Recently the board has been fortunate to have viperfred bring his enthusiasm and knowledge of CyberKnife (CK) radiation delivery under Stereotactic Body Radio Therapy (SBRT) dosing and arrangements for prostate cancer to our attention.
He has strongly advocated it as an option, arguing that it is superior to other therapies. He and some other patients who have had the therapy, as well as hospitals who now have this technology, state or imply that CK SBRT has already been proven effective and safe.
The huge appeal of CK SBRT lies in its dosing: just five radiation sessions, spread over one (five daily sessions) to two weeks (a day of rest between sessions). That is far more convenient than the long period needed for, typically, about 35 to 40 doses of 2 Gy ("Gray"; a unit for radiation dosing) each for various external beam radiation therapy programs.
The radiation also is not "intrusive" in the sense that brachytherapy is, as the latter requires the insertion of seeds through the body into the prostate whereas CK is external radiation.
This is my shot at a hopefully objective look at the current state of CK SBRT. I could not cover the key ground without making this a fairly long post. If you care to reply, I suggest you quote only short excerpts so the thread does not become even more awkward to handle.
The main issues are whether CK SBRT is as good as other kinds of prostate cancer therapy (or superior), and whether it has a side effect profile that is attractive or at least acceptable, especially compared to existing alternatives. There is some favorable, good quality but limited (not many reports) and early (less than three years average follow-up) information on these points. There is also some fairly well-based theory explaining why CK SBRT should work well, and that theory is able to link with some theory and many years of experience with High Dose Rate Brachytherapy (HDR Brachy).
I was impressed with some of the information and decided to do my own review. Here's the bottom line for me, before getting to the details: CK SBRT is very impressive at this early point for follow-up evidence on how patients are doing, both for cancer cure and side effect burden
, but at this point the approach is still investigational with some substantial risk due to unknowns that may be lurking behind the fairly short follow-up of basically less than three years
, though with a little luck we will get substantial clarification shortly, especially on the side-effect questions, perhaps in February.
Here's the approach I took. First, I searched for any papers by viperfred's doctor at Stanford U in California, Dr. Christopher King, as I've related in earlier posts. I learned that Dr. King is a leading physician/researcher for CK SBRT at Stanford, which is a very impressive credential as Stanford is one of the leading institutions for radiation therapy research in the US and I believe in the whole world as well. (I know this from paying attention to prostate cancer research for over nine years now, motivated by my challenging case, including attending FDA hearings, attending two national cancer research conventions, and participating in three prostate cancer research proposal reviews.) I then searched for some other papers on CK SBRT, in part leaning on leads provided by viperfred, and I found several. I also looked into what CK SBRT patients were writing about their experiences.
For those interested, the King team's paper is key - the only one with several years of follow-up results. It was published electronically (in advance of hard copy) by the International Journal of Radiation, Oncology and Physics, Vol. pending, No. pending, accepted for publication May 27, 2008, six pages, entitled "Stereotactic Body Radiotherapy for Localized Prostate Cancer: Interim Results of a Prospective Phase II Clinical Trial. The librarian at my hospital was kind enough to retrieve this and several other electronic papers for me. (If anyone has specific, detailed questions about what's in the paper, I can answer them.)
There is not an abundance of other papers on this approach as it is only a few years old for prostate cancer. Other papers I now have include the Fuller team's paper of 2008 in the same journal, Vol. 70, No. 5, "Virtual HDR CyberKnife Treatment for Localized Prostatic Carcinoma: Dosimetry Comparison with HDR Brachytherapy and Preliminary Clinical Observations. The Fuller team is in the San Diego/La Jolla, California, area.
I also looked at an editorial by David J. Brenner, D.Sc., from Columbia U., New York, in the same journal (Vol. 60, No. 4) entitled "Fractionation and Late Rectal Toxicity. And finally I looked at an old, archived paper in the basement of the hospital's medical library entitled "Carcinoma of Prostate Treated by Radical External Beam Radiotherapy Using Hypofractionation [meaning similar to SBRT - lots of radiation in just a few doses] - Twenty-Two Years' Experience (1962-1984), by Lloyd-Davies and colleagues from the UK.
I now possess all of these papers for reference. Regarding effectiveness in curing prostate cancer in localized cases:
The King paper indicates great success - no biological (rising PSA, etc.) or other failures at all for 41 patients with a minimum of six months follow-up who got five doses of 7.25 Gy CK radiation for a total dose of 36.25 Gy. While the minimum follow-up was set at just six months, the median (average) follow-up was 33 months, nearly three years. That's hardly long enough to be a guarantee - we would really like to see at least ten years, but at this point it is impressive, especially with that 100% rate of success! Comparison with effectiveness of other therapies:
The patients in the trial were "low risk": pre-biopsy PSA of 10 or lower, a Gleason Score of 3+3 or lower;, and a clinical T-stage of T1c or T2a/b, with allowance for a Gleason of 3+4=7 if present in fewer than 2 of 10 to 12 core biopsies and involving less than 5 mm in total tumor length. For such a low-risk patient group, other treatment methods typically achieve a very high rate of apparent cure at this early stage of follow-up, but not 100%, at least not by the five year point. A 2004 book by Grimm, Blasko, and Sylvester has a table in Chapter 8 that five year (two years more than the CK SBRT follow-up) disease-free follow-up results for low risk patients of 85% and 83% for surgery, 90% for 3D-conformal beam radiation at Memorial Sloan Kettering, and 94% for Palladium isotope seeds in Seattle. The book "A Primer on Prostate Cancer - The Empowered Patient's Guide," has a table on page 102 that shows five year follow-up results just by PSA range, including, for PSAs up to 10 a 94% disease free rate for Iodine 125 seeds plus external beam (Radiation Clinics of Georgia (RCOG in Atlanta) - Dr. Critz) and 90% for Dr. Blasko and colleagues (Seattle) for Palladium 103 seeds alone. My impression is that patients who are truly low risk across the board - including other risk criteria - have an extremely low rate of recurrence of about 1%. Side Effects - often referred to as radiation toxicity by researchers:
While all approaches, including CK SBRT but excepting Active Surveillance typically have some short term side effects ("acute toxicity" to the researchers), that is not a major issue just since those side effects are not going to last. It's the long-term side effects that we really get concerned about. With radiation, usually the urinary side effects are not substantial; it's the rectal side effects that get most of the attention, with potency also a concern. Moreover, these side effects, unlike those for surgery, typically gradually emerge, sometimes not appearing for several years, but almost always by the fifth year, as I understand it. For instance, I just had a friend who had had seeds from a highly respected expert in Northern Virginia more than three years ago who recently at the three year pointdeveloped a minor rectal bleeding problem.
I was especially concerned about CK SBRT, despite viperfred's protests, because the abstract of the King paper mentioned that a 38% rate of "severe rectal toxicities was observed" with dosing on five consecutive days (with no days off). To me that meant the team was scoring with the Radiation Therapy Oncology Group (RTOG) categories, and the word "severe" grabs your attention. However, the abstract also said there no RTOG grade 3 or 4 side effects, and those are the really bothersome side effects. It became clearer in the paper: the team was using a quality of life questionnaire as the basis for its statement that 38% experienced "severe" side effects instead of the RTOG criteria. From the researchers table on the third page, it looks like "severe" meant the patients had checked either "small problem" or "moderate problem" rather than "no problem" or "very small problem," but the table does not make that absolutely clear as patients with both daily and every-other-day dosing are mixed together. (No one checked "big problem".)
Before treatment, 8 of every 9 patients (89%) checked "no problem" in rectal quality of life, while the remaining 1 of 9 (11%) checked "very small problem" or "small problem." At the two year point after treatment, nearly half (45%) still checked "no problem," nearly half (again 45%) now checked "very small problem" or "small problem," and 9% checked "moderate problem, with no one checking "big problem." That's pretty good!
However, while the 16% who checked "moderate problem" at the three months point had declined to only 4% at the one year point, that percentage had increased to 9% at the two year point. That's why we really need to get those three year follow-up results! The results should be available, as this King paper was revised nearly a year ago in May 2008, and the average follow-up then was 33 months, just a few months short of three years. Viperfred told us about a large conference of CK SBRT users in the first week of February - next month, and hopefully the three year data will be presented then. We might even get some limited four year data.
We have learned from viperfred that the first patient in the King trial was treated in 2003; at the five year point he has no evidence of cancer and no side effects. To me that is encouraging, as it proves it is POSSIBLE to avoid side effects at the five year point; however, it does not help us gauge how LIKELY it is to avoid side effects. CAUTION!:
I was struck, as was the King team, by the contrast for CK SBRT delivery in rectal side effect reported "quality of life" from daily (38% "severe rectal toxicity") versus every-other-day (0% severe rectal toxicity). The King team had given its first 21 patients daily therapy but switched to every-other-day for its last 20 patients after noting the "mildly disappointing" rectal toxicity reports. If it were me getting this therapy, since effectiveness seems about the same, I sure as hell would want every-other-day dosing!
(On the other hand, those numbers still mean that a clear majority of men at this point in their follow-up are doing fine with daily dosing. But the researchers don't know who will fall into which group at this point. Viperfred has told us that his dosing was on Monday, Wednesday, Friday, Monday and Wednesday, giving what looks like a key day of rest between doses.) The twenty two years experience from England (published in 1990, Urology) with "hypofractionation," which is medicalese meaning just a few radiation sessions with more radiation per session, which basically is quite similar to SBRT dosing being used with CK:
The UK researchers were trying to determine if they could save money and still get good results by packing more radiation punch in just a few radiation sessions, basically six sessions over three weeks. Their survival rates were not that impressive by today's standards, but they asserted that long term urinary and rectal success appeared excellent. They provided little supporting detail. At the least, it appears they did not have a substantial group of dissatisfied customers. To me, in a general way their results support the likelihood of side effect success with CK SBRT. My diminished concern with leaning on High Dose Rate (HDR) Brachytherapy results for predicting CK SBRT cure rates and side effects:
Viperfred (and CK SBRT researchers) had enthusiastically compared the long track record of HDR brachy (seeds that are briefly inserted via a catheter, and then withdrawn, in just a few dosing sessions) with CK SBRT, believing that the results should be the same since just a few doses of higher dose radiation were used in both approaches. I was concerned they were not that similar since CK is delivered through the body, while HDR seeds have only a very brief exposure to non-prostate cells as they travel to the prostate to deliver a temporary dose.
However, the study by Fuller and team showed that the planned radiation doses for CK SBRT would be highly similar (or even superior) to the HDR brachy doses regarding rectal and other issues, and that provides a lot of assurance that leaning on the HDR brachy results is reasonable. That said, the researchers themselves stated they would like to see other groups confirm their findings. Is CK SBRT still in the "investigatory" stage versus "standard therapy":
As the terms are understood by researchers and Government officials, CK SBRT is still investigatory. (So is my therapy - intermittent triple hormonal blockade with maintenance, though it has been around at least since the 1990s. Being "investigatory" is not necessarily bad.) That doesn't mean the therapy is not fairly widely available; viperfred has told us there are 40 CyberKnife centers treating prostate cancer in the US, and a total of about 100 CyberKnife centers in the US, so there is room there for growth in existing facilities. You don't have to be in a clinical trial to get it. I've read that more than 1,000 patients have been treated with CK SBRT for prostate cancer, and facilities are scattered around the country. Still being "investigatory" doesn't mean that CK SBRT should not be covered by insurance; thanks to hard work by viperfred and others, CK SBRT is now often covered.
But being "investigatory" does mean that wrinkles in the therapy approach are still being worked out, as is dramatically illustrated by the issue of daily versus every-other-day dosing. Also, the King team refers to "evolving refinement" of their methods. It also means that key follow-up data is not in yet. If I were a patient who had had CK SBRT, I would be eager to convince myself that I would continue to do fine if I were doing fine at, say, the two or three year point. But that is just not always so with radiation therapy. It will really help when we get some three year follow-up data, and we can probably have some solid conclusions when we get five year data. The King team clearly recognize this and even anticipate that their patients will see some additional problems as the years tick by, though they express a confident tone in their paper. Learning curve issues - can any doctor do this well now?
A couple of pioneering CK SBRT doctors who interact a lot with the patient community believe that the learning curve is quite short and that many doctors will be able to do a fine job delivering CK SBRT.
I'm not so sure, and I would want to go with a doctor with plenty of experience and a track record he updated, based on disciplined follow up, that he could describe to me. For most therapies, it pays to find an expert if you can. It would be nice if a therapy would emerge that any doctor could deliver well, but regarding CK SBRT, that remains to be seen for my money.
I came across a few patients who were not happy with their CK SBRT experiences. At least one poor guy had suffered radiation burns, something the two doctors above had trouble believing. It seems the poor guy's doctor had cautioned him in advance that he might suffer burns. To me, that would be an alarm bell loudly sounding its warning!
I hope this helps move the CK SBRT discussion forward. I'll admit I'm pretty impressed, but I want to see a bit longer follow-up.