International Journal of Radiation Oncology*Biology*Physics
Clinical InvestigationHealth-Related Quality of Life After Single-Fraction High-Dose-Rate Brachytherapy and Hypofractionated External Beam Radiotherapy for Prostate Cancer
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.
References (28)
The emerging role of high-dose-rate brachytherapy for prostate cancer
Clin Oncol (R Coll Radiol)
(2005)- et al.
High dose rate brachytherapy in combination with external beam radiotherapy in the radical treatment of prostate cancer: Initial results of a randomised phase three trial
Radiother Oncol
(2007) - et al.
Comparison of three radiotherapy modalities on biochemical control and overall survival for the treatment of prostate cancer: A systematic review
Radiother Oncol
(2009) - et al.
High-dose-rate brachytherapy in the curative treatment of patients with localized prostate cancer
Mayo Clin Proc
(2008) - et al.
CTCAE v3.0: Development of a comprehensive grading system for the adverse effects of cancer treatment
Semin Radiat Oncol
(2003) - et al.
Development and validation of the Expanded Prostate Cancer Index Composite (EPIC) for comprehensive assessment of health-related quality of life in men with prostate cancer
Urology
(2000) - et al.
The International Index of Erectile Function (IIEF): A multidimensional scale for assessment of erectile dysfunction
Urology
(1997) - et al.
Health-related quality of life 2 years after treatment with radical prostatectomy, prostate brachytherapy, or external beam radiotherapy in patients with clinically localized prostate cancer
Int J Radiat Oncol Biol Phys
(2008) - et al.
Health-related quality of life after permanent I-125 brachytherapy and conformal external beam radiotherapy for prostate cancer—A matched-pair comparison
Radiother Oncol
(2009) - et al.
A prospective analysis of long-term quality of life after permanent I-125 brachytherapy for localised prostate cancer
Radiother Oncol
(2007)
Long-term urinary quality of life after permanent prostate brachytherapy
Int J Radiat Oncol Biol Phys
Health related quality of life before and after laparoscopic radical prostatectomy
J Urol
Differing perceptions of quality of life in patients with prostate cancer and their doctors
J Urol
The impact of radiation dose to the urethra on brachytherapy-related dysuria
Brachytherapy
Cited by (56)
Real-world utilisation of brachytherapy boost and patient-reported functional outcomes in men who had external beam radiation therapy for prostate cancer in Australia
2022, Clinical and Translational Radiation OncologyDose accumulation for personalized stereotactic MR-guided adaptive radiation therapy in prostate cancer
2021, Radiotherapy and OncologyLow-Dose-Rate Brachytherapy Combined With Ultrahypofractionated Radiation Therapy for Clinically Localized, Intermediate-Risk Prostate Cancer: Results From a Prospective Trial
2020, International Journal of Radiation Oncology Biology PhysicsProgress in Low Dose Rate Brachytherapy for Prostate Cancer
2020, Seminars in Radiation OncologyA Prospective Single-Arm Phase 2 Study of Stereotactic Magnetic Resonance Guided Adaptive Radiation Therapy for Prostate Cancer: Early Toxicity Results
2019, International Journal of Radiation Oncology Biology Physics
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.