Aggressive, trimodal therapy active in treatment of selected men with M1 prostate cancer


A new report in the journal Urology has shown that a subset of men with metastatic disease can be placed in long-term remission through the use of a combination of androgen deprivation therapy (ADT) + surgery + radiation therapy.

The paper by O’Shaughnessy et al. (from the Memorial Sloan-Kettering Cancer Center in New York) is based on data from a pilot study in just 20 carefully selected men who presented with what we assume to have been newly diagnosed metastatic prostate cancer. Five of the patients had extra-pelvic positive lymph nodes (i.e., M1a disease) and the other 15 all had evident bone metastasis (with or without positive lymph nodes, i.e., M1b disease). We have been able to read the abstract of the actual paper as well as additional information on the ScienceDaily web site.

The patients were all treated with

  • ADT
  • Radical prostatectomy (inclusive of retroperitoneal lymph node dissection when necessary)
  • External beam radiation therapy to visible metastatic bone lesions

The ADT could be stopped after a minimum of 6 months if an undetectable PSA level was evident after completion of combination therapy.

The goal of this study was to eliminate all detectable disease, and the primary end point for the study was therefore an undetectable PSA level after termination of ADT and consequent recovery of standard testosterone levels (i.e., “no evidence of disease” or NED).

The basic results were as follows:

  • 19/20 patients (95 percent) achieved an undetectable PSA level with multimodal treatment.
    • 5/20 patients (25 percent) achieved an undetectable PSA after ADT alone.
    • 15/20 patients achieved an undetectable PSA after ADT + surgery.
    • 19/20 patients achieved an undetectable PSA after ADT + surgery + radiation therapy.
  • 4/20 patients (20 percent) achieved the primary study endpoint at 20 months of follow-up.
  • Of the four patients who achieved the primary study endpoint,
    • All four patients had initially been diagnosed with M1b disease.
    • Two patients subsequently progressed (at 25 and 26 months of follow-up).
    • Two patients were still in remission after 27 and 46 months of follow-up, respectively.
  • The trimodal treatment regimen was said to be “well tolerated”.

Now before readers get too excited, we should point out that long-term remissions on ADT after multimodal therapy have been well understood and recognized for years. Clinicians at the Mayo Clinic were reporting such data as much as 20 years ago, so this is not exactly a revolutionary finding. On the other hand, what is new here is the two continuing long-term remissions in this set of patients after the stoppage of ADT and recovery of standard testosterone levels, i.e., the concept that NED after recovery of standard testosterone levels could be used as a primary study endpoint in the treatment of advanced prostate cancer.

The data raise a number of interesting questions:

  • Were there common characteristics among the four long-term responders compared to the non-responders?
  • Would the addition of docetaxel-based chemotherapy have increased the number of responders and the period of their response?
  • Would the use of other types of therapy (e.g., abiraterone acetate/Zytiga or enzalutamide/Xtandi) in combination with the ADT + surgery + radiation therapy have improved outcomes?

The word “cure” is (of course) raised in the article on the ScienceDaily web site. The “New”Prostate Cancer InfoLink would note that while a 4-year outcome of NED in 1/20 patients with M1b disease is certainly a great result for that patient, it is premature to be suggesting that this form of therapy is curative. If this patient is still in remission at 10+ years, we can have that discussion.

What this study does do is open a door to further, potentially interesting new trials in the treatment of men with relatively low levels of metastatic disease at diagnosis, thereby expanding on the data from the STAMPEDE and CHAARTED trials to explore more aggressive forms of therapy that include radical prostatectomy (debulking of the prostate) as a key component of multimodal therapy as opposed to the radiation therapy + ADT + chemotherapy that was used in the STAMPEDE trial.

According to Dr. Howard Scher of Memorial Sloan-Kettering Cancer Center, the team is already looking at implementation of a Phase II trial to further test the viability of NED as an endpoint in the treatment of metastatic prostate cancer using multimodal therapy.

4 Responses

  1. I have have overwhelming proof in my own mCRPC reality that a low cholesterol/glucose diet and an ongoing elimination of drug-to-drug interaction experiments with all my prescription medication has been equally instrumental in lowing my PSA and allowing my enzalutamide/sipeucel-T therapy to work.

    I was taking (proudly I might add) some 15 different prescription medications and supplements, thinking this would cover all the bases in the treatment-response profile, which seemed to work for a while. But, my cancer/immunotherapy seemed to lower my PSA to a certain point before it started rising again until I stopped all non-cancerous medications and supplements to see what would happen. And, to my ongoing amazement my PSA has hit a first-time-ever 0.230 ng/ml from a post-treatment of 1000+ ng/ml, plus 9-10 Gleason grade. …

    Furthermore (and more frightening) I have had no support or acknowledgement from my so-called VA Treatment Team who seem happy writing prescriptions without the (DD) interaction due-diligence!

    Question: Where does the Cancer Research Community and Clinics responsibility needs to interactive with a patient’s struggling to get as much potency out of the medications as possible?

  2. Dear Dyke: I am sorry but I can’t answer your question because I don’t understand it. However, what you appear to have proven (at least in your own case) is that excessive polypharmacy (including the use of multiple supplements) is probably not one of the best ideas at all … and I have been suggesting that for years.

  3. Debulking and Cure/Long Term Remission for Metastatic Prostate Cancer

    My impression is that leading doctors consider “debulking”, in other words eliminating cancer in the prostate itself, important or essential to a meaningful chance of cure or long-term remission for men with proven metastatic disease. This paper from one of our leading centers and prominent physician/researchers lends pilot study level support to this concept. A major alternative view is that it is of little use to debulk the disease if it is already metastatic, but perhaps that view is losing steam.

    Dr. Nick Vogelzang, MD, a well-known physician/researcher/trials leader practicing in Nevada, spoke in support of debulking during his talk on “Hormone Resistance and Bone Metastasis” at the 2016 Conference on Prostate Cancer in Los Angeles. In his “Principles of the Evolving Solution” for advanced disease, he stated that surgery or radiation for primary cancer [meaning the prostate itself] is always a component of the cure, and he mentioned testicular, breast, and colon cancers as examples. (Disc 2: 1:16:09) Some other presenters and panel members echoed this point.

  4. Just Watched An M. D. Anderson Doctor Also Recommending Debulking for Advanced Cancer

    Dr. Ana Aparacio, MD, from M. D. Anderson, was interviewed about advanced prostate cancer, especially the challenging small cell and endometrial varieties. In the course of this 8-minute talk she mentioned that debulking the cancer was important, especially for preventing complications for the patient.

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