With widespread use of prostate-specific antigen (PSA) screening, a majority of newly diagnosed prostate cancers are confined to the organ and are typically treated with radical prostatectomy or radiotherapy.
An emerging radiotherapy option is stereotactic ablative radiosurgery (SABR), also called stereotactic body radiation therapy (SBRT), in which multiple- focused radiation beams deliver a large ablative or destructive dose of radiation to a tumor target.
SABR, which is administered in far fewer but larger doses than conventional radiotherapy, has the potential to benefit a substantial proportion of patients with low-, intermediate-, and potentially even high-risk prostate cancers. While all patients are potentially eligible for radiation treatmenfigut, these shortened courses may be the treatment of choice for those who, due to comorbidities, are not candidates for surgery, or those who have difficulty meeting scheduling demands of traditional, longer-term radiotherapy.
Clinical trials over the past decade have revealed therapeutic advantages of various short-course, or hypofractionated, approaches in prostate cancer, including SABR. Investigations also are underway to address a specific challenge associated with SABR to the prostate: the potential for rectal injury.
Evidence has indicated that dose escalation of conventionally fractionated external-beam radiation improves prostate cancer control and can provide a survival advantage for patients with intermediate- or high-risk disease.1,2,3
With this approach, 3-dimensional conformal or intensity-modulated radiation therapy (IMRT) approaches can limit toxicity—although many fractions are required, typically 5 days a week for a period of 8 or 9 weeks.
Given prostate cancer’s damage-repair characteristics, which indicate that the disease might be better eradicated with fewer, more powerful radiation doses than with longer, lower-dose courses of treatment,4,5
modest hypofractionated regimens (with fraction sizes ranging from ~2-3 Gy) have been proposed to improve treatment efficacy as well as patient convenience. Recent clinical trials using regimens that are more hypofractionated than conventional treatment schedules have shown that efficacious therapy can be delivered more efficiently, and with manageable toxicity, using equivalent effective doses with hypofractionation.6-10
Subsequently, a handful of studies have demonstrated excellent therapeutic outcomes, along with acceptable safety profiles, using even more hypofractionated approaches (6.5-10 Gy per fraction). Among them:
- In a phase I/II trial, 40 men with low-risk prostate cancer (Gleason score ≤6, PSA <10 ng/mL and clinical stage ≤T2a) received 5 fractions, 6.7 Gy per fraction, for a total dose of 33.5 Gy targeting the prostate plus a 4 to 5 mm margin. Four-year actuarial freedom from biochemical recurrence was 90% under the Phoenix failure definition (nadir + 2 ng/mL).11
- A phase II trial involving 67 patients with low-to-intermediate risk (Gleason score 3+3 or 3+4, PSA ≤10 ng/mL, and clinical stage ≤T2b) tested 5 fractions of 7.25 Gy, a total dose of 36.25 Gy, delivered to the prostate with a margin of 3 to 5 mm. PSA relapse-free survival was 94% at 4 years.12
- In a trial testing SABR in 304 low-, intermediateand high-risk patients with prostate cancer, the majority of whom were low risk, 50 patients were administered 5 fractions of 7 Gy (total dose 35 Gy); the rest received 5 fractions of 7.25 Gy (36.25 Gy total). With median follow-up of 30 months for the lower-dose patients and 17 months for the higher-dose group, actuarial 5-year biochemical recurrence-free survival was 97% for the patients with low-risk cancers, almost 91% for intermediate- risk patients, and 74% for high-risk patients.13 In a phase I/II study led by the UT Southwestern Medical Center at Dallas and 4 other sites,14,15 investigators have tested SABR in low- and intermediate-risk patients using substantially higher doses, starting in 15 patients at 45 Gy in 5 fractions—similar to those used in hypofractionated high-dose-rate brachytherapy.16