Postprostatectomy Radiation Therapy Yields Low Toxicity and Favorable Patient-Reported Quality of Life
A prospective study of guideline-based, postoperative, image-guided intensity-modulated radiation therapy in patients with prostate cancer found low toxicity profiles and favorable patient-reported quality of life following treatment, with researchers concluding that toxicity and health-related quality of life should not impact the recommendation of radiation therapy following prostatectomy. The research was published by Berlin et al in Practical Radiation Oncology.
Study Details
Postprostatectomy radiation therapy has been reported as underutilized, with randomized trials showing the benefit of adjuvant radiation therapy, but only about 10% of patients receiving the treatment. One potential reason for underutilization could be concern over side effects or a negative impact on health-related quality of life.
Study authors of the phase II trial set out to determine whether this reason was accurate, using a consensus guideline for defining the clinical target volume, looking at the treatment-related toxicities, health-related quality of life, and biochemical outcomes of patients treated with postoperative, image-guided intensity-modulated radiation therapy for prostate cancer following prostatectomy.
In the study, 68 men considered for radiation therapy after prostatectomy at the Princess Margaret Cancer Centre/University Health Network were enrolled between August 2007 and October 2008. The median age at diagnosis was 59.8 (range, 43.7–74.2).
Of them, 53 patients (77.9%) were treated with salvage radiation therapy, and 15 (22.1%) were treated with adjuvant radiation therapy. Published consensus guidelines were used to delineate the clinical target volume, or prostate bed, with patients receiving a dose of 66 Gy in 33 fractions. The radiation treatment plan prioritized rectal dose constraints over target volume coverage, according to the study authors. Intensity-modulated radiation therapy and daily cone beam computed tomographic guidance delivered the treatment.
Routine follow-up occurred every 3 to 6 months during the first 5 years. Median follow-up after treatment completion was 5.9 years (range, 0.1–6.7 years).
Toxicity was graded according to the National Cancer Institute’s Common Terminology Criteria for Adverse Events, and the health-related quality of life was measured according to the Expanded Prostate Cancer Index Composite (EPIC) questionnaire, which was collected prospectively at baseline; week 5 (during radiation therapy); 3 months after radiation therapy completion; and at 1-, 2-, 3-, and 5-year follow-up visits.
Researchers calculated the cumulative toxicity and biochemical relapse-free rates by the Kaplan-Meier method. Changes in health-related quality of life were measured using paired Student t-tests with multiple testing correction.
According to the study, the main primary planning objectives were met in 97.1 and 98.5% of cases (dose received by 99% of the planning target volume = 54 Gy, and rectal wall maximum dose (1 cc) = 66 Gy, respectively). Secondary planning target volume coverage objective was volume of planning target volume receiving at least 95% of the prescribed dose = 95%, which was met in two-thirds of cases.
Study Findings
“With modern radiotherapy and the continuous improvements in treatment techniques, the present study rejects the notion that the use of radiation treatment after prostatectomy may have a negative impact in the patient’s quality of life pertaining to sexual, urinary, or bowel function,” said Cynthia Ménard, MD, and Alejandro Berlin, MD, MSc, both from the Princess Margaret Cancer Centre/University Health Network.
The cumulative 5-year incidence of late gastrointestinal grade 2 toxicity was 12.3% (95% confidence interval [CI], 11.1%–13.5%), and genitourinary grade 2 toxicity was 10.6% (95% CI, 9.5%–11.6%). No grade 3 or 4 late toxicities were observed.
Researchers observed transient declines in EPIC gastrointestinal domain summary score (mean 87.66 at 3 months vs 92.76 at baseline; P = .006) and genitourinary irritative subscale (week 5 mean score 83.37 vs 89.45 at baseline; P = .007). Complete recovery occurred between 3 and 12 months after therapy, which remained stable compared with baseline at 5-year follow-up.
Sexual health-related quality of life remained stable at 5 years, with an improving trend in bother subscale, with the 5-year mean score at 58.17 vs 44.81 at baseline. This improvement might be because patients became accustomed to erectile dysfunction over time, Dr. Berlin said.
At 5 years, the biochemical relapse-free rate was 72.7% (95% CI, 61.9%–83.5%).
Some Study Weaknesses
The study authors cited weaknesses and cautionary notes from the study, the first being that the study had a relatively small sample size. However, having the patients’ answer the EPIC questionnaire was effective in obtaining results directly impacted by treatment, especially in an area without a great deal of patient-reported information, they said.
“Studies evaluating the results, particularly quality of life after postprostatectomy radiotherapy, are scarce,” Dr. Berlin said. “This is even more relevant with the use of current modern techniques. Despite the small sample size, each patient is [his] ‘own control,’ as the variations in quality of life are compared to the preradiation baseline status, providing strength to the analysis.”
Other study weaknesses were the completion rate of the EPIC questionnaire, which declined over time (but the authors cited that, because of the “stability and reproducibility” of results over the follow-up, a clinically meaningful change to results would be small). In addition, they pointed out that the volume definition of organs at risk may be different at other institutions, so “caution should be used in determining the equivalence of other normal tissue dosimetric parameters to be applied for plan evaluation when different contouring techniques are used,” they said.
Overall, “results are encouraging and continue to support the use of a well-established treatment for specific indications after prostatectomy, e.g., rising prostate-specific antigen, extraprostatic extension, positive margins, etc., contrasting with the literature reporting that only a small proportion of these actually receive postoperative radiation,” Dr. Ménard said.
“Additionally, when consensus definition of target volumes was developed, concerns were raised due to larger volumes compared to historical practice. Therefore, the low toxicity rates observed, particularly rectal toxicity, were positively surprising. This study provides clinical validation and evidence to support the use of current guidelines for postprostatectomy radiotherapy,” Dr. Berlin said.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
