Definition of Biochemical Failure

[PhilipSZacarias]

According to the Phoenix Criteria for biochemical failure (BCR), a PSA 2 ng/ml above nadir is defined as failure and the threshold where next line therapy should be initiated. (1)

I find the rationale for this criteria lacking because nadir after ADT and chemotherapy is correlated with time to recurrence and cancer specific survival (2). A nadir less or equal to 0.2 ng/ml typically indicates a good response to therapy and the likelihood of longer progression free and cancer specific survival. Adding 2 ng/ml to a nadir > 1.0 ng/ml, for example, as a criterion for progression is quantitatively different with respect to progression free survival and overall survival, compared to achieving a nadir of 0.2 ng/ml or less. Some will argue that the PSA test is not accurate and therefore 2 ng/ml threshold is necessary because of the scatter. In contrast, I have found that PSA results from two different laboratories in Canada have agreed fairly will and that the amount of scatter is low. In my opinion, a linear or polynomial correlation coefficient of 0.9 or better for 4 to 6 consecutive PSA results (1 – 2 months apart) indicates a reliable trend.

Furthermore, a consistent upward trend in monthly PSA results from any nadir, including a nadir <= 0.2 ng/ml, is an indication of failure and the doubling time an indication of the aggressiveness. Consistent increases and rates of increase from any nadir are indications of failure and aggressiveness and the need for immediate next line therapy. The exception to this rule of course would be the development of or increase in neuroendocrine-like character of the cancer at later stages, which does not express PSA at the same levels and is associated with metastatic progression according to bone and CT scans without significant increases in PSA. Additional measures such as ALP, LDH, neutrophil/lymphocyte ratio (inflammation marker), circulating tumor cells (CTCs), bone and CT scans to assess metastatic progression are necessary to determine the status of a patient.

(1) ncbi.nlm.nih.gov/pmc/articl...

(2) ncbi.nlm.nih.gov/pubmed/274...

Comments, opinions would be appreciated...

Cheers,

Phil

[Tall_Allen]

Not exactly...

" a PSA 2 ng/ml above nadir is defined as failure and the threshold where next line therapy should be initiated" Nadir+2 is defined as biochemical failure - the point at which clinical failure is suspected.

"because nadir after ADT and chemotherapy is correlated with time to recurrence and cancer specific survival (2)." The Phoenix criterion is for BCR after primary radiotherapy, not ADT and chemo.

Nadirs below 0.5 have been shown to be prognostic for progression-free survival. A nadir is the lowest PSA reached so far. However, it may take years to reach the nadir (it took me 4 years). The Phoenix definition gets around the problem by raising suspicions when PSA rises 2 ng/ml or more above the lowest point reached so far. Even so, I think many ROs will want to monitor it for at least 6 months before beginning clinical testing. PSAs can be very bouncy after primary radiation.

"Furthermore, a consistent upward trend in monthly PSA results from any nadir, including a nadir <= 0.2 ng/ml, is an indication of failure and the doubling time an indication of the aggressiveness." Nope. That's exactly why they switched from the previous ASTRO definition (3 consecutive rises) to the Phoenix definition (nadir+2). The consecutive rises criterion was giving too many BCRs that didn't turn out to be clinically recurrent.

[PhilipSZacarias in reply to Tall_Allen]

Very good. Thank you for rectifying my errors in interpretation and misunderstanding of the criteria. Cheers, Phil

[kenner in reply to Tall_Allen]

My last PSA was 0.27 after 19 years..I had a radical in 2000. Going for my PSA in 2 more weeks. hope I am still staying low. I know i am a miracle in progress with a former pre op PSA of 39.5and a Gleason score of 4 -3.

[j-o-h-n in reply to kenner]

You're a wenner kenner.....

Good Luck, Good Health and Good Humor.

j-o-h-n Saturday 02/08/2020 11:00 AM EST

[Tall_Allen in reply to kenner]

time for salvage?

[kenner in reply to Tall_Allen]

I have a double artificial sphincter that is in the prostate bed...my PSA actually went down twice in a row the highest reading was 0.29 18 months ago.Things are definitely perplexing ...don't want to tamper as I still have some"spark" too...hate to give that up. My new urologist doesn't seem concerned.My PSA velocity is so slow...actually ata stand still.Going for my PSA in a week. Have my fingers crossed.

[tallguy2 in reply to Tall_Allen]

I will simply add that, if insurance permits, scans prior to hitting the PSA=2.0 threshold might reveal mets with actionable results. I got lucky and got an MRI approved with a PSA less than 2.0 (for a back issue). The result was to get a head start on treatments.

[Hidden]

PSA alone is not determinant.

[PhilipSZacarias in reply to Hidden]

Yes I know.

[Hidden in reply to PhilipSZacarias]

I think it matters what the situation is with your cancer.

If you just had an RP, your PSA should be very close to 0. so an increase of .1 in this case is significant. Someone who has stage 4 on ADT would be considering changes above 2 as significant when evaluating castrate resistance. Those who are castrate resistant and on chemotherapy would be less focused on PSA and looking more at imaging than anything else. So I don't think there is really an exact formula for every situation.