Despite advances in surgical techniques and the introduction of extended lymph node dissection, surgery alone in MIBC is associated suboptimal outcomes due in large part to high rates of systemic failure (distant metastasis). Cisplatin-based chemotherapy given prior to the surgery has become the standard of care based on an overall survival benefit shown in phase III studies. However, neoadjuvant chemotherapy (NAC) has been under-utilized despite the supportive level I evidence.[1]
One reason for low NAC use is the hypothetical concern for a negative impact in outcome due to delay of definitive surgery. In fact, definitive surgery after NAC can be delayed for various reasons including complications from the chemotherapy and poor coordination between medical oncology and urology. However, the clinical implication of such delay following NAC has not been adequately evaluated. Although several studies have shown that delay of cystectomy more than 12 weeks from diagnosis is associated with poor survival, these reports mainly evaluated patients who were treated with surgery alone or mixed populations with small portions of patients receiving NAC.[2-4]
Our retrospective study analyzed 201 patients with MIBC all treated with NAC followed by radical cystectomy between 1996 and 2014 at the Johns Hopkins Hospital.[5] In this study, 3 treatment-related time intervals were analyzed for correlation with survival: 1) the interval from MIBC diagnosis on TURBT to the initiation of NAC, 2) the interval from initiation of NAC to the radical cystectomy, and 3) the total interval from MIBC diagnosis to radical cystectomy. The median durations of each time interval were 6 weeks, 22 weeks, and 28 weeks, respectively. None of the treatment time intervals were significantly associated with overall survival.
This is the first report that analyzed the impact of each treatment time interval on overall survival in patients with MIBC who received NAC. Our findings reinforce the role of cisplatin-based NAC for MIBC patients and suggest that NAC should not be withheld from eligible patients due to concerns of unfavorable impacts on overall survival from chemotherapy-associated delays in cystectomy. Limitations of our study include an inherent selection bias present in retrospective studies, a relatively small sample size, and a short follow up duration. Thus, our observations should not be used to legitimize unnecessary delays in curative cystectomy scheduling.
Written by: Jong Chul Park, MD The Sidney Kimmel Comprehensive Cancer Center Johns Hopkins Medical Institutions
References:
1. Park JC, Citrin DE, Agarwal PK, Apolo AB: Multimodal management of muscle-invasive bladder cancer. Current problems in cancer 2014, 38(3):80-108.
2. Sanchez-Ortiz RF, Huang WC, Mick R, Van Arsdalen KN, Wein AJ, Malkowicz SB: An interval longer than 12 weeks between the diagnosis of muscle invasion and cystectomy is associated with worse outcome in bladder carcinoma. The Journal of urology 2003, 169(1):110-115; discussion 115.
3. Mahmud SM, Fong B, Fahmy N, Tanguay S, Aprikian AG: Effect of preoperative delay on survival in patients with bladder cancer undergoing cystectomy in Quebec: a population based study. The Journal of urology 2006, 175(1):78-83; discussion 83.
4. Gore JL, Lai J, Setodji CM, Litwin MS, Saigal CS, Urologic Diseases in America P: Mortality increases when radical cystectomy is delayed more than 12 weeks: results from a Surveillance, Epidemiology, and End Results-Medicare analysis. Cancer 2009, 115(5):988-996.
5. Park JC, Gandhi NM, Carducci MA, Eisenberger MA, Baras AS, Netto GJ, Liu JJ, Drake CG, Schoenberg MP, Bivalacqua TJ et al: A Retrospective Analysis of the Effect of Time from Diagnosis to Cystectomy on Survival in Patients with Muscle-Invasive Bladder Cancer Receiving Neoadjuvant Chemotherapy. The Journal of urology 2015.