Histopathology and Response of Bladder Cancer to Neoadjuvant Therapy
LJ Eisengart, SM Rohan, G MacVicar, XJ Yang. Northwestern University, Chicago, IL
Background: Radical cystectomy is the mainstream treatment for muscle-invasive urothelial carcinoma. Several large randomized trials have suggested a survival benefit for neoadjuvant therapy followed by cystectomy as compared to cystectomy alone. As neoadjuvant therapy becomes more common, it will be important to document response of different carcinoma variants to these therapies and to recognize treatment associated histologic changes. We evaluated the histology of post-neoadjuvant cystectomy specimens as compared to the diagnostic biopsy.
Design: Slides from the diagnostic biopsies and post-chemotherapy cystectomy specimens from 14 patients were reviewed. Tumor grade, histologic subtype, presence of divergent differentiation, depth of invasion, and lymphovascular invasion (LVI) were recorded for both biopsy and cystectomy specimens. Percent tumor necrosis, presence of foreign body giant cells, and TNM stage at cystectomy were also recorded.
Results: All biopsies showed high grade urothelial carcinoma with muscularis propria invasion. At cystectomy, 6 of 14 patients (43%) showed a good histologic response to chemotherapy: 3 (21%) showed no residual tumor, 1 contained only non-invasive papillary carcinoma, and 2 had a single focus of microscopic tumor in the superficial muscularis propria. Five patients showed some response to chemotherapy, with 10-50% tumor necrosis. Three patients showed no response to chemotherapy. Those with some or no response had pT3 or pT4 disease. 6 cases had LVI on biopsy, 4 of which had none at cystectomy. Eight patients had no LVI on biopsy but 3 of those did at cystectomy. Patients with lymph node metastases were evenly distributed across groups with residual tumor. Only 1 of 6 with good response was of a specific subtype (micropapillary), whereas 4 of 5 with some response and 3 of 3 with no response showed divergent differentiation or belonged to a specific histologic variant (plasmacytoid, micropapillary, small cell neuroendocrine carcinoma) (p=0.026, two-tailed Fisher's exact test).
Conclusions: In this series, neoadjuvant therapy resulted in either no or microscopic residual invasive carcinoma in 43% of the cystectomy specimens. LVI was eradicated in 4 of 6 cases. Our results suggest that neoadjuvant therapy might be less effective for histologic variants of urothelial carcinoma and in cases with divergent differentiation. Larger studies will be valuable to substantiate these findings and to design more effective neoadjuvant therapy protocols.
Category: Genitourinary (including renal tumors)
Tuesday, March 23, 2010 1:00 PM
Poster Session IV # 100, Tuesday Afternoon