5-year follow-up data after proton beam therapy

A new article in the International Journal of Radiation Oncology (the “Red” Journal) provides us with recent 5-year outcomes for men diagnosed with localized prostate cancer and treated with proton beam radiation therapy (PBRT). A summary of some data from the trial appears in a short article in the Sun-Sentinel.

After initial diagnosis, all patients were treated between August 2006 and October 2007 at the University of Florida’s proton beam radiation facility.

Here are the key data reported by Mendenthall et al.:

  • The study enrolled a total of 211 patients.
    • 20 Patients had very low-risk disease
    • 69 patients had low-risk disease.
    • 82 patients had intermediate-risk disease (and 28 of these patients had a higher level form of intermediate risk, i.e., a PSA >15 ng/ml, a clinical stage of T2c, and/or a Gleason score of 4 + 3)
    • 40 patients had high-risk disease.
  • The average (median) follow-up was 5.2 years (range, 0.1 to 6.0 years).
  • The median prostate size was 35.8 cm3 (range, 10.3 to 135.0 cm3).
  • Clinical and biochemical-free survival rates at 5 years were
    • 99 percent for very low- and low-risk patients
    • 99 percent for intermediate-risk patients
    • 76 percent for high-risk patients.
  • Overall survival rates at 5 years were
    • 93 percent for very low- and low-risk patients
    • 88 percent for intermediate-risk patients
    • 90 percent for high-risk patients
  • Grade 3 gastrointestinal toxicity occurred in 1.4 percent of all patients.
  • Grade 3 genitourinary toxicity occurred in 5.3 percent of all patients.

The paper’s abstract provides additional information about bowel function, urinary continence, and urinary irritability, and sexual summary scores.

The authors conclude that:

This study demonstrates extremely high efficacy for proton therapy in low-risk, intermediate-risk, and high-risk localized prostate cancer as well as minimal toxicity and excellent patient-reported outcomes.

We should be clear that no one has ever argued that PBRT is not an effective or safe form of treatment for localized prostate cancer. The question has always been whether PBRT is any safer or more effective than other, less costly forms of radiotherapy.

This new study does not appear to bolster the case of the advocates for PBRT. At least 20 patients (and maybe more) probably never needed treatment at all at the time it was administered (the men with very low-risk disease and some of those with low-risk disease). The Grade 3 toxicity levels are similar to those reported from large series of men treated with IMRT in a similar timeframe. And the 5-year survival data are well within the normal range for any similar group of patients receiving any form of treatment with curative intent.

14 Responses

  1. Thanks, Mike. I’m still wondering about the cost argument, which has been made for diagnosis … with multiparametric MRI being too costly, but PBRT is OK for treatment? Are health insurance companies open to paying for proton therapy? I thought the current cost of PBRT treatment is $75K. Is that right?

  2. I read it differently. as a patient on AS, I am a test or a biopsy away from having to choose a treatment. I think PBRT has the advantage of less side effects than other comparable forms of treatment? It is about the quality of life after the treatment that is also quite important to me aside from trying to cure myself from prostate cancer.

    As for the 20 or more patients that may not have needed the treatment, no one will ever know. I have had two biopsies, first one found 3 out 14, all G6. Second one found one out of 15, also a G6. Meanwhile my PSA jumped from 4.1 to 4.9 (could be a one-time jump). Both biopsies done under MRI-fused, 3D color-Doppler ultrasound.

    I wish there was a way to absolute determine whether the prostate cancer is an aggressive form or not. My Prolaris test shows a 10 year mortality rate of 2%, but that was based on the sampled tissues. What about those that may have been hidden and not sampled?

    I am hoping that the insurance company will reconsider covering PBRT again.

  3. I don’t understand your analysis. This study blows away anything else I have seen, in terms of biochemical progression-free survival at 5 years. The only major problem was the sexual side effects.

  4. Precisely what large insurance companies are paying today for PBRT (if and when they are willing to cover the costs) is unknown. $75,000 is a price you can find in the media, but whther it is really what a company like Kaiser Permanente would pay is a very different question.

    It is certainly the case that getting approval for PBRT from one’s insurance provider is getting a great deal more difficult.

  5. When I checked on it 18 months ago, Loma Linda quoted around $65,000. This did not include travelling and accommodation for the entire duration of treatment. At the time, my insurance company was willing to pay for it but I chose AS instead. Meanwhile the same insurance company refused to pay for parametric 3-T MRI as a tool for AS, calling it experimental, though they paid for it the first time, before my first biopsy.

    My new insurance company approved the MRI procedure that I recently had. I do not know if they will cover the PBRT or not as I have not tried.

  6. Dear AKAI:

    I am still waiting for anyone to show me clear data that PBRT comes with a lower risk for side effects than other modern form of external beam radiation therapy. It certainly has a lower incidence of side effects than older forms of radiation therapy (e.g., 3D conformal radiation therapy), but no well-equipped prostate cancer radiotherapy center has been using 3D-CRT to treat localized prostate cancer since the early 2000s!

  7. As a (high-risk, Gleason 9) prostate cancer patient who was treated with IMRT at Johns Hopkins in 2010, I have naturally been focused on the post-treatment biochemical progression of patients like me. (Thus far, touch wood, I am progression-free after almost 4 years!). My physics background suggests to me that proton-beam therapy may fall short in “zapping” disease which has begun to creep just beyond the prostate (into the seminal vesicles, nearby lymph nodes, etc.). I would therefore be particularly interested in seeing comparisons between the progression-free survival after 5 and 10 years of PBRT versus modern IMRT. Some studies seem to point to a 10-year “success rate” (i.e., no biochemical progression) of about 80% for IMRT administered to high-risk patients. In this Mendenthall paper, it appears that 4 of the 40 high-risk patients had died (of something) at the 5-year point, while 6 showed biochemical and/or clinical progression.

    These numbers for high-risk patients are far too small to provide any statistical significance to a PBRT/IMRT comparison, but one can probably say that curative “failure” in 6 out of 36 after just 5 years isn’t that great! It certainly isn’t suggestive of any stand-out superiority of PBRT for this sub-group of patients. On the other hand, the penetration characteristics of the PBRT beam do seem to be providing some superiority in the genitourinary toxicity numbers.

    [Full disclosure; although I have no connection with any radiation equipment supplier I have substantial securities positions in several, dating back to more than 30 years ago. My retirement portfolio includes both IMRT and PBRT equipment suppliers, as well as oncology pharmaceutical developers. My physics degree is from Cambridge University, UK]

  8. Dear Ken:

    Clearly your prostate cancer had no evident impact on your ability to pick appropriate companies to invest in over time … so that’s an upside! Maybe we should be considering that ability as an endpoint in the requisite clinical trials!

  9. Ken,

    99% 5 year BFS is (I think) unheard of in intermediate-risk patients. Either the figures are being fudged or this is a breakthrough. It seems like there is a bias from the mainstream against PBRT.

    Mayo is building 2 PBT units, even though they are fairly slow to use new technology.

    I have not had PBRT, but these are compelling numbers,


  10. Ken,

    Glad your post IMRT is going well for you. But for you to suggest that you only have a physics degree from Cambridge is suspect. =-)

    I agree that we need to have a comparative study as to the efficacy of PBRT/IMRT but I would throw in RP, HIFU, and every other type of focal therapy into the mix so future prostate cancer patients can at least easily obtain quantifiable evidence of treatments. And about those pesky side effects that doctors seem anathema to discuss …

  11. Jim:

    Nice idea … but we already have very clear evidence that Americans would refuse to be randomized to such a trial.



    Last year I chose TomoTherapy IMRT instead of proton beam or other therapy. In part that made sense for me because of the suspicion, despite negative Na18F PET/CT bone (late 2011) and feraheme USPIO MRI/CT lymph node (spring 2012) scans, of spread to the pelvis, based mainly on my initial presentation in late 1999/early 2000 with a PSA over 100, all cores positive (most 100% cancer) per Johns Hopkins, Gleason 4 + 3 = 7, Stage III, and perineural invasion. Proton beam alone would not have been adequate to address such risk of spread beyond its reliable target area. If I had gone to a proton beam center, I’m assuming they would have used supplemental IMRT for the pelvic area beyond the prostate.

    However, I too am impressed by that 99% biochemical progression-free survival at the 5-year point. Though I’m still a skeptic whether proton beam is better for intermediate and high-risk cases in terms of effectiveness against the cancer, this report is a point in its favor. Moreover, 5 years seems to be a key metric for radiation: by that time success often stays relatively even as time goes by. However, that is a generalization. I know of a previous study led by Rossi, published in 2007, that documented a success rate for intermediate-risk patients of nearly 80% at about the 5-year point for conformal proton beam. I don’t have at hand a more recent study highlighted here that I believe.

    I’m not impressed with the success for low-risk patients as such success is typical for accepted therapies; many of these patients would likely have done equally well on active surveillance at a much reduced cost and no side effects.

    Regarding side effects, reports I’ve seen have not established superiority of proton beam, with some reports suggesting inferiority. That said, I’ve talked to a number of patients who had an easy time with side effects and none who have had difficulty. All have been pleased, but that is highly anecdotal. My own side effects have been mild to moderate, all within what I expected. I’m nearing the completion of 18 months of triple ADT as support to the radiation (my fourth round of IADT3).

    Regarding cost, I’m among those concerned about the cost of proton beam. That said, my own therapy last year cost just upwards of $100,000 for 39 sessions (78 Gy) that included a dose to the pelvis (46 Gy). That cost was fully covered by my insurer once I had met my $5,000 catastrophic limit (for 2013).

  13. Jim,

    I’m in a number of prostate groups on the Internet, and my unscientific impression is that the proton gang are far more pleased with their outcomes than any other group.

    Especially on side effects.

    By the time this is all proved definitively, we will be very old men.


  14. I received proton beam therapy for salvage at Loma Linda in January 2010 after a failed radical prostatectomy in Canada. PSA < 0.01 at 5 years; no side effects. Proton is #1.

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