Record 10-year SBRT study among low risk patients

Alan Katz has now published the study with the longest-running follow-up of any study of external beam radiation therapy for prostate cancer among low risk patients, in this case, using SBRT. 10-year follow-up among intermediate and high-risk patients will be presented at next year's ASTRO meeting. This study ties in longest length of follow-up with the Memorial Sloan Kettering (MSK) study of IMRT. IMRT involves 40-45 radiation treatments over the course of about 9 weeks; SBRT shortens the number of treatments to 4 or 5 over the course of about 11 days.

Focusing on their low risk cohort only, the Katz study has a distinct advantage over the MSK study in sample size:

• The Katz study started with 230 low risk patients and, because of later start dates and some loss to follow-up, had 57 evaluable low-risk patients who were tracked for 10 years.
• The MSK study started with 49 low risk patients and, because of later start dates and loss to follow-up, ended with only 2 patients tracked for 10 years.
• Median follow-up was 108 months for Katz and 99 months for MSK

The IMRT study used a prescribed dose of 81 Gy in 45 fractions. The Katz study used a dose of 35 Gy in 5 fractions on 42 patients and 36.25 Gy in 5 fractions on 188 patients (average = 36 Gy). The biologically effective dose for cancer control was 17% higher in the Katz study.

It is risky to compare SBRT and IMRT when patients are not randomized to treatment with one or the other. There has been such a randomized trial, and partial results have been reported (see this link). The median age was the same in both studies (69 years of age), and the same definitions for the low risk category, and for biochemical failure were used. To highlight some of the differences and similarities in outcome:

• 10-year biochemical disease-free survival was 94% for Katz vs. 81% for MSK
• 10-year distant metastasis free-survival was 98.4% for Katz and 100% for MSK
• No prostate cancer-related deaths at 10 years in either study

Late-term urinary and rectal side effects were infrequent and mild in both studies:

• Late-term urinary side effects:
• Grade 2: 9%, Grade 3: 3% in the Katz study
• Grade 2: 9%, Grade 3: 5% in the MSK study
• Late-term rectal side effects:
• Grade 2: 4%, Grade 3: 0% in the Katz study
• Grade 2: 2%, Grade 3: 1% in the MSK study

Of those who were previously potent before radiation, 56% were potent (sufficient for intercourse) 10 years later (median age 79) in both studies.

Other interesting outcomes of the Katz study included:

• Median PSA fell to 0.1 ng/ml after a median of 48 months
• 21% experienced a PSA bounce along the way.
• Cure rates were independent of whether patients received 35 Gy or 36.25 Gy
• Urinary toxicity was higher in the group that got the higher dose
• Rectal toxicity was no different in the two groups
• Patient-evaluated urinary and rectal function declined acutely but returned to baseline within a year
• Sexual function declined by 23% at 6-12 months, and continued to decline by 38% by 8 years. It is unknown what percent of that decline was age related (but see this link).

Looking at the higher local control rates of SBRT and HDR brachytherapy, Dr. Katz sees evidence that IMRT is sub-optimal in delivering biological effective dose. He also believes that no more than 35 Gy in 5 fractions is necessary to achieve that control, and that it would minimize side effects.

Of course, probably half of the low risk men in this study might have gone those ten years without needing any kind of treatment at all. But for those who may not want or may not be good candidates for active surveillance, SBRT is a low cost, low bother, low side-effect alternative that delivers high rates of long-term oncological control.

Amazingly, I still hear that there are insurance companies that will not cover SBRT because longer follow-up is needed. Dr. Katz had already reported the nine-year follow-up (see this link), and with this addition and the 10-year higher-risk update at ASTRO next year, it's hard to see what any objection might be.

Dr. Katz is to be congratulated for continuing to update his study for 10 years. It is a lot of work to follow up with so many patients, and collect and tabulate their reported outcomes. He is a radiation oncologist not associated with a large tertiary care facility that might have more resources at its disposal.