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.

Keywords: Bladder cancer; Chemotherapy; Neoadjuvant; Small cell urothelial cancer; Surgery.

Fig. 1

(A) Overall survival (OS) and (B) disease-specific survival (DSS) from diagnosis of small cell urothelial cancer in patients undergoing cystectomy. Patients treated with neoadjuvant chemotherapy had improved OS and 5-yr DSS (median OS: 159.5 mo; 95% confidence interval [CI], 74.8 to ∞ 5-yr DSS: 79%) compared with those treated with initial surgery (median OS: 18.3 mo; 95% CI, 14.8–25.5 mo; 5-yr DSS: 20%; log-rank p < 0.001).

Fig. 2

(A) Overall survival (OS) and (B) disease-specific survival (DSS) from diagnosis of small cell urothelial cancer in patients treated with neoadjuvant chemotherapy. Patients who were downstaged to ≤pT2N0M0 had an improved median OS and 5-yr DSS (median OS: 187 mo; 95% confidence interval [CI], 160 to ∞; 5-yr DSS: 94.4%) compared with those with ≥ pT3, N+, or M+ disease at surgery (median OS: 10.8 mo; 95% CI, 10.8 to ∞; 5-yr DSS: 20.5%; log-rank p < 0.001).

Fig. 3

(A) Overall survival (OS) and (B) disease-specific survival (DSS) from diagnosis of patients with T4b or N+ or M+ disease, stratified by surgical consolidation or no surgery. Eight patients with node-positive disease had a clinical complete response to chemotherapy and had surgical consolidation with cystectomy and extended lymph node dissection. The median OS for those who did not have surgery was 11.8 mo (95% confidence interval [CI], 9.2–15.8). For the eight patients having surgical consolidation of clinically evident lymph node metastases, median OS and DSS were 23.3 mo (95% CI, 20.9 to ∞) and 21.8 mo (95% CI, 19.42 to ∞), respectively, with a 5-yr OS of 38%.