Clear cell papillary renal cell carcinoma: Characteristics and survival outcomes from a large single institutional series.

OBJECTIVES: To investigate the clinical characteristics and survival outcomes of a large clear cell papillary renal cell carcinoma cohort. METHODS AND MATERIALS: A retrospective review of patients with clear cell papillary renal cell carcinoma at a single academic center was performed after Institutional Review Board approval. Patients underwent either partial or radical nephrectomy from September 2009 to July 2019. Demographic and clinical characteristics, recurrence, and cancer specific and overall survival were reported. RESULTS: A total of 90 patients were included in the study. Median follow up was 26.5 months. Median age was 61 (range 27 to 87). 47.8% of patients were African American. 26.7% of patients had end stage renal disease. 37.8% had multifocal renal tumors. 48.9% underwent partial nephrectomy, while the remainder underwent radical nephrectomy. 43.3% underwent an open surgical approach, 40.0% a robotic approach, and 16.7% a laparoscopic approach. Pathologic stage included T1a (90.0%), T1b (1.1%), and T2b (8.9%). Fuhrman grades 1-3 were present in 18.9%, 77.8%, and 3.3% of patients, respectively. There were no cancer specific deaths. There was one local recurrence and no metastases. The overall survival at a median follow up of 26.5 months was 92.1% (95% confidence interval 83.1%-96.4%). CONCLUSIONS: Clear cell papillary renal cell carcinoma typically presents at a low stage and grade and has favorable survival outcomes. A nephron-sparing approach to treatment should be considered when feasible due to the tumor's indolent nature and propensity towards multifocality.

Management of stage I testicular germ cell tumours.

Clinical stage I testicular germ cell tumours (TGCT) are highly curable neoplasms. The treatment of stage I testicular cancer is complex and requires a multidisciplinary approach. Standard options after radical orchiectomy for seminoma include active surveillance, radiation therapy or 1-2 cycles of carboplatin, and options for nonseminoma include active surveillance, retroperitoneal lymph node dissection (RPLND) or 1-2 cycles of bleomycin plus etoposide plus cisplatin (BEP). All the options should be discussed with each patient and treatment choices should be made by shared decision making as virtually all patients with clinical stage I TGCT can be cured of their disease. Long-term survival of men with stage I disease is ∼99% and care must be taken to limit the long-term risks of treatment. Orchiectomy is curative in the majority of patients. The management of clinical stage I TGCT remains controversial among experts at high-volume centres throughout the world. The main controversy is whether to overtreat a substantial number of patients with stage I disease to prevent relapse, or to observe and treat only patients who experience disease relapse as adjuvant treatment and surveillance strategy both bring curative outcome. Thus, a summary of the available evidence in stage I disease and recommendations for disease management from a high-volume centre such as Indiana University might be of interest to treating clinicians.

Neoadjuvant chemotherapy in urothelial bladder cancer: impact of regimen and variant histology.

AIM: We compared the efficacy of methotrexate/vinblastine/doxorubicin/cisplatin (MVAC) versus gemcitabine/cisplatin in urothelial cancer and neoadjuvant chemotherapy (NACT) efficacy in variant histology (VH). MATERIALS & METHODS: Radical cystectomy patients were retrospectively compared with those who received NACT. Factors associated with survival, pathologic complete response (pCR) and downstaging (pDS) were evaluated in multivariable models. RESULTS: 9% of radical cystectomy patients (84/919) received NACT, with improved survival, pCR and pDS on both regimens. MVAC lead to higher pDS without an increase in pCR. On multivariable analysis, there was a nonsignificant increase in pDS with MVAC. NACT conferred similar responses in squamous and glandular differentiation VH. CONCLUSION: NACT was associated with improved survival, pCR and pDS. Furthermore, responses to NACT were not dependent on presence of VH.

Differentiating reconstructive techniques in partial nephrectomy: a propensity score analysis.

INTRODUCTION: To assess whether volumetric measurements can differentiate functional changes between reconstructive techniques after partial nephrectomy. MATERIALS AND METHODS: One hundred and fifty-six patients undergoing partial nephrectomy for a single renal mass were retrospectively studied between 2008 and 2012. Computed tomography scans were available for volume calculations on 56 (18 non-renorrhaphy and 38 renorrhaphy). Institutional review board approval was obtained. The primary outcome was %volume loss in the operated kidney, which was calculated from three-dimensional reconstructions using a semiautomatic segmentation algorithm. Multivariable regression and propensity score analysis was performed. RESULTS: Volumetric analysis detected a difference in mean %volume loss between two-layer reconstruction (cortical renorrhaphy and base-layer) and base-layer only (15.6% versus 3.8%, p < 0.001). The mean %glomerular filtration rate (GFR) loss was also greater in the two-layer group (8.9% versus 2.4%, p = 0.03). Demographics were similar between groups except the two-layer group was older, had more males, and increased ischemia time. On multivariable regression the presence of two-layer closure (ß = -15.2%, p < 0.001) and tumor diameter (ß = -7.4, p = 0.004) were significant predictors of %volume loss while ischemia time (p = 0.88) was not. Two-layer closure remained a predictor on propensity-adjusted analysis (ß = -14.3, p = 0.004). The base-layer only group had two (5.3%) urine leaks and two (5.3%) bleeding complications. The two-layer group had two (1.7%) urine leaks and three (2.5%) bleeding complications (p = 0.23, 0.41). CONCLUSIONS: Volume loss calculated from CT scans can be used to monitor postoperative renal function. Techniques for renal reconstruction and tumor diameter are associated with volume and functional loss after partial nephrectomy and should be controlled for in future studies.

Three-tiered nodal classification system for bladder cancer: a new proposal.

AIM: To evaluate a three-tiered prognostic stratification using one, two to five and >five positive lymph nodes (LNs) and this nodal staging system performs across different pelvic LN dissection (PLND) templates and adjuvant chemotherapy status. METHODS: We evaluated 244 patients with positive LN urothelial cancer who underwent radical cystectomy and PLND between 2000 and 2011. Survival analyses utilizing the Kaplan-Meier method and log rank test were performed. Median follow-up was 55.3 months (range: 0.4-141). Multivariable Cox proportional hazards models were built to evaluate the prognostic stratification. RESULTS: Extended PLND template was performed on 152 (62.3%) patients and standard on 92 (37.7%). The median number of LNs resected was 14 in the standard group vs 22 in the extended group (p < 0.01) and positive LNs was 2 vs 3 (p = 0.09), respectively. Stratification in patients with: one positive LN, two to five positive LNs or >five positive LNs lead to 5-year recurrence-free survival of: 48.6, 34.5 and 15.9% for each group, while the 5-year overall survival was: 43.0, 22.1 and 11.3%, respectively. Stratification in the three groups was also verified irrespective of PLND template and adjuvant chemotherapy. Two multivariable models confirmed the findings when controlling for demographic features and known pathologic risk factors. CONCLUSION: Three-tiered nodal classification system using the number of metastatic LNs (one, two to five and >five) stratifies patients with lymphatic disease into distinct prognostic groups.

Does Squamous Differentiation Portend Worse Outcomes in Urothelial Bladder Cancer?

INTRODUCTION: Interest on the impact of variant histology in bladder cancer prognosis is increasing. Although squamous differentiation is the most well characterized, only recently have less common variants gained increased recognition. We assessed whether squamous differentiation conferred a worse prognosis than nonvariant urothelial bladder cancer in a contemporary cohort of patients treated with radical cystectomy given the increased awareness of other less common variants. METHODS: We identified patients with squamous differentiation or nonvariant histology on transurethral resection of bladder tumor and/or cystectomy pathology during a 10-year period. Disease specific and overall survival were evaluated using Kaplan-Meier methodology. Cox regression was used to assess variables associated with mortality. RESULTS: Between 2003 and 2013, 934 patients underwent cystectomy for urothelial bladder cancer. Overall 617 nonvariant and 118 squamous differentiation cases were identified, and the remainder was nonsquamous differentiation variant histology. Overall 75% of patients with squamous differentiation had muscle invasive disease at diagnosis compared with 59% of those with nonvariant histology (p=0.002). Nonorgan confined disease at cystectomy was more common in patients with squamous differentiation (57% vs 44%, p=0.009). Among cases on neoadjuvant chemotherapy 20% (9 of 45) of nonvariant and 13% (1 of 8) of squamous differentiation were pT0N0 (p=0.527). Median followup was 52 months. Adjusted for demographics, pathological stage and chemotherapy, squamous differentiation was not associated with an increased risk of disease specific (HR 1.35, 95% CI 0.90-2.04, p=0.150) or all cause mortality (HR 0.90, 95% CI 0.60-1.25, p=0.515). CONCLUSIONS: In a contemporary cohort of urothelial bladder cancer with recognition and characterization of less commonly described variants, squamous differentiation is not associated with a worse disease specific and all cause mortality when compared to a pure nonvariant cohort.

The changing reality of urothelial bladder cancer: should non-squamous variant histology be managed as a distinct clinical entity?

OBJECTIVES: To assess the effect of non-squamous differentiation (non-SQD) variant histology on survival in muscle-invasive bladder urothelial cancer (UC). PATIENTS AND METHODS: A cohort of 411 radical cystectomy (RC) cases performed with curative intent for muscle-invasive primary UC was identified between 2008 and June 2013. Survival analysis was evaluated using Kaplan-Meier methodology comparing non-variant (NV) + SQD histology to non-SQD variant histology (non-SQD variants). Multivariable cox proportional hazards regression assessed all-cause and disease-specific mortality. RESULTS: Of the 411 RC cases, 77 (19%) had non-SQD variant histology. The median overall survival (OS) for non-SQD variant histology was 28 months, whereas the NV+SQD group had not reached the median OS at 74 months (log-rank test P < 0.001). After adjusting for sex, age, pathological stage, and any systemic chemotherapy, patients with non-SQD variant histology at RC had a 1.57-times increased adjusted risk of all-cause mortality (P = 0.027) and 1.69-times increased risk of disease-specific mortality (P = 0.030) compared with NV+SQD patients. CONCLUSIONS: While SQD behaves similarly to NV, non-SQD variant histology portends worse OS and disease-specific survival regardless of neoadjuvant or adjuvant chemotherapy and pathological stage. Non-SQD variants of UC could perhaps be considered a distinct clinical entity in UC with goals for developing new treatment algorithms through novel clinical trials.

Contemporary bladder cancer: variant histology may be a significant driver of disease.

OBJECTIVES: To evaluate pathologic and survival outcomes among patients with variant histology (VH) urothelial carcinoma of the bladder. METHODS: A retrospective review of an institutional database was performed to identify all patients who underwent radical cystectomy with curative intent for urothelial carcinoma between 2008 and June 2013. VH was assigned by genitourinary pathologists. Descriptive statistics comparing clinicopathologic outcomes were performed using the Pearson chi-square test and analysis of variance. Survival was evaluated using the Kaplan-Meier methodology and the Cox proportional hazards regression. RESULTS: In total, 624 patients were identified. Overall, 26% (n = 162) had VH, with the most common being squamous differentiation (n = 68), micropapillary variant (MPV, n = 28), plasmacytoid variant (PCV, n = 25), and sarcomatoid variant (n = 15); 64% of MPV and 72% of PCV had positive lymph nodes. Compared with 8% of patients with a non VH, 44% of those with VH were categorized as pT4 (P<0.001). MPV and PCV were independently associated with twice the risk of all-cause mortality compared with nonvariant, when adjusting for demographics, American Society of Anesthesiologists class, transurethral resection of bladder tumor stage, cystectomy stage, positive lymph nodes, and reception of chemotherapy (odds ratio = 2.20, 95% CI: 1.28-3.78; P = 0.004; odds ratio = 2.42, 95% CI: 1.33-4.42; P = 0.004, respectively). There was no difference in risk of mortality associated with squamous differentiation or sarcomatoid variant (P>0.05 each). CONCLUSIONS: MPV and PCV are associated with increased risk of mortality. Improved recognition of VH will enable larger cohorts of study and better prognostic understanding of the significance of specific VH involvement.

The impact of bleomycin on retroperitoneal histology at post-chemotherapy retroperitoneal lymph node dissection of good risk germ cell tumors.

PURPOSE: Induction chemotherapy for International Germ Cell Cancer Collaborative Group (IGCCCG) good risk metastatic testicular cancer includes 3 cycles of bleomycin, etoposide and cisplatin (BEP x3) or 4 cycles of etoposide and cisplatin (EP x4). We examine differences in active cancer in the retroperitoneum between patients receiving BEP x3 compared to EP x4. MATERIALS AND METHODS: The Indiana University Testis Cancer database was queried to identify IGCCCG good risk patients who received BEP x3 or EP x4 induction chemotherapy before retroperitoneal lymph node dissection. The primary outcome of interest was retroperitoneal histology. The association between the use of bleomycin in the induction regimen with active cancer in the retroperitoneal specimen was tested using a propensity score adjusted analysis. RESULTS: A total of 179 men (79%) received BEP x3 while 47 (21%) received EP x4. Median age of the bleomycin, etoposide and cisplatin group was 27 years (range 15 to 50) vs 30 years (range 18 to 71) in the etoposide and cisplatin group. The incidence of active cancer in the retroperitoneal specimen at post-chemotherapy retroperitoneal lymph node dissection was significantly higher in the EP x4 group compared to the BEP x3 group (31.9% vs 7.8%, p <0.01). This significant difference in the bleomycin, etoposide and cisplatin vs etoposide and cisplatin groups remained in the propensity adjusted analysis (22.9% vs 7.8%, p=0.015). CONCLUSIONS: There was a higher incidence of active cancer in the retroperitoneal specimen in good risk patients who received 4 cycles of induction etoposide and cisplatin chemotherapy compared to 3 cycles of bleomycin, etoposide and cisplatin in this retrospective analysis. The overall burden of treatment may be higher for men receiving EP x4 for induction chemotherapy.

Oncologic and quality-of-life outcomes with wide resection in robot-assisted laparoscopic radical prostatectomy.

OBJECTIVES: To assess urinary quality-of-life (QoL) and oncologic outcomes between wide resection (WR) robot-assisted laparoscopic radical prostatectomy (RALP) and non-WR (NWR) RALP in men with intermediate- or high-risk (Cancer of the Prostate Risk Assessment [CAPRA]-9 >2) prostate adenocarcinoma. METHODS: Patients undergoing RALP (2004-2013) for intermediate- or high-risk prostate adenocarcinoma were analyzed. Kaplan-Meier methodology with Cox proportional hazards regression evaluated biochemical recurrence-free survival (BCR-FS). Multiple logistic regression was used to determine the relationship between (1) WR with positive surgical margins (+SM) and (2) WR with posterolateral+SM after adjusting for demographics and CAPRA-9 score. University of California, Los Angeles-Prostate Cancer Index and Extended Prostate Cancer Index Composite questionnaires assessed urinary QoL. Multiple mixed-effects linear regression adjusting for demographics and CAPRA-9 evaluated differences in QoL between WR and NWR. RESULTS: A total of 483 RALP cases met inclusion criteria-129 (26.7%) underwent WR and 354 (73.3%) underwent NWR-RALP. There were no demographic differences between groups. Burden of disease was greater in patients undergoing WR (P<0.001). There was no difference in+SM rates between WR and NWR (P = 0.505). Adjusting for demographics and CAPRA-9 score, WR patients had a clinically relevant 27% decrease in posterolateral+SM (odds ratio = 0.73; 95% CI: 0.38-1.41; P = 0.351). WR was not associated with worse BCR-FS (hazard ratio = 1.24; 95% CI: 0.83-1.86, P = 0.30). Adjusting for pathology, University of California, Los Angeles and Extended Prostate Cancer Index Composite urinary domain scores were similar between WR and NWR groups. CONCLUSION: Despite WR patients having worse clinical disease, WR-RALP can be performed with minimal detriment to BCR-FS and urinary QoL. The greater incidence of occult metastasis in higher risk patients may make surgical technique a nonsignificant factor. Nevertheless, WR remains a reasonable option for complete surgical excision.

Critical analysis of the 2010 TNM classification in patients with lymph node-positive bladder cancer: influence of lymph node disease burden.

OBJECTIVES: In 2010, a new TNM staging system was published by American Joint Committee on Cancer, changing the nodal classification to include the presence of common iliac lymph node (LN) involvement as N3 category. The objective of this study was to define the capability of the current TNM nodal classification to separate patients with different prognostic stages and to evaluate the effect of LN disease burden. METHODS AND MATERIALS: A total of 93 patients with metastatic LNs after radical cystectomy and extended LN dissection for urothelial carcinoma of the bladder between 1999 and 2012 were included. The median follow-up was 21.5 months. The correlation between N3 and indicators of LN disease burden was analyzed using the Spearman correlation coefficient. Recurrence-free survival (RFS) and overall survival (OS) analysis was performed using the Kaplan-Meier and Cox proportional hazards methods. RESULTS: The presence of N3 disease was associated with higher number of metastatic LNs (7 vs. 2, P<0.01); however, this was highly variable and correlation coefficients between common iliac metastatic LNs and other lymphatic disease burden indicators demonstrated weak association (0.39-0.63). Patients with N1 lesions were found to have a distinct RFS and OS (P<0.01 and P = 0.01, respectively). A trend toward worse RFS (P = 0.07) and OS (P = 0.08) was observed in patients with N3 lesions. However, no difference in RFS or OS was found between patients with N2 and N3 lesions (P = 0.83 and 0.50, respectively). CONCLUSIONS: The N3 category in the current TNM classification defines a group of patients with high but heterogeneous disease burden. This may be the explanation for its lack of prognostic stratification when compared with N2 category bladder cancer.

Plasmacytoid variant urothelial bladder cancer: is it time to update the treatment paradigm?

OBJECTIVES: Plasmacytoid variant (PCV) urothelial cancer (UC) of the bladder is rare, with poor clinical outcomes. We sought to identify factors that may better inform expectations of tumor behavior and improve management options in patients with PCV UC. MATERIALS AND METHODS: A retrospective analysis of the Indiana University Bladder Cancer Database between January 2008 and June 2013 was performed comparing 30 patients with PCV UC at cystectomy to 278 patients with nonvariant (NV) UC at cystectomy who underwent surgery for muscle-invasive disease. Multivariable logistic regression was used to assess precystectomy variables associated with non-organ-confined disease at cystectomy and Cox regression analysis to assess variables associated with mortality. RESULTS: Patients with PCV UC who were diagnosed with a higher stage at cystectomy (73% pT3-4 vs. 40%, P = 0.001) were more likely to have lymph node involvement (70% vs. 25%, P<0.001), and positive surgical margins were found in 40% of patients with PCV UC vs. 10% of patients with NV UC (P<0.001). Median overall survival and disease-specific survival were 19 and 22 months for PCV, respectively. Median overall survival and disease-specific survival had not been reached for NV at 68 months (P<0.001). Presence of PCV UC on transurethral resection of bladder tumor was associated with non-organ-confined disease (odds ratio = 4.02; 95% CI: 1.06-15.22; P = 0.040), and PCV at cystectomy was associated with increased adjusted risk of mortality (hazard ratio = 2.1; 95% CI: 1.2-3.8; P = 0.016). CONCLUSIONS: PCV is an aggressive UC variant, predicting non-organ-confined disease and poor survival. Differentiating between non-muscle- and muscle-invasive disease in patients with PCV UC seems less important than the aggressive nature of this disease. Instead, any evidence of PCV on transurethral resection of bladder tumor may warrant aggressive therapy.

Management of germ cell tumors with somatic type malignancy: pathological features, prognostic factors and survival outcomes.

PURPOSE: Germ cell tumors with somatic type malignancy are rare, occurring in approximately 2.7% to 8.6% of germ cell tumor cases. Prognostic factors and optimal management remain poorly defined. MATERIALS AND METHODS: The Indiana University testis cancer database was queried from 1979 to 2011 for patients demonstrating germ cell tumor with somatic type malignancy at orchiectomy or subsequent resection. Patients with transformation to primitive neuroectodermal tumor only were excluded from study due to distinct management. Chart review, pathological review and survival analysis were performed. RESULTS: A total of 121 patients met the study inclusion criteria. The most common somatic type malignancy histologies were sarcoma (59), carcinoma (31) and sarcomatoid yolk sac tumor (17). Of these patients 32 demonstrated somatic type malignancy at germ cell tumor diagnosis. For those with delayed identification, median time from germ cell tumor to somatic type malignancy diagnosis was 33 months. This interval was longest for carcinomas (108 months). At a median followup of 71 months, 5-year cancer specific survival was 64%. Predictors of poorer cancer specific survival included somatic type malignancy diagnosed at late relapse (p = 0.017), referral to Indiana University for reoperative retroperitoneal lymph node dissection (p = 0.026) and grade (p = 0.026). None of these factors maintained prognostic significance on multivariate analysis. Somatic type malignancy histology subtype, stage, risk category and number of resections were not predictive of cancer specific survival. CONCLUSIONS: Germ cell tumor with somatic type malignancy is associated with poorer cancer specific survival than traditional germ cell tumor. Established prognostic factors for germ cell tumor lose predictive value in the setting of somatic type malignancy. Aggressive and serial resections are often necessary to optimize cancer specific survival. Tumor grade is an important prognostic factor in sarcomas and sarcomatoid yolk sac tumors.

National trends in the utilization of robotic-assisted radical cystectomy: an analysis using the Nationwide Inpatient Sample.

OBJECTIVES: To determine temporal and regional trends in utilization of robotic-assisted radical cystectomy (RARC) in the United States and to explore factors associated with utilization of robotic assistance. MATERIALS AND METHODS: Using 2009 to 2011 data from the Nationwide Inpatient Sample, we identified radical cystectomy cases that were performed using either open or robotic assistance and applied Nationwide Inpatient Sample discharge weights to determine national incidence. Univariable and multivariable logistic regressions were performed to assess regional trends and characteristics associated with having RARC. Descriptive analysis was performed using the chi-square test, the Student t test, and the Mann-Whitney U test. RESULTS: Of the 29,719 radical cystectomy patients, 3,733 were RARC (12.6%). Although there was no change in the proportion of RARC performed annually (P = 0.702). Length of stay was 1 day longer for open cystectomy than RARC (P<0.001). On multivariate regression, patients whose primary payer was Medicaid were less likely than private insurance patients to undergo RARC (odds ratio = 0.60, P = 0.074). Additionally, patients in the south were at 50% reduced odds of undergoing RARC (odds ratio = 0.49, P = 0.044). Median hospital costs were $5,000 greater for RARC (P<0.001). CONCLUSIONS: Regional variation in utilization should be monitored to ensure equal access to new technology and to assess potential overuse of new technology. Although RARC is associated with higher median hospital costs, further studies to assess its benefits are warranted.

Survival analysis of pure seminoma at post-chemotherapy retroperitoneal lymph node dissection.

PURPOSE: Viable seminoma encountered at post-chemotherapy retroperitoneal lymph node dissection for pure testicular seminoma is rare due to the chemosensitivity of this germ cell tumor. In this study we define the natural history of viable seminoma at post-chemotherapy retroperitoneal lymph node dissection. MATERIALS AND METHODS: The Indiana University testis cancer database was queried from 1988 to 2011 to identify all patients with primary testicular or retroperitoneal pure seminoma and who were found to have pure seminoma at post-chemotherapy retroperitoneal lymph node dissection. Clinical characteristics were reviewed and survival analysis was performed. RESULTS: A total of 36 patients met the study inclusion criteria. All patients received standard first line cisplatin based chemotherapy and 17 received salvage chemotherapy. The decision to proceed to retroperitoneal lymph node dissection was based on enlarging retroperitoneal mass and/or positron emission positivity in the majority of cases. Seven patients had undergone previous retroperitoneal lymph node dissection. Additional surgical procedures were required in 19 patients to achieve a complete resection. The 5-year cancer specific survival rate was 54%. However, only 9 of 36 patients remained continuously free of disease and of these patients 4 received adjuvant chemotherapy. Mean time from post-chemotherapy retroperitoneal lymph node dissection to death was 6.9 months. Second line chemotherapy, reoperative retroperitoneal lymph node dissection and earlier era of treatment were associated with poorer cancer specific survival. CONCLUSIONS: A total of 36 patients with pure seminoma were found to have viable pure seminoma at post-chemotherapy retroperitoneal lymph node dissection. While 5-year cancer specific survival was 54%, these surgeries are technically demanding and only a minority of patients achieves a durable cure from surgery alone.

Short-term morbidity and mortality of Indiana pouch, ileal conduit, and neobladder urinary diversion following radical cystectomy.

PURPOSE: Literature surrounding Indiana pouch (IP) urinary diversion suggests a higher incidence of complications and longer operative time compared with ileal conduit (IC) and neobladder (NB). We sought to assess short-term complications of IP diversions compared with other diversions at our institution. MATERIALS AND METHODS: Using institutional National Surgical Quality Improvement Program data, we identified radical cystectomy cases performed for bladder cancer at Indiana University from January 2011 until June 2013. During this time period, the National Surgical Quality Improvement Program randomly evaluated approximately 70% of radical cystectomies performed for urothelial carcinoma at our institution. Multivariable logistic regression was performed to identify factors associated with Clavien grade III-V complications. RESULTS: A total of 233 cases were identified, 139 IC, 39 IP, and 55 NB. Mean (standard deviation) operative times for IC, IP, and NB were 257 (84), 383 (78), and 327 (88) minutes, respectively (P<0.001). Half of the patients required blood transfusion during the hospitalization. The overall rate of complications was significantly lower among NB (P = 0.009). Overall, 12% of patients developed a Clavien grade III-V complication, with no difference observed between groups (P = 0.884). After controlling for preoperative confounders, IP patients were not at increased odds of developing a Clavien III-V complication compared with IC (odds ratio = 1.38, P = 0.599). CONCLUSIONS: At a high-volume center, the incidence of serious complications was similar between diversion types. IP patients were more likely to experience minor complications. Patients should be counseled regarding rates of short-term complications and blood transfusion.

Limited ability of existing nomograms to predict outcomes in men undergoing active surveillance for prostate cancer.

OBJECTIVE: To assess the ability of current nomograms to predict disease progression at repeat biopsy or at delayed radical prostatectomy (RP) in a prospectively accrued cohort of patients managed by active surveillance (AS). MATERIALS AND METHODS: A total of 273 patients meeting low-risk criteria who were managed by AS and who underwent multiple biopsies and/or delayed RP were included in the study. The Kattan (base, medium and full), Steyerberg, Nakanishi and Chun nomograms were used to calculate the likelihood of indolent disease ('nomogram probability') as well as to predict 'biopsy progression' by grade or volume, 'surgical progression' by grade or stage, or 'any progression' on repeat biopsy or surgery. We evaluated the associations between each nomogram probability and each progression outcome using logistic regression with (area under the receiver-operating characteristic curve (AUC) values and decision curve analysis. RESULTS: The nomogram probabilities of indolent disease were lower in patients with biopsy progression (P < 0.01) and any progression on repeat biopsy or surgical pathology (P < 0.05). In regression analyses, nomograms showed a modest ability to predict biopsy progression, adjusted for total number of biopsies (AUC range 0.52-0.67) and any progression (AUC range 0.52-0.70). Decision curve analyses showed that all the nomograms, except for the Kattan base model, have similar value in predicting biopsy progression and any progression. Nomogram probabilities were not associated with surgical progression in a subgroup of 58 men who underwent delayed RP. CONCLUSIONS: Existing nomograms have only modest accuracy in predicting the outcomes of patients undergoing AS. Improvements to existing nomograms should be made before they are implemented in clinical practice and used to select patients for AS.

Plasmacytoid bladder cancer: variant histology with aggressive behavior and a new mode of invasion along fascial planes.

OBJECTIVE: To examine differences in disease progression and nature of tumor invasion that may lead to more accurate expectations of tumor behavior and improved management options for plasmacytoid variant (PCV) histology urothelial bladder cancer patients. METHODS: Using the Indiana University Bladder Cancer Database, we conducted a retrospective analysis of patients undergoing radical cystectomy from 2008 to June 2013 to identify patients with PCV, micropapillary variant (MPV), or nonvariant (NV) histology and either positive ureteral margins (+UM), paravesical surgical margins (+PSM), or lymph node (+LN) involvement. Pearson's chi-squared test and analysis of variance were used for descriptive analysis. RESULTS: Of 510 patients who met inclusion criteria, 30 had +UM on final pathology. The incidence of +UM in NV patients was 17 of 457 (3.7%), in MPV 5 of 28 (17.9%), and in PCV 8 of 25 (32.0%) (P <.001). Carcinoma in situ on the luminal margin was noted for all cases, except in 5 of the 8 PCV patients with +UM, in whom retrograde longitudinal invasion along the subserosal and adventitia was noted. +PSM and +LN were significantly higher for both PCV (28.0%, 72.0%) and MPV (10.7%, 64.3%) than NV (2.6%, 18.6%, P <.001, each). CONCLUSION: PCV exhibits a unique pattern of spread along the ureter. This proposes a new mode of invasion along the fascial sheath. The incidence of +PSM and +LN liken PCV to the known aggressive MPV, and in conjunction with the increased incidence of +UM, may lead to a paradigm shift, with surgeons and pathologists being more vigilant with surgical margins.

Temporal trends and predictors of salvage cancer treatment after failure following radical prostatectomy or radiation therapy: an analysis from the CaPSURE registry.

BACKGROUND: Prostate cancer treatment after failure of primary therapy by either radical prostatectomy or radiation therapy can vary greatly. This study sought to determine trends and predictors of salvage treatment after failure of primary treatment in a community cohort over the past 10 years. METHODS: From the community-based Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) database, 6275 patients were identified who initiated a form of primary treatment for prostate cancer; 839 of these were identified as failing treatment by biochemical recurrence or initiation of secondary treatment between 2000 and 2010. Salvage therapy was categorized as either systemic, local, or none. Patient characteristics were tested for association with salvage therapy using analysis of variance, Pearson chi-square tests, and multinomial logistic regression analysis. RESULTS: Of the 839 patients identified as failing therapy, 390 (47%), 146 (17%), and 303 (36%) received systemic, local, or no salvage therapy, respectively. Type of primary treatment received was associated with type of salvage therapy (P < .01). There has been an increasing trend in the use of local salvage therapy over the past 10 years (P = .04). Primary treatment type and biopsy Gleason score were significantly associated with type of salvage therapy. CONCLUSIONS: The use of local salvage therapy has increased over the past decade, whereas the use of systemic salvage therapy has declined. Primary treatment is an important factor in determining which type of salvage therapy a patient will receive.

Impact of androgen deprivation therapy on mental and emotional well-being in men with prostate cancer: analysis from the CaPSURE™ registry.

PURPOSE: While androgen deprivation therapy can delay cancer progression and reduce tumor burden, its use can be limited by adverse side effects. We evaluated the effect of androgen deprivation therapy on mental and emotional well-being in men with nonmetastatic prostate cancer. MATERIALS AND METHODS: Participants were enrolled in the national CaPSURE (Cancer of the Prostate Strategic Urologic Research Endeavor) registry, and treated with radical prostatectomy, external beam radiation therapy or brachytherapy with no androgen deprivation therapy (local); local with androgen deprivation therapy (combination); or primary androgen deprivation therapy. Emotional quality of life was evaluated by SF-36® social function, role emotional, vitality and mental health subscales before and up to 24 months after treatment. Subscales were assessed as continuous scores and as clinically meaningful declines of at least half a standard deviation since pretreatment. Associations between treatment and quality of life changes over time were evaluated with mixed modeling. Quality of life declines were evaluated with logistic regression. RESULTS: Among 3,068 men the combination and primary androgen deprivation therapy groups were older, single, with less education and higher clinical CAPRA (Cancer of the Prostate Risk Assessment) score risk than the local group (all values p <0.01). Androgen deprivation therapy exposure was associated with significant changes with time in adjusted role emotional (-8.4 points, p = 0.01) and vitality (-9.2 points, p = 0.02) scores. Treatment group was not associated with any clinically meaningful quality of life declines. A potential limitation is the observational nature of the study. CONCLUSIONS: Use of androgen deprivation therapy was associated with changes in mental and emotional well-being but did not result in clinically meaningful declines at 24 months. Patients must be counseled on possible quality of life changes related to androgen deprivation therapy as well as interventions to attenuate these effects before receiving treatment for prostate cancer.