SBRT for high-risk prostate cancer patients

As we have seen, stereotactic body radiation therapy (SBRT) is a preferred therapy for low- and intermediate-risk patients (see this link). It is effective, safe, convenient, and relatively inexpensive. However, its use for high-risk patients remains controversial. van Dams et al. have recently accumulated data from eight institutions that have used SBRT for 344 high-risk patients. They were treated as follows:

  • They received from 35 to 40 Gy in five treatments (7-8 Gy per treatment).
  • 72 percent received adjuvant androgen deprivation therapy (ADT) for a median of 9 months.
  • 19 percent received elective nodal radiation therapy.

After a median follow-up of 49.5 months:

  • 4-year biochemical recurrence-free survival  (bRFS) was 82 percent.
  • Higher dose, longer ADT, and nodal radiation were associated with better bRFS.
  • 4-year metastasis-free survival was 89 percent.
  • Late genitourinary (GU) toxicity of grade 3 or higher was 2.3 percent.
  • Late gastrointestinal (GI) toxicity of grade 3 or higher was 0.9 percent.
  • Toxicity was associated with dose and ADT use.

Although the results of different prospective trials aren’t comparable, the following table gives an idea of 4- to 6-year outcomes of prospective trials of high-risk patients using various therapies.

References: 1. van Dams R. et al. (2021); 2. Cleveland Clinic. Predicting PSA recurrence following salvage radiation therapy (with Gleason 8 disease); 3. Carrie C, et al. (2016); 4. Hoskin P, et al. (2012); 5. Morris WJ, et al. (2017); 6. Strouthos I, et al. (2018); 7. Zapatero A, et al. (2015).

As we’ve seen (see this link), brachy boost therapy is the gold standard for long-term recurrence-free survival. At about 5 years, however, all therapies seem to be about equally effective, with biochemical recurrence-free survival in the range of 78-91 percent. However, they differ markedly in the incidence of serious late-term urinary side effects. For LDR Brachy Boost therapy, the risk of urinary retention is high, while the risk of incontinence and urinary retention is elevated among patients having salvage radiation (SRT). External beam monotherapy, using either IMRT or SBRT, had a low risk of serious late-term urinary side effects (and almost no risk of serious rectal side effects).

IMRT, as a primary therapy for high-risk patients, requires long-term use of ADT to be effective. The DART RADAR trial showed that for high-risk patients, 6 months of adjuvant ADT wasn’t nearly enough. Nabid et al. suggest that 18 months of adjuvant ADT may be optimal when paired with IMRT. SBRT seems to be equally effective with less adjuvant ADT, but the optimal duration is yet to be determined.

The question that will only be resolved with longer follow-up is whether the recurrence rates are stable after 4 years, or whether they will deteriorate with longer follow-up. In the ASCENDE-RT trial of brachy boost therapy vs external beam radiation only, biochemical recurrence rates were similar after 5 years. Recurrence increased at a rate of 5 percent per year among those treated with external beam radiation therapy (EBRT) alone, but only at a rate of 1 percent per year if they got the brachy boost. There was similar stability of outcomes when HDR brachytherapy was used. Recurrence after salvage radiation increased from 22 percent at 5 years to 30 percent at 10 years. There is every reason to believe that SBRT, which uses biologically effective doses (BEDs) of radiation similar to brachy boost therapy, will follow a stable recurrence pattern over time, but that remains to be shown.

Insuring the safety of patients is critical, and high-risk patients are usually treated with wider margins that can affect toxicity. As we saw, for SBRT there are many factors that must be considered when giving radiation this intense (see this link).

The first randomized trial (see this link) of radiation delivered in six treatments compared to 39 treatments to intermediate- to high-risk patients proved that the cancer control and toxicity were similar. Another randomized trial (PACE-B) has already shown that the toxicity is lower with SBRT. An ongoing arm of that trial (PACE-C) is focusing on high-risk patients.

The treatment guidelines from the National Comprehensive Cancer Network (NCCN) has included SBRT as a reasonable standard-of-care option for high-risk patients (see Table 1 Principles of Radiation Therapy PROS-E 3 of 5 in NCCN Physicians Guidelines 3.2020). Due to the pandemic, an international panel of radiation oncologists is recommending that high-risk patients consider its use (see this link).

Editorial comment: This commentary was written by Allen Edel for The “New” Prostate Cancer InfoLink. Allen would like to thank Dr. Amar Kishan for allowing him to review a full-text copy of the paper by van Dams et al. abovementioned.

5 Responses

  1. How does proton compare?

  2. Very helpful research and comparisons!

  3. 1. “preferred therapy”? Evidence for this claim.

    2. This study, while interesting, and certainly not be dismissed, appears to be non-controlled (let alone randomized), and the subjects appear to be men who would otherwise have been offered active surveillance.

    3. It’s a fairly small study, and it’s duration, while better than many “novel therapies”, does not justify the claims made for it.

    4. In my day, researchers would offer the limitations of their studies, not hope that they’d pass unnoticed.

  4. Doug,

    The 5-year bRFS at the University of Florida Jacksonville proton center for high-risk patients was 74% (see here). Serious late-term urinary and rectal toxicity occurred in 2.9% and 0.6% of patients, respectively.

  5. heenan73:

    1. I provided a link.

    2. It was all high-risk patients. None would be offered active surveillance. It was uncontrolled. Randomized trials are discussed in the penultimate paragraph. I provided some historical controls as a rough reference.

    3. 344 patients is a large study of high-risk patients. By comparison, DART RADAR 01/05 had only 161 high-risk patients. I agree that only time will tell if results hold up as they have for other high-dose therapies or if they deteriorate rapidly as low-dose therapies do. This is discussed above.

    4. The researchers certainly did discuss limitations in their full text, which you are welcome to purchase and read for yourself.

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