Abstract
Simple SummaryBladder cancer is one of the leading causes of death worldwide. About 75% of patients initially present with non-muscle-invasive disease, while the rest presents with primary muscle-invasive disease. Up to a third of non-muscle-invasive bladder cancers progresses into secondary muscle-invasive bladder cancer. Little is known about clinical outcomes after upfront neoadjuvant cisplatin-based chemotherapy and subsequent radical cystectomy for secondary muscle-invasive bladder cancer compared to primary muscle-invasive bladder cancer. Here, we systematically reviewed the current literature evaluate oncological outcomes between primary and secondary muscle-invasive bladder cancer.To evaluate oncological outcomes of primary versus secondary muscle-invasive bladder cancer treated with radical cystectomy. Medline, Embase, Scopus and Cochrane Library were searched for eligible studies. Hazard ratios for overall survival (OS), cancer specific survival (CSS) and progression free survival (PFS) were calculated using survival data extracted from Kaplan-Meier curves. A total of 16 studies with 5270 patients were included. Pooled analysis showed similar 5-year and 10-year OS (HR 1, p = 0.96 and HR 1, p = 0.14) and CSS (HR 1.02, p = 0.85 and HR 0.99, p = 0.93) between primMIBC and secMIBC. Subgroup analyses according to starting point of follow-up and second-look transurethral resection revealed similar results. Subgroup analyses of studies in which neoadjuvant chemotherapy was administered demonstrated significantly worse 5-year CSS (HR 1.5, p = 0.04) but not 10-year CSS (HR 1.36, p = 0.13) in patients with secMIBC. Patients with secMIBC had significantly worse PFS at 5-year (HR 1.41, p = 0.002) but not at 10-year follow-up (HR 1.25, p = 0.34). This review found comparable oncologic outcomes between primMIBC and secMIBC patients treated with RC regarding OS and CSS. Subgroup analysis showed worse 5-year CSS but not 10-year CSS for neoadjuvant chemotherapy in the secMIBC group. Prospective clinical trials incorporating molecular markers, that allow precise risk stratification of secMIBC and further research uncovering underlying molecular and clinical drivers of the heterogeneous group of secMIBC is needed.
Highlights
Bladder cancer ranks as the ninth most common cancer worldwide with an estimated yearly incidence of about 430,000 new cases, and it ranks 13th regarding yearly cancer mortality [1]
In all studies the “time-to-event” analyses started at the time of Radical cystectomy (RC) except for the one conducted by Schrier, which started calculation of survival from the time of muscle-invasive bladder cancer (MIBC) diagnosis and not RC
Therapy of non-muscle-invasive bladder cancer (NMIBC) consisted of transurethral resection of bladder tumor (=TURBT) and adjuvant instillation therapy
Summary
Bladder cancer ranks as the ninth most common cancer worldwide with an estimated yearly incidence of about 430,000 new cases, and it ranks 13th regarding yearly cancer mortality [1]. In NMIBC tumor recurrence is rather common and up to 30% in the high-risk group (all T1 high-grade without carcinoma in situ [CIS] and all CIS patients) [3] will progress to MIBC [4], despite adequate initial treatments [5]. Radical cystectomy (RC) with or without neoadjuvant cisplatin-based combination chemotherapy, when possible, is the standard management of patients with MIBC. The same is true for the likelihood of response to neoadjuvant cisplatin-based combination chemotherapy [20]. These findings suggest that the prognosis between secMIBC and primMIBC should be explored further to help guide decision making regarding intensity and type of therapy
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