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Purpose We report the outcomes in patients with muscle invasive bladder cancer from 2 institutions who experienced a clinically complete response to neoadjuvant platinum based chemotherapy and elected active surveillance. It was unknown whether conservative treatment could be safely implemented in these patients. Materials and Methods We retrospectively reviewed the records of patients with muscle invasive bladder cancer at our institutions who elected surveillance following a clinically complete response to transurethral resection of bladder tumors and neoadjuvant chemotherapy from 2001 to 2017. A clinically complete response was defined as absent tumor on post-chemotherapy transurethral resection of bladder tumor, negative cytology and normal cross-sectional imaging. Results In the 148 patients followed a median of 55 months (range 5 to 145) the 5-year disease specific, overall, cystectomy-free and recurrence-free survival rates were 90%, 86%, 76% and 64%, respectively. Of the patients 71 (48%) experienced recurrence in the bladder, including 16 (11%) with muscle invasive disease and 55 (37%) with noninvasive disease. Salvage radical cystectomy prevented cancer specific death in 9 of 12 patients (75%) who underwent cystectomy after muscle invasive relapse and in 13 of 14 (93%) after noninvasive relapse. Conclusions We observed high rates of overall and disease specific survival with bladder preservation in patients who achieved a clinically complete response to neoadjuvant chemotherapy. These outcomes support the safety of active surveillance in carefully selected, closely monitored patients with muscle invasive bladder cancer. Future studies should aim to improve patient selection by identifying biomarkers predicting invasive relapse and developing novel imaging methods of early detection. [ABSTRACT FROM AUTHOR]

Purpose Active surveillance is emerging as a safe and effective strategy for the management of small renal masses (4 cm or less). We characterized the growth rate and its pertinence to clinical outcomes in a prospective multi-institutional study of patients with small renal masses. Materials and Methods Since 2009, the DISSRM (Delayed Intervention and Surveillance for Small Renal Masses) prospective, multi-institutional registry of patients with small renal masses has enrolled patients who elect primary intervention or active surveillance. Patients who elect active surveillance received regularly scheduled imaging and those with 3 or more followup images were included in the current study to evaluate growth rates. Results We evaluated 318 patients who elected active surveillance, of whom 271 (85.2%) had 3 or more followup images available with a median imaging followup of 1.83 years. The overall mean ± SD small renal mass growth rate was 0.09 ± 1.51 cm per year (median 0.09) with no variables demonstrating statistically significant associations. The growth rate and variability decreased with longer followup (0.54 and 0.07 cm per year at less than 6 months and greater than 1 year, respectively). No patients had metastatic disease or died of kidney cancer. No statistically significant difference was noted in the growth rate in patients with biopsy demonstrated renal cell carcinoma or in those who died. Conclusions Small renal mass growth kinetics are highly variable early on active surveillance with growth rates and variability decreasing with time. Early in active surveillance, especially during the initial 6 to 12 months, the growth rate is variable and does not reliably predict death or adverse pathological features in the patient subset with available pathology findings. An elevated growth rate may indicate the need for further assessment with imaging or consideration of biopsy prior to progressing to treatment. Additional followup will inform the best clinical pathway for elevated growth rates. [ABSTRACT FROM AUTHOR]

Purpose To our knowledge quality of life has not been evaluated in rigorous fashion in patients undergoing active surveillance for small renal masses. The prospective, multi-institutional DISSRM (Delayed Intervention and Surveillance for Small Renal Masses) Registry was opened on January 1, 2009, enrolling patients with cT1a (4.0 cm or less) small renal masses who elected primary intervention or active surveillance. Materials and Methods Patients were enrolled following a choice of active surveillance or primary intervention. The active surveillance protocol includes imaging every 4 to 6 months for 2 years and every 6 to 12 months thereafter. The SF12® quality of life questionnaire was completed at study enrollment, at 6 and 12 months, and annually thereafter. MCS (Mental Component Summary), PCS (Physical Component Summary) and overall score were evaluated among the groups and with time using ANOVA and linear regression mixed modeling. Results At 82 months among 3 institutions 539 patients were enrolled with a mean ± SD followup of 1.8 ± 1.7 years. Of the patients 254 were on active surveillance, 285 were on primary intervention and 21 were on active surveillance but crossed over to delayed intervention. A total of 1,497 questionnaires were completed. Total and PCS quality of life scores were better for primary intervention at enrollment through 5 years. There were generally no differences in MCS scores among the groups and there was a trend of improving scores with time. Conclusions In a prospective registry of patients undergoing active surveillance or primary intervention for small renal masses those undergoing primary intervention had higher quality of life scores at baseline. This was due to a perceived benefit in the physical health domain, which persisted throughout followup. Mental health, which includes the domains of depression and anxiety, was not adversely affected while on active surveillance, and it improved with time after selecting a management strategy. [ABSTRACT FROM AUTHOR]

Purpose Although associated with an overall favorable survival rate, the heterogeneity of non-muscle invasive bladder cancer (NMIBC) affects patients’ rates of recurrence and progression. Risk stratification should influence evaluation, treatment and surveillance. This guideline attempts to provide a clinical framework for the management of NMIBC. Materials and Methods A systematic review utilized research from the Agency for Healthcare Research and Quality (AHRQ) and additional supplementation by the authors and consultant methodologists. Evidence-based statements were based on body of evidence strength Grade A, B, or C and were designated as Strong, Moderate, and Conditional Recommendations with additional statements presented in the form of Clinical Principles or Expert Opinions. 1 Results A risk-stratified approach categorizes patients into broad groups of low-, intermediate-, and high-risk. Importantly, the evaluation and treatment algorithm takes into account tumor characteristics and uniquely considers a patient’s response to therapy. The 38 statements vary in level of evidence, but none include Grade A evidence, and many were Grade C. Conclusion The intensity and scope of care for NMIBC should focus on patient, disease, and treatment response characteristics. This guideline attempts to improve a clinician’s ability to evaluate and treat each patient, but higher quality evidence in future trials will be essential to improve level of care for these patients. [ABSTRACT FROM AUTHOR]

Purpose We compared the pathological and survival outcomes of patients who underwent radical cystectomy soon after bacillus Calmette-Guérin failure with those of patients who received additional salvage intravesical chemotherapy before cystectomy for nonmuscle invasive bladder cancer. We also identified predictors of prognosis in the entire cohort. Materials and Methods We retrospectively analyzed the records of 117 patients who underwent radical cystectomy for recurrent nonmuscle invasive bladder cancer at our institution from 1990 to 2012. The cohort was divided into group 1 of 61 patients treated only with bacillus Calmette-Guérin with or without interferon-α and group 2 of 56 who received at least 1 additional salvage intravesical chemotherapy after bacillus Calmette-Guérin. Results Final pathology and survival outcomes did not differ significantly between the groups. Five-year overall and cancer specific survival was similar in groups 1 and 2 at 80% and 85%, respectively, at approximately equivalent followups. Median bladder retention was 1.7 years longer in group 2 (p <0.001). On multivariate Cox regression analysis delayed cystectomy in group 2 did not convey a significant hazard for all cause mortality after cystectomy (HR 1.08, p = 0.808). Only up-staging to cT1 (HR 1.88, p = 0.045), lymph node invasion (HR 2.58, p = 0.023) and prostatic urethra involvement (HR 1.95, p = 0.029) achieved significance. Conclusions With appropriate selection for salvage intravesical chemotherapy patients who elect bladder sparing treatment instead of earlier radical cystectomy after bacillus Calmette-Guérin fails do not sacrifice positive pathological or oncologic outcomes while retaining bladder function for a significantly longer duration. [ABSTRACT FROM AUTHOR]

Purpose We compared renal function outcomes among patients in the surveillance and intervention arms of the DISSRM registry. Materials and Methods Patients were grouped into chronic kidney disease stages by estimated glomerular filtration rate range. Cases were considered up staged if a more advanced chronic kidney disease stage was entered during followup. Chronic kidney disease up staging-free survival was compared among groups using Kaplan-Meier analysis and paired comparisons log rank tests. Multivariate Cox regression identified independent predictors of chronic kidney disease up staging-free survival. Results A total of 162 patients met the study inclusion criteria, with 68 in the surveillance arm, 65 undergoing partial nephrectomy, 15 undergoing radical nephrectomy and 14 undergoing cryoablation. Median tumor size was 2.2 cm. Mean estimated glomerular filtration rate change was significantly larger for radical nephrectomy vs surveillance (−9.2 vs −0.5 ml/minute/1.73 m 2 ) and for radical vs partial nephrectomy (−9.2 vs −1.9 ml/minute/1.73 m 2 ) (p=0.001). No other groups differed significantly. On Kaplan-Meier analysis patients undergoing radical nephrectomy had significantly worse chronic kidney disease up staging-free survival vs those treated with partial nephrectomy (p=0.029), surveillance (p=0.007) and cryoablation (p=0.019). No other groups differed significantly. On multivariate analysis radical nephrectomy independently predicted poor chronic kidney disease up staging-free survival (odds ratio vs surveillance 30.6, p=0.001). Neither partial nephrectomy (p=0.985) nor cryoablation (p=0.976) predicted poor chronic kidney disease up staging-free survival relative to surveillance. Conclusions Patients in the surveillance arm had superior estimated glomerular filtration rate preservation compared to those in the radical nephrectomy but not the partial nephrectomy arm. In certain patients with small renal masses surveillance and partial nephrectomy may offer comparable renal functional outcomes. This could be partly attributable to a modest estimated glomerular filtration rate decrease associated with surveillance itself. A thorough understanding of the renal functional impacts of treatment modalities is critical in the management of small renal masses. [ABSTRACT FROM AUTHOR]

Purpose We analyze the relationship among various patient, operative and tumor characteristics to determine which factors correlate with renal parenchymal volume loss after nephron sparing surgery using a novel 3-dimensional volume assessment. Materials and Methods We conducted a retrospective review of an institutional database of patients who underwent nephron sparing surgery from 1992 to 2014 for a localized renal mass. Tumors were classified according to the R.E.N.A.L. nephrometry system. Using 3-dimensional reconstruction imaging software, preoperative and postoperative renal parenchymal volume was calculated for the ipsilateral and contralateral kidney. Results A total of 158 patients were analyzed. Mean patient age was 58.7 years and mean followup was 40.1 months. Mean preoperative tumor volume was 34.0 cc and mean tumor dimension was 3.4 cm. Mean R.E.N.A.L. nephrometry score was 6.2, with 60.1%, 34.2% and 5.7% of tumors classified as low, medium and high complexity, respectively. Mean change in renal parenchymal volume after nephron sparing surgery was −15.3% for the ipsilateral kidney and −6.8% for total kidney volume. On univariate analysis ischemia time, tumor size, R.E.N.A.L. nephrometry score, complexity grouping and the individual nephrometry components of tumor size, percent exophytic, anterior/posterior, depth and tumor proximity to the renal artery or vein were associated with greater renal parenchymal volume loss. On multivariate analysis only ischemia time, tumor size, posterior location and percent exophytic were independently associated with more renal parenchymal volume loss. Conclusions Using precise 3-dimensional volumetric analysis we found that ischemia time, tumor size and endophytic/exophytic properties of a localized renal mass are the most important determinants of renal parenchymal volume loss. [ABSTRACT FROM AUTHOR]

Purpose The impact of cardiopulmonary bypass in level III-IV tumor thrombectomy on surgical and oncologic outcomes is unknown. We determine the impact of cardiopulmonary bypass on overall and cancer specific survival, as well as surgical complication rates and immediate outcomes in patients undergoing nephrectomy and level III-IV tumor thrombectomy with or without cardiopulmonary bypass. Materials and Methods We retrospectively analyzed 362 patients with renal cell cancer and with level III or IV tumor thrombus from 1992 to 2012 at 22 U.S. and European centers. Cox proportional hazards models were used to compare overall and cancer specific survival between patients with and without cardiopulmonary bypass. Perioperative mortality and complication rates were assessed using logistic regression analyses. Results Median overall survival was 24.6 months in noncardiopulmonary bypass cases and 26.6 months in cardiopulmonary bypass cases. Overall survival and cancer specific survival did not differ significantly in both groups on univariate analysis or when adjusting for known risk factors. On multivariate analysis no significant differences were seen in hospital length of stay, Clavien 1-4 complication rate, intraoperative or 30-day mortality and cancer specific survival. Limitations include the retrospective nature of the study. Conclusions In our multi-institutional analysis the use of cardiopulmonary bypass did not significantly impact cancer specific survival or overall survival in patients undergoing nephrectomy and level III or IV tumor thrombectomy. Neither approach was independently associated with increased mortality on multivariate analysis. Greater surgical complications were not independently associated with the use of cardiopulmonary bypass. [ABSTRACT FROM AUTHOR]

Purpose Response rates to current second line intravesical therapies for recurrent nonmuscle invasive bladder cancer range between 10% and 30%. Nanoparticle albumin bound (nab-)paclitaxel has increased solubility and lower toxicity compared to other taxanes. Results of the phase I intravesical trial of this compound demonstrated minimal toxicity during dose escalation. We now report the results of a phase II trial to assess efficacy. Materials and Methods This study was an investigator initiated, single center, single arm, phase II trial investigating the use of nab-paclitaxel in patients with recurrent Tis, T1 and Ta urothelial carcinoma in whom at least 1 prior regimen of intravesical bacillus Calmette-Guérin failed. Patients received 500 mg/100 ml nab-paclitaxel administered in 6 weekly intravesical instillations. Efficacy was evaluated with cystoscopy, biopsy, cytology and imaging. If complete response was achieved, patients were treated with full dose monthly maintenance treatments for 6 months. Results A total of 28 patients were enrolled in the study. Of these patients 10 (35.7%) exhibited a complete response after initial treatment. At 1 year all of these responses remained durable after maintenance therapy. At a mean followup of 21 months (range 5 to 47) 19 of 28 (67.8%) patients retained their bladders without progression or distant metastases. A single patient had progression to muscle invasive disease at radical cystectomy. Treatment related adverse events were noted in 9 of 28 (32.1%) patients and were limited to grade 1 or 2. Conclusions Intravesical nab-paclitaxel has minimal toxicity and a 35.7% response rate in patients with nonmuscle invasive bladder cancer and previous bacillus Calmette-Guérin failure. Complete response remained durable at 1 year followup in this heavily pretreated patient population. [ABSTRACT FROM AUTHOR]

Purpose We describe the clinical course of patients who achieved cT0 status after neoadjuvant chemotherapy for muscle invasive bladder cancer. There is no established treatment paradigm for these patients. Materials and Methods We retrospectively reviewed the records of 109 patients with muscle invasive bladder cancer (T2 or greater urothelial carcinoma of the bladder) who underwent platinum based neoadjuvant chemotherapy at our institution from 1988 to 2012. Post-chemotherapy assessment of the response included cytology, cystoscopy with biopsy and cross-sectional imaging. Results Of 109 patients 32 (29.4%) achieved cT0 status after neoadjuvant chemotherapy. Mean ± SD age of the cohort was 68.3 ± 9.6 years. Of the patients 21 received MVAC, 8 received gemcitabine and cisplatin, and 3 received another regimen. Seven complete responders elected immediate radical cystectomy after the completion of neoadjuvant chemotherapy. Of 25 patients who refused radical cystectomy after achieving cT0 status 7 experienced relapse after the completion of neoadjuvant chemotherapy and proceeded to radical cystectomy. The remaining 18 patients (72%) retained the bladder, including 6 (18.8% of the cohort) in whom nonmuscle invasive relapses were managed conservatively and 12 (37.5%) with no recurrence. In the 25 patients who elected bladder preservation after achieving cT0 status following neoadjuvant chemotherapy 5-year cancer specific survival was 88%. Conclusions With proper counseling and identification of treatment goals patients with cT0 after neoadjuvant chemotherapy for muscle invasive bladder cancer may have the option to retain the bladder with durable survival. Larger studies are needed to identify possible predictors of response on the clinical, pathological and molecular levels. [ABSTRACT FROM AUTHOR]

Purpose: Docetaxel is a safe agent for intravesical therapy. Adding monthly maintenance treatments can extend response durability. We report our cumulative experience with intravesical docetaxel in a larger cohort with extended followup. Materials and Methods: A total of 54 patients received salvage intravesical docetaxel for bacillus Calmette-Guérin refractory nonmuscle invasive bladder cancer between 2003 and 2012, including 18 treated during the original phase I trial. All patients received 6 weekly instillations of intravesical docetaxel. After the phase I trial, those with a complete response to induction treatment were offered single dose monthly maintenance treatments for a total of up to 12 months of docetaxel therapy. Recurrence was defined as positive biopsy or urine cytology. Recurrence-free, disease specific and overall survival was determined by Kaplan-Meier analysis. Results: Median followup was 39.1 months. Of the 54 patients 32 (59%) had a complete initial response after induction therapy, including 18 who received additional monthly maintenance treatments. Median time to recurrence in initial responders treated with vs without docetaxel maintenance was 39.3 vs 19.0 months. One and 3-year recurrence-free survival rates for the entire cohort were 40% and 25%, respectively. Of the 54 patients 17 (24%) underwent radical cystectomy at a median of 24 months of followup. Five-year disease specific and overall survival rates were 85% and 71%, respectively. Conclusions: Intravesical docetaxel appears to be a promising agent with significant efficacy and durability for bacillus Calmette-Guérin refractory nonmuscle invasive bladder cancer. Adding maintenance treatments may increase the duration of recurrence-free survival. [ABSTRACT FROM AUTHOR]

Purpose: We assessed the safety, pharmacokinetics and anticancer activity of intravesical CG0070, a cancer selective, replication competent adenovirus, for the treatment of nonmuscle invasive bladder cancer. Materials and Methods: A total of 35 patients received single or multiple (every 28 days × 3 or weekly × 6) intravesical infusions of CG0070 at 1 of 4 dose levels (1 × 1012, 3 × 1012, 1 × 1013 or 3 × 1013 viral particles). Response to treatment was based on cystoscopic assessment and biopsy or urine cytology. Urine and plasma CG0070, and granulocyte-monocyte colony-stimulating factor were measured in all patients. A subset of 18 patients was assessed for retinoblastoma phosphorylation status. Results: Grade 1–2 bladder toxicities were the most common adverse events observed. A maximum tolerated dose was not reached. High levels of granulocyte-monocyte colony-stimulating factor were detected in urine after administration in all patients. Virus replication was suggested based on an increase in urine CG0070 genomes between days 2 and 5 in 58.3% of tested patients (7 of 12). The complete response rate and median duration of the complete response across cohorts was 48.6% and 10.4 months, respectively. In the multidose cohorts the complete response rate for the combined groups (every 28 days and weekly × 6) was 63.6% (14 of 22 patients). In an exploratory, retrospective assessment patients with borderline or high retinoblastoma phosphorylation who received the multidose schedules had an 81.8% complete response rate (9 of 11). Conclusions: Intravesical CG0070 was associated with a tolerable safety profile and antibladder cancer activity. Granulocyte-monocyte colony-stimulating factor transgene expression and CG0070 replication were also suggested. [ABSTRACT FROM AUTHOR]

Purpose: Routine sampling of the transition zone during prostate biopsy has become increasingly common. Although approximately 10% of prostate cancers originate in the transition zone, the benefit of transition zone biopsies may be limited. We evaluated the usefulness of transition zone biopsy in patients with prostate cancer enrolled in active surveillance. Materials and Methods: Patients on active surveillance followed at our institution between 1993 and 2011 were identified in the urological oncology database. All surveillance biopsies were stratified by transition and peripheral zone pathology results. The usefulness of transition zone biopsy was assessed by whether transition zone specific cancer characteristics, eg volume and grade, changed disease management recommendations. Results: A single surgeon performed a total of 244 prostate biopsies in 92 men. Each patient underwent initial positive prostate biopsy and at least 1 active surveillance prostate biopsy. Mean age was 69 years. A mean of 2.7 biopsies were done per patient. Nine patients (10%) had positive transition zone cores on initial positive prostate biopsy, of whom 3 had transition zone unique cancers. One of these patients showed transition zone disease progression on active surveillance prostate biopsy, which led to up staging and exclusion from active surveillance. A total of 16 patients (17%) had positive transition zone cores on active surveillance prostate biopsy, of whom 13 had a negative transition zone on initial positive prostate biopsy. Transition and peripheral zone Gleason scores were identical in 9 of these patients and the transition zone score was lower in 4. Thus, transition zone pathology did not result in up staging or disease management alterations in any patient with new transition zone pathology. Conclusions: Up staging due to transition zone specific pathology is exceedingly rare. Transition zone biopsy in patients on active surveillance should be limited to those with transition zone involvement on initial positive prostate biopsy only. [Copyright &y& Elsevier]

Purpose: We determined the total amount of diagnostic radiation that a patient with testicular cancer receives during the course of treatment and the associated risk of secondary malignancy. Materials and Methods: At a single institution 119 men with seminomatous and nonseminomatous germ cell tumors of the testis were retrospectively identified. Annual and lifetime exposure to radiation was determined for each histological subtype. Values were assessed for compliance with International Commission of Radiological Protection guidelines. Results: The cohorts included 55 patients with seminomatous and 64 with nonseminomatous germ cell tumor. Between the groups no difference was found in the lifetime (215.5 and 214.1 mSV, p = 0.96) or the annual (104.6 and 104.6 mSV, respectively, p = 1.0) radiation dose. Of the 41 patients with more than 5-year followup 32 (78%) were in violation of guidelines by exceeding 20 mSV per year of radiation. Also, 74 patients (61.7%) received 50 mSV or greater of radiation during a 1-year period. Using the previously calculated excess relative risk for solid cancer and leukemia, excluding chronic lymphocytic leukemia, the RR was 68 and 329, respectively, with a 2.1% lifetime risk of fatal cancer over the baseline risk. Conclusions: At a tertiary care center with experience with managing testicular cancer 78% of patients with more than 5 years of followup exceeded current national and standard safety limits for radiation exposure. Imaging should be done judiciously in this population at high risk for radiation overexposure. [ABSTRACT FROM AUTHOR]

Purpose: After encouraging results from 2 clinical trials performed at our institution to test intravesical taxane based chemotherapy for bacillus Calmette-Guérin refractory, nonmuscle invasive bladder cancer we designed a study to identify molecular markers linked to the optimal response to such treatment modality. Materials and Methods: Included in the institutional review board approved study were 32 patients with nonmuscle invasive, bacillus Calmette-Guérin refractory bladder cancer who received intravesical taxane chemotherapy, that is docetaxel or nanoparticle albumin-bound paclitaxel. Immunophenotype analysis on tissue samples obtained before intravesical taxane therapy was done using a panel of molecular markers, including Ki-67, p53, and the microtubule associated proteins tau and stathmin. Results: Increased total tau (cytoplasmic and nuclear) and stathmin expression before intravesical taxane therapy was significantly associated with decreased recurrence-free survival (p <0.0001 and 0.007, respectively). A tau positive phenotype was an independent prognostic factor for recurrence-free survival on multivariate analysis (HR 15.66, 95% CI 2.68–91.71, p = 0.002). Neither the proliferation index assessed by Ki-67 expression nor p53 status was significantly associated with recurrence-free survival. Conclusions: Assessment of tau and stathmin protein expression should be considered to select patients before intravesical taxane based chemotherapy for nonmuscle invasive, bacillus Calmette-Guérin refractory bladder cancer since those who have tumors with low tau/stathmin protein expression show a better response to therapy. [ABSTRACT FROM AUTHOR]

Purpose: We used a large, population based registry to assess whether a difference in overall and cardiovascular survival may exist between radical nephrectomy and partial nephrectomy for renal cell carcinoma 2 cm or less. Materials and Methods: From the SEER (Surveillance, Epidemiology and End Results) registry we identified 4,216 patients with histologically confirmed renal cell carcinoma 2 cm or less who were treated with partial or radical nephrectomy. Patient and tumor characteristics were compared between the 2 patient groups. Multivariate logistic regression was done to predict the odds of undergoing radical nephrectomy. Cardiovascular survival and overall survival were compared between the 2 cohorts, adjusting for patient and tumor characteristics. Results: Overall 2,301 patients (55%) underwent partial nephrectomy. Partial nephrectomy use steadily increased during the study period from 27% of all cases in 1998 to 66% in 2007. Patients who underwent partial nephrectomy were an average of 2.5 years younger than those treated with radical nephrectomy (56.4 vs 58.9 years, p <0.001). They were more likely to be white and from the western or northeastern United States. Older age was the only independent predictor of radical nephrectomy (OR 1.02, 95% CI 1.01–1.03). When controlling for patient characteristics and surgery year, radical nephrectomy was associated with worse overall mortality (HR 2.24, 95% CI 1.75–2.84) and cardiovascular mortality (HR 2.53, 95% CI 1.51–4.23). Conclusions: Radical nephrectomy is associated with worse overall and cardiovascular survival compared to partial nephrectomy in patients with localized renal cell carcinoma 2 cm or less. These findings justify the widespread application of nephron sparing techniques to treat localized kidney cancer. [Copyright &y& Elsevier]

Purpose: Up to 50% of patients treated with intravesical agents for high grade nonmuscle invasive bladder cancer will have disease recurrence. Response rates to current second line intravesical therapies are low and for these high risk patients novel agents are necessary. Our previously completed phase I trial showed docetaxel was a safe agent for intravesical use. Nanoparticle albumin-bound paclitaxel (Abraxane®, ABI-007) has been shown to have increased solubility and lower toxicity compared to docetaxel in systemic therapy. Thus, we assessed the dose limiting toxicity and maximum deliverable dose of intravesical nanoparticle albumin-bound paclitaxel. Materials and Methods: Inclusion criteria for this institutional review board approved phase I trial were recurrent high grade Ta, T1 and Tis transitional cell carcinoma of the bladder for which at least 1 prior standard intravesical regimen failed. Six weekly instillations of nanoparticle albumin-bound paclitaxel were administered with a modified Fibonacci dose escalation model used until the maximum deliverable dose was achieved. The primary end point was dose limiting toxicity and the secondary end point was response rate. Results: A total of 18 patients were enrolled in the study. One patient demonstrated measurable systemic absorption after 1 infusion. Grade 1 local toxicities were experienced by 10 (56%) patients with dysuria being the most common, and no grade 2, 3 or 4 drug related local toxicities were encountered. Of the 18 patients 5 (28%) had no evidence of disease at posttreatment evaluation. Conclusions: Intravesical nanoparticle albumin-bound paclitaxel exhibited minimal toxicity and systemic absorption in the first human intravesical phase I trial to our knowledge. A larger phase II study has begun to formally evaluate the activity of this regimen. [Copyright &y& Elsevier]

Purpose: We retrospectively evaluated our single center experience with patients with renal cortical neoplasms who elected active surveillance. Materials and Methods: We retrospectively evaluated our urological oncology database between January 1993 and January 2009, identifying a total of 223 renal cortical neoplasms in 212 patients that were initially managed by active surveillance. We described patient and tumor characteristics, and assessed the differences between patients who remained on AS and those who underwent delayed intervention or progressed with metastasis. Results: Median patient age was 71 years at active surveillance initiation and the median Charlson comorbidity index was 3. Median tumor size was 2.8 cm (range 0.5 to 13.7) at study enrollment and 3.7 cm (range 0.9 to 14.1) at final assessment. The median growth rate in the entire cohort was 0.34 cm per year (range 0.29 to 2.3). Median followup was 35 months (range 6 to 137). Active surveillance failed in 15 patients (7%), of whom 4 (2%) progressed to metastasis and 11 (5%) required intervention. When comparing cases of failed active surveillance with those that continued, there were statistical differences in initial tumor size (2.61 vs 3.64 cm, p = 0.019), final tumor size (3.56 vs 5.17 cm, p = 0.001) and growth rate (0.34 vs 1.75, p = 0.001). There was no correlation between initial tumor size and growth rate (Pearson''s coefficient r = 0.006, p = 0.932). A total of 14 patients died of another medical condition. Only 1 cancer related death (0.5%) was reported in the entire cohort. Conclusions: Active surveillance for renal cortical neoplasms in select older patients with comorbidities is a reasonable treatment option. At 3-year followup we noted a 7% failure rate. [Copyright &y& Elsevier]

Purpose: Black American and Afro-Caribbean men may experience the highest incidence of prostate cancer globally. We examined the effect of race/ethnicity on the initiation and maintenance of annual prostate specific antigen screening and the role of physicians in screening continuity in these high risk groups. Materials and Methods: Stratified cluster sampling of census tract blocks in Brooklyn, New York yielded 533 male participants 45 to 70 years old. The men were classified into 4 racial/ethnic groups, including white men born in the United States, black men born in the United States, immigrant Jamaican men, and immigrant men from Trinidad and Tobago. Participants recorded the number of prostate specific antigen tests performed in the last 10 years. Subject adherence was calculated as annually screened, less than annually screened and never screened. Multinomial logistic regression was used to compare screening behavior across the ethnic groups. Results: Overall 28.3% of participants reported annual screening, 44.5% reported screening less than annually and 27.2% reported having never been screened. Jamaicans (OR 3.1) and men from Trinidad and Tobago (OR 5.4) were more likely to screen less than annually compared to not at all. However, black American men (OR 0.3), Jamaican men (OR 0.3), and men from Trinidad and Tobago (OR 0.2) were less likely to maintain annual screening compared with white men, as were men who did not undergo an annual physical examination (OR 0.3) and those with low prostate cancer knowledge (0.5). Conclusions: Afro-Caribbean men are not less likely than white men to undergo initial prostate specific antigen screening but they are much less likely to maintain annual screening. Through comprehensive discussion and annual examinations physicians have an important role in ensuring prostate specific antigen screening continuity. Our results suggest the need for more culturally appropriate outreach efforts and educational interventions to improve screening compliance. [Copyright &y& Elsevier]

Purpose: Significant variability exists in the urological community regarding the number of cores that should be taken during prostate biopsy. Using CaPSURE™ we determined trends in prostate biopsy patterns during the last decade and assessed whether changes in biopsy number have had an impact on outcomes after radical prostatectomy. Materials and Methods: In CaPSURE between 1995 and 2004 we identified 6,450 men with newly diagnosed prostate cancer who underwent biopsy with 6 cores or greater. The number of cores removed, number of cores positive for cancer and percent of cores containing cancer were analyzed by year of diagnosis. For 1,757 men who underwent radical prostatectomy these variables were entered into Cox proportional hazards models controlling for preoperative prostate specific antigen, biopsy Gleason sum and clinical stage to predict recurrence-free survival. Results: The mean number of removed cores increased from 6.9 in 1995 to 10.2 in 2004 (p <0.0001). The mean number of positive cores remained unchanged from 2.9 in 1995 to 3.2 in 2004 (p = 0.40). The percent of positive cores decreased from 42.6% in 1995 to 32.1% in 2004 (p <0.0001). The number and percent of positive cores were associated with recurrence-free survival after radical prostatectomy throughout the study period (each p <0.001). Conclusions: The percent of positive cores is an independent predictor of disease recurrence after radical prostatectomy. The total number of tissue cores sampled increased during the last decade, thereby driving down the mean percent of positive cores from 42.6% to 32.1%. The trend toward an increasing number of removed cores may have contributed indirectly to improved outcomes after radical prostatectomy in the last decade. [Copyright &y& Elsevier]

Purpose: Multiple investigators have argued that PSA may no longer be an accurate marker of prostate cancer biology. We determined whether the impact of PSA in predicting biochemical failure after radical prostatectomy has changed since the beginning of the PSA era. Materials and Methods: A total of 1,246 patients were identified from the Columbia University Comprehensive Urological Oncology Database who underwent radical prostatectomy by 1 of 3 surgeons between 1988 and 2003. Cox proportional hazards models were fit to the data to estimate the impact of PSA (logPSA) in predicting BCF (PSA 0.2 ng/ml or greater). To determine if the predictive impact of PSA changed over time, patients were classified based on year of surgery, and an interaction term between PSA and time was included. Finally concordance indexes were estimated to determine if the predictive ability of PSA has changed over time. Results: In a Cox model including PSA, year of surgery and a year/PSA interaction term, the impact of PSA appears to change over time (p = 0.002). However, when correcting for the effects of stage and grade there was no significant change in the impact of PSA. In addition, concordance analysis indicated that the predictive ability of PSA has remained constant throughout the PSA era (0.65, 0.66 and 0.64 for each period, respectively). Conclusions: This study demonstrates that the predictive ability of PSA as a cancer outcomes biomarker has not changed significantly since the beginning of the PSA era. Despite suggestions to the contrary, PSA remains an important variable in predicting risk of BCF after RP. [Copyright &y& Elsevier]

ABSTRACT: Purpose: Few published studies have simultaneously analyzed multiple prognostic factors to predict recurrence after surgery for conventional clear cell renal cortical carcinomas. We developed and performed external validation of a postoperative nomogram for this purpose. We used a prospectively updated database of more than 1,400 patients treated at a single institution. Materials and Methods: From January 1989 to August 2002, 833 nephrectomies (partial and radical) for renal cell carcinoma of conventional clear cell histology performed at Memorial Sloan-Kettering Cancer Center were reviewed from the center''s kidney database. Patients with von Hippel-Lindau disease or familial syndromes, as well as patients presenting with synchronous bilateral renal masses, or distant metastases or metastatic regional lymph nodes before or at surgery were excluded from study. We modeled clinicopathological data and disease followup for 701 patients with conventional clear cell renal cell carcinoma. Prognostic variables for the nomogram included pathological stage, Fuhrman grade, tumor size, necrosis, vascular invasion and clinical presentation (ie incidental asymptomatic, locally symptomatic or systemically symptomatic). Results: Disease recurrence was noted in 72 of 701 patients. Those patients without evidence of disease had a median and maximum followup of 32 and 120 months, respectively. The 5-year probability of freedom from recurrence for the patient cohort was 80.9% (95% confidence interval 75.7% to 85.1%). A nomogram was designed based on a Cox proportional hazards regression model. Following external validation predictions by the nomogram appeared accurate and discriminating, and the concordance index was 0.82. Conclusions: A nomogram has been developed that can be used to predict the 5-year probability of freedom from recurrence for patients with conventional clear cell renal cell carcinoma. This nomogram may be useful for patient counseling, clinical trial design and effective patient followup strategies. [Copyright &y& Elsevier]