There is randomized evidence that moderately hypofractionated radiation therapy (typically 2.5 – 4 Gy per fraction) is a valid alternative for some patients with prostate cancer. Extreme hypofractionation, typically defined as >6 Gy per fraction, delivered with SBRT in 4 or 5 treatments, also has some encouraging supportive data. 

The present study, the ONE-SHOT trial, addresses the role of single fraction SBRT in prostate cancer. The radiation therapy was 19 Gy in a single fraction of SBRT designed to spare the urethra, with the Calypso System used to continuously track motion. 6 patients with localized (low or intermediate risk) prostate cancer received this treatment. There was no acute toxicity greater than grade 2 during the 3-month follow-up. 50% of patients experienced grade 1 or 2 GU toxicities which decreased to baseline at week 12. 33% of patients had grade 1 rectal toxicity at week 6 which was resolved by week 12.  

Although the results are intriguing and warrant further study, this is a very small number of patients and there is no long-term follow-up data available, so it should remain investigational for the time being. Longer follow-up and larger prospective comparative studies would be needed before adopting this into practice.  

Reference (PubMed Link): Zilli T, Franzese C, Bottero M, et al. Single fraction urethra-sparing prostate cancer sbrt: Phase i results of the one shot trial. Radiother Oncol 2019;139:83-86.

Key Institution: Geneva University Hospital, Switzerland 
Keywords: Prostate SBRT, urethral sparing radiation therapy, single-fraction treatment 

More ultra-hypofractionated regimens are being implemented in treatment of prostate cancer. This study is a phase 3 non-inferiority study comparing prostate stereotactic body radiation therapy (SBRT) to conventionally-fractionated radiation therapy with co-primary endpoints of acute gastrointestinal (GI) and genitourinary (GU) toxicity. Very early outcomes (median follow-up of 12 weeks) are reported. At 12 weeks, SBRT appeared non-inferior to conventionally-fractionated radiation therapy in regards to acute GI and GU toxicity. Though this information is important to physicians, we need longer follow-up to determine the risks of late toxicity before broad application in the clinic. 

(Open Access)

Reference (PubMed Link): Brand DH, Tree AC, Ostler P, et al. Intensity-modulated fractionated radiotherapy versus stereotactic body radiotherapy for prostate cancer (pace-b): Acute toxicity findings from an international, randomised, open-label, phase 3, non-inferiority trial. Lancet Oncol 2019;20:1531-1543.

Key Institution: Multi-Institutional (Royal Marsden Hospital, Institute of Cancer Research, London, UK)
Keywords: Prostate cancer,  SBRT, acute toxicity 

Stereotactic body radiation therapy (SBRT) is an attractive alternative to traditionally fractionated external beam radiation therapy in patients diagnosed with localized prostate adenocarcinoma.  

This meta-analysis reviewed the results from more than 6000 patients enrolled on 38 studies with localized prostate cancer treated between 1980 and 2018 with SBRT. Studies included patients with low, intermediate, and high risk disease, although the former was substantially more represented than the latter. The study investigated the biochemical RFS, patient reported quality of life, and acute and late toxicities. 5 and 7 year bRFS was above 90%, GI/GU toxicities were 1-2% with the Expanded Prostate Cancer Index Composite urinary and bowel domain scores returning to baseline at 2 years.  

The results of this study further confirm the efficacy of SBRT as an excellent treatment modality for localized prostate cancer. While we await the final outcome of a phase II study comparing SBRT with standard fractionation proton IMRT (link below), this study continues to show encouraging results in this emerging therapy. 

Reference (PubMed Link): Jackson WC, Silva J, Hartman HE, et al. Stereotactic body radiation therapy for localized prostate cancer: A systematic review and meta-analysis of over 6,000 patients treated on prospective studies. Int J Radiat Oncol Biol Phys 2019;104:778-789.

Key Institution: University of Michigan Medical Center
Keywords: SBRT, localized prostate cancer, Quality of Life

In the HYPO-RT-PC trial, over 1200 men with intermediate- and high-risk prostate cancer were randomized to receive either standard fractionation (2 Gy x 39 = 78 Gy) or ultra (6.1 Gy x 7 = 42.7 Gy)—this latter dose was chosen to be equi-effective for late normal tissue complications. Barely 10% of enrollees ultimately fit this description. And while cT3a disease was also allowed, only 5% had it. So what we end up with is a largely intermediate-risk population, though nobody received androgen deprivation. The trial was initially designed to prove superior failure-free survival (FFS) at 5 years with ultra. However, an interim analysis demonstrated much better FFS (87%) than anticipated (70-80%), so the trial was switched to a non-inferiority design with a 4% absolute non-inferiority margin. At 5 years, the rate of FFS was 84% in both arms, which was deemed non-inferior, with similar overall survival. Ultra-hypofractionated treatment resulted in slightly worse acute grade 2+ GU toxicity (28 versus 23%) but similar grade 2+ GI and GU toxicity at 5 years (<5%). Finally, rates of erectile function dropped from 70% at enrollment to 35% at 5 years.

Reference (PubMed Link): Widmark A, Gunnlaugsson A, Beckman L, et al. Ultra-hypofractionated versus conventionally fractionated radiotherapy for prostate cancer: 5-year outcomes of the hypo-rt-pc randomised, non-inferiority, phase 3 trial. Lancet 2019;394:385-395.

Key Institution: Umea University, Umea Sweden 
Keywords: HYPO-RT, ultra-hypofractionation, prostate cancer, intermediate-risk, high-risk  

The question of how aggressively to treat oligometastatic disease, and whether or not there is a benefit to doing so, is an evolving paradigm in multiple disease sites. This is of particular importance in primary histologies with a long natural history, such as breast and prostate cancer, where patients may live for years with a diagnosis of metastatic disease. These authors report on the results of a Phase II, multi-center study in which patients with asymptomatic patients with prostate cancer and fewer than 4 extracranial metastases were randomized to either surveillance or metastasis-directed therapy (MDT) at all detected lesions (using either surgery or stereotactic body radiotherapy). The primary endoint was androgen-deprivation free survival, and ADT was started at symptomatic progression, progression to more than 3 metastases, or local progression of known metastases. This study enrolled 62 patients, with 31 patients in each arm. The median ADT-free survival time was 13 months for patients in the surveillance arm and 21 months in the MDT arm (HR 0.60, 80% CI 0.40 –0.90). There were no symptomatic or local progression events observed in the MDT group, whereas 3 and 6 events occurred in the surveillance arm, respectively. The authors conclude that MDT is safe and effective compared to surveillance.
This is an important study that provides support of metastasis-directed therapy for oligometastatic disease. Metastasis-directed therapy has become more common in recent years, particularly as SBRT becomes more widely used and available. 

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Journal & Date: Journal of Clinical Oncology 36, no. 5 (February 2018) 446-453.
Key Institution: Ghent University Hospital, Ghent, Belgium
Keywords: Oligometastatic disease, prostate cancer, metastasis-directed therapy