International Journal of Radiation Oncology*Biology*Physics
Clinical InvestigationDose Escalation for Prostate Adenocarcinoma: A Long-Term Update on the Outcomes of a Phase 3, Single Institution Randomized Clinical Trial
Introduction
External beam radiation therapy is a curative treatment option for localized prostate cancer and is used in roughly a quarter of all treated cases in the United States.1 Based on quantitative biological modeling studies2, 3 and supported by clinical observations,4 it is well established that high doses of radiation are necessary for adequate prostate cancer cell killing to achieve cure. However, until 3-dimensional conformal radiation therapy (3DCRT) and intensity modulated radiation therapy (IMRT) techniques could be implemented clinically, dose escalation to the prostate was limited out of concern for toxicity to surrounding organs at risk. Although several randomized controlled trials have examined dose escalation in prostate cancer,5, 6, 7, 8, 9 none report median follow-up beyond 10 years. Moreover, these trials had heterogeneous use of concurrent androgen deprivation therapy, which is now the standard of care for many patients. Given the frequently indolent nature of the disease and protracted time to failure, extensive follow-up may provide unique and valuable insight. Here, we present long-term follow-up of a prospective trial involving patients with localized prostate adenocarcinoma treated without hormonal therapy, randomized to standard versus dose escalated radiation therapy.
Section snippets
Protocol eligibility and participants
Between 1993 and 1998, patients at our high-volume academic institution were enrolled in an institutional review board–approved phase 3 randomized trial (CRT 93-001). Informed consent was obtained from each participant. Eligibility criteria included clinical stage T1-T3, N0, M0 prostate cancer based on the 1992 American Joint Commission on Cancer staging system; a documented pretreatment serum prostate-specific antigen (PSA) measurement ≤30 ng/mL; histopathologic confirmation of diagnosis and
Results
As of January 2018, the median follow-up was 14.3 years and median time since last contact among living patients was 1 month (range, 0-43 months). Of the 301 patients, 71% (214) were confirmed to be deceased and 7.3% (22) requested to stop contact and/or were lost to follow-up (>48 months since last contact). Examining the patients lost to follow-up more closely, 8 versus 14 were in the 70 Gy versus 78 Gy arm, respectively, which was not significantly different (P = .682). On subgroup analysis,
Discussion
The long-term results of this phase 3 randomized, single institution trial found that increasing the radiation dose from 70 to 78 Gy without androgen deprivation resulted in a significant improvement in the primary endpoint of biochemical or clinical failure, with significant reductions in the development of distant metastases, the need for subsequent therapy, and death from prostate cancer at a median follow-up of 14 years. Radiation therapy was associated with a 2.3% incidence of in-field
Conclusions
Moderate dose escalation from 70 to 78 Gy demonstrates sustained improvement in clinical or biochemical disease control, which translated into lower salvage rates and prostate cancer mortality. Long-term follow-up also shows a low incidence of related solid tumor secondary malignancies.
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Cited by (0)
Supported in part by grants CA 06294 and CA 16672 awarded by the National Cancer Institute, U.S. Department of Health and Human Services; DOD Grant DAMD 17-98-1-8483; and the Prostate Cancer Research Program at MD Anderson Cancer Center.
Disclosures: A.P., S.J.F., and C.T. disclose funding support by Varian Medical Systems.