Early mortality risk disclosures

@jeffmarc Thanks Jeff for the Medscape hyperlink. For those who have not yet read the article, here is a snapshot. I suggest you read the full article, see the context

Below is from the first of two hyperlinks provided by @jeffmarc -- it lists the home countries of the study participants. I noted that the subjects had metastatic PCa, therefore those of us with lower grade non-metastic can't read too much from this, except that we can infer that our prognosis possibly be better than shown in the report I first cited. Even if for general information only, I suggest reading both articles.

Thanks for posting this important study, even if the conclusion is quite sobering.

I noted, at the end of your 2nd link, that an important “ TRIPLE-SWITCH” RCT has been initiated to answer the last concern mentioned in your post.

The TRIPLE-SWITCH trial is a randomized phase III clinical trial designed to address a specific gap in the management of metastatic castration-sensitive prostate cancer (mCSPC).

The trial focuses on patients with mCSPC who have a suboptimal PSA response (PSA ≥ 0.2 ng/mL) after initial treatment with androgen deprivation therapy (ADT) plus an androgen receptor pathway inhibitor (ARPI), such as abiraterone, enzalutamide, or apalutamide.

The TRIPLE-SWITCH trial aims to answer this Key Question:

Does adding docetaxel (chemotherapy) to the existing doublet therapy (ADT + ARPI) improves outcomes for mCSPC patients with suboptimal PSA response, compared to continuing the doublet therapy alone?

Specifically, it investigates whether this triplet therapy (ADT + ARPI + docetaxel) delays progression to castration-resistant prostate cancer (CRPC) and improves survival in this subgroup, which is at higher risk of early disease progression.

Hopefully, an improved therapy will be proven for those in the worst affected (>0.20 PSA) mCSPC group.
https://clinicaltrials.gov/study/NCT06592924

Just a quick note that you left Darolutamide off your list of ARPI’s.

https://www.newyorker.com/magazine/2025/06/23/the-catch-in-catching-cancer-early.
Jeff, please read this fascinating article and how it relates to early detection of cancer, screenings - and most importantly - outcomes.
Quite revealing of how cold, hard numbers aren’t always what they seem! The Medscape article is quite sobering - almost depressing - but the New Yorker article really challenges the validity, necessity and overall importance of any of these studies. The endpoint data is simply too general…
According to the author, Increasing specificity and sophistication of DNA cancer markers (similar to Decipher) is the real diagnostic tool of the future. Best,
Phil

I really like the promise of this small section from the article

“We’ve typically looked for single-gene mutations—BRCA1, BRCA2, MLH1—that signal elevated risk. But most inherited risk isn’t carried by one rogue gene. It emerges from the accumulation of many—a polyphony of small variations, each nudging risk ever so slightly higher. Today, advances in genome sequencing and computational modelling have begun to untangle this architecture. Sophisticated algorithms can scan entire genomes, mapping how thousands of tiny genetic variations interact. One such model, attuned to thousands of genetic loci, can already predict adult height. Nutrition still matters, but the precision of these forecasts represents a remarkable advance.”

My father died of prostate cancer, and my brother has it, but neither has BRCA2. I know a number of people who are brothers and all brothers got PC. This DNA testing may finally give people a clue as to the likelihood of it happening. Maybe they can use crisper technology To modify some of the genes so that it won’t happen. Well, that’s the future, Probably not our future.

It’s interesting that the article specifically avoided prostate cancer. We do have tools that have changed things so that, for example, Gleason six people can usually avoid doing anything. We don’t know if somebody’s cancer is likely to be metastatic, but we now have the decipher and other similar tests to give a chance of knowing the odds. We have the PSE test that can decipher those fragments in the blood and decide, with high percentage accuracy, whether or not there is at least cancer there.

It seems that it is unlikely that a Gleason 4+3 And above will be able to get through a long life without problems. It’s possible, but knowing about an aggressive prostate cancer and treating it does give you the opportunity to do something that will in all likelihood extend your life.