Elsevier

European Urology

Volume 64, Issue 6, December 2013, Pages 931-938
European Urology

Platinum Priority – Prostate Cancer
Editorial by Albert J. Chang and Mack Roach III on pp. 939–940 of this issue
Patterns and Predictors of Amelioration of Genitourinary Toxicity After High-dose Intensity-modulated Radiation Therapy for Localized Prostate Cancer: Implications for Defining Postradiotherapy Urinary Toxicity

https://doi.org/10.1016/j.eururo.2013.02.001Get rights and content

Abstract

Background

Treatment-related toxicity and quality of life (QoL) considerations are important when counseling patients with localized prostate cancer (PCa).

Objective

To determine the incidence and longitudinal pattern of late genitourinary (GU) toxicity and QoL after high-dose, intensity-modulated radiotherapy (IMRT).

Design, setting, and participants

A total of 268 patients with localized PCa were treated between June 2004 and December 2008 at a tertiary referral center. Median follow-up was 5 yr (range: 3–7.7 yr).

Intervention

Patients underwent IMRT to a total dose of 86.4 Gy; 50% of patients underwent neoadjuvant and concurrent androgen-deprivation therapy.

Outcome measurements and statistical analysis

Patients were evaluated with the prospectively obtained International Prostate Symptom Score (IPSS) questionnaire. GU toxicity was also scored using the Common Terminology Criteria for Adverse Events (CTCAE) v.4.0; toxicity events were defined as increase over baseline. Differences in increases in IPSS sums and QoL index between baseline IPSS sum and QoL index groups were analyzed using the Kruskal-Wallis and Mann-Whitney tests. Univariate and multivariate Cox regression models were applied.

Results and limitations

The overall median IPSS sum increase during follow-up was 3 and was less pronounced among patients with severe baseline symptoms compared with those with mild baseline symptoms (median increase: 0 vs 4; p < 0.0001). Overall QoL index was unchanged after IMRT but appeared to improve in patients with dissatisfied baseline QoL compared with satisfied baseline QoL (p < 0.0001). Fifty-five (20%) and 2 (1%) patients developed grade 2 and 3 late GU toxicities, respectively; however, in 28 of 57 patients (49%), toxicity resolved during follow-up. Even though the IPSS data were prospectively obtained, most patients were not treated within a prospective protocol.

Conclusions

Late GU toxicity after high-dose IMRT was mild; severe, late GU toxicity was rare. Changes in IPSS sum and QoL index were dependent on the baseline GU function, which might be useful for future patient counseling.

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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