5ARIs & PCa

[pjoshea13]

New study, so a separate post, but will interest those who followed the recent Finasteride thread. This is more of the same.

"A retrospective 20‐year cohort study in Saskatchewan men ..."

"5ARI use was associated with lower risk of a PC diagnosis, regardless of comparison group. Risk of high‐grade PC was higher among both 5ARI users and α‐blocker users compared with non‐users; however, this did not translate into higher risk of PC mortality."

-Patrick

onlinelibrary.wiley.com/doi...

Impact of 5α‐Reductase Inhibitors and α‐Blockers for Benign Prostatic Hyperplasia on Prostate Cancer Incidence and Mortality

Maria I. Van Rompay J. Curtis Nickel Gayatri Ranganathan Philip W. Kantoff Keith R. Solomon Jennifer L. Lund John B. McKinlay

First published: 14 September 2018

doi.org/10.1111/bju.14534

This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/bju.14534

About

Abstract

Objective

To investigate the use of 5α‐reductase inhibitors (5ARIs) and α‐blockers among men with benign prostatic hyperplasia (BPH) in relation to prostate cancer (PC) incidence, severity, and mortality.

Patients and Methods

A retrospective 20‐year cohort study in Saskatchewan men aged 40‐89 years with a BPH‐coded medical claim between 1995 and 2014 was conducted. Cox proportional hazards regression was used to compare incidence of a PC diagnosis, metastatic PC, Gleason score 8‐10 PC, and PC mortality among 5ARI users (n=4,571), α‐blocker users (n=7,764), and non‐users (n=11,677).

Results

In comparison with both non‐users and α‐blocker users, 5ARI users had approximately 40% lower risk of a PC diagnosis (11.0% and 11.4% vs. 5.8%, respectively); α‐blocker users had 11% lower risk of a PC diagnosis compared with non‐users. Overall, there was no significant increase in metastatic PC or PC mortality among 5ARI or α‐blocker users (metastatic PC: 0.8% and 1.5% vs. 1.4% [non‐users]; PC mortality: 1.2% and 2.4% vs. 2.2% [non‐users], respectively, P>0.05 for both drugs) but there was approximately 30% higher risk of Gleason score 8‐10 cancer (1.4% and 1.8% vs. 2.0% [non‐users], aHR: 1.37, 95% CI: 1.03‐1.82, P=0.03 and aHR: 1.28, 95% CI: 1.03‐1.59, P=0.02, respectively) compared with non‐users.

Conclusion

5ARI use was associated with lower risk of a PC diagnosis, regardless of comparison group. Risk of high‐grade PC was higher among both 5ARI users and α‐blocker users compared with non‐users; however, this did not translate into higher risk of PC mortality.

[cesanon]

Patrick,

1. Is Finasteride of any relevance after you have been diagnosed with prostate cancer? How about after there has been metastasis?

2. If Finasteride is good, shouldn/t Avodart be even better?

[pjoshea13 in reply to cesanon]

For Dr. Myers, the purpose of ADT was ultimately the inhibition of DHT. His view was that one could not infer DHT levels from T levels. Some of his patients were DHT producers in spite of having castrate T. He prefered Avodart (Dutasteride) over Finasteride for obvious reasons.

Avodart has a long half-life & it takes many weeks to reach a plateau. When that happened, his DHT producers sometimes needed no more than one cap/week.

Myers mentioned that CRPC cells sometimes produced DHT from a pathway that did not include T. I don't see how a blood test would necessarily detect autocrine DHT. Seems prudent to use Avodart IMO.

-Patrick

[cesanon in reply to pjoshea13]

Is Finasteride of any relevance after you have been diagnosed with prostate cancer? How about after there has been metastasis?

[homer13 in reply to pjoshea13]

Dr Myers put me on Avodart daily. My DHT dropped quickly from 105 to around 3 for nearly two years. I asked my current doc to move me to twice weekly because of recent impact on libido. Within 6 weeks my DHT was over 8. He quickly put me back to daily. In two months, I am now in the 4's. In several months if it gets to the 3's I will ask to slowly reduce starting with 6 days a week. It will be interesting.

[podsart in reply to pjoshea13]

Yes, he started me on 1 per day then to 2 per day and then included grapefruit juice with 2 to try to stop my system from clearing the avodart too quickly - now even that may not be enough to stay on dr Myers target

[Darryl Partner]

I thought 5ARIs was about sari’s. :>).

[pjoshea13 in reply to Darryl]

Hi Darryl,

Lazy of me to resort to an acronym. I was rushed, but knew I should't do it. LOL

-Patrick

[FCoffey]

Interesting, it's too bad the article is behind a paywall.

I'm having trouble understanding this statement:

" there was approximately 30% higher risk of Gleason score 8‐10 cancer (1.4% and 1.8% vs. 2.0% [non‐users]"

The context provided by the earlier parts of the abstract suggest that this means men taking 5α reductase inhibitors had 1.4% chance of Gleason 8-10 cancer, men who were α‐blocker users had a 1.8% chance, and the non-user control had a 2% chance. How does that become a 30% increase in risk?

Even if true, it is curious that more aggressive cancers don't cause increases in metastatic PC or PC mortality. I'd like to read the author's discussion of these findings.

Also interesting is that the mortality due to prostate cancer was ~half in the users of 5α reductase inhibitors compared to the control group - 1.2% versus 2.2% in non-users, but this difference doesn't rise to statistical significance, possibly because of few deaths.

No mention of all-cause mortality. That would be an interesting comparison.