Seeking information about CAMs in the prevention and management of prostate cancer

That National Cancer Institute has very recently updated the available information about complementary and alternative medicines in the management of prostate cancer on the Physician Data Query or PDQ® system.

As most of us will be well aware, many men are interested in the value of complementary and alternative medicines (CAMs) in the prevention and the treatment of prostate cancer. The single most reliable source of information about the potential roles of CAMs to prevent and/or treat prostate cancer can be found in the sections on “Prostate cancer, nutrition, and dietary supplements” in the PDQ. This comes in two “flavors”:

  • This set of information been written specifically for patients, their care-givers, and men at risk for prostate cancer.
  • This set of information has been written for physicians and other health professionals, and is a good deal more technical.

Readers should understand that the PDQ does not necessarily address the potential use of every possible form of CAM in the treatment and prevention of of every possible disease. Thus, information about the use of specific CAMs in the management of prostate cancer is limited to about 11 core products, including calcium, green tea, lycopenes, modified citrus pectin, pomegranate, selenium, soy protein, vitamin D, vitamin E, and a few others. However, you can also search the PDQ system and related informational resources on the web site directly to find information on things like acupuncture, or reliable information on older products you may have heard of, such as PC-SPES (which was taken off the market because it was found to contain prescription drugs).

Another highly reliable source of information about CAMs that we recommend to patients in the prevention and management of cancers is the About Herbs database, developed by the Integrative Medicine service at Memorial Sloan-Kettering Cancer Center (MSKCC) as one component of their broader set of informational services about herbs, botanicals and other products. A third useful and reliable resource is the section on herbs, supplements, and vitamins within the Mayo Clinic’s online drugs and supplements database. However, the information on the MSKCC and the Mayo Clinic web sites does not deal explicitly with the use of particular CAMs in prevention and treatment of prostate cancer.

8 Responses

  1. Hmm. I just checked their section on “pomegranate” (I’ll look at the others later) and there is no mention of the two randomized clinical trials — by Stenner-Liewen et al. and Pantuck et al. that proved it had no effect. There is also no discussion of the fact that PSADT is a very suspect indicator of effectiveness on the Phase II trials. When the US government puts its imprimatur on information, we reasonably expect it is up-to-date, accurate, and not misleading in any way. I wonder who is compiling this, and whether it is peer-reviewed as a review would be in a professional publication.

  2. Dear Allen:

    The process used to compile content for PDQ is complex and requires multiple levels of review. The content of PDQ should therefore be seen more like “guidance” than a formal review in which every available article is necessarily addressed and evaluated. It is also therefore going to be the case that, as with guidelines, the final content tends to reflect the opinions of those involved in the process.

    Governments always have a hard time with processes like this. Political as well as personal issues are always floating in the background. Look at the USPSTF process if you need a reminder.

  3. Even the USPSTF wouldn’t ignore Level 1 evidence (I hope). But you are right to point out my naiveté about such things. I hope patients will read it with the skepticism it deserves.

  4. Interesting Evidence Regarding Pomegranate Supplementation and Prostate Cancer in the Phase III, Placebo Controlled, Double Blind Trial Cited by Allen

    First, thanks very much Allen for providing the link to the complete Pantuck paper. I had been quite discouraged upon reading a copy of the poster (at least its abstract) presented at a conference as the abstract indicated that pomegranate supplementation did not help, and, while trusting that the abstract probably gave a meaningful description of the gist of the results, I wanted to check the full paper just to make sure. Here are a couple of brief points from the complete paper.

    “An additional analysis was performed in patients who received a minimum of 12 months of blinded treatment to determine whether length of treatment had any additional impact on PSADT. Median PSADT increased 3.5 months in Placebo patients from 12.2 at baseline to 15.7 months (P < 0.0001), 18 months from 16.1 at baseline to 34.1 months in juice patients (P = 0.05) and 5.6 months from 13.9 at baseline to 19.5 months in Extract patients (P = 0.0003)” (from the Results section just following Figure 1). In other words, among those patients in both arms who got at least the initially planned minimum of a year of the placebo or pomegranate juice, while those on placebo had a favorable extension in doubling time of 3.5 months from 12.2 at baseline to 15.7 months, those getting the real pomegranate juice enjoyed in increase in doubling time of 18 months from 16.1 at baseline to 34.1 months, which more than doubles their PSADT compared to the modest increase of 29% in the placebo group!

    Here's another very interesting finding regarding the 22% of all patients in the trial that had a certain genetic makeup, abbreviated in the following sentence as AA: "Placebo AA patients experienced a 1.8 month change in median PSADT from 10.9 months at baseline to 12.7 months (P = 0.22), while extract patients experienced a 12 month change in median PSADT from 13.6 at baseline to 25.6 months (P = 0.03)." In other words, while the placebo AA patients had a non-significant benefit of 1.8 months, the pomegranate juice patients had a 6.7 times greater increase in doubling time of 12 months to a new total of 25.6 months, and that increase was statistically significant despite shortfalls in the trial!

  5. Jim,

    I suspect you are trying to make a silk purse out of a sow’s ear here. None of the mean changes in PSADT were statistically significant. You have to be very careful in trying to draw any conclusions about the patients who got juice — there were only 17 of them. Furthermore, there was absolutely no impact on disease progression (Figure 2). As the authors say, the MnSOD analysis probably has more to do with the antioxidant effect of any isoflavonoid. (Pomegranate is not special in this regard.) But, as we’ve learned, antioxidants can actually interfere with the body’s natural defenses against cancer, so it would be reckless to recommend it without a genetic test.

  6. Sorry to continue on this tangent, but I feel some clarification is in order about the Pantuck study.

    The dramatic prolongation of median PSADT was observed not just in the juice arm (n = 17) but also in the extract arm (n = 102). And it does seem to be significant (P = 0.03 for the extract arm). But still, among all the study participants, only 34 were found to be MnSOD-AA positive, and with such small numbers it is hard to reach any firm conclusion.

    The idea of looking at MnSOD status did not come out of a hat. It was pre-planned as a secondary endpoint, and MnSOD genotyping was performed on participants at baseline.

    Unfortunately, Table 2 does not break out disease progression for the MnSOD-AA positive subset. It puzzles me that the authors don’t report this. Given that this subset is only about 20% of the study participants, it would be understandable for any benefit they experienced to not be evident in Table 2.

    It appears to me that anyone can order a test for $99 from that shows MnSOD status (among many other things). If a person got this test and found he had the AA genotype, it seems to me that supplementing with pomegranate or other anti-oxidant would be a very reasonable thing to do. Although — as has already been pointed out — it would be a shot in the dark, as there is no evidence for long-term benefit.

  7. TomT:

    I think you misread the results. It was only in the group with the MnSOD mutation that there was a significant increase in PSADT of the extract relative to placebo. Across the entire study sample, the placebo actually had a greater (+ 4.5 months) and more statistically significant (p < 0.001) increase in PSADT. The extract group had a smaller increase (+ 1.6 months) in PSADT that was not statistically significant (p = 0.13). Based on this, one might want to avoid pomegranate extract.

  8. Allen:

    I did not misread it, but failed to make my point clearly. In your October 14 reply to Jim, you seemed to assume that the claim for benefit in the MnSOD-AA group was based solely on the juice arm, which had just 17 men. I wanted to point out that it was also based on the extract arm, which was much larger (102 men). But this may be just a matter of nit-picking, since the purported benefit was found only in the subset who had the AA genotype, which was much smaller.

    So we both agree that the purported benefit for the MnSOD-AA group is based on very small numbers. In spite of the small numbers, I was impressed by the apparent degree of benefit in that group, and, unlike you, thought it might deserve a closer look. What I’d really like to see is a plot of the before-and-after PSA for each individual in that group. If the results are so scattered as to show no visual trend, I could be persuaded into your camp.

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