Elsevier

European Urology

Volume 64, Issue 2, August 2013, Pages 307-313
European Urology

Urothelial Cancer
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

https://doi.org/10.1016/j.eururo.2012.04.020Get rights and content

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.

Introduction

Small cell urothelial carcinoma (SCUC) is an aggressive malignancy characterized by rapid progression and early microscopic metastases, even in surgically resectable disease. The current approach in most centers, initial cystectomy, has resulted in poor outcomes, with many patients pathologically upstaged, resulting in relapse and death within 2 yr of cystectomy [1], [2], [3], [4], [5]. Recent small case series [2], [6] as well as the first prospective clinical trial in SCUC [7] suggest a potential benefit using neoadjuvant chemotherapy. Given the paucity of data, it is imperative that centers with significant experience treating SCUC share their approaches and outcomes.

Section snippets

Data collection

We identified 172 patients with SCUC treated at MDACC between 1985 and 2010. The MDACC institutional review board reviewed and approved this retrospective review. Patients must have had a definitive small cell component based on review of the pathology. Patients with an equivocal diagnosis, with small cell differentiation in a small cluster of cells, or with small cell of nonurothelial origin were excluded. Records were reviewed for demographic, clinical, pathologic, treatment, and outcome

Patient and tumor characteristics

Most patients were older white men with a median age of 69.3 yr (Table 1a). Small cell was the predominant histology in 82%; 38% were characterized as having pure small cell histology. The majority of patients (125; 73%) presented with surgically resectable disease (≤cT4aN0M0).

Surgically resectable disease

Of the 172 cases reviewed, 125 patients had surgically resectable disease (clinical staging ≤cT4aN0M0). Patients with clinically enlarged lymph node metastases historically have survival similar to other metastatic

Discussion

Neoadjuvant chemotherapy for SCUC was associated with a higher rate of pathologic downstaging at surgery, improving long-term survival. With initial surgery, there is an increased risk of pathologic upstaging, at times leading to an aborted cystectomy and resulting in poor outcomes. Other centers also suggest very poor survival with initial surgery, with few patients alive beyond 2 yr [1], [3], [8], [9]. A small subset of patients with node-only metastases who achieve near-complete response

Conclusions

Our findings support neoadjuvant chemotherapy for the treatment of SCUC and suggest pathologic downstaging to ≤pT1N0 as an appropriate surrogate marker for eventual cure. Surgical consolidation with cystectomy and extended lymph node dissection should be considered for patients with lymph node metastases who have an excellent response to chemotherapy. Due to the high frequency of CIS and associated risk of future tumors, we advocate for surgery as the optimal local control modality.

This

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