US research team wins contract to study comparative effectiveness of prostate cancer treatments

According to a media release issued yesterday by the University of North Carolina Lineberger Cancer Center, researchers at this institution have been  awarded the first contract we are aware of  “to conduct comparative effectiveness research comparing different management strategies for localized prostate cancer.”

The fact that the range of treatments that may be suggested as an appropriate therapy for the management of localized prostate cancer is confusing is well known. The fact that invasive treatment may not even be necessary is less well known. The relative merits of the different forms of treatment — compared to each other and compared to so-called active surveillance (monitoring without invasive therapy) — in carefully defined groups of patients are almost completely unknown.

A research team led by Paul Godley, MD, PhD and Ronald Chen, MD, MPH has now received a contract from the Agency for Healthcare Research and Quality (AHRQ) to “fill gaps in evidence” about which forms of treatment are most effective. Dr. Chen was kind enough to talk with us about this project earlier today.

The plan is to use data available in North Carolina to identify and offer to enroll up to 1,200 patients who have been newly diagnosed with any stage of prostate cancer that is localized to the prostate and the seminal vesicles (i.e., AJCC stages I- III or clinical stages T1-3N0M0). Participation in the study will be entirely voluntary. Once enrolled, patients will be categorized by age, ethnicity, socioeconomic status, and disease risk. They will be asked to complete a range of questionnaires over time, and they will permit the research team to have access to their medical records so that patient perceptions can be cross-checked against the actual records. The initial contract provides funding to follow patients for up to 3 years, but Dr. Chen and his colleagues are clear that they want to be able to follow these patients for as long as possible, and they are already planning to identify follow-up funding over time.

In the first component of the study, the goal is to assess patients’ health-related quality of life (HRQoL) and correlate that to the form of therapy (or monitoring) that they receive. The study will specifically assess things like patients’ urinary, sexual, and bowel function over time regardless of treatment type. In other words, the study is not primarily intended to determine which form of treatment has the “best” oncologic outcome. Rather, it is intended to assess the impact of each treatment on the patient’s overall quality of life over time (although oncologic outcome data will inevitably be an element of all the data collected).

In a second component of the study, the research team will specifically examine outcomes in African American patients and in patients living in medically underserved areas to see whether (and how) differences in patient demographics affect their treatment selection and outcomes. There are several areas of North Carolina that meet federal criteria for being medically underserved, and the research team is particularly interested in being able to assess how access to care affects patient decision processes and subsequent outcomes.

Effectively, this study appears to be potential pilot for the development of a national prostate cancer registry, which The “New” Prostate Cancer InfoLink has called for on a number of occasions as a means to investigate the relative merits of different forms of therapy over time. The Lineberger team recognizes that there are limits to their study in that there will be significant variation in the data collected and available on each individual patient. However, this study may, in itself, allow us to learn a great deal more about the management of prostate cancer outside major medical centers. Currently only two other patient databases offer large-scale information on the management of prostate cancer in the community setting: the CaPSURE database coordinated through the University of California at San Francisco and the SEARCH database, which is derived from data collected at a number of Veterans Administration hospitals.

Whether this study will meet objective criteria for prospective evaluation of the “comparative effectiveness” of differing forms of therapy for prostate cancer is important. Failure to meet such objective criteria is likely to mean that no one takes the results of the study seriously. However, The “New” Prostate Cancer InfoLink is of the opinion that the research team has a sound basic structure to their project. The hard part will be convincing a wide enough variety of patients to participate fully in the study over time. If the research team enrolls 1,200 patients but most of them drop out after a couple of years, then a lot of work will produce data of very limited utility.

4 Responses

  1. Of course this is a welcome study. Thanks for presenting this review. I have several thoughts about the study.

    I believe this formal work will help nail down objective results covering side effects of various treatments/active surveillance in a community setting, and I’m not aware that that has been done before. Three years of follow-up should be enough to cover much of this area, though probably not all, especially for late radiation toxicity and for prolonged effects of intermittent/one time androgen deprivation therapy, especially triple blockade, should that be chosen by any patients in the study.

    I have a concern about the “comparative effectiveness” aspect of the study. Comparative effectiveness assessment must be in terms of both sides of the therapeutic index — both benefits and costs (side effects, complications, monetary). Clearly, this study only covers the costs side. While 3 years of follow-up will give us useful information about side effects and complications (perhaps as well as monetary costs), 3 years is grossly inadequate for even a preliminary assessment of effectiveness in curing/controlling prostate cancer. I don’t see a problem with that so long as that inadequacy is appreciated. However, that inadequacy means that patients will still not have a prospective comparative study involving both sides of the therapeutic index available to aid in their choice of an approach.

    The inadequacy of objective comparisons of prostate cancer treatments has, of course, been a widespread, long-term concern. The best attempt I know of to compare treatments is the work reported by the Prostate Cancer Results Study Group, based on the literature review performed by a group of experts from many disciplines within prostate cancer. I believe they are working to publish their results, but I’m not aware of any publication to date. Informally, the Prostate Cancer Treatment Center has published their key results, including some excellent graphic comparisons of treatments, with one axis of the graph showing years of follow-up after treatment and the other axis showing percent of patients who were recurrence free. Different symbols are used for different forms of therapy.

    The group used a number of criteria for including studies in its comparison. For one thing, fairly modern ranges of radiation had to be used for external beam. For another, only studies that reported clinical pathology were used, thereby putting surgery and radiation on an equal playing field; that prevented inflation of surgery success rates based on shifting higher surgical pathology Gleason and stage cases to higher risk categories.

    The Results Group study also included comments on side effects.

    I was impressed with the list of experts involved in the research. Dr. John Blasko presented this research to prostate cancer survivors at the 2009 Prostate Cancer Conference sponsored by the Prostate Cancer Research Institute in Los Angeles.

  2. Jim,

    Where can I find some reliable data on long-term sexual potency outcomes (more than 3-5 years post treatment) for men in good health (not obese or diabetic, physically fit, sexually functional) <60 (or 65) years of age who have undergone brachytherapy treatment?

  3. Always helpful for me to note that Jim has already provided his comments. He is so well informed and knowledgeable that he covers most anything I might think of to comment on. Jim and I go back several years and have been following a relatively similar journey in the treatment of our prostate cancer. Well said, Jim.

  4. Hi Tracy (and thanks Chuck — the feeling is mutual of course).

    Here are some leads and thoughts related to your post of July 27 at 4:34 PM.

    Dr. John Blasko, the noted brachytherapy pioneer from Seattle, presented some visuals to us at the 2009 Prostate Cancer Conference coordinated by the Prostate Cancer Research Institute in Los Angeles. In addressing this area, he referred to a prospective study involving patients at Massachusetts General Hospital and Harvard, treated with EBRT, RP, or seeds, with baseline data prior to treatment and follow-up at 3, 12, 24, and 36 months post-treatment. Essentially, the results for “sexual dysfunction” showed trends only through 24 months, with RP and EBRT nearly equal at 70% dysfunction at 24 months and brachytherapy at about 45% at that point, with a slowly increasing incidence of dysfunction (30% at 0 months; 40% at 3 months; about 42% at 12 months, and about 45% at 24 months. While that clearly favors brachytherapy, it would be valuable to have further follow-up. Maybe you could learn more from the complete study, especially the age and physical parameters that interest you. You could also contact the correspondence author about any follow-up. Frankly, given the speed of research in prostate cancer, a 2003 study is rather old. (And 24 months follow-up is rather short.)

    Michael Dattoli, MD, is another of the leading experts in radiation for prostate cancer, and one of his books, for patients, is “<a href= Prostate Cancer Without Surgery — The New Gold Standard Treatment That Can Save Your Life and Lifestyle.” He co-authored the book with Jennifer Cash, ARNP, MS, OCN, and Don Kaltenbach, a noted prostate cancer survivor. I have the 2005 edition (may be the only one), and he addresses “What is the Risk of Erectile Dysfunction after Seed Implantation?” on pages 77-78 and “How do Seed Implants Affect Sexual Activity?” on pages 78-79. He says that, “Generally speaking, patients having prostate brachytherapy will have erectile dysfunction in about 15% to 20% of cases, although some institutions are reporting higher rates of incidence. Brachytherapy does not appear to produce the steady decline of potency that we have seen with full course external beam radiation through the years …. Essentially, where you are at two to three years after treatment is where you will likely be as far as erectile function …. (goes on to address aging and other medical conditions)

    John P. Mulhall, MD, is a noted expert in sexual function for Memorial Sloan-Kettering, with a particular focus on prostate cancer. He too presented at the 2009 conference, and his book was included in our attendee goodie bag: “Saving Your Sex Life — A Guide for Men with Prostate Cancer.” Pages 73-84 (Chapter 5) deal with “Prostate Radiation and Sexual Function.” He has a table of study results for various institutions on page 82. You could review the various studies cited, but most involve older men, and the results are, with one exception, not as good as reported by Dr. Dattoli, but, with one striking exception (a 1998 study) all at 51% or lower erectile dysfunction.

    You could also go directly to the PubMed web site and use the limits feature to try to home in on research that addresses your concern.

    Good luck.

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