Clinical Investigation
Health-Related Quality of Life After Single-Fraction High-Dose-Rate Brachytherapy and Hypofractionated External Beam Radiotherapy for Prostate Cancer

https://doi.org/10.1016/j.ijrobp.2010.04.046Get rights and content

Purpose

To investigate the change in health-related quality of life for men after high-dose-rate brachytherapy and external beam radiotherapy for prostate cancer and the factors associated with this change.

Methods and Materials

Eligible patients had clinically localized intermediate-risk prostate cancer. The patients received high-dose-rate brachytherapy as a single 15-Gy implant, followed by external beam radiotherapy to 37.5 Gy in 15 fractions. The patients were monitored prospectively for toxicity (Common Terminology Criteria for Adverse Events, version 3.0) and health-related quality of life (Expanded Prostate Cancer Index Composite [EPIC]). The proportion of patients developing a clinically significant difference in the EPIC domain score (minimally important difference of >0.5 standard deviation) was determined and correlated with the baseline clinical and dosimetric factors. The study accrued 125 patients, with a median follow-up of 24 months.

Results

By 24 months, 23% had Grade 2 urinary toxicity and only 5% had Grade 2 bowel toxicity, with no Grade 3 toxicity. The proportion of patients reporting a significant decrease in EPIC urinary, bowel, sexual, and hormonal domain scores was 53%, 51%, 45%, and 40% at 12 months and 57%, 65%, 51%, and 30% at 24 months, respectively. The proportion with a >1 standard deviation decrease in the EPIC urinary, bowel, sexual, and hormonal domain scores was 38%, 36%, 24%, and 20% at 12 months and 46%, 48%, 19%, and 8% at 24 months, respectively. On multivariate analysis, the dose to 10% of the urethra was associated with a decreasing EPIC urinary domain score (p = .0089) and, less strongly (p = .0312) with a decreasing hormonal domain score. No association was found between the prostate volume, bladder dose, or high-dose volume and urinary health-related quality of life. A high baseline International Index of Erectile Function score was associated (p = .0019) with a decreasing sexual domain score. The optimal maximal dose to 10% of the urethra cutpoint for urinary health-related quality of life was 120% of the prescription dose.

Conclusion

EPIC was a more sensitive tool for detecting the effects on function and bother than were the generic toxicity scales. The urethral dose had the strongest association with a deteriorating urinary quality of life.

Introduction

High-dose-rate brachytherapy (HDR-BT) delivers a large, conformal radiation dose to the prostate. The source dwell times are optimized after catheter placement, and the resultant dose distribution is more conformal than that achievable with external beam radiotherapy (EBRT) (1). HDR-BT is most often used as a method of dose escalation combined with supplemental EBRT (2). Mounting evidence, including the results from at least one randomized trial, has shown that dose escalation with HDR-BT provides better disease control than that achieved with EBRT alone 3, 4.

Most investigators have combined two or more HDR-BT fractions of 6–10 Gy each with 40–50 Gy of EBRT (5). We have previously reported the results of a prospective clinical trial of a single fraction of 15 Gy HDR-BT followed by hypofractionated EBRT to 37.5 Gy in 15 fractions (6). That protocol was calculated as having a biologic effect on late normal tissues equivalent to that of a “standard” fractionation of two HDR-BT fractions of 10 Gy combined with 45 Gy EBRT in 25 fractions. We reported a favorable early toxicity profile and encouraging disease control rates.

Toxicity is most commonly reported using toxicity scales (e.g., Common Terminology Criteria for Adverse Events [CTCAE] version 3) (7). Toxicity is assessed by a health professional after a review of the patient or clinical notes. The score assigned is subject to interpretation by the health professional. Although capable of detecting major toxicities, the CTCAE, version 3, is not a validated instrument and could miss many items of importance to the patient. Patient-reported outcome measures (e.g., health-related quality of life [HRQOL]) are more sensitive and avoid the “filtering” effect of interpretation by the health professional. HRQOL is often measured using a validated patient-reported questionnaire with questions in specific domains relevant to that particular disease or condition. The Expanded Prostate Cancer Index Composite (EPIC) is a validated tool that measures HRQOL in four domains relevant to patients with localized prostate cancer (8). A change in HRQOL domain scores is most commonly reported as a mean value at different points. An alternative approach is to determine the proportion of patients reporting a clinically significant change. As reported by Norman et al. (9), the minimally important difference (MID) for HRQOL instruments is almost universally one-half the standard deviation (SD) of the baseline values. Sanda et al. (10) used this definition of a clinically relevant change to report the change in HRQOL after prostatectomy, EBRT, or brachytherapy.

Our purpose was to determine the proportion of patients who experienced a clinically significant change in HRQOL after a protocol of single-fraction HDR-BT and hypofractionated EBRT and to determine the clinical and dosimetric factors associated with this change. Our goal would then be to use this information to help better select patients and define the dosimetric planning parameters.

Section snippets

Patient characteristics

A Phase I-II clinical trial protocol evaluating single-fraction HDR-BT combined with EBRT was undertaken at the Odette Cancer Centre, with research ethics board approval. Eligible patients had intermediate-risk carcinoma of the prostate, defined as clinical Stage T1c–T2b with either Gleason score 6 and a serum prostate-specific antigen (PSA) level of 10–20 ng/mL or Gleason score 7 and a PSA level <20 ng/mL. The prostate volume was limited to 60 cm3, and patients who had undergone transurethral

Results

All patients completed the scheduled treatment without interruption. Data are reported for a median follow-up of 2.0 years (range, 0.07–3.53). No clinical or biochemical recurrences had developed at the last follow-up visit.

Discussion

Treatment was well tolerated acutely, with a low rate of urinary and bowel toxicity, as determined by the CTCAE, version 3.0. After 24 months, the rate of Grade 2 urinary toxicity was 23% and that of Grade 2 bowel toxicity only 5%. A different finding emerges when we used the patient-reported HRQOL data, which revealed that >50% of patients experienced a small, but clinically significant, decrease in HRQOL within the urinary, bowel, and sexual domains, with the least change in bother occurring

Conclusion

We identified decreasing EPIC scores in all domains in a large proportion of patients after single-fraction HDR-BT and hypofractionated EBRT. We found an association between the HDR-BT dosimetry, in particular the dose to the urethra, and increasing urinary symptoms and bother. Our findings suggest limiting the D10 to 120% and the maximal urethral point dose to 130% of the prescription dose when this fractionation scheme is used.

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Supported by a grant from the Canadian Association of Radiation Oncologists Abbott Uro-Oncologic Award and by a grant from the Motorcycle Ride for Dad Foundation.

Conflict of interest: none.

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