Decreases in Suicide Deaths and Attempts Linked to the White Mountain Apache Suicide Surveillance and Prevention System, 2001-2012.

OBJECTIVES: We evaluated the impact of a comprehensive, multitiered youth suicide prevention program among the White Mountain Apache of Arizona since its implementation in 2006. METHODS: Using data from the tribally mandated Celebrating Life surveillance system, we compared the rates, numbers, and characteristics of suicide deaths and attempts from 2007 to 2012 with those from 2001 to 2006. RESULTS: The overall Apache suicide death rates dropped from 40.0 to 24.7 per 100 000 (38.3% decrease), and the rate among those aged 15 to 24 years dropped from 128.5 to 99.0 per 100 000 (23.0% decrease). The annual number of attempts also dropped from 75 (in 2007) to 35 individuals (in 2012). National rates remained relatively stable during this time, at 10 to 13 per 100 000. CONCLUSIONS: Although national rates remained stable or increased slightly, the overall Apache suicide death rates dropped following the suicide prevention program. The community surveillance system served a critical role in providing a foundation for prevention programming and evaluation.

Long-term survival rates after resection for locally advanced kidney cancer: Memorial Sloan Kettering Cancer Center 1989 to 2012 experience.

PURPOSE: We analyzed the 23-year Memorial Sloan Kettering Cancer Center experience with surgical resection, and concurrent adrenalectomy and lymphadenectomy for locally advanced nonmetastatic renal cell carcinoma. MATERIALS AND METHODS: We retrospectively reviewed the records of 802 patients who underwent nephrectomy with or without concurrent adrenalectomy or lymphadenectomy for locally advanced renal cell carcinoma, defined as stage T3 or greater and M0. Patients who received adjuvant treatment within 3 months of surgery or had fewer than 3 months of followup or bilateral renal masses at presentation were excluded from analysis. Five and 10-year progression-free and overall survival was estimated by the Kaplan-Meier method. Differences between groups were analyzed by the log rank test. RESULTS: A total of 596 (74%) and 206 patients (26%) underwent radical and partial nephrectomy, respectively. Renal cell carcinoma progressed in 189 patients and 104 died of the disease. Median followup in patients without progression was 4.6 years. Symptoms at presentation, ASA(®) classification, tumor stage, histological subtype, grade and lymph node status were significantly associated with progression-free and overall survival. On multivariate analysis adrenalectomy use decreased with time but lymphadenectomy use increased (OR 0.82 vs 1.16 per year). Larger tumors were associated with a higher likelihood of concurrent adrenalectomy and lymphadenectomy. CONCLUSIONS: In our series of patients with locally advanced nonmetastatic renal cell carcinoma survival was favorable in those in good health who were asymptomatic at presentation with T3 tumors and negative lymph nodes. Further, there has been a trend toward more selective use of adrenalectomy and increased use of lymphadenectomy.

Long-term oncological outcomes of a phase II trial of neoadjuvant chemohormonal therapy followed by radical prostatectomy for patients with clinically localised, high-risk prostate cancer.

OBJECTIVE: To determine long-term oncological outcomes of radical prostatectomy (RP) after neoadjuvant chemohormonal therapy (CHT) for clinically localised, high-risk prostate cancer. PATIENTS AND METHODS: In this phase II multicentre trial of patients with high-risk prostate cancer (PSA level >20 ng/mL, Gleason ≥8, or clinical stage ≥T3), androgen-deprivation therapy (goserelin acetate depot) and paclitaxel, carboplatin and estramustine were administered before RP. We report the long-term oncological outcomes of these patients and compared them to a contemporary cohort who met oncological inclusion criteria but received RP only. RESULTS: In all, 34 patients were enrolled and followed for a median of 13.1 years. Within 10 years most patients had biochemical recurrence (BCR-free probability 22%; 95% confidence interval [CI] 10-37%). However, the probability of disease-specific survival at 10 years was 84% (95% CI 66-93%) and overall survival was 78% (95% CI 60-89%). The CHT group had higher-risk features than the comparison group (123 patients), with an almost doubled risk of calculated preoperative 5-year BCR (69% vs 36%, P < 0.01). After adjusting for these imbalances the CHT group had trends toward improvement in BCR (hazard ratio [HR] 0.76, 95% CI 0.43-1.34; P = 0.3) and metastasis-free survival (HR 0.55, 95% CI 0.24-1.29; P = 0.2) although these were not statistically significant. CONCLUSIONS: Neoadjuvant CHT followed by RP was associated with lower rates of BCR and metastasis compared with the RP-only group; however, these results were not statistically significant. Because this treatment strategy has known harms and unproven benefit, this strategy should only be instituted in the setting of a clinical trial.

Changes in pelvic organ prolapse surgery in the last decade among United States urologists.

PURPOSE: Surgical correction of pelvic organ prolapse underwent transformation in the last decade. Training in pelvic organ prolapse surgery, the ease of mesh kit use, and Food and Drug Administration warnings about mesh have influenced practice patterns. We investigated trends in pelvic organ prolapse procedures. MATERIALS AND METHODS: Case logs of pelvic organ prolapse procedures, mesh use and pessary placement were obtained from the American Board of Urology for 2003 to 2012. We evaluated associations between surgeon characteristics and the use of pelvic organ prolapse procedures. RESULTS: Of 6,355 nonpediatric urologists applying for certification or recertification 2,192, representing a 10% annual sample of all urologists, reported performing pelvic organ prolapse procedures during the study period. The number of procedures increased steadily from 930 in 2003 to 6,978 in 2012. The number of colporrhaphies increased from 806 to 2,670 and the number of colpopexies increased from 32 to 1,414 between 2003 and 2012. The number of vaginal colpopexies increased from 24 to 1,016 during the study period. The number of sacrocolpopexies increased from 8 to 398 with exponential increases in laparoscopic sacrocolpopexy (282 cases by 2012). Mesh insertion increased from 10 cases reported by applicants in 2005 to 1,552 reported in 2012 (p <0.0005). Mesh revision, first reported in 2007 with 52 performed, consistently increased to 214 in 2012. Urologists trained in female urology performed a median of 16 pelvic organ prolapse procedures, double the number reported by surgeons trained in other urological fellowships. Urologists of the female gender also reported performing approximately 8 more procedures annually than male urologists. CONCLUSIONS: The number of pelvic organ prolapse operations done by urologists increased dramatically in the last decade with a similar increase in mesh use. More colpopexies are now performed with laparoscopic sacrocolpopexy showing an exponential increase. The recent trend of mesh revision is notable with a much faster rate of increase than mesh insertion.

Preoperative predictors of renal function decline after radical nephroureterectomy for upper tract urothelial carcinoma.

OBJECTIVES: To model renal function after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). To identify predictors of renal function decline after surgery, thereby allowing the identification of patients likely to be ineligible for cisplatin-based chemotherapy in the adjuvant setting. PATIENTS AND METHODS: We retrospectively identified 374 patients treated with RNU for UTUC at three centres between 1995 and 2010. Estimated glomerular filtration rate (eGFR) was calculated using Chronic Kidney Disease Epidemiology Collaboration equation before RNU and at early (1-5 months after RNU) and late (>5 months) time points after RNU. Only patients deemed eligible for cisplatin-based chemotherapy before RNU (preoperative glomerular filtration rate [GFR] ≥60 mL/min/1.73 m(2) ) were included. Multivariable analysis identified the preoperative predictors of eGFR after RNU at early postoperative and late postoperative time points. RESULTS: A total of 163 patients had an eligible early post-RNU eGFR measurement and 172 had an eligible late eGFR measurement. The median eGFR declined by 32% and did not show a significant trend toward recovery over time (P = 0.4). On multivariable analysis preoperative eGFR and patient age were significantly associated with early and late postoperative eGFR, while Charlson comorbidity index score was significantly associated with late postoperative eGFR alone. CONCLUSIONS: In patients with normal preoperative eGFR (≥60 mL/min/1.73 m(2) ), renal function decreases by one-third after RNU and does not show evidence of recovery over time. Elderly patients and those with pre-RNU eGFR closer to 60 mL/min/1.73 m(2) (lower eGFR in the present cohort) are more likely to be ineligible for adjuvant cisplatin-based chemotherapy regimens because of renal function loss after RNU.

Clinically significant prostate cancer is rarely missed by ablative procedures of the prostate in men with prostate specific antigen less than 4 ng/ml.

PURPOSE: Laser vaporization of the prostate is widely used to treat lower urinary tract symptoms. It may decrease the hospital cost and morbidity associated with transurethral resection of the prostate. However, prostate cancer may go undetected because tissue is not taken at laser vaporization. To our knowledge the rate of clinically significant prostate cancer missed by laser vaporization has not been assessed to date. We determined the rate of clinically significant prostate cancer detected by transurethral resection of the prostate compared to the estimated number of cancers missed by laser vaporization. MATERIALS AND METHODS: A total of 74,505 men diagnosed with stage T1 prostate cancer between 2004 and 2006 were identified from the SEER (Surveillance, Epidemiology and End Results) program in the United States. The total number of laser vaporizations and transurethral resections were calculated based on Medicare claims for the same period. Clinically significant cancer was defined as that with a Gleason score of 7 or greater in men 40 to 75 years old. RESULTS: If prostate specific antigen screening were used uniformly (excluding men with prostate specific antigen greater than 4 ng/ml), only 1 of 382 transurethral resections of the prostate would identify clinically significant prostate cancer for a total of 390 in the American population in 3 years. Based on Medicare reported laser vaporization use a total of only 163 clinically significant cancers would be missed in more than 60,000 procedures. CONCLUSIONS: The incidence of T1a and T1b prostate cancer remains low and few patients have clinically significant prostate cancer. When prostate specific antigen screening is used, the number of clinically significant tumors missed by ablative procedures is low (average of 0.26% of all procedures) and can be identified by prostate specific antigen screening.

Contemporary practice patterns of endoscopic surgical management for benign prostatic hyperplasia among urologists in the United States.

PURPOSE: We describe contemporary trends in endoscopic surgical management for benign prostatic hyperplasia. We examined case logs submitted by urologists for American Board of Urology certification or recertification. We compared electrosurgical transurethral resection of the prostate vs laser vaporization or laser enucleation and determined the impact of surgeon age on practice patterns. MATERIALS AND METHODS: We analyzed case logs from 2004 to 2010 for trends and used logistic regression models to assess the impact of surgeon age on endoscopic surgery use. RESULTS: A total of 3,955 urologists included at least 1 endoscopic surgical management in the case logs, while 2,334 (59%) exclusively performed electrosurgical transurethral resection of the prostate and 309 (8%) exclusively performed laser vaporization or laser enucleation. We observed a large increase in the number and proportion of laser procedures from 11% in 2004 to 44% in 2010. Although there was no difference in median age between urologists who performed exclusively electrosurgical transurethral resection and those who performed laser procedures, the latter had a substantially higher case volume. Older urologists were significantly less likely to perform laser vaporization or enucleation when undergoing the second recertification (OR 0.56/10 years of age, 95% CI 0.36-0.87, p = 0.009), but not the initial certification. CONCLUSIONS: There was a substantial increase in laser vaporization or laser enucleation procedures performed by urologists who underwent board certification or recertification in 2004 to 2010. However, of those undergoing the second recertification older age was significantly associated with a lower likelihood of performing laser procedures. These data provide estimates of current practice patterns and further our understanding of evolving surgical treatment for benign prostatic hyperplasia.

Urine neutrophil gelatinase-associated lipocalin as a marker of acute kidney injury after kidney surgery.

PURPOSE: We evaluated urine NGAL as a marker of acute kidney injury in patients undergoing partial nephrectomy. We sought to identify the preoperative clinical features and surgical factors during partial nephrectomy that are associated with renal injury, as measured by increased urine NGAL vs controls. MATERIALS AND METHODS: Using patients treated with radical nephrectomy or thoracic surgery as controls, we prospectively collected and analyzed urine and serum samples from patients treated with partial or radical nephrectomy, or thoracic surgery between April 2010 and April 2012. Urine was collected preoperatively and at multiple time points postoperatively. Differences in urine NGAL levels were analyzed among the 3 surgical groups using a generalized estimating equation model. The partial nephrectomy group was subdivided based on a preoperative estimated glomerular filtration rate of less than 60, or 60 ml/minute/1.73 m(2) or greater. RESULTS: Of 162 patients included in final analysis more than 65% had cardiovascular disease. The median estimated glomerular filtration rate was greater than 60 ml/minute/1.73 m(2) in the radical and partial nephrectomy, and thoracic surgery groups (61, 78 and 84.5 ml/minute/1.73 m(2), respectively). Preoperatively, a 10 unit increase in the estimated glomerular filtration rate was associated with a 4 unit decrease in urine NGAL in the partial nephrectomy group. Postoperatively, urine NGAL in the partial nephrectomy group was not higher than in controls and did not correlate with ischemia time. Patients with partial nephrectomy with a preoperative estimated glomerular filtration rate of less than 60 ml/minute/1.73 m(2) had higher urine NGAL postoperatively than those with a higher preoperative estimated rate. CONCLUSIONS: Urine NGAL does not appear to be a useful marker for detecting renal injury in healthy patients treated with partial nephrectomy. However, patients with poorer preoperative renal function have higher baseline urine levels and appear more susceptible to acute kidney injury, as detected by urine levels and Acute Kidney Injury Network criteria, than those with a normal estimated glomerular filtration rate.

Prognostic impact of subclassification of radical prostatectomy positive margins by linear extent and Gleason grade.

PURPOSE: We evaluated the relationship of progression to positive surgical margin linear length and Gleason grade at a positive surgical margin. MATERIALS AND METHODS: We studied 2,150 prostatectomies done for pT2 or pT3a disease to determine grade, stage and surgical margin status. In patients with positive surgical margins we recorded the location, number, positive margin linear length and highest Gleason grade at a positive margin. The Kaplan-Meier method and log rank test were used to determine differences in progression-free probability among positive margin features. The concordance index was used to discriminate the accuracy of grouping surgical margin status as negative/positive vs positive margin linear length/highest Gleason grade. RESULTS: A total of 207 cases (10%) showed positive surgical margins, including 93 (45%) that were pT2+ and 114 (55%) that were pT3a. Patients with pT3a and positive margins had greater prostate specific antigen and tumor volume, and Gleason score 7 or greater than those with pT2+. A total of 45 patients with positive margins progressed. We then subcategorized positive margins. Of the patients 164 (79%) had 1 positive margin. Positive margin linear length was 1 mm or less, 1.1 to 3 and greater than 3 in 104 (50%), 55 (27%) and 48 cases (23%), respectively. Two-year progression-free probability was 95%, 91%, 83% and 47% in patients with negative margins and the 3 positive margin linear length groups, respectively (p <0.001). Gleason grade at a positive margin was 3 and 4/5 in 154 (74%) and 53 patients (26%), respectively. The latter group was significantly more likely to progress (p <0.001). The overall margin status concordance index was 0.636. It was not considerably enhanced by categorizing by positive surgical margin linear length/highest Gleason grade at positive margins. CONCLUSIONS: The linear extent of and highest Gleason grade at a positive surgical margin are associated with progression. However, subcategorization does not importantly add to predictive models using margin status only. More robust markers are needed in patients with positive surgical margins to warrant routine reporting and identify those at risk for biochemical recurrence.

Urinary diversion practice patterns among certifying American urologists.

PURPOSE: We investigated trends in urinary diversion use and surgeon characteristics in the performance of incontinent and continent urinary diversion using American Board of Urology data. MATERIALS AND METHODS: Annualized case log data for urinary diversion were obtained from the American Board of Urology for urologists who certified or recertified from 2002 to 2010. We evaluated the association between surgeon characteristics and the performance of any urinary diversion or the type of urinary diversion. RESULTS: Of the 5,096 certifying or recertifying urologist case logs examined 1,868 (37%) urologists performed any urinary diversion. The median number of urinary diversions was 4 per year (IQR 2, 6) and 222 urologists (4%) performed 10 or more per year. On multivariate analysis younger urologists, those self-identified as oncologists or female urologists, those who certified in more recent years and those in larger practice areas or outside the Northeast region of the United States were more likely to perform any urinary diversion. Only 9% of the total cohort (471 urologists) performed any continent urinary diversion. The likelihood of performing any continent urinary diversion increased with the number of urinary diversions (p <0.0001). As urinary diversion volume increased, the proportion representing continent urinary diversion also increased (p <0.0005). Surgeons in private practice settings and those in the Northeast were less likely to perform continent urinary diversion. CONCLUSIONS: Few urologists perform any urinary diversion. Continent urinary diversion is most frequently done by high volume surgeons. The type of urinary diversion that a patient receives may depend in part on surgeon characteristics.

TMPRSS2-ERG rearrangement in dominant anterior prostatic tumours: incidence and correlation with ERG immunohistochemistry.

AIM: To study prostate cancer zonal differences in TMPRSS2-ERG gene rearrangement. METHODS AND RESULTS: We examined 136 well-characterized dominant anterior prostatic tumours, including 61 transition zone (TZ) and 75 anterior peripheral zone (PZ) lesions, defined using strict anatomical considerations. TMPRSS2-ERG FISH and ERG protein immunohistochemistry were performed on tissue microarrays. FISH results, available for 56 TZ and 71 anterior PZ samples, were correlated with ERG staining and TZ-associated 'clear cell' histology. Fewer TZ cancers (four of 56; 7%) were rearranged than anterior PZ cancers (18 of 71; 25%) (P = 0.009); deletion was the sole mechanism of TZ cancer rearrangement. ERG protein overexpression was present in 4% (two of 56; both FISH+) and 30% (21 of 71; 17 FISH+) of TZ and anterior PZ tumours, respectively. 'Clear cell' histology was present in 21 of 56 (38%) TZ and eight of 71 (11%) anterior PZ tumours. Seven per cent of cancers with and 21% without this histology had rearrangement, regardless of zonal origin. CONCLUSIONS: TMPRSS2-ERG rearrangement occurs in dominant TZ and anterior PZ prostate cancers, with all rearranged TZ cancers in this cohort showing deletion. ERG immunohistochemistry demonstrated excellent sensitivity (86%) and specificity (96%) for TMPRSS2-ERG rearrangement. TMPRSS2-ERG fusion is rare in TZ tumours and present at a low frequency in tumours displaying 'clear cell' histology.

Surgical practice patterns for male urinary incontinence: analysis of case logs from certifying American urologists.

PURPOSE: Several options exist for the surgical correction of male stress urinary incontinence including periurethral bulking agents, artificial urinary sphincters and the recently introduced male urethral slings. We investigated contemporary trends in the use of these treatments. MATERIALS AND METHODS: Annualized case log data for incontinence surgeries from certifying and recertifying urologists were obtained from the ABU (American Board of Urology), ranging from 2004 to 2010. Chi-square tests and logistic regression models were used to evaluate the association between surgeon characteristics (type of certification, annual volume, practice type and practice location) and the use of incontinence procedures. RESULTS: Among the 2,036 nonpediatric case logs examined the number of incontinence treatments reported for certification has steadily increased over time from 1,936 to 3,366 treatments per year from 2004 to 2010 (p = 0.008). Nearly a fifth of urologists reported placing at least 1 sling. The proportion of endoscopic procedures decreased from 80% of all incontinence procedures in 2004 to 60% in 2010, but they remained the exclusive incontinence procedure performed by 49% of urologists. A urologist's increased use of endoscopic treatments was associated with a decreased likelihood of performing a sling procedure (OR 0.5, p <0.0005). Artificial urinary sphincter use remained stable, accounting for 12% of procedures. CONCLUSIONS: Incontinence procedures are on the rise. Urethral slings have been widely adopted and account for the largest increase among treatment modalities. Endoscopic treatments continue to be commonly performed and may represent overuse in the face of improved techniques. Further research is required to validate these trends.

Comparative outcomes of pure squamous cell carcinoma and urothelial carcinoma with squamous differentiation in patients treated with radical cystectomy.

PURPOSE: We compared clinical outcomes, and identified predictors of cancer specific and overall survival after radical cystectomy in patients with urothelial carcinoma with squamous differentiation and those with pure squamous cell carcinoma. MATERIALS AND METHODS: We reviewed data on 2,031 patients treated with radical cystectomy and pelvic lymph node dissection at a single high volume referral center. Of these patients 78 had squamous cell carcinoma and 67 had squamous differentiation. Survival estimates by histological subtype were described using Kaplan-Meier methods. Within histological subtypes pathological stage, nodal invasion, soft tissue margins, age and gender were evaluated as predictors of cancer specific survival and overall survival using univariate Cox regression. RESULTS: Median followup was 44 months. Of 104 patient deaths 60 died of their disease. We did not find a statistically significant difference between survival curves of patients with squamous cell carcinoma and squamous differentiation (log rank overall survival p = 0.6, cancer specific survival p = 0.17). Positive soft tissue margins were associated with worse cancer specific survival (HR 6.92, 95% CI 2.98-16.10, p ≤0.0005) and overall survival (HR 3.68, 95% CI 1.84-7.35, p ≤0.0005) in patients with pure squamous cell carcinoma. Among patients with squamous differentiation, pelvic lymphadenopathy was associated with decreased overall survival (HR 2.52, 95% CI 1.33-4.77, p = 0.004) and cancer specific survival (HR 3.23, 95% CI 1.57-6.67, p = 0.002). CONCLUSIONS: There appears to be no evidence of a difference in cancer specific survival or overall survival between patients with squamous cell carcinoma and those with squamous differentiation treated with radical cystectomy and pelvic lymph node dissection. Patients with squamous differentiation and tumor metastases to pelvic lymph nodes should be followed more closely, and adjuvant treatment should be considered to improve survival. Wide surgical resection is critical to achieve local tumor control and improve survival in patients with squamous cell carcinoma.

Evaluating the utility of a preoperative nomogram for predicting 90-day mortality following radical cystectomy for bladder cancer.

OBJECTIVE: To evaluate the performance of the Isbarn nomogram for predicting 90-day mortality following radical cystectomy in a contemporary series. PATIENTS AND METHODS: We identified 1141 consecutive radical cystectomy patients treated at our institution between 1995 and 2005 with at least 90 days of follow-up. We applied the published nomogram to our cohort, determining its discrimination, with the area under the receiver operating characteristic curve (AUC), and calibration. We further compared it with a simple model using age and the Charlson comorbidity score. RESULTS: Our cohort was similar to that used to develop the Isbarn nomogram in terms of age, gender, grade and histology; however, we observed a higher organ-confined (≤pT2, N0) rate (52% vs 24%) and a lower overall 90-day mortality rate [2.8% (95% confidence interval 1.9%, 3.9%) vs 3.9%]. The Isbarn nomogram predicted individual 90-day mortality in our cohort with moderate discrimination [AUC 73.8% (95% confidence interval 64.4%, 83.2%)]. In comparison, a model using age and Charlson score alone had a bootstrap-corrected AUC of 70.2% (95% confidence interval 67.2%, 75.4%). CONCLUSIONS: The Isbarn nomogram showed moderate discrimination in our cohort; however, the exclusion of important preoperative comorbidity variables and the use of postoperative pathological stage limit its utility in the preoperative setting. The use of a simple model combining age and Charlson score yielded similar discriminatory ability and underscores the significance of individual patient variables in predicting outcomes. An accurate tool for predicting postoperative morbidity/mortality following radical cystectomy would be valuable for treatment planning and counselling. Future nomogram design should be based on preoperative variables including individual risk factors, such as comorbidities.

Systematic classification and prediction of complications after nephrectomy in patients with metastatic renal cell carcinoma (RCC).

UNLABELLED: Study Type - Harm (case series) Level of Evidence 4. What's known on the subject? and What does the study add? Radical nephrectomy for patients with metastatic renal cell carcinoma results in greater rates of morbidity than for those with less advanced disease. This study systematically characterizes complications associated with nephrectomy for metastatic RCC and identifies patient and disease characteristics that are associated with a greater risk of developing complications. Overall complications were relatively frequent, but major complications (grade 3 or greater) were rare. Increasing age and worsening performance status were associated with increased probability of complications. When complications were sustained, patients were less likely to receive systemic therapy in a timely fashion. These observations may influence the timing or patient selection for surgery or systemic therapy. OBJECTIVE: • To evaluate and identify factors predictive for morbidity after radical nephrectomy in patients with metastatic renal cell carcinoma (mRCC). PATIENTS AND METHODS: • We identified patients with mRCC who underwent nephrectomy at Memorial Sloan-Kettering Cancer Center (MSKCC) between 1989 and 2009. • Postoperative complications were characterised using a modified version of the Clavien-Dindo classification system. • Patient and disease characteristics, including a previously validated MSKCC risk-stratification system using calcium, haemoglobin (Hb), lactate dehydrogenase, and Karnofsky Performance Status (KPS), were evaluated as predictors of postoperative complications using univariate and multivariable logistic regression models. • The area under the receiver operating characteristic curve (AUC) was calculated for each model to assess predictive accuracy and corrected for overfit using 10-fold cross validation. RESULTS: • Over the study period, 195 patients with mRCC underwent nephrectomy; 53 (27%) developed grade ≥ 2 complications within 8 weeks of surgery. • Pulmonary, thromboembolic events and anaemia requiring transfusion were the most common types of complications after nephrectomy in the metastatic setting. • In univariate analysis, age, low albumin, low KPS, high corrected serum calcium, low serum Hb, and unfavourable MSKCC risk score were predictive of complications. • Patients who sustained postoperative complications were less likely to receive systemic therapy within 56 days (odds ratio [OR] 0.32; 95% confidence interval [CI] 0.12-0.86; P= 0.024). • A multivariable model containing KPS (OR 14.5; 95%CI 4.34-48.6; P < 0.001) and age (OR 1.04; 95%CI 1.01-1.08; P= 0.014) showed the greatest predictive accuracy (corrected AUC 0.72; 95%CI 0.63-0.80) for postoperative complications. CONCLUSIONS: • Postoperative complications after radical nephrectomy in the setting of mRCC are common and occur frequently in older patients and those with worse KPS. • These complications are important because they may delay or deny receipt of subsequent systemic therapy.

Role of prostate specific antigen and immediate confirmatory biopsy in predicting progression during active surveillance for low risk prostate cancer.

PURPOSE: We evaluated predictors of progression after starting active surveillance, especially the role of prostate specific antigen and immediate confirmatory prostate biopsy. MATERIALS AND METHODS: A total of 238 men with prostate cancer met active surveillance eligibility criteria and were analyzed for progression with time. Cox proportional hazards regression was used to evaluate predictors of progression. Progression was evaluated using 2 definitions, including no longer meeting 1) full and 2) modified criteria, excluding prostate specific antigen greater than 10 ng/ml as a criterion. RESULTS: Using full criteria 61 patients progressed during followup. The 2 and 5-year progression-free probability was 80% and 60%, respectively. With prostate specific antigen included in progression criteria prostate specific antigen at confirmatory biopsy (HR 1.29, 95% CI 1.14-1.46, p <0.0005) and positive confirmatory biopsy (HR 1.75, 95% CI 1.01-3.04, p = 0.047) were independent predictors of progression. Of the 61 cases 34 failed due to increased prostate specific antigen, including only 5 with subsequent progression by biopsy criteria. When prostate specific antigen was excluded from progression criteria, only 32 cases progressed, and 2 and 5-year progression-free probability was 91% and 76%, respectively. Using modified criteria as an end point positive confirmatory biopsy was the only independent predictor of progression (HR 3.16, 95% CI 1.41-7.09, p = 0.005). CONCLUSIONS: Active surveillance is feasible in patients with low risk prostate cancer and most patients show little evidence of progression within 5 years. There is no clear justification for treating patients in whom prostate specific antigen increases above 10 ng/ml in the absence of other indications of tumor progression. Patients considering active surveillance should undergo confirmatory biopsy to better assess the risk of progression.

Prognostic significance of lymphovascular invasion in radical prostatectomy specimens.

UNLABELLED: Study Type - Prognosis (case series). LEVEL OF EVIDENCE: 4. What's known on the subject? and What does the study add? The reported incidence of lymphovascular invasion (LVI) in radical prostatectomy specimens ranges from 5% to 53%. Although LVI has a strong and significant association with adverse clinicopathologic features, it has almost uniformly not been found to be a predictor of biochemical recurrence (BR) on multivariate analysis. This study confirms that LVI is associated with features of aggressive disease and is an independent predictor of BCR. Given that LVI may play a role in the metastatic process, it may be useful in clinical decision-making regarding adjuvant therapy for patients treated with RP. OBJECTIVES: To determine whether lymphovascular invasion (LVI) in radical prostatectomy (RP) specimens has prognostic significance. The study examined whether LVI is associated with clinicopathological characteristics and biochemical recurrence (BCR). PATIENTS AND METHODS: LVI was evaluated based on routine pathology reports on 1298 patients treated with RP for clinically localized prostate cancer between 2004 and 2007. LVI was defined as the unequivocal presence of tumour cells within an endothelium-lined space. The association between LVI and clinicopathological features was assessed with univariate logistic regression. Cox regression was used to test the association between LVI and BCR. RESULTS: LVI was identified in 10% (129/1298) of patients. The presence of LVI increased with advancing pathological stage: 2% (20/820) in pT2N0 patients, 16% (58/363) in pT3N0 patients and 17% (2/12) in pT4N0 patients; and was highest in patients with pN1 disease (52%; 49/94). Univariate analysis showed an association between LVI and higher preoperative prostate-specific antigen levels and Gleason scores, and a greater likelihood of extraprostatic extension, seminal vesicle invasion, lymph node metastasis and positive surgical margins (all P < 0.001). With a median follow-up of 27 months, LVI was significantly associated with an increased risk of BCR after RP on univariate (P < 0.001) and multivariate analysis (hazard ratio, 1.77; 95% confidence interval, 1.11-2.82; P = 0.017). As a result of the relatively short follow-up, the predictive accuracy of the standard clinicopathological features was high (concordance index, 0.880), and inclusion of LVI only marginally improved the predictive accuracy (0.884). CONCLUSIONS: Although associated with features of aggressive disease and BCR, LVI added minimally to established predictors on short follow-up. Further study of cohorts with longer follow-up is warranted to help determine its prognostic significance.

Long-term follow-up of 3-month neoadjuvant hormone therapy before radical prostatectomy in a randomized trial.

OBJECTIVE: To report our long-term follow-up of an institutional randomized prospective trial of radical prostatectomy (RP) with or without a 3-month course of neoadjuvant hormone therapy (NHT), which results in pathological downstaging, but generally no reduction in biochemical recurrence (BCR) on early follow-up (at 3 years). PATIENTS AND METHODS: From December 1992 to June 1996, 148 patients with clinically localized prostate cancer were randomized to RP only or 3 months of goserelin acetate and flutamide before RP. BCR was defined as a detectable serum prostate specific antigen level (>0.1 ng/mL) at least 6 weeks after surgery, with a confirmatory increase. RESULTS: The median follow-up for BCR-free patients was 8 years. There was no significant difference in BCR-free probabilities between groups (P = 0.7). The BCR-free probability at 7 years was 78% for patients undergoing RP only and 80% for patients undergoing NHT and RP (difference of 2%; 95% confidence interval, CI, 12-16%). A Cox regression showed no significant relationship between NHT and BCR (hazard ratio 1.16; 95% CI, 0.56-2.39, P = 0.7). Overall, two patients had local recurrence and six developed metastases, and were evenly distributed among the RP only and NHT groups. CONCLUSION: Although our study was not originally powered to detect differences in BCR, there was no overall benefit in BCR-free probability, local recurrence or metastasis with 3 months of NHT at 8 years of follow-up. Pending evidence of improvement in patient outcomes, NHT before RP appears to be unjustified outside of clinical trials.

Developments in the surgical management of sporadic synchronous bilateral renal tumours.

OBJECTIVE: To examine our experience with managing sporadic bilateral renal masses, focusing on trends in surgical management over time, because as loss of renal function is associated with adverse cardiovascular outcomes, nephron-sparing approaches are increasingly emphasized in the treatment of kidney tumours, creating new challenges for the treatment of bilateral tumours. PATIENTS AND METHODS: We identified all patients who underwent partial or radical nephrectomy (PN or RN) at Memorial Sloan-Kettering Cancer Center (MSKCC) during 1989-2008. We compared patients presenting with synchronous bilateral renal masses with those with unilateral tumour and evaluated trends in management using logistic regression. RESULTS: Of the 2777 patients studied, 73 (3%) presented with synchronous bilateral disease. The overall survival and clinical/pathological features between groups were similar. Of those patients receiving bilateral operations for synchronous tumours, three had bilateral RN (all before 2003), 28 (38%) had an RN followed by a PN, 10 (14%) had a PN then an RN, and 32 (44%) had bilateral PN. Over time, the proportion of patients receiving bilateral PN increased (P < 0.001); 13 of 14 patients after 2005 had bilateral PN, compared with only 34% (16 of 45) between 1995 and 2004. Forty-five patients (62%) had the larger tumour removed during the first operation. The concordance rate between tumours in a specific histological subtype was 70% (51/73), and concordance for benign vs malignant disease was 90% (66/73). CONCLUSION: The use of PN in the management of synchronous bilateral renal masses has increased over time. The contemporary treatment of synchronous bilateral renal masses at MSKCC involves staged PN when feasible, with the more involved kidney (often larger tumour) operated on first.

Fibrin clot inhibitor medication and efficacy of bacillus Calmette-Guerin for bladder urothelial cancer.

PURPOSE: Studies suggest that the antitumor effect of bacillus Calmette-Guerin depends on bacillus Calmette-Guerin attachment to fibronectin at fibrin clot formation sites and medications that impact fibrin clot formation may modify bacillus activity. We evaluated the impact of fibrin clot inhibitors on the clinical efficacy of bacillus Calmette-Guerin. MATERIALS AND METHODS: We reviewed the records of 907 consecutive patients treated with bacillus Calmette-Guerin between 1990 and 2006. Time to disease recurrence and progression to surgery were compared in patients who did and did not receive fibrin clot inhibitors by Kaplan-Meier methods and multivariate Cox regression models. RESULTS: Overall 221 patients (24%) received at least 1 fibrin clot inhibitor, including 170, 34 and 52 on aspirin, clopidogrel and warfarin, respectively. Patients on warfarin had shorter time to progression than patients not on warfarin (median 2.1 vs 9.0 years, p <0.005). Patients on aspirin had a significantly improved 5-year probability of freedom from surgery (66% vs 56%, p = 0.029). On multivariate analysis warfarin was associated with an increased risk of progression to surgery (HR 1.89, 95% CI 1.31, 2.74, p = 0.0007), while aspirin was associated with a decreased risk (HR 0.71, 95% CI 0.52, 0.96, p = 0.024). Warfarin alone was associated with an increased risk of tumor recurrence (HR 1.39, 95% CI 1.00, 1.94, p = 0.047). CONCLUSIONS: These data suggest that the risks of recurrence and progression to surgery after bacillus Calmette-Guerin are higher in patients on warfarin, while the risk of progression is lower in patients on aspirin. These findings may have important treatment implications in patients in whom bacillus Calmette-Guerin is contemplated.