Platinum Priority – Prostate CancerEditorial by Albert J. Chang and Mack Roach III on pp. 939–940 of this issuePatterns and Predictors of Amelioration of Genitourinary Toxicity After High-dose Intensity-modulated Radiation Therapy for Localized Prostate Cancer: Implications for Defining Postradiotherapy Urinary Toxicity
Introduction
Radical prostatectomy as a monotherapy and high-dose external-beam radiation therapy (RT), if indicated with concomitant androgen-deprivation therapy (ADT), are considered similarly effective for patients with localized prostate cancer (PCa) [1]. Especially for early-stage patients, the decision to select a particular therapy is often based on quality of life (QoL) considerations. Thus treatment-related toxicity and QoL are important for patient counseling and decision making.
A significant proportion of patients with localized PCa present with pre-RT genitourinary (GU) symptoms, predominantly voiding side effects of obstruction due to coexisting benign prostate hyperplasia [2]. These baseline symptoms should be incorporated into the definition of GU toxicity to more accurately identify patients with treatment-related toxicities. However, to the best of our knowledge, no such recommendations are available for commonly used toxicity-grading systems such as the US National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) or the Radiation Therapy Oncology Group (RTOG) system. One possibility is to characterize the presence of toxicity only when the symptom grade increases over baseline [3]. Impaired GU function at baseline is commonly described as a significant predictor of late GU toxicity after RT for PCa [4], [5], [6]. This suggests that patients with adverse baseline symptoms are at higher risk for development of late GU symptoms after RT; however, this may be an artifact, as baseline symptoms were not routinely accounted for in the definition of late GU toxicity events for these cohorts. Others have demonstrated that patients who had poor baseline GU function often improved after therapy, highlighting the critical need to account for baseline function [7].
High-dose RT (>74 Gy) showed improved biochemical recurrence-free survival compared with lower-dose RT for localized PCa [8]; however, late GU toxicity also increased [9], [10]. As patient-reported toxicity is most reliable [11], this study incorporates data from patient-reported International Prostate Symptom Score (IPSS) questionnaires [12] from patients treated with 86.4 Gy IMRT to provide a detailed description of incidence and longitudinal pattern of GU toxicity.
Section snippets
Patient selection
Between August 1997 and December 2008, 1002 consecutive patients with localized PCa were treated with definitive IMRT to a prescribed dose of 86.4 Gy [13]. Of these, 269 patients were treated between June 2004 and December 2008, had available IPSS data at baseline with a minimum of 3 yr of follow-up, and had available treatment-planning dosimetry. One patient who received salvage brachytherapy <3 yr after IMRT was excluded and eight patients receiving salvage treatment ≥3 yr post-IMRT were
Patients
The median follow-up for the entire cohort was 5 yr (range: 3–7.7 yr). Baseline demographics and clinical characteristics are summarized in Table 1.
International Prostate Symptom Score data
The median baseline IPSS sum was 7 (interquartile range [IQR]: 8.75). One hundred thirty-seven (51%), 111 (41%), and 20 (8%) patients had mild (0–7), moderate (8–19), and severe (20–35) baseline symptoms, respectively. There was no substantial quantitative increase in IPSS sum (Fig. 1), with the median IPSS-sum increase being 3 (IQR: 7). When
Discussion
The observed changes in IPSS sum and QoL after high-dose IMRT indicated generally a very well-tolerated treatment. There was no substantial change in IPSS sum or QoL during follow-up. Likewise, the maximal, CTCAE, grade 2 and 3 late GU toxicity rates after consideration of baseline GU symptoms were 20% and 1%, respectively, which declined to 10% and 1%, respectively, at last follow-up. This was consistent with the observations of Fonteyne et al., who found that 36 mo after IMRT using ≤78 Gy, the
Conclusions
Our findings may help to counsel patients with localized PCa, who can be reassured that the risk of late GU toxicity and worsening of QoL after our protocol of high-dose IMRT was low. Moreover, the risk for development of late GU toxicity or worsening of QoL was dependent on baseline function such that patients with excellent baseline function were more prone to experience worsening, and patients with impaired baseline function are more likely to experience improvement after therapy.
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