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.

Importance The long-term impact of axillary pathologic complete response (pCR) on survival among women treated with primary systemic chemotherapy (PST) is unknown. Objective To assess the long-term impact of axillary pCR on relapse-free and overall survival. Design We retrospectively analyzed the impact of axillary pCR on 10-year overall (OS) and relapse-free survival (RFS) among women treated with PST at one institution. Women were stratified by post-PST axillary status, and survival outcomes were estimated and compared according to response in the breast and axilla. Setting A retrospective analysis of women who received neoadjuvant chemotherapy in a large U.S. comprehensive cancer center. Participants All women (N=1600) diagnosed with breast cancer stages II to III with cytologically confirmed axillary metastases between 1989 and 2007 who received PST at our institution were included. Main Outcome Measure Outcomes of interest were relapse-free and overall survival. Results Of 1600 women treated, 454 (28.4%) achieved axillary pCR. These patients were more likely to have HER2-positive and triple-negative disease, high-grade tumors, and lower clinical and pathologic T stage. Ten-year OS rates were 84% and 57% (P<.001) and 10-year RFS rates 79% and 50% (P<.001) for patients with axillary pCR and residual axillary disease, respectively. For patients with axillary pCR, 10-year OS rates were 90% for those with breast pCR and 72% for those with residual breast disease (P<.001). For patients with residual axillary disease, 10-year OS rates were 66% for patients with and 56% for patients without breast pCR (P=.02). Of patients receiving HER2-targeted therapy for HER2-positive disease, 67.1% (100/149) achieved axillary pCR; 10-year OS rates were 92% and 57% (P=.006) and 10-year RFS rates 89% and 44% (P<.001) for those with axillary pCR and residual axillary disease, respectively. Conclusion and Relevance Axillary pCR is associated with improved 10-year OS and RFS. Patients with axillary and breast pCR after PST have superior long-term survival outcomes. Patients undergoing HER2-targeted therapy for HER2-positive disease had high rates of axillary pCR, and those with axillary pCR had excellent 10-year overall survival.

Background. The impact of multifocal (MF) or multicentric (MC) breast cancer on locoregional (LR) control rates is unknown. Methods. MF was defined as two or more separate invasive tumors in the same quadrant of the breast. MC was defined as two or more separate invasive tumors occupying more than one quadrant of the same breast. Patients were categorized by LR treatment: breast conservation therapy (BCT; n ϭ 256), mastectomy (n ϭ 466), or mastectomy plus postmastectomy radiation therapy (PMRT; n ϭ 184). All patients with MC disease had mastectomy (10 patients treated with BCT for MC disease were excluded). The Kaplan-Meier product limit method was used to calculate 5-year LR control rate. Cox proportional hazards models were used to determine independent associations of multifocality or multicentricity with LR control.Results. A total of 906 patients had either MF disease (n ϭ 673) or MC disease (n ϭ 233). With median follow-up of 52 months, the 5-year LR control rate was 99% for MF, 96% for MC, and 98% for unifocal tumors (p ϭ .44). Subset analysis revealed no difference in LR control regardless of the LR treatment (p ϭ .67 for BCT, p ϭ .37 for mastectomy, p ϭ .29 for mastectomy plus PMRT). There were five in-breast recurrences after BCT in the MF group. MF and MC did not have an independent impact on LR control rate on multivariate analysis. Conclusion. MF and MC disease are not independent risk factors for LR recurrence. Patients with MF and MC breast cancer had rates of LR control similar to those of their unifocal counterparts. These data suggest that BCT is a safe option for patients with MF tumors and that MF or MC disease alone is not an indication for PMRT. The Oncologist 2013;18:1167-1173 Implications for Practice: This work reviews the risk of locoregional recurrences in patients with breast cancer treated with different approaches, as currently recommended by standard guidelines. We looked at 2,816 cases with unifocal disease, 673 cases with multifocal (MF) disease, and 233 cases with multicentric (MC) disease. We showed that MF and MC breast cancers are not independently associated with increased locoregional recurrence rates and that breast conservation therapy is a safe option for patients with MF tumors. MF or MC disease alone is not an indication for postmastectomy radiation therapy.

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1104 Background: Studies have consistently shown a correlation between multifocal (MF) and multicentric (MC) breast cancers and the rate and extent of lymph node metastases, but the literature is divided on whether there is a corresponding impact on survival outcomes. In the absence of compelling evidence to dictate otherwise, the convention according to current TNM staging guidelines has been to stage and treat MF and MC cancers according to the diameter of the largest lesions, without taking other foci of disease into consideration. We evaluated a large single institution cohort of MF and MC breast cancers to determine their frequency, clinico-pathological characteristics and effect on survival outcomes. Methods: MF and MC were defined pathologically as more than one lesion in the same quadrant and more than one lesion in separate quadrants, respectively. Patients were categorized by presence or absence of MF or MC disease. Kaplan-Meier product limit method was used to calculate relapse-free survival (RFS), breast cancer-specific survival (BCSS) and overall survival (OS). Cox proportional hazards models were fit to determine independent associations of MF/MC disease with survival outcomes. Results: Out of 3924 patients, 942 (24%) had MF (n=695) or MC (n=247) disease. MF and MC disease was associated with higher T-stages (T2 26% vs. 21.6%; T3 7.4% vs. 2.3%, P<0.001), higher nuclear grade (grade 3 44% vs. 38.2%, P<0.001), lymphovascular invasion (26.2% vs. 19.3%, P<0.001) and lymph node metastases (43.1% vs. 27.3%, P<0.001). After a median follow up of 51 months, MC but not MF breast cancers were associated with significantly worse 5-year RFS (90% vs. 95%, P=0.02) and BCSS (95% vs. 97%, P=0.01), and a trend towards worse 5-year OS (92% vs. 93%, P=0.08). After controlling for other risk factors, multifocality and multicentricity did not have an independent impact on RFS, BCSS or OS. This was true for the subset of T1N0 breast cancers as well. Conclusions: MF and MC breast cancers occurred in 24% of the cases and were associated with poor prognostic factors, but they were not independent predictors of worse survival outcomes. Our findings support the current TNM staging system of using the diameter of the largest lesion to assign T-stage.