You are missing a lot; I think that's because you don't understand the context. You have to start with the 3 RCTs I keep referring to that proved that immediate treatment had better outcomes than waiting. That is the context for all the subsequent studies. They are the source for the current AUA/ASTRO guidelines:/www.auanet.org/common/pdf/education/clinical-guidance/Radiation-After-Prostatectomy.pdf
See page 5
Because immediate treatment of everyone
with risk factors would undoubtedly result in overtreatment, we have looked for a way of finding a point where we can wait for more assurance without waiting too long, and risking metastases. That is called "early salvage."
You can read about
this concept here:When should the patient and doctor consider salvage radiation therapy?
That study dealt with men who had "aggressive" or adverse pathology. Any PSA that reached 0.03 was found to eventually go higher. There is no point in waiting for a higher PSA because they will always
go higher, and as the 3 RCTs proved, waiting could be dangerous.
(1) In the Koulikov study of post-op men regardless of pathology results, they found that one can comfortably wait until PSA rose to 0.03. If those men, who may have had favorable pathology, reached 0.03 and their PSA was unstable, they were at risk for progression. Men whose PSA never reached 0.03 or, if it did, and their PSA was stable, were not at risk for progression.Low detectable PSA after prostatectomy – watch or treat?
(2) Dr Stish at Mayo wrote in his paper:"This observation suggests that SRT at the lowest PSA level is most beneficial for long-term therapeutic efficacy." He amplified that in his letter to me:"We chose a PSA cutoff of 0.5 ng/ml to allow comparison with other previously reported studies that have cited this arbitrary point of dichotomy. As you read the paper, you will note that our data suggest salvage radiotherapy is most efficacious when the PSA is lowest, and in general we advocate for SRT to be considered at the earliest detectable values
following prostatectomy."How early salvage radiation therapy can be used to prevent metastases and save lives
(3) I don't understand what you are saying about
the Kang paper. They found that in pT2 men with rising PSA:
• a first post-op PSA≥0.03 was 4 times as likely to predict time to BCR than one below that cutoff. After looking at the other risk factors (Gleason score and pre-op PSA) they found that only
PSA≥0.03 and margin status predicted time to BCR.
• 44% of the BCRs were predicted by a first PSA≥0.03, whereas only 16% were preceded by an undetectable PSA on a conventional PSA test.
• a first post-op PSA< 0.03 was associated with a median time to BCR of 61 months, whereas a PSA≥0.03 was associated with a median time to BCR of just 10 months.
post-op PSA≥0.03 predicted BCR (100% sensitivity) even if the first post-op PSA was <0.03.
• Using a cut-off of 0.03 gave a lead time advantage of 33 months compared to waiting for PSA to rise to ≥0.2
(4) You misinterpreted the Toussi paper. Their analysis sets an upper
limit on how high the PSA should ever be allowed to get before considering salvage therapy. 3/4 patients who reached 0.4 ng/ml had detectable systemic progression within 5 years, indicating that 0.4 is a clear signal that the cancer had already progressed too far
. But it seems to me that the whole point of setting a biochemical recurrence cutpoint is to find the lowest
PSA that reliably signals clinical local recurrence. We want to start salvage treatment at the earliest time to avoid systemic progression, while not treating so early that many men would be over-treated. (see comments on the 3 RCTs above)
(5) You didn't mention it, but you should also look at Johns Hopkins' analysis of the same subject, also indicating that 0.03 is the lowest appropriate cut-off:Johns Hopkins: ultrasensitive PSA after surgery predicts biochemical relapse
It helps to have read the full texts and not just the abstracts.