Alain Duclos

A population based assessment of perioperative mortality after cystectomy for bladder cancer.

PURPOSE Large variability exists in the rates of perioperative mortality after cystectomy. Contemporary estimates range from 0.7% to 5.6%. We tested several predictors of perioperative mortality and devised a model for individual perioperative mortality prediction. MATERIALS AND METHODS We relied on life tables to quantify 30, 60 and 90-day mortality rates according to age, gender, stage (localized vs regional), grade, type of surgery (partial vs radical cystectomy), year of cystectomy and histological bladder cancer subtype. We fitted univariable and multivariable logistic regression models using 5,510 patients diagnosed with bladder cancer and treated with partial or radical cystectomy within 4 SEER (Surveillance, Epidemiology, and End Results) registries between 1984 and 2004. We then externally validated the model on 5,471 similar patients from 5 other SEER registries. RESULTS At 30, 60 and 90 days the perioperative mortality rates were 1.1%, 2.4% and 3.9%, respectively. Age, stage and histological subtype represented statistically significant and independent predictors of 90-day mortality. The combined use of these 3 variables and of tumor grade resulted in the most accurate model (70.1%) for prediction of individual probability of 90-day mortality after cystectomy. CONCLUSIONS The accuracy of our model could potentially be improved with the consideration of additional parameters such as surgical and hospital volume or comorbidity. While better models are being developed and tested we suggest the use of the current model in individual decision making and in informed consent considerations because it provides accurate predictions in 7 of 10 patients.

Gender-related Differences in Patients With Stage I to III Upper Tract Urothelial Carcinoma: Results From the Surveillance, Epidemiology, and End Results Database

OBJECTIVES To examine the effect of gender in upper tract urothelial carcinoma (UTUC) stage at nephroureterectomy (NU), as well as on cancer-specific mortality (CSM) after NU in patients with American Joint Committee on Cancer stages I-III UTUC. METHODS Our analyses relied on 2903 (59.9%) males and 1947 (40.1%) females who underwent an NU for pT(1-3)N(0/x)M(0) UTUC between 1988 and 2006, within 17 Surveillance, Epidemiology, and End Results registries. Univariable and multivariable logistic regression models examined the effect of gender on stage and grade distribution at NU. Subsequently, cumulative incidence plots explored the impact of gender on CSM rates, after accounting for other-cause mortality (OCM). Finally, competing-risks regression models tested the independent predictor status of gender in CSM analyses. Covariates consisted of pT stage, pN stage, tumor grade, primary tumor location, type and year of surgery, age, and race. RESULTS Relative to males, females had a higher proportion of pT(3) UTUC (43.1% vs 39%; P = .02) and a higher proportion of grade III/IV UTUC (63.8% vs 59.8%; P = .04) at NU. The female gender represented an independent predictor of pT(3) UTUC at NU (hazard ratio [HR]: 1.15; P = .03). After accounting for OCM, CSM rates in females were higher than those in males (HR: 1.18; P = .03). However, in multivariable competing-risks regression models, no statistically significant differences in survival were recorded between males and females (HR: 1.07; P = .4). CONCLUSIONS Females are more likely to have more advanced pathologic T stage and higher tumor grade at NU than males. After accounting for OCM, stage, grade, and noncancer characteristics, gender no longer affects CSM.

The Rate of Secondary Malignancies After Radical Prostatectomy Versus External Beam Radiation Therapy for Localized Prostate Cancer: A Population-Based Study on 17,845 Patients

PURPOSE External-beam radiation therapy (EBRT) may predispose to secondary malignancies that include bladder cancer (BCa), rectal cancer (RCa), and lung cancer (LCa). We tested this hypothesis in a large French Canadian population-based cohort of prostate cancer patients. METHODS AND MATERIALS Overall, 8,455 radical prostatectomy (RP) and 9,390 EBRT patients treated between 1983 and 2003 were assessed with Kaplan-Meier and Cox regression analyses. Three endpoints were examined: (1) diagnosis of secondary BCa, (2) LCa, or (3) RCa. Covariates included age, Charlson comorbidity index, and year of treatment. RESULTS In multivariable analyses that relied on incident cases diagnosed 60 months or later after RP or EBRT, the rates of BCa (hazard ratio [HR], 1.4; p = 0.02), LCa (HR, 2.0; p = 0.004), and RCa (HR 2.1; p <0.001) were significantly higher in the EBRT group. When incident cases diagnosed 120 months or later after RP or EBRT were considered, only the rates of RCa (hazard ratio 2.2; p = 0.003) were significantly higher in the EBRT group. In both analyses, the absolute differences in incident rates ranged from 0.7 to 5.2% and the number needed to harm (where harm equaled secondary malignancies) ranged from 111 to 19, if EBRT was used instead of RP. CONCLUSIONS EBRT may predispose to clinically meaningfully higher rates of secondary BCa, LCa and RCa. These rates should be included in informed consent consideration.

Should Bladder Cuff Excision Remain the Standard of Care at Nephroureterectomy in Patients with Urothelial Carcinoma of the Renal Pelvis? A Population-based Study

BACKGROUND A large, multi-institutional, tertiary care center study suggested no benefit from bladder cuff excision (BCE) at nephroureterectomy in patients with upper tract urothelial carcinoma (UC). OBJECTIVE We tested and quantified the prognostic impact of BCE at nephroureterectomy on cancer-specific mortality (CSM) in a large population-based cohort of patients with UC of the renal pelvis. DESIGN, SETTING, AND PARTICIPANTS A cohort of 4210 patients with UC of the renal pelvis were treated with nephroureterectomy with (NUC) or without (NU) a BCE between 1988 and 2006 within 17 Surveillance, Epidemiology, and End Results registries. MEASUREMENTS Cumulative incidence plots and competing risks regression models compared CSM after either NUC or NU. Covariates consisted of pathologic T and N stages, grade, age, year of surgery, gender, and race. RESULTS AND LIMITATIONS Respectively, 2492 (59.2%) and 1718 (40.8%) patients underwent a nephroureterectomy with or without BCE. In univariable and multivariable analyses, BCE omission increased CSM rates in patients with pT3N0/x, pT4N0/x, and pT(any)N1-3 UC of the renal pelvis. For example, in patients with pT3N0/x disease, holding all other variables constant, BCE omission increased CSM in a 1.25-fold fashion (p=0.04). Similarly, in patients with pT4N0/x disease, BCE omission resulted in a 1.45-fold increase (p=0.02). The main limitation of our study is the lack of data on disease recurrence. CONCLUSIONS Nephroureterectomy with BCE remains the standard of care in the treatment of UC of the renal pelvis and should invariably be performed in patients with locally advanced disease. Conversely, patients with pT1 and pT2 disease could be considered for NU without compromising CSM. However, recurrence data are needed to fully confirm the validity of this option.

Adenocarcinoma Versus Urothelial Carcinoma of the Urinary Bladder: Comparison Between Pathologic Stage at Radical Cystectomy and Cancer-specific Mortality

OBJECTIVES To compare stage at radical cystectomy (RC) and cancer-specific mortality (CSM) after RC between non-urachal adenocarcinoma (ADK) and urothelial carcinoma (UC) of the urinary bladder. METHODS Within 17 Surveillance, Epidemiology and End Results registries, we identified ADK and UC patients who underwent a RC between 1988 and 2006. We examined differences in stage and grade at RC between ADK and UC patients. Kaplan-Meier plots depicted CSM after RC. Cox regression analyses examined CSM rates, adjusted for T and N stages, tumor grade, age, gender, race, and year of surgery. Thereafter, we relied on statistically significant variables from the multivariate Cox regression model to match ADK and UC patients. Finally, we plotted Kaplan-Meier survival curves of the matched ADK and UC patients. RESULTS Of 306 ADK and 11 697 UC patients, 188 (61.4%) and 5538 (47.3%), respectively, showed extravesical disease (pT(3-4); P <.001) and 26.5% vs 21.7% had lymph node metastases at RC (P = .04), respectively. After adjustment for all covariates, including stage and grade, ADK was not associated with worse prognosis than UC (hazard ratio, 1.05; P = .6). Similarly, after matching, no difference in CSM was recorded between the 2 histologic subtypes (hazard ratio, 1.07; P = .5). CONCLUSIONS ADK patients undergo RC at more advanced disease stages. However, stage- and grade-adjusted CSM is the same between ADK and UC patients. Efforts should be aimed at providing definitive treatment at earlier stages, especially in patients with ADK histologic subtype.

Population-based Study of Perioperative Mortality After Retroperitoneal Lymphadenectomy for Nonseminomatous Testicular Germ Cell Tumors

OBJECTIVES To determine whether retroperitoneal lymphadenectomy (RPLND) perioperative mortality (PM) rates reported from a center of excellence (Indiana University: 0% for primary and 0.8% for postchemotherapy RPLND) are applicable to institutions at large. METHODS We used the data from 882 assessable patients with nonseminomatous testicular germ cell tumor treated with RPLND from 1988 to 1997 accessed from the Surveillance, Epidemiology, and End Results (SEER) database. These data did not include data from Indiana University. The observed PM rates were stratified according to age and SEER stage. RESULTS The median age at RPLND was 29 years. Of the 882 cases, 435 (49.3%) were performed for localized (Stage I), 380 (43.1%) for regional (Stage II), and 67 (7.6%) for metastatic (Stage III) SEER stage. Of the 882 patients, 7 patients died during the initial 90 days after RPLND, for a 0.8% PM rate. PM increased with increasing age: < or =29 years, 0.0%; 30-39 years, 1.3%; and > or =40 years, 2.7% (chi(2) trend test, P = .002). PM also increased with increasing stage: 0.0% for localized, 0.8% for regional, and 6.0% for metastatic disease (chi(2) trend test, P < .001). CONCLUSIONS RPLND is associated with virtually no or low PM in patients with localized and regional disease. The PM rates for these 2 groups replicated those of Indiana University. In contrast, the PM rate of 6% for patients with distant metastases implies that RPLND for these higher risk patients should ideally be performed at centers of excellence, with the intent of reducing the PM rate.

A Simple and Accurate Model for Prediction of Cancer-Specific Mortality in Patients Treated with Surgery for Primary Penile Squamous Cell Carcinoma

Purpose: Cancer-specific mortality (CSM) of patients with primary penile squamous cell carcinoma (PPSCC) may be quite variable. Recently, a nomogram was developed to provide standardized and individualized mortality predictions. Unfortunately, it relies on a large number (n = 8) of specific variables that are unavailable in routine clinical practice. We attempted to develop a simpler prediction rule with at least equal accuracy in predicting CSM after surgical removal of PPSCC. Experimental Design: The predictive rule was developed on a cohort of 856 patients identified in the 1988 to 2004 Surveillance, Epidemiology and End Results (SEER) database. The predictors consisted of age, race, SEER stage (localized versus regional versus metastatic), tumor grade, type of surgery (excisional biopsy, partial penectomy, and radical penectomy), and of lymph node status (pN0 versus pN1-3 versus pNx). A look-up table based on Cox regression model-derived coefficients was used for prediction of 5-year CSM. The predictive rule accuracy was tested using the Harrells modification of the area under the receiver operating characteristics curve. Results: SEER stage and histologic grade achieved independent predictor status and qualified for inclusion in the model. The model achieved 73.8% accuracy for prediction of CSM at 5 years after surgery. Both predictors achieved independent predictor status in competing risk regression models addressing CSM, where other cause mortality was controlled for. Conclusion: Despite equivalent accuracy, our predictive rule predicting 5-year CSM in patients with PPSCC is substantially less complex (2 versus 8 variables) than the previously published model.

A population-based comparison of survival after nephrectomy vs nonsurgical management for small renal masses

To examine population‐based rates of cancer‐specific and other‐cause mortality after either non‐surgical management (NSM) or nephrectomy, in patients with small renal masses, as several reports from selected institutions support the applicability of surveillance in patients with small renal masses, but there are no population‐based studies confirming the general applicability of this therapy.

Race affects access to nephrectomy but not survival in renal cell carcinoma

To assess whether, in contemporary patients with renal cell carcinoma (RCC), access to nephrectomy is the same between the Blacks and Whites, and that there is no difference in mortality after stratification for treatment type.

Development and external validation of a highly accurate nomogram for the prediction of perioperative mortality after transurethral resection of the prostate for benign prostatic hyperplasia.

PURPOSE Benign prostatic hyperplasia affects 60% of men at the age of 60 years. Transurethral resection of the prostate is the gold standard of therapy. We assessed the 30-day mortality rate after transurethral resection of the prostate for benign prostatic hyperplasia, identified risk factors related to 30-day mortality and developed a model that discriminates among individual 30-day mortality risk levels. MATERIALS AND METHODS We performed development (7,362) and external validation (7,362) of a multivariable logistic regression model predicting the individual probability of 30-day mortality after transurethral resection of the prostate based on an administrative data set (Quebec Health Plan) of 14,724 patients 43 to 99 years old treated between January 1, 1989 and December 31, 2000. RESULTS Overall 30-day mortality occurred in 58 patients (0.4%) undergoing transurethral resection of the prostate. On univariable analyses increasing age (p <0.001) and increasing Charlson comorbidity index (p <0.001) were statistically significant predictors of 30-day mortality after transurethral resection of the prostate. Conversely annual surgical volume was not. On multivariable analyses age (p <0.001) and Charlson comorbidity index (p <0.001) reached independent predictor status. The accuracy of the age and Charlson comorbidity index based nomogram that predicts the individual probability of 30-day mortality after transurethral resection of the prostate was 83% in the external validation cohort. CONCLUSIONS Age and Charlson comorbidity index are important determinants of 30-day mortality after transurethral resection of the prostate. The combination of these parameters allows an 83% accurate prediction of individual 30-day mortality risk after transurethral resection of the prostate. Despite limitations such as the need for additional external validations and possibly the need for inclusion of clinical parameters, the use of the current model is warranted for the purpose of informed consent before transurethral resection of the prostate and/or for patient counseling.