Clinical Investigation
Patterns of Failure After Radical Cystectomy for pT3-4 Bladder Cancer: Implications for Adjuvant Radiation Therapy

This work will be presented at the 12th annual American Society of Clinical Oncology Genitourinary Cancers Symposium, January 7-9, 2016.
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Purpose

In patients with muscle-invasive bladder cancer, local-regional failure (LF) has been reported to occur in up to 20% of patients following radical cystectomy. The goals of this study were to describe patterns of LF, as well as assess factors associated with LF in a cohort of patients with pT3-4 bladder cancer. This information may have implications towards the use of adjuvant radiation therapy.

Methods and Materials

Patients with pathologic T3-4 N0-1 bladder cancer were examined from an institutional radical cystectomy database. Preoperative demographics and pathologic characteristics were examined. Outcomes included overall survival and LF. Local-regional failures were defined using follow-up imaging reports and scans, and the locations of LF were characterized. Variables were tested by univariate and multivariate analysis for association with LF and overall survival.

Results

A total of 334 patients had pT3-4 and N0-1 disease after radical cystectomy and bilateral pelvic lymph node dissection. Of these, 46% received perioperative chemotherapy. The median age was 71 years old, and median follow-up was 11 months. On univariate analysis, margin status, pT stage, and pN stage, were all associated with LF (P<.05), however, on multivariate analysis, only pT and pN stages were significantly associated with LF (P<.05). Three strata of risk were defined, including low-risk patients with pT3N0 disease, intermediate-risk patients with pT3N1 or pT4N0 disease, and high-risk patients with pT4N1 disease, who had a 2-year incidence of LF of 12%, 33%, and 72%, respectively. The most common sites of pelvic relapse included the external and internal iliac lymph nodes (LNs) and obturator LN regions. Notably, 34% of patients with LF had local-regional only disease at the time of recurrence.

Conclusions

Patients with pT4 or N1 disease have a 2-year risk of LF that exceeds 30%. These patients may be the most likely to benefit from local adjuvant therapies.

Introduction

Bladder cancer is the second most common genitourinary cancer in the United States and results in approximately 15,000 deaths each year (1). The most common treatment for muscle-invasive bladder cancer is radical cystectomy, with or without perioperative chemotherapy for more advanced stages of disease (2). Although the predominant site of treatment failure is distant, up to 20% of patients treated with radical cystectomy develop local-regional failure (LF) 3, 4, 5, 6, 7, with increasing risk with more advanced stages (8).The development of LF is associated with inferior cancer-specific survival 8, 9. For select patients, it is possible that adjuvant treatment of patients at risk for LF may improve survival.

Although there is no well-defined role for adjuvant radiation therapy (RT) in the treatment of resectable muscle-invasive bladder cancer, some studies have suggested that adjuvant RT can decrease the incidence of LF 10, 11, 12 and improve cancer-specific survival 11, 12, 13. Patients with the highest risk of LF may be the best candidates for adjuvant RT, and defining patterns of failure could help guide field design of adjuvant RT after radical cystectomy. The goals of this study were to define the patterns of pelvic failure in a high-risk (pT3 to 4N0-1) cohort of patients treated with radical cystectomy, describe the locations of LF, and assess factors associated with LF.

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Methods and Materials

Between January 2007 and June 2014, 334 patients with pathologic T3-4N0-1 bladder cancer were treated with radical cystectomy and bilateral pelvic lymph node dissection (PLND) at a tertiary care center. Radical cystectomy included removal of the bladder, prostate, and seminal vesicles in men and anterior pelvic exenteration in women. Borders of PLND included the genitofemoral nerve laterally, 1 to 2 cm above the bifurcation of the common iliac vessels superiorly, hypogastric vessels inferiorly,

Results

Patient characteristics are presented in Table 1. Of the 334 patients, 243 (73%) were men, and 91 (28%) were women. The median age at cystectomy was 71 years old (IQR: 62-78; range: 26-93 years), and median body mass index was 27 (IQR: 24-31). Platinum-based chemotherapy was administered to 153 patients (46%), either in adjuvant (n=117 [35%]) or neoadjuvant (n=43 [13%]) fashion. Chemotherapy was given in 59 patients (33%) with pN0 disease and 97 patients (63%) with node-positive disease (P

Discussion

In this analysis of patients with pT3-4 bladder cancer treated with radical cystectomy, we demonstrated that LFs occurred in 31% of patients with either T4 or N1 disease at 2 years. Meanwhile, patients with pT3N0 disease had <15% risk of LF at 2 years. The most common sites of pelvic failure are in the external and internal iliac LNs and obturator LN regions. This coincides with the bounds of a standard pelvic lymphadenectomy and the typical treatment field for definitive radiation in

Conclusions

This study of 334 patients with locally advanced bladder cancer provides useful information regarding patterns of failure after radical cystectomy. To our knowledge, this is the first study to assess LF and patterns of LF in a cohort of pT3-4 patients. Patients at the highest risk of LF were those with pT4 stage or LN involvement. The hypothesis that adjuvant RT can improve pelvic relapse-free survival in men with pT3-4N0-2 bladder cancer after radical cystectomy is currently being tested in a

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