Karim Chamie

IMPORTANCE: Bladder cancer is a common malignancy in women and is the fourth most common malignancy in men. Bladder cancer ranges from unaggressive and usually noninvasive tumors that recur and commit patients to long-term invasive surveillance, to aggressive and invasive tumors with high disease-specific mortality. OBSERVATIONS: Advanced age, male sex, and cigarette smoking contribute to the development of bladder cancer. Bladder tumors can present with gross or microscopic hematuria, which is evaluated with cystoscopy and upper tract imaging depending on the degree of hematuria and risk of malignancy. Non-muscle-invasive tumors are treated with endoscopic resection and adjuvant intravesical therapy, depending on the risk classification. Enhanced cystoscopy includes technology used to improve the detection of tumors and can reduce the risk of recurrence. Patients with high-risk non-muscle invasive tumors that do not respond to adjuvant therapy with the standard-of-care immunotherapy, bacille Calmette-Guérin (BCG), constitute a challenging patient population to manage and many alternative therapies are being studied. For patients with muscle-invasive disease, more aggressive therapy with radical cystectomy and urinary diversion or trimodal therapy with maximal endoscopic resection, radiosensitizing chemotherapy, and radiation is warranted to curb the risk of metastasis and disease-specific mortality. Treatment of patients with advanced disease is undergoing rapid changes as immunotherapy with checkpoint inhibitors, targeted therapies, and antibody-drug conjugates have become options for certain patients with various stages of disease. CONCLUSIONS AND RELEVANCE: Improved understanding of the molecular biology and genetics of bladder cancer has evolved the way localized and advanced disease is diagnosed and treated. While intravesical BCG has remained the mainstay of therapy for intermediate and high-risk non-muscle-invasive bladder cancer, the therapeutic options for muscle-invasive and advanced disease has expanded to include immunotherapy with checkpoint inhibition, targeted therapies, and antibody-drug conjugates.

BACKGROUND: Patients with bladder cancer are apt to develop multiple recurrences that require intervention. The recurrence, progression, and bladder cancer-related mortality rates were examined in a cohort of individuals with high-grade non-muscle-invasive bladder cancer. METHODS: Using linked Surveillance, Epidemiology, and End Results (SEER)-Medicare data, subjects were identified who had a diagnosis of high-grade, non-muscle-invasive disease in 1992 to 2002 and who were followed until 2007. Multivariate competing-risks regression analyses were then used to examine recurrence, progression, and bladder cancer-related mortality rates. RESULTS: Of 7410 subjects, 2897 (39.1%) experienced a recurrence without progression, 2449 (33.0%) experienced disease progression, of whom 981 succumbed to bladder cancer. Using competing-risks regression analysis, the 10-year recurrence, progression, and bladder cancer-related mortality rates were found to be 74.3%, 33.3%, and 12.3%, respectively. Stage T1 was the only variable associated with a higher rate of recurrence. Women, black race, undifferentiated grade, and stage Tis and T1 were associated with a higher risk of progression and mortality. Advanced age (≥ 70) was associated with a higher risk of bladder cancer-related mortality. CONCLUSIONS: Nearly three-fourths of patients diagnosed with high-risk bladder cancer will recur, progress, or die within 10 years of their diagnosis. Even though most patients do not die of bladder cancer, the vast majority endures the morbidity of recurrence and progression of their cancer. Increasing efforts should be made to offer patients intravesical therapy with the goal of minimizing the incidence of recurrences. Furthermore, the high recurrence rate seen during the first 2 years of diagnosis warrants an intense surveillance schedule.

BACKGROUND: In the current study, the authors attempted to describe the incidence, most common sites, and mortality of second primary malignancies among survivors of common cancers. METHODS: The authors identified patients aged ≥18 years who were diagnosed with a primary malignancy from the 10 most common cancer sites (prostate, breast, lung, colon, rectum, bladder, uterus, kidney, melanoma, and non-Hodgkin lymphoma) between 1992 and 2008 from Surveillance, Epidemiology, and End Results data. Factors associated with the incidence of second primary malignancies were explored using bivariable and multivariable models, and mortality attributable to first and second primary malignancies was examined. RESULTS: A cohort of 2,116,163 patients was identified, 170,865 of whom (8.1%) developed a second primary malignancy. Survivors of bladder cancer had the highest risk of developing a second cancer. In a multivariable model controlling for age, race, tumor grade, stage of disease, marital status, educational level, and income, a history of non-Hodgkin lymphoma (hazard ratios of 2.70 and 2.88, respectively, for men and women) and bladder cancer (hazard ratios of 1.88 and 1.66, respectively, for men and women) predicted the highest risk of developing a second cancer. For patients with 2 incident cancers, 13% died of their initial cancer, but greater than one-half (55%) died of their second primary malignancy. Lung cancer was the cause of death in 12% of patients with 2 incident cancers. CONCLUSIONS: Nearly 1 in 12 patients diagnosed with a common cancer developed a second malignancy, the most common of which was lung cancer. Greater than one-half of patients with 2 incident cancers died of their secondary malignancy. The findings from the current study may inform care strategies among cancer survivors. Cancer 2016;122:3075-3086. © 2016 American Cancer Society.

PURPOSE: Previous studies of the impact of renal cell carcinoma histopathology on survival are conflicting and generally limited to institutional analyses. Thus, we determined the role of renal cell carcinoma histopathology on the stage specific survival rate in a large population based cohort. MATERIALS AND METHODS: We used the 2000 to 2005 National Cancer Institute SEER (Surveillance, Epidemiology and End Results) database to identify 17,605 patients who underwent surgery for renal cell carcinoma and met study inclusion criteria. Patients were stratified by histological subtype (clear cell, papillary, chromophobe, collecting duct and sarcomatoid differentiation) and pathological stage. We performed Cox proportional hazard modeling and Kaplan-Meier survival analysis to determine overall and cancer specific survival. RESULTS: Patients with papillary and chromophobe pathology were less likely to present with T3 or greater disease (17.6% and 16.9%, respectively) while patients with collecting duct and sarcomatoid variants were more likely to present with T3 or greater disease (55.7% and 82.8%, respectively) compared to those with clear cell histology (p <0.001). On multivariate analysis histology was significantly associated with overall and cancer specific survival. Patients with chromophobe pathology had improved survival (HR 0.56, 95% CI 0.40-0.78) while those with collecting duct and sarcomatoid variants had worse survival (HR 2.07, 95% CI 1.44-2.97 and 2.26, 95% CI 1.93-2.64, respectively). CONCLUSIONS: Renal cell carcinoma histological subtype predicts overall and cancer specific survival. Patients with collecting duct and sarcomatoid variants of renal cell carcinoma have poor survival, even those who present with low stage disease. These data suggest inherent differences in renal cell carcinoma biology and may ultimately form the basis of future histologically targeted therapies.