Abstract Context The incidence of bladder cancer is three to four times greater in men than in women. However, women are diagnosed with more advanced disease at presentation and have less favorable ...outcomes after treatment. Objective To review the literature on potential biologic mechanisms underlying differential gender risk for bladder cancer, and evidence regarding gender disparities in bladder cancer presentation, management, and outcomes. Evidence acquisition A literature search of English-language publications that included an analysis of the association of gender with bladder cancer was performed using Pubmed. Ninety-seven articles were selected for analysis with the consensus of all authors. Evidence synthesis It has been shown that the gender difference in bladder cancer incidence is independent of differences in exposure risk, including smoking status. Potential molecular mechanisms include disparate metabolism of carcinogens by hepatic enzymes between men and women, resulting in differential exposure of the urothelium to carcinogens. In addition, the activity of the sex steroid hormone pathway may play a role in bladder cancer development, with demonstration that both androgens and estrogens have biologic effects in bladder cancer in vitro and in vivo. Importantly, gender differences exist in the timeliness and completeness of hematuria evaluation, with women experiencing a significantly greater delay in urologic referral and undergoing guideline-concordant imaging less frequently. Correspondingly, women have more advanced tumors at the time of bladder cancer diagnosis. Interestingly, higher cancer-specific mortality has been noted among women even after adjusting for tumor stage and treatment modality. Conclusions Numerous potential biologic and epidemiologic factors probably underlie the gender differences observed for bladder cancer incidence, stage at diagnosis, and outcomes. Continued evaluation to define clinical applications for manipulation of the sex steroid pathway and to improve the standardization of hematuria evaluation in women may improve future patient outcomes and reduce these disparities. Patient summary We describe the scientific basis and clinical evidence to explain the greater incidence of bladder cancer in men and the adverse presentation and outcomes for this disease in women. We identify goals for improving patient survival and reducing gender disparities in bladder cancer.
The role of surgery in metastatic bladder cancer (BCa) is unclear.
In this collaborative review article, we reviewed the contemporary literature on the surgical management of metastatic BCa and ...factors associated with outcomes to support the development of clinical guidelines as well as informed clinical decision-making.
A systematic search of English language literature using PubMed-Medline and Scopus from 1999 to 2016 was performed.
The beneficial role of consolidation surgery in metastatic BCa is still unproven. In patients with clinically evident lymph node metastasis, data suggest a survival advantage for patients undergoing postchemotherapy radical cystectomy with lymphadenectomy, especially in those with measurable response to chemotherapy (CHT). Intraoperatively identified enlarged pelvic lymph nodes should be removed. Anecdotal reports of resection of pulmonary metastasis as part of multimodal approach suggest possible improved survival in well-selected patients. Cytoreductive radical cystectomy as local treatment has also been explored in patients with metastatic disease, although its benefits remain to be assessed.
Consolidative extirpative surgery may be considered in patients with clinically evident pelvic or retroperitoneal lymph nodal metastases but only if they have had a response to CHT. Surgery for limited pulmonary metastases may also be considered in very selected cases. Best candidates are those with resectable disease who demonstrate measurable response to CHT with good performance status. In the absence of data from prospective randomized studies, each patient should be evaluated on an individual basis and decisions made together with the patient and multidisciplinary teams.
Surgical resection of metastases is technically feasible and can be safely performed. It may help improve cancer control and eventually survival in very selected patients with limited metastatic burden. In a patient who is motivated to receive chemotherapy and to undergo extirpative surgical intervention, surgery should be discussed with the patient among other consolidation therapies in the setting of multidisciplinary teams.
A multimodal approach that includes radical cystectomy and lymphadenectomy seems to improve cancer control and survival in bladder cancer patients with nodal metastasis. Metastasectomy is feasible and can be safely performed with a possible survival advantage in well-selected patients.
Purpose Multidisciplinary management improves complex treatment decision making in cancer care, but its impact for bladder cancer (BC) has not been documented. Although radical cystectomy (RC) ...currently is viewed as the standard of care for muscle-invasive bladder cancer (MIBC), radiotherapy-based, bladder-sparing trimodal therapy (TMT) that combines transurethral resection of bladder tumor, chemotherapy for radiation sensitization, and external beam radiotherapy has emerged as a valid treatment option. In the absence of randomized studies, this study compared the oncologic outcomes between patients treated with RC or TMT by using a propensity score matched-cohort analysis. Methods Data from patients treated in a multidisciplinary bladder cancer clinic (MDBCC) from 2008 to 2013 were reviewed retrospectively. Those who received TMT for MIBC were identified and matched (for sex, cT and cN stage, Eastern Cooperative Oncology Group status, Charlson comorbidity score, treatment date, age, carcinoma in situ status, and hydronephrosis) with propensity scores to patients who underwent RC. Overall survival and disease-specific survival (DSS) were assessed with Cox proportional hazards modeling and a competing risk analysis, respectively. Results A total of 112 patients with MIBC were included after matching (56 who had been treated with TMT, and 56 who underwent RC). The median age was 68.0 years, and 29.5% had stage cT3/cT4 disease. At a median follow-up of 4.51 years, there were 20 deaths (35.7%) in the RC group (13 as a result of BC) and 22 deaths (39.3%) in the TMT group (13 as a result of BC). The 5-year DSS rate was 73.2% and 76.6% in the RC and TMT groups, respectively ( P = .49). Salvage cystectomy was performed in 6 (10.7%) of 56 patients who received TMT. Conclusion In the setting of a MDBCC, TMT yielded survival outcomes similar to those of matched patients who underwent RC. Appropriately selected patients with MIBC should be offered the opportunity to discuss various treatment options, including organ-sparing TMT.
Jena and colleagues noted that it is odd that so many apparently fit patients (77% with Eastern Cooperative Oncology Group performance status of 0) would choose trimodality therapy in an era when ...most urologists in North America tended to recommend radical cystectomy for muscle-invasive bladder cancer.1 Massachusetts General Hospital and Princess Margaret Cancer Centre (with Toronto General Hospital) have collectively operated multidisciplinary bladder cancer clinics for decades, which allowed patients the opportunity to discuss and choose between treatment options, when they are deemed candidates for either radical cystectomy or trimodality therapy. ...29% represents the percentage of patients with muscle-invasive bladder cancer operated on by radical cystectomy (among the total radical cystectomies performed at the contributing institutions) who presented with the inclusion criteria of our study. ...research is needed to inform the full range of eligibility for trimodality therapy.
The high recurrence and progression rates of non-muscle invasive bladder cancer (NMIBC) have led investigators to study the use of intravesical therapy in order to prevent them. Bacillus ...Calmette-Guérin (BCG) has been successfully used for this indication to treat NMIBC for more than four decades. BCG is the only intravesical agent shown to reduce the risk of progression of NMIBC to muscle-invasive disease. Despite over 40 years of clinical use, the precise mechanism of action for what has often been considered the most successful cancer immunotherapy in humans remains largely unknown. Unfortunately, BCG therapy is not a universal panacea and it still fails in up to 40% of patients. Many of these patients, especially in the high-risk category (T1 high-grade disease, carcinoma in situ) will require aggressive therapy like cystectomy or in selected cases, bladder-sparing options like chemo-radiation. Indeed, there is no gold standard intravesical treatment after BCG failure.
Abstract Context Non–muscle-invasive bladder cancer (NMIBC) commonly recurs, requiring invasive and costly transurethral resection of bladder tumor (TURBT). A meta-analysis of seven trials published ...in 2004 demonstrated that intravesical chemotherapy (IVC) following TURBT reduces recurrences. Despite European Association of Urology endorsement, adoption of this practice has been modest. Objective To investigate whether immediate postoperative IVC prolongs the recurrence-free interval (RFI) and early recurrences (ERs) in light of new trial data and to explore the quality of evidence supporting its use. Evidence acquisition A systematic literature review of random controlled trials (RCTs) published before March 2013 was performed using the Medline, Embase, and Cochrane databases. Trials examining NMIBC recurrence for adults receiving IVC immediately following TURBT were included. RFI was estimated by hazard ratio (HR), and ER was estimated by absolute risk reduction (ARR) of recurrences within 1 yr of TURBT. Both outcomes were synthesized using random-effects models. Risk of bias was assessed using the Cochrane Collaboration risk-of-bias tool, and quality of evidence for each outcome was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation system. Evidence synthesis Thirteen studies with 2548 patients were included. IVC prolonged RFI by 38% (HR: 0.62; 95% confidence interval CI, 0.50–0.77; p < 0.001; I2 : 69%), and ERs were 12% less likely in the intervention population (ARR: 0.12; 95% CI, −0.18 to −0.06; p < 0.001, I2 : 0%). The number needed to treat to prevent one ER was 9 (95% CI, 6–17 patients). There was high risk of bias present in 12 of 13 publications. Quality of evidence for RFI was very low and low for ERs. Conclusions Our updated meta-analysis supports that IVC prolongs RFI and reduces ERs of NMIBC when administered immediately after TURBT. However, contemporary methodology suggests low evidence quality for examined outcomes. Thus RCTs with careful randomization and blinding are still warranted to clarify the usefulness of immediate postoperative IVC in this population.
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