“The best” therapy for Gleason 10 prostate cancer

We recently saw (see this link) that men diagnosed with a Gleason score (GS) of 9 or 10 had lower rates of metastasis and better prostate-cancer survival if they were treated with a combination of external beam radiation (EBRT) plus a brachytherapy boost to the prostate (“brachy boost therapy” or BBT) than if they were initially treated with EBRT, or if they were initially treated with surgery (RP).

The same researchers have also looked at a subset of patients who were initially diagnosed as GS 10.

There were only 112 patients who were biopsy-determined as GS 10. Of those,

  • 26 were initially treated with RP (median age 61)
  • 48 were initially treated with EBRT (median age 68)
  • 38 were initially treated with BBT (median age 67)

The median follow-up was relatively short:

  • 9 years for RP
  • 8 years for EBRT
  • 7 years for BBT

It should also be noted that

  • Upfront androgen deprivation therapy (ADT) was given to 98 percent of EBRT patients vs. 79 percent of BBT patients
  • Post-RP radiation therapy was given to 34 percent of surgical patients
  • Pre-RP systemic therapy was given to 35 percent of surgical patients

At 5 years of follow-up:

  • 3 percent of the BBT cohort received systemic salvage therapy vs. 23 percent of the RP group and 21 percent of the EBRT group
  • Distant-metastasis-free survival (adjusted) was 64 percent for RP,  62 percent for EBRT, and 87 percent for BBT
  • Prostate cancer-specific survival (adjusted) was 87 percent for RP. 75 percent for EBRT, and 94 percent for BBT
  • Overall survival was not significantly different in the 5-year time frame

While GS 10 is often more aggressive, it is noteworthy that 87 percent of those treated with BBT had no distant metastases detected within 5 years. Among men who received RP, 57 percent were upstaged to T3/4 and 41 percent were downgraded to GS 7 to 10 by post-prostatectomy pathology. We have no reason to believe those percentages would differ markedly among those who received radiation.

Although the numbers here are small, this is the largest analysis of Gleason 10s broken down by the therapy that they received that we have ever seen. Only a randomized clinical trial can provide a definitive answer. Given the aggressive course of GS 10, patients with this diagnosis are advised to talk to a radiation oncologist who specializes in this therapy.

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

11 Responses

  1. Your sitemaster wishes to emphasize a point clearly made by Allen Edel in the above commentary: “Only a randomized clinical trial” could provide us with a rtruly accurate answer to the question of whether any one form of treatment is “better” — in terms of oncological outcomes — compared to others in the treatment of any specific form of prostate cancer.

    He would also observe that many other issues would also affect outcomes, above and beyond the issue of Gleason score.

    Having said that, there is no doubt at all that BBT (with or without neoadjuvant ADT as appropriate) is now an accepted and appropriate form of localized treatment for higher-risk forms of prostate cancer — if it is being carried out by a skilled and experienced brachytherapy team.

  2. A difference in outcome might reflect selection for BBT compared to EBRT and RP. So the study should give much detail as to the balance to exclude a selection bias. If good results with BBT were due to a dose-response phenomenon, then patients given a total radiation dose to the index lesion with more than 200 Gy in EQ2 should have better gain from BBT than those given only a total radiation dose less than 120 Gy. Such analyses would help to create the best randomized trial with a defined total radiation dose to the index lesion.

  3. The radiation oncologist Michael Dattoli, in Sarasota, Florida, has been a proponent for, and administerer of, BBT for many years and I have recommended to patients with Gleason scores of 3 + 4 = 7 and higher at diagnosis to discuss BBT with their treating physician.

    Unfortunately, as is the case in Wichita, Kansas, and likely a great many other locations where EBRT is available, brachytherapy is not. Traveling to locations where both are available could be costly, let alone time away from one’s employment, considering the length of time the patient would have to remain at that location for daily treatment.

  4. In 2004, I was diagnosed with Gleason 9, localized prostate cancer. I was treated with EBRT plus 2 years of ADT. As you can see, it definitely was successful.

    Also, I disagree with those who say not to test after age 70. At the time, I was almost 75 years old.

  5. You may take conventional radiotherapy with 1.8 Gy 5 days a week but you might also take hypofractionated treatment with an equivalent cumulative radiation dose given in a few treatments. You might have the same effect from the same total radiation dose.

  6. I most certainly agree with “tugboat” as to an age cap in which men should no longer be even considered for PSA and DRE testing. I am in my 86th year of life, and were I one who had not yet been diagnosed with this insidious men’s disease, I would certainly still want to have PSA, DRE, and any other newer forms of testing performed to at least be aware I had prostate cancer.

    Men over 70 — as well as on up to my age and beyond — would certainly prefer NOT to die of prostate cancer. My parents lived into their mid 90s and despite my continuing prostate cancer since 1992 (and reasonably still manageable with ADT medications), my intent is certainly to match their longevity. We “chronologically gifted” (better term than old or elderly!) should not be denied any forms of health tests or treatments as long as we are still alive! Not doing so is tantamount to prescribing a death sentence.

  7. Finn:

    The dose-response curve seems to level out above a BED over 200 Gy. This is achievable only with BBT or with extreme hypofractionation (which is the subject of some clinical trials).

  8. As a further afterthought there is potential issue in regard to “doctor’s delay” in the management of prostate cancer.

    As a high Gleason score is indicative of very aggressive disease, the role of any delay (by the patient or by the doctors) in addressing suspected disease may have a larger impact on outcomes than would be the case for patients with intermediate-risk prostate cancer. I would also suspect that the doctor’s delay might be longer for younger men with prostate cancer (at an age of < 50 years) because most persons might not think of malignancy as a risk at that age.

    I wonder how much awareness there is for prostate cancer related symptoms.

    Recently I worked as a consultant in internal medicine. The staff regularly measured the degree of emptying the bladder. Older men commonly had a large amount of residual urine in the bladder. For these men I ordered PSA. I sent patients with clearly elevated PSA levels to the urologist for further evaluations.

    The urologist complained about why I was sending so many more patients for urologic service than all the other consultants in internal medicine so I wonder how often this procedure is used in departments of internal medicine.

  9. Dear Finn:

    Since age is, all on its own, and independently, a risk factor for an elevated PSA level and a risk factor for prostate cancer, I can see why a urologist might wonder why you were referring more patients than other internal medicine colleagues.

    Delay in the diagnosis of prostate cancer has been a problem for most of the past 60+ years (i.e, since we were actually able to diagnose localized, clinically sigificant prostate cancer with any degree of accuracy). It continues to be a problem — despite the PSA test — because we have no simple and straightforward way to quickly identify prostate cancer with a high degree of accuracy at a reasonable cost.

    In nations which have a “socialized” medical system, there is a problem with over-use of PSA testing because it is all too easy to find “problems” that don’t need to be found in men who don’t have a problem that needs treatment. Of course here in America in a “for profit” healthcare system, urologists would love to see the patients you were referring because they would be making money on each one they got to evaluate. (The patients’ health insurance providers would probably be less enthusiastic.)

    Whether referring all these patients to a urologist is a good idea or not is rather going to depend on personal and societal points of view — raising a set of philosophical and ethical issues that are way over my pay scale (or anyone else’s as far as I can tell).

  10. OK. In internal medicine, most male patients were relatively old. The patients’ PSA levels were screened by nurses and they found values of up to 70 ng/ml. I ran a unit and had many hundreds of admissions during 5 years of service.

    I referred maybe 10 patients to urology. The patients had no symptoms of prostatitis. The patients had had no PSA measurements before and had no knowledge of prostate cancer.

    I am not supposed to follow the fate of the patients later on, so I don’t know how many cancers were detected and how many had treatments.

    But I am sure that physicians who think in terms of prostate cancer as a risk will refer more patients than physicians who think prostate cancer is unlikely.

  11. 1. Between January and June 2009 I got the Boost and 3 years of ADT at the Uppsala Academic Hospital. a.k.a. Akademiska.
    2. At that time, high-risk cases like mine (Gleason 4 + 4, T2cN0M0, PSA 31 ng/ml) of age 80 got it, if they were fit enough.
    3. Some of the work aimed at identifying prostate tissue sensitivity to EBRT and the Boost was done here. Two Uppsala oncologists were or are experts in this treatment. They stood at the controls for 4.5 hours.
    4. It was enjoyable, interesting, and painless. I was the only patient there who knew about the Linear Quadratic Model and its mechanical model. I had studied enough physics and cell biology to understand it.
    5. I left Amsterdam to get it here and wound up a permanent resident.
    6. By international agreements this was fully covered, except for the flight here and of course living expenses.
    7. Any insurance provider, public or private, should cover such moves.
    8. This assumes two points: that insurers are interested in our survival, and that travel arrangements are routinely available.
    9. The Dutch insurance system is private: one must choose between about nine companies. They fix prices, with government “regulating” this (!). I’m glad to be living under a public health system.
    10. No private system is primarily interested in our survival. Public ones are losing interest.
    11. No insurance entity that I know of, public or private, covers travel expenses. This partly proves point 10. I could leave due to my knowledge of EU travel regulations. No Dutch doctor told me about it. As the Dutch saying goes, they “know it better.” Right before I left a Dutch radiologist defended general isolationism by telling me that “we have our own ideas about this.” He meant an idea to not have the boost in the Netherlands. He was morally wrong not to tell me or anyone else about the Boost, for at least a decade. (You can get it now, 9 years later, at one clinic.)
    12. They should, in America too. If they do not they want us to die.
    13. This is as good an argument as any for preserving the EU with its Schengen Agreement permitting free movement, and for improving American coverage. I fear that Brexit will start the balkanisation of the EU, which might well end Schengen. The UK never signed up to it, I think.

    Why did this happen in Holland, to me and others? Ask the insurers about expenses. And the politicians who “regulated care” for older men.

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