Mortality increases when radical cystectomy is delayed more than 12 weeks

BACKGROUND:

Single‐institution series have documented the adverse impact of a 12‐week delay between resection of muscle‐invasive bladder cancer and radical cystectomy. These data are derived from tertiary centers, in which referral populations may confound outcomes. The authors sought to examine the survival impact of a delay in radical cystectomy using nationally representative data.

METHODS:

From the linked Surveillance, Epidemiology, and End Results–Medicare dataset, the authors identified subjects with stage II transitional cell carcinoma (TCC) of the bladder who underwent radical cystectomy between 1992 and 2001. They examined delays of 8, 12, and 24 weeks and incorporated these delay cutoffs into multivariate Cox proportional hazards survival models. Covariates included age, race/ethnicity, marital status, Charlson comorbidity index, and cancer grade.

RESULTS:

The authors identified 441 subjects with stage II TCC who underwent cystectomy during the study period. Compared with immediate surgery (ie, within 4‐8 weeks of transurethral resection), longer time to cystectomy increased the risk of both disease‐specific and overall mortality (hazard ratio [HR], 2.0; P < .01 and HR, 1.6; P < .01, respectively, for those delayed 12‐24 weeks; HR, 2.0; P < .01 for disease‐specific and overall death among those delayed beyond 24 weeks 1 year after diagnosis). Covariates associated with overall mortality included older age (HR, 1.04; P < .01) and comorbidity (HR, 2.0 for Charlson ≥3 vs Charlson 0‐1; P < .01).

CONCLUSIONS:

Delay in definitive surgical treatment beyond 12 weeks conferred an increased risk of disease‐specific and all‐cause mortality among subjects with stage II bladder cancer. Cancer 2009. © 2009 American Cancer Society.     

Cost‐effectiveness analysis of immediate radical cystectomy versus intravesical Bacillus Calmette‐Guerin therapy for high‐risk,high‐grade (T1G3) bladder cancer

BACKGROUND:

Although both radical cystectomy and intravesical immunotherapy are initial treatment options for high‐risk, T1, grade 3 (T1G3) bladder cancer, controversy regarding the optimal strategy persists. Because bladder cancer is the most expensive malignancy to treat per patient, decisions regarding the optimal treatment strategy should consider costs.

METHODS:

A Markov Monte‐Carlo cost‐effectiveness model was created to simulate the outcomes of a cohort of patients with incident, high‐risk, T1G3 bladder cancer. Treatment options included immediate cystectomy and conservative therapy with intravesical Bacillus Calmette‐Guerin (BCG). The base case was a man aged 60 years. Parameter uncertainty was assessed with probabilistic sensitivity analyses. Scenario analyses were used to explore the 2 strategies among patients stratified by age and comorbidity.

RESULTS:

The quality‐adjusted survival with immediate cystectomy and BCG therapy was 9.46 quality‐adjusted life years (QALYs) and 9.39 QALYs, respectively. The corresponding mean per‐patient discounted lifetime costs (in 2005 Canadian dollars) were $37,600 and $42,400, respectively. At a willingness‐to‐pay threshold of $50,000 per QALY, the probability that immediate cystectomy was cost‐effective was 67%. Immediate cystectomy was the dominant (more effective and less expensive) therapy for patients aged <60 years, whereas BCG therapy was dominant for patients aged >75 years. With increasing comorbidity, BCG therapy was dominant at lower age thresholds.

CONCLUSIONS:

Compared with BCG therapy, immediate radical cystectomy for average patients with high‐risk, T1G3 bladder cancer yielded better health outcomes and lower costs. Tailoring therapy based on patient age and comorbidity may increase survival while yielding significant cost‐savings for the healthcare system. Cancer 2009. © 2009 American Cancer Society.     

Contemporary use of perioperative cisplatin‐based chemotherapy in patients with muscle‐invasive bladder cancer

BACKGROUND:

Level I evidence indicates that neoadjuvant cisplatin‐based chemotherapy, in combination with radical cystectomy (RC), is associated with a significant survival advantage for patients with muscle‐invasive bladder cancer. Despite this, neoadjuvant chemotherapy is not uniformly used. Our objective was to determine the patterns of utilization of neoadjuvant chemotherapy in patients undergoing RC for muscle invasive bladder cancer in a contemporary cohort in a tertiary care center.

METHODS:

A retrospective review was performed of patients with bladder cancer who underwent RC between 2003 and 2008 at our institution. Clinical stage, pathologic stage, renal function, and perioperative chemotherapy treatments were tabulated. Primary outcome measures were the type and use of neoadjuvant chemotherapy among eligible patients. Secondary measures were the utilization patterns of adjuvant chemotherapy, renal function, pathologic outcomes, and disease specific and overall survival. Reasons for nonutilization of chemotherapy were also examined.

RESULTS:

Among 238 patients who underwent RC for bladder cancer, 145 had a preoperative clinical stage ≥T2. Only 17% (25 of 145) of these patients received cisplatin‐based neoadjuvant chemotherapy. The renal function was adequate (CrCl > 60 ml/min) in 97 (67%) of these patients. Patients who received neoadjuvant chemotherapy had higher p0 rates (29% vs 8%) than patients who did not receive neoadjuvant therapy. Advanced patient age, comorbidities, concerns over toxicity of chemotherapy, and the modest nature of benefit from neoadjuvant chemotherapy may explain why this treatment is not often used.

CONCLUSIONS:

Despite level I evidence, neoadjuvant cisplatin‐based chemotherapies continue to be underutilized in the management of bladder cancer, even at a high‐volume tertiary center. A prospective evaluation of management choices, including the patient and physician factors involved in the use of perioperative cisplatin‐based chemotherapy in bladder cancer, is indicated. Cancer 2011. © 2010 American Cancer Society.     

Estimating breast cancer‐specific and other‐cause mortality in clinical trial and population‐based cancer registry cohorts

BACKGROUND:

To compute net cancer‐specific survival rates using population data sources (eg, the National Cancer Institute's Surveillance, Epidemiology, and End Results [SEER] Program), 2 approaches primarily are used: relative survival (observed survival adjusted for life expectancy) and cause‐specific survival based on death certificates. The authors of this report evaluated the performance of these estimates relative to a third approach based on detailed clinical follow‐up history.

METHODS:

By using data from Cancer Cooperative Group clinical trials in breast cancer, the authors estimated 1) relative survival, 2) breast cancer‐specific survival (BCSS) determined from death certificates, and 3) BCSS obtained by attributing cause according to clinical events after diagnosis, which, for this analysis was considered the benchmark “true” estimate. Noncancer life expectancy also was compared between trial participants, SEER registry patients, and the general population.

RESULTS:

Among trial patients, relative survival overestimated true BCSS in patients with lymph node‐negative breast cancer; whereas, in patients with lymph node‐positive breast cancer, the 2 estimates were similar. For higher risk patients (younger age, larger tumors), relative survival accurately estimated true BCSS. In lower risk patients, death certificate BCSS was more accurate than relative survival. Noncancer life expectancy was more favorable among trial participants than in the general population and among SEER patients. Tumor size at diagnosis, which is a potential surrogate for screening use, partially accounted for this difference.

CONCLUSIONS:

In the clinical trials, relative survival accurately estimated BCSS in patients who had higher risk disease despite more favorable other‐cause mortality than the population at large. In patients with lower risk disease, the estimate using death certificate information was more accurate. For SEER data and other data sources where detailed postdiagnosis clinical history was unavailable, death certificate‐based estimates of cause‐specific survival may be a superior choice. Cancer 2009. © 2009 American Cancer Society.     

Understanding the variation in treatment intensity among patients with early stage bladder cancer

BACKGROUND:

Given the uncertainty surrounding the optimal management for early stage bladder cancer, physicians vary in how they approach the disease. The authors of this report linked cancer registry data with medical claims to identify the sources of variation and opportunities for improving the value of cancer care.

METHODS:

By using data from the Surveillance, Epidemiology, and End Results‐Medicare database (1992‐2005), patients with early stage bladder cancer were abstracted (n = 18,276). The primary outcome was the intensity of initial treatment that patients received, as measured by all Medicare payments for bladder cancer incurred in the 2 years after diagnosis. Multilevel models were fitted to partition the variation in treatment intensity attributable to patient versus provider factors, and the potential savings to Medicare from reducing the physician contribution were estimated.

RESULTS:

Provider factors accounted for 9.2% of the variation in treatment intensity. Increasing provider treatment intensity did not correlate with improved cancer‐specific survival (P = .07), but it was associated with the subsequent receipt of major interventions, including radical cystectomy (P < .001). If provider‐level variation was reduced and clinical practice was aligned with that of physicians who performed in the 25th percentile of treatment intensity, then total payments made for the average patient could be lowered by 18.6%, saving Medicare $18.7 million annually.

CONCLUSIONS:

The current results indicated that a substantial amount of the variation in initial treatment intensity for early stage bladder cancer is driven by the physician. Furthermore, a more intensive practice style was not associated with improved cancer‐specific survival or the avoidance of major interventions. Therefore, interventions aimed at reducing between‐provider differences may improve the value of cancer care. Cancer 2010. © 2010 American Cancer Society.     

Lack of pathologic down‐staging with neoadjuvant chemotherapy for muscle‐invasive urothelial carcinoma of the bladder

BACKGROUND:

The postcystectomy survival benefit associated with the combination of methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) neoadjuvant chemotherapy (NC) for muscle‐invasive bladder cancer has been most evident in patients who achieve a pathologic complete response. The outcome of NC and open radical cystectomy (RC) was evaluated in a contemporary cohort of patients in a tertiary referral setting.

METHODS:

From January 2006 to November 2007, 117 patients underwent open RC at Cleveland Clinic for muscle‐invasive bladder cancer, 29 (25%) of whom received NC. Patient information was obtained from a prospective database.

RESULTS:

Clinical stage at the time of diagnosis in the NC cohort was T2 in 23 (79%) and T3‐4a in 6 (21%) patients. A total of 20 (69%) patients received the combination of gemcitabine and cisplatin (GC), 4 (14%) received MVAC, and 5 (17%) received other regimens. The median interval from the time of diagnosis of muscle‐invasive bladder cancer to RC was 208 days (interquartile range, 149 days ‐327 days) in the NC cohort. Overall, only 2 patients (7%; 95% confidence interval [95% CI], 0 patients‐17 patients) achieved a pathologic complete response, 18 (62%; 95% CI, 43 patients‐81 patients) had nonorgan‐confined residual cancer, and the overall median progression‐free survival was 10.5 months (95% CI, 7 months ‐14 months).

CONCLUSIONS:

Few RC patients in these investigators' recent experience achieved a pathologic complete response with NC, and most experienced rapid disease progression. These poor outcomes may be related to the use of non‐MVAC‐based regimens or excessive delay in performing RC. In the absence of supportive data for GC in the neoadjuvant setting, MVAC remained the preferred regimen. Excessive delays in performing RC may negate the benefit of NC. Cancer 2009. © 2009 American Cancer Society.     

Comparison of American Joint Committee on Cancer pathologic stage T3a versus T3b urothelial carcinoma: Analysis of patient outcomes

BACKGROUND:

The radical cystectomy experience at Vanderbilt University Medical Center was scrutinized to determine whether there was a difference in survival between patients with lymph node‐negative pathologic T3a versus pathologic T3b urothelial carcinoma of the bladder.

METHODS:

Pathologic and clinical data were reviewed on patients who underwent radical cystectomy for urothelial carcinoma between 1995 and 2005. We excluded patients with nontransitional cell cancer, lymph node disease, or with unknown lymph node status. Of the 790 reviewed patients, 75 patients (9.4%) were diagnosed with pathologic T3 urothelial cancer of the bladder. The impact of pathologic substaging (pT3a vs pT3b) was examined to determine the effect on overall, disease‐specific, and recurrence‐free survival.

RESULTS:

The mean age was 68.6 years (36 years to 83 years). Median overall follow‐up was 25.3 months (1.13 months to 130.17 months). Median follow‐up for patients alive at last follow‐up was 55.9 months (25.3 months to 130.2 months). Actuarial overall survival at 5 years was 29.5% for pT3a and 29.3% for pT3b (P = .79). Actuarial disease‐specific survival at 5 years was 54.1% for pT3a and 42.4% for pT3b (P = .21). Actuarial recurrence‐free survival at 5 years was 68.1% for pT3a and 71.9% for pT3b (P = .53).

CONCLUSIONS:

There were no significant differences in overall, disease‐specific, or recurrence‐free survival when comparing lymph node‐negative pT3a versus pT3b urothelial cancer of the bladder following radical cystectomy. Simplification of pathologic staging for urothelial carcinoma of the bladder should be considered at future revisions of the American Joint Committee on Cancer staging system. Cancer 2009. © 2009 American Cancer Society.     

Reactive antibodies against bacillus Calmette‐Guerin heat‐shock protein‐65 potentially predict the outcome of immunotherapy for high‐grade transitional cell carcinoma of the bladder

BACKGROUND:

Intravesical immunotherapy with Mycobacterium bovis (M. bovis) bacillus Calmette‐Guerin (BCG) is the current standard of care against superficial, high‐grade transitional cell carcinoma (TCC) of the urinary bladder (carcinoma in situ and pathologic T1, grade 3 disease). However, individual patient outcome is barely predictable because of the lack of serum markers. Consequently, progression to muscle‐invasive bladder cancer and critical delay of treatments (such as neoadjuvant combination chemotherapy and/or radical cystectomy) often occur. The objectives of this study were to identify a marker for measuring the BCG‐induced immune response and to predict the outcomes and potential improvements of BCG immunotherapy.

METHODS:

Because host immunoresponse mediates BCG activity, the authors screened a combinatorial random peptide library on the circulating pool of immunoglobulins (Igs) purified from an index patient after successful BCG immunotherapy to identify the corresponding target antigen(s).

RESULTS:

An immunogenic peptide motif was selected, isolated, and validated from M. bovis BCG heat‐shock protein 65 (HSP‐65) as a dominant epitope of the humoral response to treatment. Increasing IgA and IgG anti‐HSP‐65 titers specifically predicted a positive patient outcome in a cohort of patients with bladder cancer relative to several cohorts of control patients.

CONCLUSIONS:

The current results indicated that antibody production against M. bovis BCG HSP‐65 can serve as a serologic marker for the predictive outcome of BCG immunotherapy. Subsequent studies will determine the value of this candidate marker to modify BCG‐based treatment for individual patients with bladder cancer. Cancer 2010. © 2009 American Cancer Society.     

The long‐term outcome of treated high‐risk nonmuscle‐invasive bladder cancer

BACKGROUND:

The treatment of high‐risk nonmuscle‐invasive bladder cancer (NMIBC) is difficult given its unpredictable natural history and patient comorbidities. Because current case series are mostly limited in size, the authors report the outcomes from a large, single‐center series.

METHODS:

The authors reviewed all patients with primary, high‐risk NMIBC at their institution from 1994 to 2010. Outcomes were matched with clinicopathologic data. Patients who had muscle invasion within 6 months or had insufficient follow‐up (<6 months) were excluded. Correlations were analyzed using multivariable Cox regression and log‐rank analysis (2‐sided; P < .05).

RESULTS:

In total, 712 patients (median age, 73.7 years) were included. Progression to muscle invasion occurred in 110 patients (15.8%; 95% confidence interval [CI], 13%‐18.3%) at a median of 17.2 months (interquartile range, 8.9‐35.8 months), including 26.5% (95% CI, 22.2%‐31.3%) of the 366 patients who had >5 years follow‐up. Progression was associated with age (hazard ratio [HR], 1.04; P = .007), dysplastic urothelium (HR, 1.6; P = .003), urothelial cell carcinoma variants (HR, 3.2; P = .001), and recurrence (HR, 18.3; P < .001). Disease‐specific mortality occurred in 134 patients (18.8%; 95% CI, 16.1%‐21.9%) at a median of 28 months (interquartile range, 15‐45 months), including 28.7% (95% CI, 24.5%‐33.3%) of those who had 5 years of follow‐up. Disease‐specific mortality was associated with age (HR, 1.1; P < .001), stage (HR, 1.7; P = .003), dysplasia (HR, 1.3; P = .05), and progression (HR, 5.2; P < .001). Neither progression nor disease‐specific mortality were associated with the receipt of bacillus Calmette‐Guerin (P > .6).

CONCLUSIONS:

Within a program of conservative treatment, progression of high‐risk NMIBC was associated with a poor prognosis. Surveillance and bacillus Calmette‐Guerin were ineffective in altering the natural history of this disease. The authors concluded that the time has come to rethink the paradigm of management of this disease. Cancer 2012. © 2012 American Cancer Society.     

Racial disparities and survival for nonsmall‐cell lung cancer in a large cohort of black and white elderly patients

BACKGROUND:

This study aimed to examine disparities in survival and associated factors for patients with nonsmall‐cell lung cancer (NSCLC) and to determine whether racial disparities varied over time (1991‐1995, 1996‐1999, and 2000‐2002).

METHODS:

The authors studied 70,901 patients aged ≥65 years with stage I‐IV NSCLC identified from Surveillance, Epidemiology, and End Results/Medicare data. Multivariate time‐to‐event survival analyses were completed using Cox proportional regression modeling.

RESULTS:

The 5‐year observed lung cancer‐specific survival rates were 52.7% for whites and 47.5% for blacks with stage I‐II disease, and 17.7% and 19.6% for whites and blacks, respectively at stages III‐IV. After controlling for standard treatment, socioeconomic status (SES), and other factors, there were no significant differences in all‐cause mortality, or lung cancer‐specific mortality between black and white patients with stage I‐II or III‐IV lung cancer. However, blacks had an increased risk for overall all‐cause mortality at stage I‐IV (hazard ratio [HR], 1.24; 95% confidence interval, 1.13‐1.35), and during 2000‐2002 at stage III‐IV for all‐cause mortality (HR, 1.22; 95% CI, 1.02‐1.47) and lung cancer‐specific mortality (HR, 1.24; 95% CI,1.01‐1.53). Standard treatment was significantly associated with increased survival, whereas poor SES was associated with increased mortality.

CONCLUSIONS:

There were no significant differences in survival between blacks and whites with NSCLC within stage stratifications after adjusting for covariates, except for black patients at overall stage for all‐cause mortality and at stage III‐IV diagnosed in 2000‐2002. Receiving stage‐specific evidence‐based standard therapy was associated with significantly increased survival. Cancer 2009. © 2009 American Cancer Society.     

A novel algorithm to improve pathologic stage prediction of clinically organ‐confined muscle‐invasive bladder cancer

BACKGROUND:

An algorithm was created to predict pathologic stage in patients with clinically organ‐confined muscle‐invasive bladder cancer.

METHODS:

The sample consisted of 133 consecutive patients scheduled to undergo cystectomy. To develop a tool to predict nonorgan‐confined disease before surgery, principal component analysis (PCA) was applied. Patients were stratified into a training set (n = 89) and a validation set (n = 44), and 7 parameters were evaluated: levels of carcinoembryonic antigen, cancer antigen (CA) 125, and carbohydrate antigen (CA) 19‐9; clinical stage; presence of hydronephrosis; presence of carcinoma in situ; and initial tumor size >3 cm. PCA was applied to the training set to determine the weight of each parameter. A PCA score was generated for each patient in the set, and a cutoff defining nonorgan‐confined disease was established. The accuracy of the cutoff was quantified by the area under the receiver operator characteristics curve (AUC). The model was then applied to the validation set without recalculation; the AUC and the positive and negative predictive values of the validation set were calculated.

RESULTS:

On pathologic evaluation, 71 patients (53%) were found to have organ‐confined tumors and 62 patients (47%) had extravesical disease. The AUC was 0.85 in the training group (95% confidence interval [95% CI], 0.71‐0.97) and 0.84 in the validation group (95% CI, 0.75‐0.93). The positive and negative predictive values in the validation group were 88% (95% CI, 71%‐96%) and 94% (95% CI, 71%‐99%), respectively.

CONCLUSIONS:

The newly devised, internally validated, algorithm was 85% accurate in predicting nonorgan‐confined bladder disease before cystectomy. Further external validation in a large cohort was recommended as still necessary. Cancer 2009. © 2009 American Cancer Society.     

Overtreatment of men with low-risk prostate cancer and significant comorbidity

BACKGROUND:

Men with low‐risk prostate cancer and significant comorbidity are susceptible to overtreatment. The authors sought to compare the impact of comorbidity and age on treatment choice in men with low‐risk disease.

METHODS:

The authors sampled 509 men with low‐risk prostate cancer diagnosed at the Greater Los Angeles and Long Beach Veterans Affairs Medical Centers between 1997 and 2004. Rates of aggressive treatment (radical prostatectomy, radiation therapy, brachytherapy) were determined among men of different ages and with different Charlson comorbidity scores. Multivariate modeling was used to determine the influence of both variables in predicting nonaggressive treatment, and Cox proportional hazards analysis was used to compare the risk of other‐cause mortality among groups according to Charlson score and age.

RESULTS:

Men with Charlson scores ≥3 were treated aggressively in 54% of cases (30 of 56 men), while men aged >75 years at diagnosis were treated aggressively in 16% of cases (7 of 44 men). In multivariate analysis, age >75 years was a much stronger predictor of nonaggressive treatment (relative risk, 12.0; 95% confidence interval [CI], 5.4‐28.3) than a Charlson score ≥3 (relative risk, 2.0; 95% CI, 1.3‐2.9). In survival analysis, men with Charlson scores ≥3 had an 8‐fold increased risk (hazard ratio, 8.4; 95% CI, 4.2‐16.6) and 70% probability of other‐cause mortality at 10 years, whereas age >75 years was associated with a 5‐fold increased risk (hazard ratio, 4.9; 95%CI, 1.7‐13.8) and a 24% probability of other‐cause mortality.

CONCLUSIONS:

Men with significant comorbidity often were overtreated for low‐risk prostate cancer. Like advanced age, significant comorbidity should be a strong relative contraindication to aggressive treatment in men with low‐risk disease. Cancer 2011. © 2010 American Cancer Society.     

Urinary diversion and morbidity after radical cystectomy for bladder cancer

BACKGROUND:

The rate of continent urinary diversion after radical cystectomy for bladder cancer varies by patient and provider characteristics. Demonstration of equivalent complication rates, independent of diversion type, may decrease provider reluctance to perform continent reconstructions. The authors sought to determine whether continent reconstructions confer increased complication rates after radical cystectomy.

METHODS:

From the Nationwide Inpatient Sample, the authors used International Classification of Disease (ICD‐9) codes to identify subjects who underwent radical cystectomy for bladder cancer during 2001‐2005. They determined acute postoperative medical and surgical complications from ICD‐9 codes and compared complication rates by reconstruction type using the nearest neighbor propensity score matching method and multivariate logistic regression models.

RESULTS:

Adjusting for case‐mix differences between reconstructive groups, continent diversions conferred a lower risk of medical, surgical, and disposition‐related complications that was statistically significant for bowel (3.1% lower risk; 95% confidence interval [95% CI], ?6.8% to ?0.1%), urinary (1.2% lower risk; 95% CI, ?2.3%, to ?0.4%), and other surgical complications (3.0% lower risk; 95% CI, ?6.2% to ?0.4%), and discharge other than home (8.2% lower risk; 95% CI, ?12.1% to ?4.6%) compared with ileal conduit subjects. Older age and certain comorbid conditions, including congestive heart failure and preoperative weight loss, were associated with significantly increased odds of postoperative medical and surgical complications in all subjects.

CONCLUSIONS:

Mode of urinary diversion after radical cystectomy for bladder cancer is not associated with increased risk of immediate postoperative complications. These results may encourage broader consideration of continent urinary diversion without concern for increased complication rates. Cancer 2010. © 2010 American Cancer Society.     

Hospital-level variation in the quality of urologic cancer surgery

BACKGROUND:

Unexplained variation in outcomes after common surgeries raises concerns about the quality and appropriateness of surgical care. Understanding variation in surgical outcomes may identify processes that could affect the quality of surgical and postoperative care. The authors of this report examined hospital‐level variation in outcomes after inpatient urologic oncology procedures.

METHODS:

Patients who underwent radical cystectomy, radical nephrectomy, and radical prostatectomy were identified from the Washington State Comprehensive Hospital Abstract Reporting System for the years 2003 through 2007. The postoperative length of stay (LOS) was measured, and LOS that exceeded the 75th percentile was classified as prolonged. The occurrence of Agency for Healthcare Quality patient safety indicators (PSIs), readmissions, and deaths also were measured. Analyses were adjusted for patient age and comorbidity in random effects, multilevel, multivariable models that assessed hospital‐level outcomes.

RESULTS:

The authors identified 853 patients from 37 hospitals who underwent cystectomy, 3018 patients who underwent nephrectomy from 51 hospitals, and 8228 patients who underwent prostatectomy from 51 hospitals. Complications captured by PSIs were rare. Hospital‐level variation was most profound for LOS outcomes after nephrectomy and prostatectomy (variance in prolonged LOS, 8.1% and 26.7%, respectively), thromboembolic events after nephrectomy (8% of variance), and mortality after cystectomy (7.1% of variance).

CONCLUSIONS:

Hospital‐level variation confounds the care of urologic cancer patients in the state of Washington. The authors concluded that transparent reporting of surgical outcomes and local quality‐improvement initiatives should be considered to ameliorate the observed variation and improve the quality of cystectomy, nephrectomy, and prostatectomy care. Cancer 2011;. Published 2012 by the American Cancer Society.     

Delays in diagnosis and bladder cancer mortality

BACKGROUND:

Mortality from invasive bladder cancer is common, even with high‐quality care. Thus, the best opportunities to improve outcomes may precede the diagnosis. Although screening currently is not recommended, better medical care of patients who are at risk (ie, those with hematuria) has the potential to improve outcomes.

METHODS:

The authors used the Surveillance, Epidemiology, and End Results‐Medicare linked database for the years 1992 through 2002 to identify 29,740 patients who had hematuria in the year before a bladder cancer diagnosis and grouped them according to the interval between their first claim for hematuria and their bladder cancer diagnosis. Cox proportional hazards models were fitted to assess relations between these intervals and bladder cancer mortality, adjusting first for patient demographics and then for disease severity. Adjusted logistic models were used to estimate the patient's probability of receiving a major intervention.

RESULTS:

Patients (n = 2084) who had a delay of 9 months were more likely to die from bladder cancer compared with patients who were diagnosed within 3 months (adjusted hazard ratio [HR], 1.34; 95% confidence interval [CI], 1.20‐1.50). This risk was not markedly attenuated after adjusting for disease stage and tumor grade (adjusted HR, 1.29; 95% CI, 1.14‐1.45). In fact, the effect was strongest among patients who had low‐grade tumors (adjusted HR, 2.11; 95% CI, 1.69‐2.64) and low‐stage disease (ie, a tumor [T] classification of Ta or tumor in situ; adjusted HR, 2.02; 95% CI, 1.54‐2.64).

CONCLUSIONS:

A delay in the diagnosis of bladder cancer increased the risk of death from disease independent of tumor grade and or disease stage. Understanding the mechanisms that underlie these delays may improve outcomes among patients with bladder cancer. Cancer 2010. © 2010 American Cancer Society.     

Efficient delivery of radical cystectomy after neoadjuvant chemotherapy for muscle-invasive bladder cancer: a multidisciplinary approach

BACKGROUND:

Cystectomy delay >90 days after a diagnosis of muscle‐invasive bladder cancer (MIBC) adversely affects pathologic stage and survival outcomes in patients who undergo primary surgery. After neoadjuvant chemotherapy (NAC), the impact of the timing of cystectomy delivery on these outcomes is uncertain. Poor communication between urologic and medical oncologists can result in cystectomy delay after systemic treatment. The authors of this report hypothesized that a delay in cystectomy delivery after NAC is associated with adverse survival outcomes.

METHODS:

An eligible cohort of 153 patients with MIBC received NAC and underwent radical cystectomy between 1990 and 2007. At the authors' institution, the genitourinary team strives to schedule patients for surgery at the time of initial evaluation or after their first chemotherapy cycle. Clinicopathologic characteristics, including timing of cystectomy, chemotherapy delivery, vital status, and reasons for excessive surgical delay, were analyzed retrospectively using an institutional database. A Cox proportional regression model was used to test the association between the timing of cystectomy delivery and survival.

RESULTS:

The median follow‐up for all patients was 3.6 years. The median time to cystectomy was 16.6 weeks and 6.9 weeks from the first and last day of NAC, respectively. In multivariate analyses, the timing of cystectomy delivery from the termination of NAC did not significantly alter the risk of survival. The most common reason for cystectomy delivery beyond 10 weeks (28 patients; 18%) was procedural scheduling.

CONCLUSIONS:

Cystectomy delivery within 10 weeks after NAC did not compromise patient survival and, thus, provided a reasonable window for patient recovery and surgical intervention. Cancer 2012;. © 2011 American Cancer Society.     

Population‐based 10‐year oncologic outcomes after low‐dose‐rate brachytherapy for low‐risk and intermediate‐risk prostate cancer

BACKGROUND.

The objective of this study was to report the rates of disease‐free survival (DFS), cause‐specific survival (CSS), and overall survival after low‐dose‐rate (LDR) prostate brachytherapy (PB).

METHODS.

Data from 1006 consecutive patients with prostate cancer who received LDR‐PB and underwent implantation on or before October 23, 2003 were extracted from a prospective database on November 11, 2011. The selected patients had low‐risk (58%) or intermediate‐risk (42%) disease according to National Comprehensive Cancer Network criteria. The Phoenix threshold was used to define biochemical relapse. Sixty‐five percent of patients received 3 months of neoadjuvant androgen‐deprivation therapy (ADT) and 3 months of concomitant ADT. Univariate and multivariate analyses are reported in relation to patient, tumor, and treatment variables.

RESULTS.

The median follow‐up was 7.5 years. By using Fine and Gray competing risks analysis, the 5‐year and 10‐year actuarial DFS rates were 96.7% (95% confidence interval, 95.2%‐97.7%) and 94.1% (95% confidence interval, 92%‐95.6%), respectively. When applied to the whole cohort, none of the usual prognostic variables, including dose metrics, were correlated with DFS. However, in both univariate and multivariate models, increasing dose was the only covariate that correlated with improved DFS for the subset of men (N = 348) who did not receive ADT (P = .043). The actuarial 10‐year CSS rate was 99.1% (95% confidence interval, 97.3%‐99.7%). The overall survival rate was 93.8% at 5 years (95% confidence interval, 92%‐95.1%) and 83.5% at 10 years (95% confidence interval, 79.8%‐86.6%). Only age at implantation (P = .0001) was correlated with overall survival in multivariate analysis.

CONCLUSIONS.

In a consecutive cohort of 1006 men with National Comprehensive Cancer Network low‐risk and intermediate‐risk prostate cancer, the actuarial rate of recurrent disease after LDR‐PB was approximately 3% at 5 years and 6% at 10 years. Cancer 2013. © 2012 American Cancer Society.     

Projecting prostate cancer mortality in the PCPT and REDUCE chemoprevention trials

BACKGROUND.

Two recent chemoprevention trials demonstrated significant reductions in overall prostate cancer incidence. However, a possible increase in high‐grade disease has raised concerns that the harms of the drugs, including mortality because of high‐grade disease, may outweigh the benefits. The authors attempted to estimate the effect of these drugs on prostate cancer mortality to be able to better evaluate the cost‐benefit tradeoff.

METHODS.

The authors analyzed prostate cancer incidence in the Prostate Cancer Prevention Trial (PCPT) and Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial, which evaluated finasteride and the related compound dutasteride, respectively (both vs placebo). They used 13‐year prostate cancer survival data from the Prostate, Lung, Colorectal and Ovarian (PLCO) trial to project prostate cancer mortality from incidence patterns; survival rates were applied to incident cancers according to prognostic strata, which were defined by Gleason score, prostate‐specific antigen level, and clinical stage. For PCPT, the analysis was performed using both original trial results and previously published adjusted analyses that attempted to account for artifacts related to the drugs' effect on prostate volume.

RESULTS.

For the PCPT trial, the estimated relative risk (RR) for prostate cancer mortality was 1.02 (95% confidence interval [95% CI], 0.85‐1.23) using the original trial results and 0.87 (95% CI, 0.72‐1.06) and 0.91 (95% CI, 0.76‐1.09) based on the adjusted PCPT analyses. For the REDUCE trial, the RR for prostate cancer mortality was 0.93 (95% CI, 0.80‐1.08).

CONCLUSIONS.

Projecting a mortality outcome of the PCPT and REDUCE trials as an approach to weighing benefits versus harms suggests at most a small increase in prostate cancer mortality in the treatment arms, and possibly a modest decrease. Cancer 2013. © 2012 American Cancer Society.     

Prediagnostic smoking history, alcohol consumption, and colorectal cancer survival: the Seattle Colon Cancer Family Registry

BACKGROUND:

Smoking and alcohol consumption are associated with an increased risk of developing colorectal cancer. However, it is unclear whether these exposures are associated with survival after colorectal cancer diagnosis.

METHODS:

Men and women diagnosed with incident colorectal cancer between 1998 and 2007 in 13 counties in western Washington State were identified by using the Surveillance, Epidemiology, and End Results cancer registry. Information on smoking history and alcohol consumption was collected by telephone interview. Follow‐up for mortality was completed through linkage to the National Death Index. Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for associations among smoking, alcohol consumption, and mortality after colorectal cancer diagnosis. Stratified analyses were conducted by sex, age at diagnosis (<50 years, ≥50 years), tumor site (proximal, distal, rectal), stage (I‐II, III‐IV), and microsatellite instability status (stable/low, high).

RESULTS:

Disease‐specific and all‐cause mortality were significantly higher for smokers (HR, 1.30; 95% CI, 1.09‐1.74) compared with never‐smokers (HR, 1.51; 95% CI, 1.24‐1.83). However, this association was most prominent in those with tumors exhibiting high microsatellite instability (HR, 3.83; 95% CI, 1.32‐11.11) and did not extend to those with rectal cancer (HR, 1.08; 95% CI, 0.72‐1.61) or those diagnosed before age 50 years (HR, 0.99; 95% CI, 0.67‐1.48). Alcohol consumption was not associated with disease‐specific or all‐cause mortality, regardless of patient or tumor characteristics.

CONCLUSIONS:

In addition to an association with disease risk, smoking is associated with increased mortality after colorectal cancer diagnosis. This association is especially pronounced for colorectal cancer with high microsatellite instability. Cancer 2011;. © 2011 American Cancer Society.     

Prognostic factors in male urethral cancer

BACKGROUND:

Male urethral cancer is a rare neoplasm, with the published literature consisting of small single‐institution retrospective series. As such, there is no objective analysis of prognostic factors and treatment outcome. The author sought to use the population‐based Surveillance, Epidemiology, and End Results (SEER) database to evaluate prognostic factors in male urethral cancer.

METHODS:

From 1988 to 2006, 2065 men were identified in the SEER database as having primary urethral cancer. Median follow‐up was 2.5 years. Cancer‐specific and overall survival was computed using the Kaplan‐Meier method, and Cox proportional hazards analysis was used to evaluate patient age at diagnosis, year of diagnosis, race, histologic type, grade, T stage, nodal status, M stage, extent of surgery, and type of radiation as potential significant independent predictors of survival.

RESULTS:

Overall survival at 5 and 10 years was 46.2% (95% confidence interval [CI], 43.9‐48.6%) and 29.3% (95% CI, 26.6‐32.0%), respectively, whereas cancer‐specific survival at 5 and 10 years was 68.0% (95% CI, 65.5‐70.5%) and 60.1% (95% CI, 57.0‐63.2%), respectively. Advanced age, higher grade, higher T stage, systemic metastases, other histology versus transitional cell carcinoma (TCC), and no surgery versus radical resection were predictors of death and death from disease, whereas adenocarcinoma was associated with a lower likelihood of death and death from disease as compared with TCC. In addition, nodal metastasis was a predictor of death. Surgery had a better outcome than radiation for stage T₂‐T₄ nonmetastatic disease.

CONCLUSIONS:

Age, grade, TNM stage, histology, and extent of surgery were predictive of overall and cancer‐specific survival. Cancer 2011. © 2010 American Cancer Society.