Is Gleason 6 prostate cancer really “more lethal” in black men?

A commentary in Renal and Urology News this morning is entitled “Gleason 6 prostate cancer is more lethal in black men”.

The commentary is based on a research letter by Mahal et al. just published in the Journal of the American Medical Association. That research letter is entitledProstate cancer-specific mortality across Gleason scores in black vs nonblack men” and it does indeed seem to suggest that

  • Black patients on active surveillance or watchful waiting are dying with a diagnosis of Gleason 6 disease at a rate that is about 1.8 times as high as the rate in non-blacks (a prostate cancer-specific mortality rate of 0.40 percent in blacks as compared to  vs 0.22 percent in non-blacks at a median follow-up of just 36 months).

However, … we thought we would hold off on commenting on this issue until we had had a chance to look at the full text of the actual research letter itself.

What we know immediately from reading this research letter and other related sources is the following:

  • The base data are culled from information on prostate cancer-specific mortality among 31,841 black and 160,383 non-black patients diagnosed with localized prostate cancer between 2010 and 2015 and collected in  the Surveillance, Epidemiology, and End Results Prostate with Watchful Waiting database.
  • Sadly, SEER appears to lump active surveillance and watchful waiting patients into a single database and make limited efforts to differentiate with care between these two very different sets of patients.
  • These data are thus not limited to newly diagnosed men with localized prostate cancer who elect to have active surveillance. They could include men diagnosed with locally advanced, advanced, and even metastatic disease who were immediately placed on watchful waiting and received no form of immediate treatment (for any one of all sorts of reasons).
  • Such men might well have had a cursory biopsy — for the record, with as few as six cores being taken — that showed only Gleason 6 disease (even if a more careful biopsy might have shown Gleason 3 + 4 = 7 or higher).
  • The number of prostate cancer deaths associated with a diagnosis of Gleason 6 disease was very small
    • 51/12,707 (0.40 percent) among the black patients
    • 155/70,938 (0.22 percent) in non-black patients
  • The risk for prostate cancer-specific death was not statistically significantly different between black and non-black patients overall
    • 326/31 841 (1.02 percent) among black patients
    • 1,361/160,383 (0.85 percent) among non-black patients
  • Compared with the non-black patients, however, black patients with Gleason 6 disease had a higher risk of prostate cancer-specific death (adjusted hazard ratio [aHR] = 1.95).

What we can not tell from this paper is:

  • How many men in this database classified as being diagnosed with Gleason 6 disease had a repeat biopsy to confirm this (prior to being placed on active surveillance or on any other form of management)
  • How many men in this database were actually placed on true active surveillance
  • How many men in this database simply refused treatment for some reason
  • How many men in this database were placed on watchful waiting because there was no good reason for them to receive immediate treatment with curative intent (for any one of multiple possible reasons)

We also know, from an extremely careful study carried out on biopsy and pathology specimens at Johns Hopkins from > 18,000 patients, that not a single patient confirmed as having been diagnosed with Gleason 6 disease or lower has ever been known to go on to have metastatic prostate cancer (a necessary element of prostate cancer-specific mortality). It is certainly not the case that all those 18,000 patients were non-black!

This leads us to the conclusion that that there are so many critical unknowns in this analysis as to make it impossible to take the data at face value.

Quite apart from the issue raised above, no man who was diagnosed  with any form of localized prostate cancer should have been dying of prostate cancer within 3 years, which means that most of the patients in this data set who died had to have advanced disease at the time of diagnosis, and — if you can’t have metastatic prostate cancer with only Gleason 6 disease — then their Gleason score was incorrect at diagnosis (which is hardly an unusual finding!

In addition , it is well understood that many black males will either not visit their doctors at all with all sorts of serious medical conditions or will refuse therapy when it is offered. Consequently — quite apart from any issues related to socioeconomics, there is a sociocultural aspect of all this which has not been taken into account at all.

The “New” Prostate Cancer InfoLink is extremely conscious that there is a higher risk from prostate cancer among African Americans and others of Afro-Caribbean and African ethnicity. However, we are also concerned that analyses like this one, based on what the authors themselves state to be a study

limited by short follow-up and possible unadjusted confounding variables

do not serve anyone very well. This particular study may actually be providing  misleading information to black males and their families that may cause them to have unnecessary over-treatment for low-risk forms of prostate cancer … and we believe such a clear caution should have been provided. This research letter is effectively implying that African American men with true Gleason 6 disease can progress to having metastatic prostate cancer (although it does not actually say that). As far as we are aware, there is no biologic rationale for such a suggestion at this time.

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