BERKELEY, CA (UroToday.com) -
The optimal radiation schedule for the treatment of prostate cancer is unknown. Typically, the radiation sensitivity of various tissue types, denoted by the α/β ratio, guides the selection of appropriate radiation schedules. However, in the case of prostate cancer the value of the α/β ratio itself is a disputed. At one time, the α/β value for prostate cancer was thought to be close to 10 Gy, indicating a tumor that is not overly sensitive to fraction sizes. The α/β value for the major dose-limiting structure, the rectum, is about 3 to 4 Gy. In this scenario, large treatment fractions offer to proportionally damage the rectal tissue more than malignant tissue. However, recent radiobiological interpretations of clinical outcomes have suggested that the α/β ratio for prostate cancer may actually be closer to 1.5 Gy.(1, 2) If the α/β ratio for malignant tissue is indeed lower than normal tissues, hypofractionated regimens could allow radiobiological dose escalation without adversely affecting late normal tissue toxicities.
As reported in a recent paper in Technology in Cancer Research and Therapy, or TCRT,(3) our group at Georgetown University show the first example of changes to benign and malignant prostate tissues after hypofractionated robotic radiation therapy. We reported a case study of a 66 year-old man who presented with stage II, low risk adenocarcinoma of the prostate and underwent hypofractionated robotic radiation therapy (37.5 Gy in five daily fractions of 7.5 Gy). One year later, following development of progressive urinary retention, transurethral prostatic resection was performed offering us the opportunity to perform a histological analysis of the resected tissue. Consistent with the high BED2 achieved by our treatment plan (approximately 96 Gy assuming an α/β ratio of 1.5 Gy) there was no evidence of residual cancer within the TURP specimen.(4, 5) In addition, the histologic changes we observed in benign tissues were similar to those seen in conventionally fractionated irradiation (6-9) with no evidence of fibrosis or necrosis. Likewise, this is not surprising given the similar normal tissue BED2 between conventionally fractionated radiation therapy and our hypofractionated approach (approximately 78 Gy assuming a normal tissue α/β ratio of 3.0 Gy).
Little is known about how fractionation affects histopathologic changes. Our TCRT report shows an example of the changes to be expected after hypofractionated robotic radiation therapy. As predicted, there was no evidence of residual cancer in the TURP specimen and the normal tissue changes we observed were similar to those described for conventional irradiation. Our histopathological evaluation of prostatic tissues treated with hypofractionated robotic radiation therapy offers some insight into an area of little known tissue effects and represents an area ripe for clinical investigation. Clearly, these results will need to be confirmed in a large patient cohort with post therapy random prostate biopsies. As such, we have opened and are now enrolling patients on a phase two trial that includes biopsies two years after treatment to further evaluate the histopathologic changes associated with hypofractionated robotic radiation therapy.
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- Fowler JF. The radiobiology of prostate cancer including new aspects of fractionated radiotherapy. Acta Oncol 2005;44:265-276.
- Suy S, Oermann E, Hanscom HN, et al. Histopathologic Effects of Hypofractionated Stereotactic Body Radiation Therapy (SBRT) on Malignant and Benign Prostate Tissue. Technol Cancer Res Treat 2010;9:583-587.
- Zelefsky MJ, Leibel SA, Gaudin PB, et al. Dose escalation with three-dimensional conformal radiation therapy affects the outcome in prostate cancer. Int J Radiat Oncol Biol Phys 1998;41:491-500.
- Kestin LL, Goldstein NS, Vicini FA, et al. Pathologic evidence of dose-response and dose-volume relationships for prostate cancer treated with combined external beam radiotherapy and high-dose-rate brachytherapy. Int J Radiat Oncol Biol Phys 2002;54:107-118.
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- Crook JM, Bahadur YA, Robertson SJ, et al. Evaluation of radiation effect, tumor differentiation, and prostate specific antigen staining in sequential prostate biopsies after external beam radiotherapy for patients with prostate carcinoma. Cancer 1997;79:81-89.
- Gaudin PB, Zelefsky MJ, Leibel SA, et al. Histopathologic effects of three-dimensional conformal external beam radiation therapy on benign and malignant prostate tissues. Am J Surg Pathol 1999;23:1021-1031.
Sean P. Collins, MD, PhD1 as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations, etc., of their research by referencing the published abstract.
1 Department of Radiation Medicine, Georgetown University Hospital, Washington, DC