Clinical Investigation
A Novel Risk Stratification to Predict Local-Regional Failures in Urothelial Carcinoma of the Bladder After Radical Cystectomy

This work was presented in part at the American Society of Clinical Oncology Genitourinary Cancers Symposium, San Francisco, CA, February 2-4, 2012.
https://doi.org/10.1016/j.ijrobp.2012.03.007Get rights and content

Purpose

Local-regional failures (LF) following radical cystectomy (RC) plus pelvic lymph node dissection (PLND) with or without chemotherapy for invasive urothelial bladder carcinoma are more common than previously reported. Adjuvant radiation therapy (RT) could reduce LF but currently has no defined role because of previously reported morbidity. Modern techniques with improved normal tissue sparing have rekindled interest in RT. We assessed the risk of LF and determined those factors that predict recurrence to facilitate patient selection for future adjuvant RT trials.

Methods and Materials

From 1990-2008, 442 patients with urothelial bladder carcinoma at the University of Pennsylvania were prospectively followed after RC plus PLND with or without chemotherapy with routine pelvic computed tomography (CT) or magnetic resonance imaging (MRI). One hundred thirty (29%) patients received chemotherapy. LF was any pelvic failure detected before or within 3 months of distant failure. Competing risk analyses identified factors predicting increased LF risk.

Results

On univariate analysis, pathologic stage ≥pT3, <10 nodes removed, positive margins, positive nodes, hydronephrosis, lymphovascular invasion, and mixed histology significantly predicted LF; node density was marginally predictive, but use of chemotherapy, number of positive nodes, type of surgical diversion, age, gender, race, smoking history, and body mass index were not. On multivariate analysis, only stage ≥pT3 and <10 nodes removed were significant independent LF predictors with hazard ratios of 3.17 and 2.37, respectively (P<.01). Analysis identified 3 patient subgroups with significantly different LF risks: low-risk (≤pT2), intermediate-risk (≥pT3 and ≥10 nodes removed), and high-risk (≥pT3 and <10 nodes) with 5-year LF rates of 8%, 23%, and 42%, respectively (P<.01).

Conclusions

This series using routine CT and MRI surveillance to detect LF confirms that such failures are relatively common in cases of locally advanced disease and provides a rubric based on pathological stage and number of nodes removed that stratifies patients into 3 groups with significantly different LF risks to simplify patient selection for future adjuvant radiation therapy trials.

Introduction

Localized, muscle-invasive urothelial bladder cancer is usually treated with radical cystectomy (RC) plus pelvic lymph node dissection (PLND) with or without chemotherapy. There is no defined role for radiation therapy (RT) although local-regional failure (LF) after surgery with or without chemotherapy is increasingly recognized as a more significant problem than was previously appreciated (1).

Use of postoperative RT was explored decades ago and demonstrated robust local control 2, 3, 4, but serious gastrointestinal toxicity using pre-1980s RT techniques 2, 3, 5 discouraged its use. Improvements in targeting radiation have rekindled interest in adjuvant RT for high-risk patients. This study’s goals were to assess the risk of pelvic failure and to determine those factors that predict LF to identify patients most likely to benefit from adjuvant RT.

Section snippets

Methods and Materials

Between 1990 and 2008, 486 consecutive patients undergoing RC plus PLND with or without chemotherapy were followed prospectively at the University of Pennsylvania. None of the patients had distant metastases on preoperative imaging of the chest, abdomen, pelvis, and bones. Cystectomy included en bloc excision of the bladder, prostate, and seminal vesicles in men and uterus, ovaries, and anterior vagina in women. All patients had bilateral PLND to the inferior common iliac nodes proximally, the

Results

Of 486 cystectomy patients, 37 patients were excluded because they did not have transitional cell carcinoma and 7 because they had received radiation. Table 1 characterizes the remaining 442 patients, 130 (29%) of whom received chemotherapy. Mean age was 65.8 years (median, 67.0 years; range, 34.3-84.2 years). Mean follow-up was 44.1 months (median, 26.4 months) with a minimum of 1 year follow-up. Eighty patients developed pelvic recurrences. The 5-year cumulative incidence of LF for the entire

Discussion

Invasive urothelial bladder cancer causes 14,000 deaths annually in the United States. Radical cystectomy and PLND provide 5-year survival rates of ∼60% for organ-confined disease (≤pT2N0) and ∼40% when disease extends beyond the bladder (≥pT3N0) (8).

The high risk of distant relapse has encouraged investigations of the use of chemotherapy. Randomized trials of neoadjuvant chemotherapy have demonstrated improved survival 8, 9, while adjuvant chemotherapy trials had mixed results (10).

Conclusions

Local-regional failure after radical cystectomy is a significant problem. The risk of such failure can be stratified into 3 groups: low-risk (≤pT2), intermediate-risk (≥pT3 and ≥10 nodes removed), and high-risk (≥pT3 and<10 nodes) disease with 5-year LF rates of 8%, 23%, and 42%, respectively. This study provides a simple rubric to identify patients most at risk for pelvic recurrence who are most likely to benefit from adjuvant local-regional therapy.

Acknowledgment

We gratefully acknowledge Dr. Eli Glatstein for assistance.

References (28)

  • I. Honma et al.

    Local recurrence after radical cystectomy for invasive bladder cancer: an analysis of predictive factors

    Urology

    (2004)
  • H.W. Herr et al.

    Surgical factors influence bladder cancer outcomes: a cooperative group report

    J Clin Oncol

    (2004)
  • J.A. Spera et al.

    A comparison of preoperative radiotherapy regimens for bladder carcinoma. The University of Pennsylvania experience

    Cancer

    (1988)
  • J.P. Fine et al.

    A proportional hazards model for the subdistribution of a competing risk

    J Am Stat Assoc

    (1999)
  • Cited by (45)

    • Locoregional recurrence after cystectomy in muscle invasive bladder cancer: Implications for adjuvant radiotherapy

      2021, Urologic Oncology: Seminars and Original Investigations
      Citation Excerpt :

      In our study, 8 (25.8%) of 31 patients with LRR recurred in the CILN sites with superior border defined as aortic bifurcation. Similarly, CB was recommended in the consensus statement only for patients with margin positivity which was 13% in the study based on which the consensus was developed, while it was 31% in a study by Reddy et al. [12,13]. In SWOG 8710, 10% of patients had positive margins [2].

    View all citing articles on Scopus

    Conflict of interest: none.

    View full text