer foci but also in 13 (68%) examples of KSM and seven (70%) examples of NKSM. TERT promoter mutations were present in 23 foci from NLUTD specimens and 11 foci from bladder diverticula, including in foci of KSM, NKSM, and unremarkable urothelium from cases with no clinical association with previous, concurrent, or subsequent cancer. Our demonstration of temporally and spatially persistent TERT promoter mutation in examples of KSM and NKSM in cases of bladder cancer and in morphologically benign cases with neurogenic dysfunction suggests a molecular mechanism by which such pre-neoplastic lesions can potentially progress and develop into overt carcinoma. Given the interest in TERT promoter mutations as a potential biomarker for the development of bladder cancer, these findings possibly explain the association between conditions with chronic urinary bladder injury (such as the natural history of NLUTD) and higher risk of bladder cancer. TERT promoter mutations may represent an early event in bladder cancer tumorogenesis, and our findings expand on the clinical ramifications and predictive value of TERT promoter mutations in this context. PATIENT SUMMARY: Mutations in the TERT gene are the most common genetic changes in bladder cancer. We found that these mutations are also sometimes present in patients with chronic bladder irritation such as neurogenic bladder dysfunction and changes to the lining of the bladder that pathologists would consider "benign." This finding might explain why such conditions are associated with the development of bladder cancer.

The Feasibility and Impact of a Presurgical Exercise Intervention Program (Prehabilitation) for Patients Undergoing Cystectomy for Bladder Cancer.

OBJECTIVE: To assess the feasibility of a prehabilitation program for cystectomy patients and to determine the effectiveness of the program in improving strength and functional capacity in the peri-operative period. MATERIALS AND METHODS: This phase I/II study accrued patients ≥60 years old from January 2013 to October 2017 with biopsy-proven bladder cancer, Karnofsky performance score ≥70 and a sedentary baseline lifestyle to participate in a 4-week supervised preoperative exercise training program. Primary outcomes were feasibility and safety; secondary outcomes included changes in fitness, patient-reported QOL, peri-operative complications and readmissions. Student's ttests and Wilcoxon signed-rank test were performed. RESULTS: Fifty-four patients enrolled in the program. Successful completion, defined as patients who began the program and adhered to >70% of the sessions, was attained by 41 of 51 patients (80.4%, 90% CI [71%-90%]). There were no adverse events. Fitness and patient-reported QOL improved postintervention, with sustained improvements in general and mental health 90-days postsurgery. The primary limitation is no control group. CONCLUSION: Prehabilitation prior to cystectomy is feasible, safe, and results in improvements in patient strength, endurance and sustained improvements in patient-reported QOL from baseline. Efforts to further evaluate the impact of prehabilitation in this population in an expanded and randomized fashion are warranted.

Multi-institutional Survival Analysis of Incidental Pathologic T3a Upstaging in Clinical T1 Renal Cell Carcinoma Following Partial Nephrectomy.

OBJECTIVE: To evaluate whether incidental pathologic T3a (pT3a) upstaging after partial nephrectomy (PN) for clinical T1 disease results in inferior oncologic outcomes compared to pT1a-b disease. MATERIALS AND METHODS: Retrospective chart review was completed at the University of Michigan and Moffitt Cancer Center to identify patients undergoing PN for clinical T1 masses between 1995 and 2015. A total of 1955 patients were identified, of which 95 had pT3a upstaging. Median follow-up was 38.2 months. Patients with pT3a disease were individually matched by clinicopathologic features with patients undergoing PN with pT1a-b disease in a 1:2 ratio. Kaplan-Meier analysis and univariate and multivariable Cox proportional hazards regression analysis were performed. Primary endpoint was recurrence-free survival (RFS). Secondary endpoints were all-cause mortality, cancer-specific survival (CSS), and rates of local and distant recurrence. RESULTS: Recurrence rates were significantly higher in pT3a disease compared to pT1a-b controls (P <.01). In those patients with pT3a upstaging, 3- and 5-year RFS were 81% and 58%, compared to 86% and 75% in pT1a-b controls (P = .01). CSS at 3 and 5 years were 91% and 90% in pT3a disease and 100% and 97% in pT1a-b controls (P <.01). All-cause mortality at 3 and 5 years were 82% and 71% in pT3a disease and 93% and 80% in pT1a-b controls (P = .04). Univariate and multivariable analysis of pT3a disease demonstrated no association between demographic or pathologic characteristics and RCC recurrence. CONCLUSION: Patients with pT3a upstaging following PN experience a significantly reduced RFS and CSS when compared to pT1 disease.

The Urology Applicant: An Analysis of Contemporary Urology Residency Candidates.

OBJECTIVE: To better understand today's urology applicant. METHODS: All 2016 Urology Residency Match applicants to the study-participating institutions were provided a survey via email inquiring about their paths to urology, their career aspirations, how they evaluate a training program, and how they perceive residency programs evaluate them. RESULTS: Of a possible 468 applicants registered for the match, 346 applicants completed the survey. Only 8.7% had a mandatory urology rotation, yet 58.4% believed that a mandatory urology rotation would influence their career decision. Most applicants (62.1%) spent more than 8 weeks on urology rotations, and 79.2% completed 2 or more away rotations. Applicants were attracted to urology by the diversity of procedures, prior exposure to the field, and the mix of medicine and surgery, with mean importance scores of 4.70, 4.52, and 4.45 of 5, respectively. Female applicants were more likely to be interested in pediatric urology, trauma or reconstructive urology, and female pelvic medicine and reconstructive surgery. Significant differences in survey results were noted when applicants were separated by gender. Three-fourths of respondents (75.7%) applied to more than 50 residency programs. Applicants ranked operative experience, interactions with current residents, and relationships between faculty and residents as the most important criteria when evaluating training programs. Of the subspecialties, 62.1% of applicants expressed most interest in urologic oncology. At this stage in their career, a significant majority (83.5%) expressed interest in becoming academic faculty. CONCLUSION: This study provides new information that facilitates a more comprehensive understanding of today's urology applicants.