RP vs. RT as first-line treatment for prostate cancer: that word “may” again

A newly published commentary on the CancerNetwork web site is entitled, “Radical prostatectomy as primary treatment for prostate cancer leads to better survival.”
Unfortunately, however, that heading is inaccurate. The very first sentence of the actual commentary states that:

Compared with local radiation therapy (RT), radical prostatectomy (RP) as primary treatment for prostate cancer may result in a lower risk of castrate-resistant disease and superior overall survival (OS) from the time of metastasis.

The addition of the word “may” in that sentence is a crucial addition.

The data reported on the CancerNetwork web site come from a poster presented by Shahait and colleagues at the American Urological Association’s 2020 virtual annual meeting. We have not seen the actual poster.

I also appears to be the case that even the opening sentence of the commentary is inaccurate. That’s because the data used to compare two groups of patients were actually based on patients who had received (a) first-line RP with or without adjuvant RT as compared to (b) first-line RT alone. It is not clear from the commentary whether “adjuvant” RT included both early and salvage forms of RT after RP.

What Shahait and his colleagues did was actually very interesting. They sought to learn whether prior treatment type affected overall survival and survival after development of metastatic disease based on data from a cohort of 664 patients who had received prior RP with or without adjuvant RT (n = 310) or RT alone (n = 354) for local disease and had progressed to metastatic disease between 2010 and 2018. The data came from the so-called Flatiron Health electronic health record. That set of records includes data on about 2.5 million cancer patients in total. However, …

This was not a randomized clinical trial. It was not a prospective study. Multiple other factors also appear to have varied between the two groups of men (e.g., their average ages).

While it is clear from this study that there were differences between certain outcomes (see below), we also need to be extremely cautious about assigning definitive causes for these differences, because of the major differences between the two groups of men.

Here are the core findings from the study, so that they are clear:

  • Average (median) follow-up from date of metastasis was 30.0 months for the RP group and 29.4 months for the RT group.
  • Compared to the men in the first-line RP group, the men in the first-line RT group
    • Were older at time of onset of metastatic disease (69.3 ± 7.67  vs  63.8 ± 7.25 years ; P < 0.0001)
    • Had a higher PSA level at prostate cancer diagnosis (10.9 vs 7.8 ng/ml; P < 0.0001)
    • Were less likely to have a Gleason score of 8 or higher (54.5 vs 64.5 percent; P = 0.0089)
    • Had a higher PSA level at the time of metastasis (17.2 vs. 6.4 ng/mL; P < 0.0001)
    • Were more likely to receive androgen deprivation therapy (ADT) before metastasis (76.0 vs 60.7 percent; P < 0.0001).
    • Had a 32 percent higher adjusted risk of developing CRPC
    • Had a significantly higher risk for mortality after developing metastatic disease (P = 0.0013)
  • The unadjusted hazard ratio (HR) for CRPC in the group who received first-line RT was 1.45 (P <0.001).
  • This association was still significant after adjusting for patient- and disease-specific parameters (HR = 1.326; P = 0.0259).
  • On multivariable analysis, men who received RT alone had a 77 percent higher overall mortality rate after developing metastatic disease (P = 0.0013) compared with men who underwent first-line RP.

Our interpretation of these data is that they are certainly interesting but do not necessarily justify the conclusion that seems to have been drawn by the authors or by the commentary on the CancerNetwork web site. As just one example, if the men treated by first-line RT were (on average) about 6 years older than the men who had first-line RP at time of onset of metastasis, it can’t be a huge surprise that more of them died during the follow-up period!

It is also worth noting that — in a recent re-analysis of data from the ProtecT study in the UK (see Table 2) — the risks for prostate cancer-specific mortality, all-cause mortality, onset of metastatic disease, and other factors were all very low and very similar for the men treated by first-line RP and the men treated by first-line RT — and these patients did not all meet current NCCN criteria for low-risk or for favorable intermediate-risk disease. That trial enrolled > 2,500 patients who were followed prospectively and very carefully for 10 years.

It seems to us that there is a distinct issue with the conclusions of the study based on the Flatiron Health data. However, the findings are certainly interesting and it would be even more interesting if one could extract analogous data from some other long-term registry — if all the relevant data are available.



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