Starting the new year with two of the usual controversies

Strictly speaking, JAMA Oncology actually ended the old year (in its issue on December 29, 2016), rather than beginning the new one, with two articles, a letter to the editor, and an editorial that deal with two of the more controversial issues that affect the way we think about the management of prostate cancer.

In the letter to the editor by Hu et al., the authors argue that it seems as though there may have been an increase in the numbers of older men (≥ 75 years of age) who have been diagnosed with metastatic prostate cancer since the introduction of the USPSTF guidance on screening for prostate cancer (but not in men of < 75 years). However, as Thomas and Shyr point out in their brief editorial comment, may have been is the operative term, because it all appears to depend on which set of statistical techniques one uses to analyze the available SEER database. An earlier research letter by Jemal et al., on which we commented not so long ago, came to a very different set of conclusions when based on the same data set but using a different statistical technique.

Your sitemaster is no statistician, but he is quite certain that each set of statisticians would vigorously defend the differing analytical techniques they employed to assess the data. The truth is that we don’t know whether there has been a real increase in risk for diagnosis with metastatic disease in any specific subset of men in the US since the introduction of the USPSTF guidelines in 2008 and 2012. What we do know, on the other hand, is that there has been a massive reduction in risk for diagnosis with metastatic prostate cancer among all men since the introduction of PSA testing in the later 1980s and early 1990s.

In the two articles above-mentioned, two sets of authors take very different positions on the value of intermittent androgen deprivation therapy (IADT) in the management of advanced prostate cancer. Hussain and Eisenberger, in an article entitled “Intermittent androgen deprivation: primum non nocere — ‘first do NO harm’“, argue that there is no longer any role for IADT in the management of advanced prostate cancer. Klotz and Higano, in an article entitled “Intermittent androgen deprivation therapy — an important treatment option for prostate cancer“, take the opposite position that there most certainly is still a role for and value in IADT.

Unfortunately it is not possible to read the full text of either of these articles unless one has a full subscription to JAMA Oncology (which, like most of his readers, your sitemaster doesn’t either). So most of us can only read the first page of each article. However, the real message here is probably rather more nuanced, which is that IADT is potentially an appropriate form of therapy for some carefully selected men with progressive and advanced disease and a really bad idea for others — but, we don’t really know how to select the appropriate patients with great accuracy. Like the “do we or don’t we” screening debate, this is not a “black or white” issue. It is rampant with shades of grey, and your sitemaster would respectfully suggest to the editors of JAMA Oncology that they may not be helping their readers (let alone the patient community) by packaging articles like this in a pro/con debate style. The key question is, “What data would help us to determine whether there are (or are not) specific subsets of good and poor candidates for IADT, and what trials therefore need to be done to prove such a hypothesis?”

We expect both of these issues to be as controversial on January 1 , 2018, as they are today, on January 3, 2017.

2 Responses

  1. Nice commentary. Points up the limitations of our current approach to research based on group comparison designs.

    In the 1970s, when I was completing my graduate school training in psychology, a pressing concern was the question, “Does psychotherapy work?” This generated much heat but no light until it became clear that the proper question was, “Who does psychotherapy work for and under what conditions?”

    Single subject research designs can provide rigorous evidence to answer this question if carried out using sound experimental design principles, such as manipulating only one variable at a time, and if they employ sophisticated data analytic techniques.

    I conducted one such study that evaluated the effectiveness of a medical marijuana protocol by contrasting changes in my PSA kinetics across three interventions — after two treatment failures using conventional treatments (robot-assisted radical prostatectomy and salvage radiation treatment), and during the medical marijuana trial.

    I was able to document a clear initial impact of the medical marijuana protocol I followed but was unfortunately also able to document that this was only a transient improvement that I could not sustain. These impressions were corroborated by imaging studies completed at the same time.

    Would other list mates be interested in comparing notes on N = 1 research designs.

  2. And why stop the controversy here. I’ve uploaded two documents, with consent, at my site on two viewpoints concerning chemotherapy for non-metastatic patients. Of course my site requires a login to download them…

    Should chemotherapy be used in nonmetastatic prostate cancer? Two very interesting takes.

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