Prostate cancer, cardiovascular disease, and the role of ADT


A new trial to be discussed at the Genitourinary Cancers Symposium is the RADICAL-PC trial, designed to give us a greater understanding of the roles of androgen deprivation (ADT) and other factors in causing cardiovascular disease in high-risk prostate cancer patients.

The trial is actually two prospective trials in one:

  • The Role of Androgen Deprivation Therapy in Cardiovascular Disease – A Longitudinal Prostate Cancer Study (the RADICAL PC1 trial) is a prospective cohort study enrolling men diagnosed with prostate cancer not more than 1 year earlier and/or who are within 1 month of commencing ADT for the first time. This trial is designed to identify factors associated with the development of cardiovascular disease among men with prostate cancer, with a particular focus on ADT.  It will enroll a total of about 6,000 patients.
  • The Randomized Intervention for Cardiovascular and Lifestyle Risk Factors in Prostate Cancer Patients (the RADICAL PC2 trial) is a randomized, controlled trial embedded in RADICAL PC1. This second trial will test a systematic means of modification of cardiovascular and lifestyle risk factors. The intent is that 4,116 of the participants in RADICAL PC1 will be randomized to RADICAL PC2.The paired RADICAL-PC trials are being conducted exclusively in Canada and are thought to be one of the largest prospective studies designed to explore the associations between prostate cancer and cardiovascular disease.

In the RADICAL PC2 portion of the paired trials, patients will be randomized to either

  • No specific intervention or
  • A standardized intervention protocol comprising
    • Standardized advice on healthy diet and exercise
    • Treatment with a low-dose antiplatelet agent
    • Treatment with a low- to moderate-dose statin
    • Treatment with an ACE inhibitor for patients with a baseline systolic blood pressure ≥ 130 mmHg.

The “New” Prostate Cancer InfoLink would encourage all appropriate Canadian prostate cancer patients to enroll in this pair of linked trials, which may be extremely helpful in expanding out understanding of ways to minimize cardiovascular risks associated with the management of prostate cancer. As yet there is no information about these trials on the ClincialTrials.gov web site, but there is a media release about the study on the Prostate Cancer Canada web site. For more information, see also Pinthus et al. (abstract no. 178; “The RADICAL-PC trial”).

One Response

  1. A Welcome Trial and Some Concerns

    I’m glad to learn about the launching of this trial. As a veteran of 13.5 years of intermittent triple ADT (ended April 2014), cardiovascular issues were a concern during the early years of treatment. I found that, while weight was a moderate problem in early years, I was able to keep cardiovascular risk factors under excellent control. I believe that diet, nutrition, exercise, supportive medication (statin, with low-dose daily aspirin possibly also helping), and other life-style tactics were important in my success, and such tactics will be explored in the second trial. However, while I can cite some strong evidence personally, particularly regarding weight control, lipid control, overall fitness, energy, and mood, I’m interested to see the results from this trial. (I also hope I am here to see the results; I did not read a timeline for follow-up, and it appears the timeline may be established by the achievement of certain end-points.)

    I was glad to see that Dr. Laurence Klotz, the brilliant physician from Toronto who is so well known for advancing understanding of prostate cancer in so many areas, is one of three co-investigators for this project. It is a bit surprising that the 12-person research team for these Canada-wide trials is all from eastern Canada (from four institutions in Ontario and one in Quebec); I’m curious what role the well-known and productive prostate cancer researchers from Vancouver in British Columbia out west might play.

    It will be interesting to see what eligibility and exclusion requirements are established. I’m thinking that patients involved in short-term adjuvant ADT, such as is often used in support of external beam radiation for intermediate-risk patients, maybe should be excluded as they are often on ADT for no longer than 3 to 6 months around the time of radiation; including them in the trial would probably just add “random noise”. On the other hand, enrollment of patients on ADT for at least a year would probably be wise, especially in the second trial that involves countermeasures for cardiovascular side effects.

    It will be interesting to see whether eligibility requires an LHRH agonist, LHRH antagonist, or bilateral castration, in contrast to therapy such as with an antiandrogen that is not combined with one of the preceding modes of ADT. At this point it strikes me that it would be wise to rule out antiandrogen therapy that does not include one of the modes that eliminates testicular production of testosterone, as the latter seems to be associated with cardiovascular developments, but perhaps not the former, and including the former patients might just add “noise”, especially in the the second (countermeasures) trial. Also, ADT antiandrogen monotherapy (or combined with a 5-alpha-reductase inhibitor — Proscar/finasteride or Avodart/dutasteride) is apparently not favored unless the balance is tipped in favor of limiting side effects with less need to combat aggressive cancer, such as in cases of elderly men with significant other health concerns.

    Also, medication, supplements, and exercise to help preserve bone mineral density is often used with long-term ADT. (My view as a now savvy patient without enrolled medical education is that this is essential.) One way of doing this is with estrogen skin patches, a tactic I used for my fourth round of intermittent ADT after about 10 continuous years on bisphosphonate drugs (Fosamax/alendronate; Boniva). While my impression is that using estrogen in this role is not yet widespread, some of the advocates/researchers are in Canada, and use of estrogen patches may surge during the trial. I’m not overly familiar with the effect of estrogen on cardiovascular health, but my impression is that it is protective. I’m curious whether the research team has considered transdermal estrogen as a factor that could affect outcomes. (The Vivelle estrogen patches worked quite well for me, though, as expected, they caused moderate gynecomastia.)

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