No pain, no gain?

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One of my patients last week had a heartfelt discussion regarding the survival benefit of ADT vs his quality of life. He enjoys body building and showed me some pretty dramatic pictures of himself during his last ADT cycle (on intermittent therapy) versus now, when he had been off treatment for ~6-9 months. Added to his concern was his decline in libido and sexual function during ADT, a common complaint especially among younger patients. The question of quality vs quantity of life was,of course, utmost on his mind.

Starting from the initial diagnosis, every (maybe that should be every !!) prostate cancer patient will experience a decrement in quality of life. Those who elect “watchful waiting” will nevertheless experience anxiety regarding the shadow of CANCER following their footsteps. Sure, you can put it out of your mind, but turn around and there it is, like the neighbor’s unwanted cat stalking you. Then there is the anxiety over what the next PSA will be. And if on active surveillance, what will that next biopsy show?? These issues are both real, disturbing, and often under-appreciated in the discussions surrounding screening…”we should still be screening, but not treat the men who don’t need it…” Really? What about the 80% of men who die at age 90 with prostate cancer at autopsy who never had to deal with the shadow? (The inevitable counter-argument is, “yes, and what about those who had early detection of a high grade cancer whose life was saved?”)

We also tend to ignore the impact of competing mortality in our discussions. “Sure you had a stent placed last year, and you already survived that small colon cancer, so why wouldn’t we be aggressive in treating this new problem?” Dr. Sartor provided an elegant discussion of this in an editorial on the PIVOT trial you can read here. Whatever the flaws in that study, it remains clear that we are not very good at predicting the non-prostate cancer “future” for our patients, and the older you are, the thinner the ice gets regardless of how many marathons you run.

When patients choose one form of primary treatment vs another, they are weighing the different side effect profiles of surgery or radiation as much as which is “most effective”. I often give patients a copy of this article from NEJM and encourage them to spend some time looking at the graphics in Figure 1 to get some idea of what they will face in the way of side effects from treatment. As any honest physician would tell them, treatment will involve side effects, some permanent, in the best of circumstances.

In the setting of more advanced disease, for example a patient who presents with metastases outside the pelvis, the recent CHAARTED and STAMPEDE trials both suggest an advantage to the earlier use of docetaxel chemotherapy in combination with ADT as opposed to ADT alone. These data suggest that “pay me now or pay me later” analysis favors the “pay me now” approach in terms of overall survival. But at what price for quality of life? Fortunately most chemotherapy side effects are reversible, but distinctly unpleasant, potentially making the equation something like “4 months of misery to provide 14 months of longer life….not all of which will be great anyway”.

Even in the very advanced setting, there is some evidence that greater toxicity results in improved survival. A recent analysis of the TROPIC trial of cabazitaxel suggested that the patients who had the most “toxic response” in terms of dropping their neutrophil count benefited the most in terms of overall survival.

While all of this seems incredibly negative (for which I apologize), the history of oncology as a field has been the incremental improvement in survival AND the development of newer treatments that provide such advances with diminishing toxicity. Pediatric leukemia, as discussed extensively in “The Emperor of All Maladies” is a great example of how pioneering patients and physicians worked together to find cures and reduce side effects. We may only be at the beginning of such achievement in prostate cancer, but with the advent of the newer hormonal and imaging agents, increasingly sophisticated surgery and radiation, vaccines and immunotherapy, and even the chemotherapies now available, we have  no doubt reached the end of the beginning. Onward!


Filed under General Prostate Cancer Issues, Prostate cancer therapy

10 responses to “No pain, no gain?

  1. Don Price

    Dr. Glode: I was a patient of yours at UCH but thought you had retired. Are you still seeing patients?

  2. Martin

    4 months of misery to provide 14 months of longer life….not all of which will be great anyway”.

    I find this a very disappointing comment Dr. I have widespread metastatic prostate cancer. I am on ADT and halfway through a chemo course, prescribed at diagnosis. The chemo is certainly NOT 4 months of misery. I would rather not be having it and being asymptomatic the treatment is worse than what I felt on diagnosis but my quality of life is good and I am attempting to control this horrendous disease.The side effects are NOT horrendous.
    Your comments may cause people not to take on early Chemo or to be overly concerned about side effects and I think given the trial evidence that is a bad outcome.Your language is, in my opinion far to emotive.I would urge people in my situation to read up on the Chaarted and Stampede trials linked to above.

  3. Bob Lederer

    Excellent summary and reminder that all PC treatments impact our lives. You also remain so optimistic. I was A Ped Resident helping care for those leukemia kids as they were looking for the best therapy. I would have never believed it would become a curable disease. My son has a rising PSA at age 50. If it is real, he will get a copy of this blog post.

  4. Brent Campbell

    May your ice stay thick

    Sent from my iPhone


  5. Clyde hanks

    Michael –

    Insightful and thought-provoking as usual.

    I know in my own case the side effects of treatment – impotence, incontinence, loss of libido – have been a challenge. One learns to adapt as we go along. But I have been able to be here to help my wife through her illness, see my children grow and flourish, and meet and get to know my grandchild (and look forward to another that’s on the way). I just spent the weekend with my oldest daughter and my granddaughter going to the zoo and the beach here in San Diego. My gratitude for being able to experience that is boundless.

    Thanks for all you expert care and caring and keep up the good work sharing your wisdom with the masses.


    Sent from my iPad


  6. Dan Gallagher

    I gained a certain comfort in hearing of another’s struggle with strength, vitality and sexual function. Its always easy to look back and second guess my decision to stick with 18 months of ADT after IMRT, but I’m really hitting the wall after being of Lupron 14 months. Feel like I have aged a decade in the 3 years since diagnosis. Hopeful that things will improve after 2 years off ADT.

    • Bob Lederer

      Dan, While I do not know you, I hope that you can find some solace in knowing there are many of us who have been on ADT for a long time and have not been so severely impacted. I hope your “off time” will greatly improve your feelings and well being.
      Are you a member of a Support Group or some other resource for men? I find it very helpful to have a group of guys that I can safely share my feelings with and get the support I need. I would be happy to talk off-line if you are interested. Mike can share my email with you if that is of interest.

      • Dan Gallagher

        Bob, thanks for your kind words. I’m usually upbeat about things, but Michael’s comments about his patient’s experience touched me. I think in part because of what you mentioned about support groups. Shaw has a great cancer one here which I used frequently while in treatment, but I never had the luck of having any fellow prostate patients attend. Wonderful women recovering from breast cancer mostly. I have many friends who have had surgery or radiation, but I only know one who has been on ADT which was just for six months. His patients comments normalized things for me a bit. Love to have your email. Thanks Dan

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