Clinical investigation
Prostate
Predictive Factors for Late Genitourinary and Gastrointestinal Toxicity in Patients With Prostate Cancer Treated With Adjuvant or Salvage Radiotherapy

This work was presented at the 47th Annual Meeting of the American Society for Therapeutic Radiology and Oncology (ASTRO), October 16–20, 2005, Denver, CO.
https://doi.org/10.1016/j.ijrobp.2007.01.049Get rights and content

Purpose: To determine the rate and magnitude of late genitourinary (GU) and gastrointestinal (GI) toxicities after salvage or adjuvant radiotherapy (RT) for prostate cancer, and to determine predictive factors for these toxicities.

Methods and Materials: A large multi-institutional database that included 959 men who received postoperative RT after radical prostatectomy (RP) was analyzed: 19% received adjuvant RT, 81% received salvage RT, 78% were treated to the prostate bed only, and 22% received radiation to the pelvis.

Results: The median follow-up time was 55 months. At 5 years, 10% of patients had Grade 2 late GU toxicity and 1% had Grade 3 late GU toxicity, while 4% of patients had Grade 2 late GI toxicity and 0.4% had Grade 3 late GI toxicity. Multivariate analysis demonstrated that adjuvant RT (p = 0.03), androgen deprivation (p < 0.0001), and prostate bed-only RT (p = 0.007) predicted for Grade 2 or higher late GU toxicity. For GI toxicity, although adjuvant RT was significant in the univariate analysis, no significant factors were found in the multivariate analysis.

Conclusions: Overall, the number of high-grade toxicities for postoperative RT was low. Therefore, adjuvant and salvage RT can safely be used in the appropriate settings.

Introduction

Radiotherapy (RT) is often recommended after radical prostatectomy in the adjuvant setting for certain pathologic findings, or in the salvage setting for rising prostate-specific antigen (PSA) (1, 2, 3, 4, 5, 6, 7). For patients with extraprostatic extension, seminal-vesicle involvement, or positive surgical margins, adjuvant RT was demonstrated to improve biochemical disease-free survival (5, 6, 7). For patients with biochemical failure after radical prostatectomy, RT can be used as successful salvage treatment in approximately 40–50% of cases (2, 3, 4).

Despite recent evidence supporting the efficacy of adjuvant and salvage radiotherapy in prostate cancer, the use of postoperative RT has been somewhat limited, in part because of concerns regarding prohibitive cumulative toxicity, mostly urologic. Especially since a survival benefit has not yet been demonstrated, understanding the cost-benefit ratio of treatment is extremely important. Few studies have quantified the risk of long-term morbidity after postoperative RT for prostate cancer. More information is needed to aid in making rational recommendations regarding the overall benefit of adjuvant and salvage radiotherapy. In this study, a large multi-institutional database with men who received adjuvant or salvage RT after RP was analyzed for the magnitude and rate of late genitourinary (GU) and gastrointestinal (GI) toxicities. Potential predictive factors were also examined.

Section snippets

Patients

From 1986–2004, 959 men were treated with adjuvant or salvage RT after RP at 11 academic radiation oncology centers. Participating institutions included the Mayo Clinic (Rochester, MN), the University of Michigan (Ann Arbor, MI), the M. D. Anderson Cancer Center (Houston, TX), Princess Margaret Hospital (Toronto, Ontario, Canada), Washington University (St. Louis, MO), the Memorial Sloan-Kettering Cancer Center (New York, NY), the M. D. Anderson Cancer Center Orlando (Orlando, FL), the Fox

GU toxicity

Overall, 4%, 7%, and 12% of patients had Grade 2 or higher late GU toxicity at 1, 2, and 5 years, respectively. At 5 years, 10% had Grade 2, 1% had Grade 3, and <1% Grade 4 toxicity (Table 2). The majority of Grade 2 toxicities were evenly divided between hematuria and incontinence that required pads. Also observed, in order of prevalence, were frequency, cystitis, urethral stricture, bladder-neck contracture, and incontinence not requiring pads. All Grade 3 toxicities occurred at relatively

Efficacy of adjuvant and salvage radiotherapy

The benefit of adjuvant radiotherapy after prostatectomy, for certain pathologic features, has been suggested for several years. Patients with positive margins of resection, extraprostatic extension, or seminal vesicle invasion were found in several retrospective analyses to be at increased risk for local recurrence (8, 9, 10). Perhaps the strongest nonrandomized study supporting adjuvant radiotherapy is the matched-pair analysis of Valicenti et al. in 1999, which demonstrated a 34% absolute

Conclusions

Overall, the number of high-grade toxicities after postoperative RT is low. Concerns regarding the tolerance of RT should not preclude its use in patients with adverse pathologic findings or with biochemical relapse after RP.

References (27)

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Conflict of interest: none.

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