International Journal of Radiation Oncology*Biology*Physics
Clinical InvestigationHypofractionated Versus Conventionally Fractionated Radiotherapy for Prostate Carcinoma: Final Results of Phase III Randomized Trial
Introduction
Although evidence of a higher dose fraction sensitivity relative to the surrounding late responding normal tissues in radiotherapy (RT) for prostate cancer has continued to accumulate 1, 2, 3, 4, debate about whether the data are sufficiently robust for hypofractionated dose schedules to be implemented for the treatment of low- and intermediate-risk disease persists (5). Prospective data from Phase III studies of hypofractionated vs. conventionally fractionated RT for localized prostate carcinoma, including our own, have been limited by either the lack of long-term (>5 years) follow-up of patients or the use of physician-based recording of gastrointestinal toxicity 6, 7, 8, 9, such as the Radiation Therapy Oncology Group system. The Radiation Therapy Oncology Group does not include an evaluation of anorectal symptoms such as urgency of defecation or fecal incontinence 10, 11. The lack of Level II evidence of a long-term therapeutic advantage for hypofractionated compared with conventional RT dose schedules for prostate cancer is a major obstacle to the adoption of hypofractionated dose schedules in clinical practice (5), particularly with the higher radiation doses prescribed with newer techniques of three-dimensional (3D) conformal RT involving intensity modulation.
We have previously reported the updated results of this Phase III randomized study comparing the efficacy and toxicity of hypofractionated vs. conventionally fractionated RT for localized prostate carcinoma (6). The original population of 217 patients has now been followed for a median of 90 months (range, 3–138). The present study reports on more mature efficacy and toxicity data and also provides new information, including freedom from biochemical relapse (FBR) using the Phoenix definition of failure and androgen suppression (hormonal)-free survival rates.
Section snippets
Methods and Materials
As previously reported, the 217 patients (median age, 69 years; range, 44–82) with Stage T1-T2N0M0 (International Union Against Cancer 1992) prostate carcinoma were recruited for this single-institutional study between July 1996 and August 2003 (6).
Patient randomization was done using blocked computer-generated numbers administered by data managers to one of two radiation dose schedules (55 Gy in 20 fractions within 4 weeks; n = 108) and 64 Gy in 32 fractions within 6.5 weeks (n = 109), even
Results
At the data analysis, the original patient population had been followed for a median of 90 months (range, 3–138). Of the 217 patients, 101 had been lost to follow-up and 65 had <5 years of follow-up, mainly because advancing age and ill health associated with medical comorbidities and domicile distant from the centers equipped with the resources for proper evaluation of their disease prevented travel (the original patient population, drawn from South Australia and Northern Territory, resided
Discussion
The long-term (7.5-year) follow-up data of the present randomized trial of a hypofractionated vs. conventional RT schedule for localized prostate carcinoma indicated better treatment efficacy as determined by the FBR rate using the Phoenix, but not ASTRO, definition of biochemical failure. Second, no difference in GI and GU toxicity between the dose schedules at 5 years was found, even though some individual and total GI symptom scores at 1 month were worse in the hypofractionated group. Third,
Conclusions
This is the first Phase III randomized trial to demonstrate a long-term therapeutic advantage for hypofractionated vs. conventionally fractionated RT for localized, early-stage prostate carcinoma.
Acknowledgments
The authors are indebted to the Cancer Council of South Australia for research grant support and Thomas Sullivan of the Data Management & Analysis Centre, Discipline of Public Health, University of Adelaide for assistance in statistical analysis.
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Research grant support received from Cancer Council of South Australia.
Conflict of interest: none.