Monday, January 23, 2023

Why My Own Recent PSA Result Led Me To Question That "Decline In Testing Begets More Undiagnosed Metastatic Cancer"

PSA tests came to prominence again in a January 13th WSJ piece citing an American Cancer Society report that decline in PSA testing likely led to "more undiagnosed metastatic disease"  and noting (Cancer Death Rates Dropped By A Third):

"The cancer mortality rate in the U.S. has dropped by a third in the past three decades, a report showed, but an increase in advanced prostate cancer diagnoses threatens to reverse some hard-won gains."


"For prostate cancer, rates of advanced diagnoses have risen about 4.5% annually since 2011, the report found. The proportion of men diagnosed with later-stage disease has doubled."

But these conclusions badly need clarification and my own case can serve as an insight point. The bulk of the blame in the ACS report, by implication, can be attributed to a notification in 2012 by The U.S. Preventive Services Task Force which concluded:

 "There is at best a small potential benefit from prostate cancer screening and there are substantial known harms. We need a better test and we need better options. We can do better."

  The reasons were not hard to grasp, mainly that one can get false positives which put the tested person on a track for even more invasive tests including unnecessary biopsies.  These can carry their own risks, including sepsis, impotence. 

The two most critical facts I learned since my latest PSA test result (of 12.4)   2 weeks ago were;

- Two different sets of prostate cancer cells exist: a) those which are PSA-sensitive, and (b) those which are not. A drug or therapy which targets only the first will have little to no effect on the other.

- So a 'one size fits all' approach seldom works because it seeks only to target the hormone (testosterone) -sensitive cells not the others. Especially given the most malignant, "nastiest" cancer cells are generally those which are not PSA sensitive. Hence, a falling PSA after commencing ADT  (androgen deprivation) for example, can have one living in a "fool's paradise".

These insights led me to forego any use of Orgovyz (a more benign form of ADT) for now, given I have not yet shown any symptoms and starting ADT too early is not likely to offer any significant benefits but a number of downsides. ("Gonadotropin-releasing hormone analogues, either alone or with oral antiandrogen, or orchiectomy were significantly associated with stroke in patients with PC. Other studies also showed a similar association between stroke and ADT.")

That was reinforced when I also learned that (from a Swedish PCa oncology journal) 65% of all deaths for men with metastatic prostate cancer arrive from strokes, pulmonary embolisms and myocardial infarction (heart attacks) mainly from the "comorbidities" arising from ADT therapy. 

My decision is also supported after my urologist gave me an article  ('Delaying ADT Until Symptoms Appear Does Not Impact Survival') which noted: 

"A rising prostate specific antigen (PSA) on its own is not enough reason to initiate androgen deprivation therapy (ADT) a large observational study (with 14,000 patients) has found.   Rather, survival appears to be the same in these patients whether ADT is given immediately or delayed until symptoms appear or a scan shows cancer." 

But Hopkins Oncologist Patrick Walsh (Dr. Patrick Walsh’s Guide To Surviving Prostate Cancer’. p. 338):

 isn't even buying the adverse scan aspect as an ADT determinant, i.e.

"But what if you have no cancer in your bones  and no sign that anything is wrong except a rising PSA level after surgery or radiation - or the presence of cancer in your lymph nodes- and you feel fine?   Many doctors would advise you to start hormonal therapy as soon as possible.  

Others - and I'm in this group - believe that in most cases there is no evidence that starting hormonal therapy immediately, as opposed to later, will prolong life."

What does lead Dr. Walsh to advocate for immediate ADT?

"If you have metastases to bone, bone pain, or a large mass of cancer that is obstructing your kidneys or bladder, you need to start ADT right now. "

In my case, not only are there no symptoms thus far, but a subsidiary test (Alkaline Phosphate) which is generally considered a marker for bone metastases, showed nothing outside the normal range.  Thus, the urologist was ok leaving another PSMA scan for now, until and unless the situation with the subsidiary test result changes.  But I still need to get that tested - along with the PSA- every 3 months, as well as the testosterone which is a hair above "castrate level" at 160 ng/ml  giving more reasons to not start a therapy which will lower testosterone even more.   

The primary potential side effect which caused me to think twice about going to the Orgovyx now, was QT prolongation, or a dramatic slowing of heart rhythm.  This can lead to seizures, fainting or sudden death. For now then, I will bide my time and wait before taking on any more treatments or therapies, fully understanding that 80% of metastatic PCa patients seldom live more than 5 years past the initial diagnosis. (Mine was in August, 2021, e.g. Axumin Scan Shows Unusual Result )

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