7-year outcomes data after treatment with SBRT

A new article in Frontiers in Oncology now provides us with data from the median 6-year follow-up of > 450 men with prostate cancer treated with stereotactic body radiation therapy (SBRT) using the CyberKnife technology.

Katz and Kang note that this long-term, prospective study

expands upon prior studies to further evaluate SBRT efficacy for a large patient population with organ confined, low- and intermediate-risk prostate cancer patients.

They report that:

  • 477 men with low- and intermediate-risk prostate cancer were treated with SBRT.
    • 324 men (67.9 percent) were low-risk (PSA < 10 ng/ml and Gleason < 7).
    • 153 men (32.1 percent) were intermediate-risk (PSA 10 to 20 ng/mL or Gleason = 7).
  • The average (median) age of the patients was 68.6 years (range 43.9 to 89.2 years).
  • The average (median) PSA level of the patients was 5.3 ng/ml.
  • 51 men (10.7 percent) were treated with androgen deprivation therapy (ADT) for up to 6 months.
  • All men received one or other of two possible radiotherapy regimens:
    • 154 patients (32.3 percent) received a total dose of 35 Gy delivered in five daily fractions.
    • 323 patients (67.7 percent) received a total dose of 36.25 Gy in five daily fractions.
  • Biochemical failure was assessed using the Phoenix criterion (i.e., the nadir value + 2 ng/ml).
  • The average (median) follow-up was 72 months or 6 years (range, 0 to 96 months).
  • The average (median) actuarial PSA at 7 years was 0.11 ng/ml.
  • 59/477 patients (12.4 percent) had died, but none had died from prostate cancer.
  • Biochemical failures occurred in a total of 25 patients (5.2 percent)
    • 11 men with biochemical failure were low-risk patients (two of whom had local relapses).
    • 14 men with biochemical failure were intermediate-risk patients (three of whom had local relapses).
  • The rates of actuarial 7-year freedom from biochemical failure are
    • 95.6 percent for low-risk patients
    • 89.6 percent fo rintermediate-risk patient.
  • Among the men with intermediate-risk disease, rates of biochemical disease-free survival were
    • 93.5 percent for the 106 men with low intermediate-risk (Gleason 6 and PSA > 10 or Gleason 3 + 4 = 7 and PSA < 10)
    • 79.3 percent for the 47 men with high intermediate-risk (Gleason 3 + 4 = 7 and PSA 10-20 or Gleason 4 + 3 = 7)
  • The use of ADT was not a significant predictor of biochemical disease-free survival.
  • There was no difference in the median PSA nadir or biochemical disease control between the doses of 35 and 36.25 Gy (in total or in either the low-risk or the intermediate-risk groups of men).
  • With respect to side effects and complications of treatment:
    • There were no observed cases of acute grade 3 or grade 4 acute gastrointestinal or genitourinary toxicity.
    • Late grade 3 genitourinary toxicity (either retention requiring surgery or bleeding requiring laser coagulation) occurred in 9/477 patients (1.7 patients).
    • There were no observed cases of late grade 3 or grade 4 toxicity.
    • All grade 3 toxicity events occurred in the patients treated with 36.25 Gy.

Katz and Kang conclude that

SBRT produces excellent biochemical control rates. Median PSA levels compare favorably with other radiation modalities and strongly suggest durability of response. These results also strongly suggest that 35 Gy is as effective as 36.25 Gy for low- and intermediate-risk patients.

It is, of course, unclear quite how many of the men in this study (and particularly those with low-risk disease) might have done just as well on either active surveillance or watchful waiting. Having said that, these data do appear to further confirm the outcomes previously reported for shorter-term follow-up of the treatment of men with SBRT.

For those men who want to have first-line radiation therapy as treatment for localized prostate cancer, SBRT continues to offer the potential benefits of faster treatment (1 week as opposed to 7 or 8 weeks of therapy) and lower cost, without (apparently) any significant loss of therapeutic efficacy compared to other forms of radiotherapy.

6 Responses

  1. Mike — can you provide a frame of reference as to how this compares to conventional IMRT … or guide us to an IMRT study that has a similar design?

    While the results sounds excellent, the sample is for low- and intermediate-risk men of which just 40/477 (8.4%) were 4+3; they evidently were the ones who received the marginally higher dose. I believe SBRT is not so well suited to high-risk disease that requires a wider field (pelvic girdle ).

    Notwithstanding SBRT clearly offers savings in time and money.

  2. Rick:

    I am not aware of any comparable study that has used IMRT for two very simple reasons: this study has been carried out prospectively, and it has been conducted entirely within a single community radiation oncology practice, which makes it very unusual indeed.

    With respect to the applicability of SBRT to the treatment of high-risk patients, I think the key question would be why they were high risk. There is a big difference between a 60-year-old man with T1c disease and a PSA of 3.2 ng/ml who is high risk because he has a single, small biopsy core containing Gleason 8 prostate cancer that shows every indication of being organ confined and a 60-year-old man with T2b disease and a PSA of 20.2 ng/ml with several positive cores, one of which is Gleason 3 + 4, and who is therefore still only high-risk because of his PSA level.

    The first of these men might be appropriate for treatment only with SBRT. The second probably is not. And I would not think SBRT is likely to be appropriate for any patinet who has two or more indicators for high-risk disease (e.g., any two or more of T2c disease or higher, a PSA level of 20 ng/ml or higher, and a Gleason score of 8 to 10).

    In the immediately preceding update from this series of patients reported in 2013), Katz and his colleagues did include data on a small number of men with high-risk disease: there was a 74% biochemical recurrence-free survival rate in those men at an actuarial median follow-up of 6 years.

  3. Katz published his 6-year data on 97 high risk men. He also just published his 7-year toxicity data on all 515 patients.

    Rick, Katz has never found that dose makes a difference in treatment efficacy by risk level. Also, he never found that neoadjuvant ADT adds to its efficacy either. However, both of those conclusions are highly provisional because the patients were not assigned randomly. The higher dose (36.5 Gy) was the dose he started his protocol out with, but then he moved to a lower dose (35 Gy) to see if he could lower side effects without sacrificing efficacy, and that seems to have happened.

    What he does differently for high-risk men is that he treats a wider margin around the prostate — 5 mm anteriorly for high risk vs about 2 mm for low/intermediate risk.

    An open question is whether treating the pelvic lymph nodes in high-risk men with SBRT will improve oncological outcomes, and at what toxicity. There are a couple of clinical trials in the works to help answer that.

    As for comparisons with IMRT, we await the results of randomized controlled trials. The longest term (10-year) IMRT study I’ve seen in the dose-escalation era is this one from Memorial Sloan-Kettering. Sample sizes are lower than Katz’s. The median age was similar, but it’s impossible to say whether the patient populations were otherwise similar. The biologically effective dose that Katz used, even at 35 Gy, is higher than the MSK study (81 Gy). Katz’s dose is equivalent to 85 Gy if it were delivered at a typical IMRT rate schedule. That, patient selection, the earlier treatment dates for MSK (1996-98), and possibly the extra 3 years of tracking, may explain the better efficacy results with SBRT: bRFS of 96%, 90%, and 69% for Katz’s low-, intermediate-, and high-risk patients vs bRFS of 81%, 78%, and 62% for MSK’s low-, intermediate-, and high-risk patients. Urinary and bowel toxicity and erectile dysfunction were lower in the Katz study.

  4. Thanks Allen … It appears the numbers are quite comparable for high-risk men given the small sample size.

    By the way, have you seen Snuffy Myer’s most recent video where he claims that pelvic girdle radiation results in significant side effects and discourages it. Now this is in the context of a rising PSA post-RP, but he makes no disclaimer as to wide focus radiation in other contexts.

    If I am following him correctly, and I may well have missed a nuance or two, I find this recommendation bizarre. If pelvic girdle radation led to significant co-morbidities, it would have been observed, or at least hypothesized, long ago, given the many men (including myself) who have received this treatment.



  5. Hi Rick.

    Someone else just mentioned that to me, but I didn’t watch it. I generally ignore such things, relying instead on peer-reviewed studies, or better yet, large randomized controlled trials, if available. I don’t totally discount his experience, but I recognize it’s only anecdotal. I can’t react to anecdotes, only to legitimate studies. He sees a very select patient population — men who have not done well with their treatments, and his perceptions may be colored by that. If that is his experience, that’s what it is, but I question how generalizable it is. I would also caution his viewers that he is not a radiation oncologist and doesn’t have that experience. I would very much agree that it remains a controversial issue.

    The first major study to address the issue of whole pelvic radiation in men at high risk for nodal involvement was RTOG 94-13. They found a significant progression-free survival advantage. However GETUG-01 did not substantiate that. A much larger trial (RTOG 0924) may help resolve that.

    Late GI toxicity has been found to be high in some studies, but not in others. As I understand it, the problem is due to irradiating a moving target (the prostate) at the same time as the fixed target (the nodes) — correct for prostate motion and you overshoot the other target. There are techniques to deal with this by either immobilizing the prostate, use of hydrogel to protect the rectum, or complex planning algorithms. High-precision intrafractional motion tracking, hypofractionation, and rapid treatment times may mitigate adverse GI effects too. Clearly, this is something that ought not be attempted by your friendly neighborhood radiation oncologist, but should be left to those conversant with such sophisticated techniques. Perhaps Myers was reacting to WPRT in community practice.

  6. Allen:

    I fully agree with you about the anecdotal conclusions Snuffy draws … and all the failures he may not report. Thank you for the added observations on wide-focus radiation.

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