Urothelial CancerNeoadjuvant Chemotherapy in Small Cell Urothelial Cancer Improves Pathologic Downstaging and Long-term Outcomes: Results from a Retrospective Study at the MD Anderson Cancer Center
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.
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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
References (14)
- et al.
Radical cystectomy for primary neuroendocrine tumors of the bladder: the University of Southern California experience
J Urol
(2005) - et al.
Evidence supporting preoperative chemotherapy for small cell carcinoma of the bladder: a retrospective review of the M. D. Anderson cancer experience
J Urol
(2004) - et al.
Primary small cell carcinoma of the bladder: a report of 25 cases
J Urol
(1995) - et al.
Symptomatic brain metastases from small-cell carcinoma of the urinary bladder: The Netherlands Cancer Institute experience and literature review
Ann Oncol
(2010) - et al.
Small cell carcinoma of the urinary bladder: a clinicopathologic analysis of 64 patients
Cancer
(2004) - et al.
Small cell carcinoma of the urinary bladder. A clinicopathologic, morphometric, immunohistochemical, and ultrastructural study of 18 cases
Cancer
(1989) Adjuvant/neo-adjuvant etoposide/cisplatin and cystectomy for management of invasive small cell carcinoma of the bladder
J Urol
(2002)
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