Shorter-course radiation noninferior to conventional therapy for low-risk prostate cancer

Issue: December 10, 2015

Hypofractionated radiation therapy yielded a similar rate of DFS and toxicity profile as conventional radiotherapy among men with low-risk prostate cancer, according to results of a randomized phase 3 non-inferiority study presented at the ASTRO Annual Meeting.

Perspective from Savita V. Dandapani, MD, PhD

Given in larger doses over a shorter period, hypofractionated radiation therapy is being studied as a possible improved treatment option for some patients.

Howard Sandler

Howard Sandler, MD, MS, FASTRO, professor and chair of the department of radiation oncology at Cedars Sinai Medical Center in New York, and colleagues sought to evaluate whether the hypofractionated therapy schedule — or 70 Gy in 28 fractions over 5.6 weeks — resulted in a 5-year DFS that was not lower than that of the conventional schedule, or 73.8 Gy in 41 fractions over 8.2 weeks, by more than 7%.

“This is the first large scale, randomized study demonstrating the value of a shorter course of radiation therapy for low-risk prostate cancer patients,” Sandler said in a press release. “The results are not surprising, however, given that studies on the effects of hypofractionated radiation therapy in patients with early-stage breast cancer, which is similar to early-stage prostate cancer, have demonstrated similar outcomes.”

The RTOG 0415 trial — conducted from April 2006 through December 2009 at several North American institutions — included 1,115 men (median age, 65 years; median pretreatment PSA, 5.4 ng/mL) with low-risk prostate cancer (clinical stage T1 to T2a; Gleason ≤ 6; PSA ˂ 10).

Researchers randomly assigned the men to receive hypofractionated (n = 554) or conventional (n = 547) radiotherapy. Baseline characteristics appeared comparable between the cohorts.

DFS served as the primary endpoint. Secondary endpoints included OS and biochemical recurrence, or a post-treatment rise in PSA levels.

After a median follow-up of 5.9 years, rates for 7-year DFS were 81.8% (95% CI, 77.5%-85.3%) for the hypofractionated arm and 75.6% (95% CI, 70.3%-80.1%) for the conventional radiation therapy arm. These data met the protocol non-inferiority criteria (HR for convention vs. hypofractionated = 0.85; 95% CI, 0.64-1.14).

Comparison of OS (HR = 0.95; 95% CI, 0.65-1.41) and biochemical recurrence (HR = 0.77; 95% CI, 0.51-1.17) also met protocol non-inferiority criteria.

The conventional and hypofractionated groups experienced similar rates of grade 3 or worse late side effects, including genitourinary adverse events (4.5% vs. 6.4%; RR for hypofractionated vs. conventional = 1.43; 95% CI, 0.86-2.37) and gastrointestinal adverse events (3% vs. 4.6%; RR = 1.53; 95% CI, 0.86-2.83).

“The results of our study demonstrate that for men with low-risk prostate cancer, hypofractionated radiation therapy offers a shorter, more convenient treatment schedule without compromising cure or causing additional side effects,” W. Robert Lee, MD, MS, Med, professor in the department of radiation oncology at Duke University School of Medicine said in the release. – by Anthony SanFilippo

For more information: Lee WR, et al. Abstract LBA6. Presented at: ASTRO Annual Meeting; Oct. 18-21, 2015; San Antonio, Texas.

Disclosure: This work was supported by grants from NRG Oncology Operations and the NCI.

Perspective

Savita V. Dandapani, MD, PhD

Patients with low-risk prostate cancer have many options for treatment including active surveillance, radical prostatectomy and radiation. It is therefore impressive that Lee and colleagues of the RTOG 0415 trial were able to complete this randomized external beam radiation (EBRT) trial given many competing treatment modalities. The RTOG 0415 abstract demonstrated that an altered shorter fractionation schedule (5 to 6 weeks) is non-inferior to conventional longer radiation treatment schedules (8 to 10 weeks) for low-risk prostate cancer. This is good to know that shorter radiation schedules do not lead to more toxicity and we await the details of long term follow-up. We do not know if dose escalation would lead to better improved local control, which is more feasible now with use of modern radiation technology such as image-guided radiotherapy that we use currently.

Based on Lee and colleagues’ abstract, the recommendations for shorter prostate cancer radiation schedules (EBRT) would be for a select group of patients with low risk prostate cancer (ie, Gleason Score 6, PSA < 10). Other details such as rate of PSA rise, number of core prostate biopsies positive, and patient stratification based on PSA value also need to be considered before choosing altered EBRT fractionation schedule. Future prospective trials are needed to compare how this shorter altered fractionation schedule of 5 to 6 weeks compares to even shorter 5-day courses of stereotactic body radiation (SBRT) or 1-day course of brachytherapy, both of which also have good local control and reported similar toxicities. Although those trials are currently being proposed, Lee and colleagues’ abstract does demonstrate that we can treat patients with early-risk prostate cancer with moderately shorter radiation treatment schedules while preserving quality of life and improving convenience.

Savita V. Dandapani, MD, PhD

City of Hope

Disclosures: Dandapani reports no relevant financial disclosures.