Nine-year outcomes after treatment with SBRT

Katz and Kang will present their 9-year outcomes on 515 patients treated by stereotactic body radiation therapy (SBRT) at the Genitourinary Cancers Symposium tomorrow (see abstract no. 20; “Stereotactic body radiation therapy for low-, intermediate- and high-risk prostate cancer: disease control and quality of life at 9 years”). This represents the longest tracking of SBRT outcomes — just 1 year short of the IMRT tracking reported by Alicikus et al. on a starting cohort of 170 patients treated at Memorial Sloan-Kettering Cancer Center.

The patients were treated between 2006 and 2010 using the CyberKnife platform.

  • 324 were low risk, 139 were intermediate risk, and 52 were high risk according to NCCN definitions.
  • 70 patients received adjuvant ADT for up to 1 year.
  • 158 patients, all with Gleason score < 4 + 3, received 35 Gy in 5 fractions.
  • 357 patients received 36.25 Gy in 5 fractions.
  • Median patient age was 69 years.
  • Median patient PSA level at diagnosis was 6.5 ng/ml.

After a median follow-up of 84 months, the authors report the following oncological control data:

  • 9-year freedom from biochemical failure was
    • 95 percent for low-risk men
    • 89 percent for intermediate-risk men
    • 66 percent for high-risk men
  • Median PSA was 0.11 ng/ml (at 78 months)
  • No difference in biochemical control for the lower vs. the higher radiation dose (for the men with Gleason scores of < 4 + 3 = 7)
  • 2 deaths from prostate cancer (i.e., an 0.4 percent prostate cancer-specific mortality rate)
  • 74 deaths from all causes (i.e., a 14 percent overall mortality rate)

They also report the following toxicity data:

  • Late rectal toxicity:
    • Grade 2: 4 percent
  • Late urinary toxicity:
    • Grade 2: 9.5 percent
    • Grade 3: 1.9 percent
    • Grade 2 or 3: 6.9 percent for the lower radiation dose vs. 13.2 percent for the higher dose.
  • Patient-reported bowel and urinary quality-of-life (based on EPIC questionnaire data) declined at 1 month then returned to baseline by 2 years; sexual quality-of-life declined by 29 percent at last follow-up.

These are clearly excellent results for any kind of radical therapy. The authors conclude:

These long-term results appear superior to standard IMRT with lower cost and are strikingly similar to HDR therapy.

While it’s tempting to conclude that neither the higher dose of radiation, with its greater toxicity, nor the addition of ADT conferred any incremental benefit, that can only be proved with a randomized clinical trial. Until so proven, it must be understood as only a good hypothesis to be discussed by patients with their radiation oncologists. It is also worth noting that these data reflect the outcomes of one very expert practitioner. There is an SBRT registry currently collecting data across many treatment centers.

The reported outcomes are nearly identical to those reported at 7 years (see this link, this link, and this link), indicating very stable control and no additional late-term toxicity with longer follow-up. In light of that, its low cost, convenience, and the fact that the standard of care, IMRT, has only one more year of follow-up on a much smaller sample size, it’s difficult to understand why some insurance companies still balk at covering SBRT for low- and intermediate-risk patients. Medicare does cover this.

Editorial note: This commentary was written for The “New” Prostate Cancer InfoLink by Allen Edel.

6 Responses

  1. Dr. Katz has provided evidence showing that using 35 Gy in five fractions on 3 + 3 (or 3 + 4 with PSA < 10) could provide the optimal BED for localized prostate cancer. What would concern me, however, is the possibility that someone believed to have 3 + 4 lesions, as determined by an initial biopsy, "really" has a 4+3 (or worse) lesion that was missed. In this case, a higher BED dose might well be needed to destroy the more lethal grade lesion(s), since 35 Gy/5 might not be up to this task. From what I've read, there could be a ~25% chance of a biopsy-determined 3 + 4 lesion classification being upgraded to a more lethal lesion classification.

    Should this be a concern?

  2. Dear T.:

    In Dr. Katz’s series it is perfectly possible that some of the patients with biopsy-based Gleason 3 + 4 actually did, indeed, have Gleason 4 + 3 = 7 or higher. We will never know the answer to that question. But if they did, they seem to have had good outcomes anyway.

    The way, perhaps, to look at the Katz/Kang data is to consider the reverse, which is that 36.25 Gy was a very safe dose of SBRT, but if the patient wanted to minimize the total dose of radiation for some reason, it could be cut to 35 Gy without seriously impacting effectiveness.

  3. Dear Sitemaster:

    Thank you for your helpful response.

    I guess my confusion arose from the apparent distinction that Dr. Katz made in the Katz and Kang paper you referenced: “Stereotactic body radiotherapy as treatment for organ confined low- and intermediate-risk prostate carcinoma, a 7-year study.” In the Results section of that paper, I read:

    “… Among patients with intermediate-risk disease, those considered to have low intermediate-risk (Gleason 6 with PSA > 10, or Gleason 3 + 4 with PSA < 10; n = 106) had a significantly higher bDFS than patients with high intermediate-risk (Gleason 3 + 4 with PSA 10–20 or Gleason 4 + 3; n = 47), with bDFS of 93.5 vs. 79.3%, respectively …”

    From this, I figured that a bump-up from 3 + 4 lesions to 4 + 3 lesions would evidently result in a significantly different bDFS — and thus the impetus to the question I raised above. (I am also assuming that the the 4 + 3 patient could also have a PSA < 10.)

  4. T. Petrie:

    I agree with the Sitemaster. It seems you’re assuming that the 36.25 Gy dose would have been more curative and the 35 Gy dose would be less curative of the men with Gleason 4 + 3. That may be true, but is certainly far from proven. In fact, Dr. Katz contends that anything above 35 Gy is on the flat part of the dose-response curve for cancer control, but it is on the steep part of the dose-response curve for effects on healthy tissue. (It’s an S-shaped curve.) So raising the dose provides no extra benefit, only toxicity. His cancer control for men with Gleason 4 + 3 is certainly as good as what we are seeing with brachy boost therapy, but with much less toxicity.

    In general, various SBRT radiation oncologists use between 35 Gy and 40 Gy, usually in 5 fractions. Memorial Sloan-Kettering Cancer Center is in the process of conducting a randomized clinical trial of the various dose levels in 2 Gy increments — assuring low toxicity at lower levels before bumping up to the next level. Maybe they will find an optimal level for their practice, but more likely, an optimal range. Of course, there’s a lot more to treatment toxicity than just the dose used.

  5. My husband has mesothelioma and is going to do proton therapy at M. D. Anderson Cancer Center. He is currently enrolled in a clinical trial with ur hospital. Is this type of technology better than proton?

  6. Dear Sophia:

    Unfortunately we are unable to offer you any guidance in relation to the use of proton therapy or any other type of therapy in the treatment of mesothelioma. This is not something we know anything about.

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