Neoadjuvant Chemotherapy in Small Cell Urothelial Cancer Improves Pathologic Downstaging and Long-term Outcomes: Results from a Retrospective Study at the MD Anderson Cancer Center

Abstract

Background Small cell urothelial carcinoma (SCUC) is a rare, aggressive malignancy with a propensity for early microscopic metastases. Data suggest that neoadjuvant chemotherapy may lead to improved survival compared with initial surgery. Objective To determine the influence of neoadjuvant chemotherapy on survival of SCUC patients in a large single-institution cohort. Design, setting, and participants Between 1985 and 2010, 172 patients were treated for SCUC at MD Anderson Cancer Center (MDACC). Clinical, pathologic, and surgical data were collected and analyzed. Outcome measurements and statistical analysis Overall survival (OS) and disease-specific survival (DSS) were calculated using the Kaplan-Meier method. Multivariable Cox proportional hazards models were used to evaluate the effects of neoadjuvant chemotherapy on survival. Results and limitations Of 125 patients with resectable disease (≤cT4aN0M0), 95 were surgical candidates. Forty-eight received neoadjuvant chemotherapy, and 47 underwent initial surgery. Neoadjuvant treatment was associated with improved OS and DSS compared with initial cystectomy (median OS: 159.5 mo vs 18.3 mo, p < 0.001; 5-yr DSS: 79% vs 20%, p < 0.001). Neoadjuvant chemotherapy resulted in pathologic downstaging to ≤pT1N0 in 62% of tumors compared with only 9% treated with initial surgery (odds ratio: 44.55; 95% confidence interval, 10.39–191). Eight patients with clinically node-positive disease had surgical consolidation with cystectomy and extended lymph node dissection after clinical complete response to chemotherapy. Median OS and DSS in this group of patients were 23.3 mo and 21.8 mo, respectively, with 5-yr OS and DSS of 38%. Conclusions Neoadjuvant chemotherapy is associated with a high rate of pathologic downstaging and correlates with significantly higher survival compared with historical expectations. Although limited by a small sample size and retrospective analysis, in the context of a rare disease, this experience suggests neoadjuvant chemotherapy as a standard approach in treating SCUC.

Local control rate and prognosis after sequential chemoradiation for small cell carcinoma of the bladder

“…21 These promising results were recently corroborated by another report from the MD Anderson group. 22 The substantial differences in OS of patients in the present study with bladder preserving strategy versus the mentioned cystectomy series might partly be explained by small sample sizes, differences in initial tumor stage, different regimens of chemotherapy and clinical versus pathological TNM staging. Patient selection might be another confounding factor.…”

Long‐term results of radical cystectomy and role of adjuvant chemotherapy for small cell carcinoma of the bladder

“…8 More recently, MD Anderson Cancer Center investigators reported their results of a 25-year follow up of SCCB. 9 They analyzed the outcomes of 95 patients with SCCB, of which 48 underwent neoadjuvant chemotherapy followed by radical cystectomy and 47 underwent radical cystectomy. Neoadjuvant treatment was associated with improved OS and CSS compared with initial cystectomy (median OS 159.5 months vs 18.3 months, P < 0.001; 5-yr CSS 79% vs 20%, P < 0.001).…”

Management of small cell carcinoma of the bladder: Consensus guidelines from the Canadian Association of Genitourinary Medical Oncologists (CAGMO)

“…For ED, the recommendation is to administer regimens similar to those used in SCLC, such as cisplatin or carboplatin in combination with etoposide or irinotecan. 72 …”

“…20,29,31,72 Siefker-Radtke and colleagues 31,29,72 advocate for combining chemotherapy with surgery based on retrospective and phase II studies.…”

“…In a retrospective review by Lynch and colleagues, 72 172 patients with SCCB were identified. Of the 95 patients eligible for surgery, 48 received neoadjuvant chemotherapy, while 47 had initial cystectomy (21/47 received adjuvant chemotherapy).…”