I haven’t been visiting the site much lately and haven’t posted for ages. I’ve had something else taking all my attention.
In 2018 I had a PSA test. I was 61. It was very low; so low that my GP said “you don’t need another test for 5 years.” Well, 5 years later I was having a cardiac ablation to fix atrial fibrillation. I forgot about the PSA test. This year I asked about one (the GP never suggested it). I had no symptoms at all. It came back high. The repeat came back high. The MRI showed “probable tumors.” Then came the biopsy. Grade 3 cancer and it has escaped from the prostate. Then a PET scan…it is now in my lymph nodes.
So now I’m on the standard 18 months of androgen deprivation and 39 (!) sessions of radiotherapy. I’ve tired myself out reading papers on adjuvant therapies to try to add.
I’m not writing this for sympathy. I’m writing this to remind every guy here: make sure you get a PSA test done EVERY YEAR. No exceptions. I just wish someone had reminded me.
Oddly enough, if you read papers about prostate cancers, one of the main drivers is the PI3K/Akt/mTOR pathway. And we know that rapamycin inhibits that. But in my case, it didn’t seem to matter.
Highly suggest people listen to this podcast about the way to properly screen for prostate cancer. It’s very much available, provided that screenings happen regularly.
In this episode, Peter takes a deep dive into prostate cancer screening, explaining why advanced and metastatic diagnoses continue to rise despite the availability of screening tools, and what can be done to reverse this trend.He breaks down what PSA actually measures and why it is far more informative when tracked over time rather than interpreted as a single value
So interestingly, I ran the question by a group of Urologists some time ago (2-3 years). I have been below 1 for 3 or 4 years and they said, yep - there is a decent amount of population data that says I am quite unlikely to every have an issue. The trend over time is fairly significant and low values at 50 or so are a good long term predictor. I’m 56.
The arguments against screening are avoiding cost, stress and procedures that may not be helpful.
My 60yo BIL has had MRIs, biopsy and all benign. Doesn’t mean he is free and clear for life but he went through a lot and none of it changed his prognosis.
Hi DrT, I’m sorry to hear about your diagnosis and offer strong moral support - I wish you the very best.
As you say, rapamycin should have been helpful, it’s unfortunate that it doesn’t seem to have worked. It’s a good reminder that whenever there is a bell curve, someone has to be at the extreme end, and sometimes it’s you. That’s why population studies have their limits as to personal applicability. Not to pile on that point, but there’s this study which for a long time shaped my expectations:
Influence of blood prostate specific antigen levels at age 60 on benefits and harms of prostate cancer screening: population based cohort study
The bottom line, the study concluded that a single PSA reading at age 60 was a strong indicator of PC mortality risk. For those who had a reading of lower or equal to 1.00, odds were overwhelming that they would not experience metastatic PC or die of PC in the next 15 years, and the recommendation was for no further screening based on harm/benefit.
As you said, you had a reading below 1.00 at 61 - this would’ve put you in the low risk “no further screening recommended” group.
However, before anyone assumes they’re safe at or below a PSA reading of 1.00 at 60 y/o, there is an important qualification - which is why I changed my thinking (I was at 1.00 at 60).
This qualification is the following: if you are on medications which lower your PSA reading, this does not apply. Statins lower the PSA reading - so if my reading while on statins is at 1.00, it means my number is above 1.00 without the statin and so out of the “safety” range. Actually, my situation was even worse - I was on a whole gaggle of supplements which had the potential of artificially suppressing my PSA reading. Meanwhile, according to my genetic risk assessment, my risk of PC is 40% above average. This lead me to conclude that I cannot take any comfort in the Swedish study and I continued to request a PSA test yearly. Interestingly, last year my PSA (at age 67) was elevated above the “magical” 1.00 (it was 1.34) which has me somewhat worried. As a side note, there are of course factors which might elevate the PSA reading (recent ejaculation, long bike ride etc.) - and absurd as it may seem, digital prostate examination (where the doctor sticks his finger up your behind), if you then go off to have a blood test (including PSA) shortly after the doc visit. I have always tried to be careful not to get a distorted reading, and it’s something I try to be cognizant of.
The point of all this is to say that you are an individual and personalized medicine is the goal. All the population studies in the world only indicate statistical odds at population levels - you might be that minority, and at the extreme - minority of one.
I have seen this over and over again in my case and in the case of my wife. I read all those diet and lifestyle studies regarding LDL levels and despite truly epic levels of diet adjustments (as an example: over 100g of fiber daily etc.) and extreme measures my LDL remained stupidly high. So much for that. I then got on triple LLT drugs and my LDL barely budged - while studies indicated my LDL should’ve been hammered into the ground based on population studies. Exactly the same situation with my A1c - massive exercise and dietary measures - and stubbornly stuck at prediabetic levels. And so on for a lot of other “gee, I had zero risk factors” or “but, but, but all the studies said”. At this point I read the studies and dutifully follow recommendations, but have no expectations that they’ll necessarily apply to me.
I therefore strongly agree with you regarding getting tested for PSA - never mind what population derived recommendations may say. It’s your very individual body and it’s your life. Get tested. I would broaden this to many other screenings (colonoscopy even if older than 75 - where it’s no longer recommended!), get the CAC (even if many cardiologists don’t think it useful) and so on. Yes, false positives and over treatment and incidentalomas happen - but that’s where discernment is required - sticking your head in the sand is a childish reaction to complexity - sorry, life isn’t simple and you will need to step up, not hide and pretend.
Meanwhile, please take care of yourself and my thoughts are with you. Remember, you can always count on moral support from the community here. All the best, and good luck!
Medicine 3.0: Rethinking Prostate Cancer Screening
I. Executive Summary
In this clinical commentary, Dr. Peter Attia evaluates the systemic limitations of conventional preventive medicine—termed “Medicine 2.0”—using the clinical case of former President Joe Biden’s diagnosis of metastatic, castrate-resistant or advanced prostate cancer with skeletal metastases as an illustrative failure mode. Attia argues that the contemporary standard of care relies excessively on population-level actuarial tables and rigid age cutoffs that prioritize gross lifespan over healthspan, directly causing underdiagnosis of treatable malignancies. Current guidelines from bodies such as the U.S. Preventive Services Task Force (USPSTF) assign a Grade D recommendation against routine prostate-specific antigen (PSA) screening in men aged 70 and older, falsely presuming that subsequent mortality will stem from competing non-oncologic comorbidities within an arbitrary 10- to 15-year window.
Attia challenges this reductionist paradigm, emphasizing that prostate cancer remains the second leading cause of cancer mortality among American men, yet represents one of the most clinically preventable and indolent solid tumors when intercepted early. The failure of Medicine 2.0 lies in oversimplifying screening to an isolated, binary total serum PSA value, which carries well-documented false-positive and false-negative limitations. In contrast, “Medicine 3.0” implements a proactive, risk-stratified diagnostic algorithm that leverages longitudinal biomarker dynamics and advanced non-invasive diagnostics.
This protocol initiates with annual low-cost total serum PSA testing, augmented by kinetic and volumetric calculations: PSA velocity (annual rate of change), PSA density (total PSA divided by prostate volume determined via ultrasound or MRI), and the percentage of free PSA. When these baseline indices suggest occult pathology, clinicians deploy secondary blood-based reflex biomarkers—specifically the Prostate Health Index (PHI) and the 4Kscore test—before progressing to multiparametric magnetic resonance imaging (mpMRI). By restricting invasive transrectal or transperineal core needle biopsies strictly to actionable, high-probability lesions, this tiered strategy mitigates overtreatment of indolent disease while preventing lethal, debilitating metastatic progression. Attia concludes that until institutional guidelines integrate individual healthspan valuation, patients and practitioners must aggressively pursue personalized screening to avert preventable metastatic disease.
II. Insight Bullets
Metastatic prostate cancer with osteoblastic bone dissemination is an excruciating, debilitating pathology that represents an unforced diagnostic failure when routine screening is abandoned.
The announcement regarding Joe Biden’s advanced prostate cancer diagnosis indicates his routine PSA monitoring ceased around age 72, adhering strictly to standard institutional guidelines.
Institutional guidelines from bodies such as the USPSTF recommend against screening men aged 70 and older based on median population-level actuarial models rather than individual biological healthspan.
Medicine 2.0 relies on static life-expectancy tables predicting less than 10 to 15 years of remaining life to justify stopping screening, leaving robust older individuals unprotected against aggressive tumor phenotypes.
Prostate cancer represents the second leading cause of cancer-related mortality in American men, despite possessing a prolonged latent period that permits early curative intervention.
Screening must distinguish between indolent, clinically insignificant neoplasms that will remain confined to the gland and aggressive variants prone to osteotropic metastasis.
A single, isolated total serum PSA measurement is an imprecise standalone screening tool prone to both false-positive elevations (benign prostatic hyperplasia, prostatitis) and false-negative reassurances.
Longitudinal monitoring of PSA velocity (PSAV)—the rate of serum PSA elevation over 12 to 24 months—detects emerging aggressive carcinomas even when the absolute PSA concentration remains within conventional reference ranges.
Prostate-specific antigen density (PSAD), calculated by dividing total serum PSA by prostate volume in cubic centimeters, accurately differentiates benign glandular enlargement from malignant cellular proliferation.
A PSA density exceeding 0.15 ng/mL/cc strongly correlates with clinically significant prostate cancer and warrants diagnostic escalation (Pellegrino et al., 2023).
Free PSA percentage (%fPSA) measures unbound circulating PSA, where lower ratios (particularly under 10% to 15%) indicate a substantially higher probability of aggressive prostate malignancy.
Total serum PSA testing remains an accessible, high-yield diagnostic tool, costing approximately five dollars per test.
Large-scale systematic reviews confirm that the Prostate Health Index accurately discriminates between aggressive (Gleason score 7 or higher) and non-aggressive disease, dramatically reducing negative biopsy rates (Agnello et al., 2022).
The 4Kscore assay evaluates four specific kallikrein markers in blood to determine the individual probability of high-grade cancer, sparing up to 65% of unnecessary biopsies (Voigt et al., 2017).
Multiparametric MRI (mpMRI) has emerged as an indispensable non-invasive imaging modality that must precede invasive needle biopsy to localize suspicious PI-RADS lesions.
The landmark PRECISION trial demonstrated that mpMRI followed by targeted biopsy detects more clinically significant cancers while reducing the overdiagnosis of indolent disease compared to blind systematic transrectal biopsy (Kasivisvanathan et al., 2018).
Blind 12-core systematic transrectal ultrasound (TRUS) biopsies without prior mpMRI guidance carry risks of urosepsis, hemorrhage, and systematic sampling errors.
Medicine 2.0 frequently conflates biological age with chronological age, dismissing the clinical priority of preserving quality of life and functional independence.
Osteotropic metastases from advanced prostate cancer trigger severe skeletal-related events, including pathologic fractures, spinal cord compression, and intractable bone pain.
Prostate cancer and colorectal cancer represent two major solid malignancies where validated, early screening algorithms save lives when implemented systematically.
Proactive prevention—the core philosophy practiced at Dr. Attia’s clinic, Early Medical—shifts clinical focus from late-stage palliative crisis management to early molecular and volumetric interception.
Shared decision-making in men over age 70 must be guided by physiologic performance, metabolic fitness, and individual longevity goals rather than arbitrary administrative age cutoffs.
Self-advocacy is necessary within the modern healthcare apparatus to obtain secondary biomarker panels and imaging before accepting recommendations against screening or premature invasive procedures.
Monitoring: Serial serum blood draws every 6 to 12 months in patients deferred from immediate biopsy on active surveillance.
4Kscore Test:
Compound / Assay: Immunoassay measuring total PSA, free PSA, intact PSA, and human kallikrein 2 (hK2), paired with an algorithm incorporating clinical variables (age, digital rectal examination, prior biopsy status).
Target / Cutoff: Individual calculated probability score under 7.5% identifies low risk of high-grade cancer, safely deferring biopsy (Voigt et al., 2017).
Mechanism: Reflects active dysregulation of prostatic tissue kallikrein expression associated with aggressive architectural invasion.
Monitoring: Single baseline assessment when total PSA or PSAD triggers diagnostic uncertainty.
Prostate-Specific Membrane Antigen (PSMA) PET/CT for High-Risk Staging:
Target / Cutoff: Standardized uptake value (SUV) quantification in lymph nodes or axial/appendicular skeleton.
Mechanism: Targets transmembrane carboxypeptidase overexpressed in 90% of aggressive prostatic adenocarcinomas.
Monitoring: Indicated selectively upon confirmation of high-grade localized disease (Gleason 8 or higher) or rising post-treatment PSA to detect micro-metastatic spread.
