Prostate cancer outcomes today vs. outcomes yesteryear

As some of us have long suspected and understood, using data from men treated 20+ years ago as a guide to what would happen if you were treated the same way today is not really a very good idea.

A newly published paper by Cazzinaga et al. has looked carefully at the outcomes of men with localized and locally advanced forms of prostate cancer randomized to treatment with radical prostatectomy in the large and innovative Scandinavian Prostate Cancer Group Study no. 4 (SPCG-4) back in the 1980s and compared their outcomes to matched men treated by radical prostatectomy in a contemporary era, using data from the Swedish National Prostate Cancer Register (NPCR).

Basically, what Cazzinaga et al. were able to show was that:

  • At baseline, the matched men in the NPCR (all treated in 2005 and 2006) had half the risk of prostate cancer-specific moprtality compared to the similar men treated in the SPCG-4 trial (hazard ratio [HR] = 0.46)
  • When the two sets of men were re-matched by their grade group, with re-classifications being made for the known “shift” in Gleason grades over the years, this difference was smaller (HR = 0.73), but there was still a difference.

The authors conclude that the outcomes for the men who were treated in the SPGR-4 trial :

… cannot be directly applied to RP men in the current era, mainly due to grade inflation and grade migration.

and that

In order to compare historical trials with current treatments, data on temporal changes in detection, diagnostics, and treatment have to be accounted for.

This is an important lesson for the patient who is getting treated today. Much of the data from older trials — however large and however well-conducted at the time — are no longer strictly applicable to the prediction of the likely outcomes of newly diagnosed men today.

This has happened for several reasons:

  • Newly diagnosed men today are customarily much more accurately diagnosed than those being diagnosed and enrolled in clinical trials 20+ years ago.
  • New and better ways to classify patients have actually changed how patients are categorized (by Gleason score or grade group; by risk group; etc.)
  • In general the quality of treatment has significantly improved — not least because the majority of prostate cancers today get treated by specialists for whom treating prostate cancer is their bread and butter as opposed to by the nearest urologic surgeon or radiation oncologist (however few such procedures he might have done before).

However, the diagnosis and treatment of prostate cancer is still complex, and men are going to go on having complications and side effects from treatment for this disorder — regardless of how well they are treated.

The message that the reader (and in particular support group leaders and other educators) needs to take away from this study is that results from studies carried out 20 to 30 years ago, when we were really only at the beginning of the modern revolution in the management of prostate cancer, can be very scary, and they may not actually reflect the types of outcome that can be expected in  patients considering similar types of treatment today (the “not your father’s Chevrolet” paradigm).

3 Responses

  1. While there are still valuable lessons in that old SPCG-4 data, as corroborated by this new study, this new study emphasizes that absolute risks have decreased as time has passed (and technology improved). Thanks for reporting this.

    Some other details of improvements under the broad areas already mentioned are: great improvements in imaging and therefore assessing, targeting, and monitoring; other improvements in monitoring (such as what I suspect is routine use of ultrasensitive PSA testing for recurrence and managing ADT, and checking DHT, etc.); a game-changing improvement in radiation; the availability of genetic testing (such as assessing BRCA1, BRCA2, AR-V7, and other genetic factors, that is ever improving); understanding of countermeasures for side effects that enhances the tolerability and continuation of treatments; and supporting drugs for treatment such as metformin and statins when tolerable (though conclusive evidence is not yet available).

  2. This report might encourage one to question the validity and usefulness of prognostic nomograms based on databases from previous studies and treatment regimens.

  3. Dear Gene:

    I think it would be fair to say that prognostic algorithms based on original data from 20 years ago would need regular updating and re-validation if they were to be taken very seriously today.

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