International Journal of Radiation Oncology*Biology*Physics
Clinical InvestigationLong-Term Outcomes From a Prospective Trial of Stereotactic Body Radiotherapy for Low-Risk Prostate Cancer
Introduction
Hypofractionated radiotherapy has an intrinsically different normal tissue and tumor radiobiology. The particular radiobiology of prostate cancer offers a biological rationale in favor of hypofractionated radiotherapy (i.e., large dose-per-fraction) relative to the standard protracted course using conventionally fractionated doses (i.e., 1.8–2.0 Gy per fraction) with the potential for improving the therapeutic ratio of radiotherapy (i.e., simultaneous higher rates of tumor control rates and lower incidence of toxicities). To date, several studies analyzing clinical outcomes after various fractionated schedules for prostate cancer with radiobiologic modeling support this premise—namely, that prostate cancer possesses a high sensitivity to dose-per-fraction and therefore that hypofractionation would optimize radiotherapy 1, 2.
Several contemporary clinical series have suggested excellent biochemical control rates and low rectal and bladder toxicities with the use of modestly hypofractionated radiotherapy schedules. These clinical programs used external beam hypofractionated regimens, with dose-per-fraction ranging from 2.5 to 3.1 Gy 3, 4, 5, 6 delivered daily over a 4- to 6-week period. A landmark historical series from the United Kingdom in the 1980s delivered 6 fractions of 6 Gy each over a 2-week period and documented good outcomes and acceptable toxicities (7). There are two published series using Ir-192 high-dose-rate brachytherapy as monotherapy with dose-per-fraction ranging from 8–9 fractions of 6 Gy each (8) to 4 fractions of 9.5 Gy and 6 fractions of 7 Gy each (9). Only one study exists on the feasibility of using linac-based stereotactic body radiotherapy (SBRT) technique delivering 5 daily fractions of 6.7 Gy (10), but its long-term results have not been reported.
We previously reported on the early quality of life (QOL) results of our ongoing prospective Phase II clinical trial using SBRT for localized low-risk prostate cancer (11). Several factors highlight the relative impact the current study has within the context of recently opened and pending analogous trials and relate to the eagerness in the community to adopt this novel technique for practical as well as for economic reasons 12, 13. Being the first of its kind, our study therefore has the longest follow-up to date, and given the potential for late effects and late recurrences to appear after any prostate radiotherapy, it provides the basis for comparison with other approaches for the definitive treatment of prostate cancer. In this report, we present late urinary and bowel toxicities as well as the prostate-specific antigen (PSA) response rates.
Section snippets
Patient eligibility
An internal review board–approved Phase II clinical trial of hypofractionated SBRT for low-risk prostate cancer accrued 67 patients between December 2003 and June 2009. The endpoints were early and late urinary and rectal toxicities, QOL measure, and PSA response. Although details of this trial were outlined previously (11), the major features are summarized here. Eligible patients were newly diagnosed with biopsy-proven prostate cancer presenting with low- to favorable-intermediate risk
Urinary/rectal toxicity
Median follow-up was 2.7 years (25th–75th percentile, 1.8–4.5 years, max 5.9 years). At baseline, 92% of patients reported no urinary issues (translatable from the QOL scale to an RTOG Grade 0) and 8% with minor issues (translatable to an RTOG Grade between 0 and 1). The corresponding baseline function for bowel was 89% with Grade 0 and 11% with Grade between 0 and 1. In Table 1, we summarize the rates of urinary and rectal RTOG toxicity (incidence) at follow-up. There were no Grade 4
Urinary/rectal toxicity
The outcomes from this clinical trial demonstrate that a hypofractionated course using stereotactic body radiotherapy for localized prostate cancer is associated with infrequent rates of clinically significant urinary and rectal toxicities. With a median follow-up of 2.7 years, there has been no Grade 3 or higher rectal toxicity, no Grade 4 urinary toxicity, and 3.5% Grade 3 urinary toxicity. No patients experienced complete urinary obstruction, persistent urinary bleeding, or incontinence, and
Conclusion
This study shows that clinically significant late bladder and rectal toxicities from SBRT for prostate cancer are infrequent. Because of its possible association with exacerbating late urethral toxicity, we recommend a conservative approach and avoiding urologic instrumentation unless absolutely necessary. PSA relapse-free survival at 4-years compares favorably with those for radical prostatectomy, conventional external beam RT, or permanent brachytherapy. These findings support the
Acknowledgments
CRK is particularly grateful to Dr. Jack Fowler for his insightful discussions on radiobiology. Dr. John Adler is appreciated for his unique brand of doggedly exuberant encouragement over the years.
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Conflict of interest: none.