Johns Hopkins: ultrasensitive PSA after surgery predicts biochemical relapse

We’ve looked at several retrospective studies this year that found that early ultrasensitive PSA (uPSA) results following surgery can reliably predict eventual biochemical relapse. Johns Hopkins examined its own database and found the same thing.

The study by Sokoll et al.  looked at the records of 754 men treated with surgery at Johns Hopkins between 1993 and 2008 whose first post-surgery PSA, taken at about 3 months, was “undetectable” (<0.1 ng/ml). They reanalyzed the stored serum samples using an ultrasensitive PSA assay that could detect values of 0.01 ng/ml or higher. Each man was tracked until biochemical recurrence (BCR) – defined as PSA≥0.2 ng/ml – or for at least 5 years if there was no biochemical recurrence (median of 11 years).

• ·      Among men whose first uPSA was ≥ 0.01 ng/ml, about half eventually had BCR.

o   57% were BCR-free at 5 years, 49% at 11 years.

o   Mean BCR-free survival: 10 years

• ·      Among men whose first uPSA was < 0.01 ng/ml, 87% remained BCR-free.

o   92% were BCR-free at 5 years, 86% at 11 years.

o   Mean BCR-free survival: 15 years

• ·      Among men whose first uPSA was ≥ 0.03 ng/ml, 77% eventually had BCR.

o   27% were BCR-free at 5 years, 22% at 11 years.

o   Mean BCR-free survival: 5.5 years

• ·      Among men whose first uPSA was < 0.03 ng/ml, 85% remained BCR-free.

o   91% were BCR-free at 5 years, 84% at 11 years.

o   Mean BCR-free survival: 15 years

Other predictors of recurrence were the usual suspects: initial PSA, pathological stage and Gleason scores, and the presence of positive margins.

They additionally tracked a cohort of 44 men who’d had a cystoprostatectomy for bladder cancer in order to determine whether extra-prostatic sources of PSA might interfere with the uPSA test’s sensitivity to detect recurrent prostate cancer. All but two had uPSA<0.01 ng/ml, and those two had low values, 0.01 and 0.02 ng/ml.

So we see that a uPSA cutoff of 0.01 ng/ml on a first test is no better than a coin toss at predicting eventual BCR, and would lead to a great deal of overtreatment. On the other hand, a uPSA cutoff of 0.03 ng/ml correctly predicted eventual BCR 77% of the time. It missed about 15% of the men who would eventually recur, but was no worse than the lower cutoff in this regard. Clearly, a uPSA cutoff of 0.03 ng/ml is prognostic of BCR and a lower cutoff is not. The authors seem to miss this point in their conclusion.

Their analysis seems congruent with the other studies we’ve seen lately. Koulikov et al. also found that the 0.03 ng/ml cutoff was prognostic, but only when uPSA was increasing steadily. Kang et al. also found that a cutoff of 0.03 ng/ml at any time after surgery optimized BCR predictions with a median 18-month lead-time advantage among men diagnosed with adverse pathology (pT3 and/or positive margins). In a separate analysis among men with more favorable pathology (pT2, irrespective of margin status), Kang et al. found that a cutoff of 0.03 ng/ml on a first uPSA was predictive of later (median of 33 months) BCR.

While we await more definitive results from randomized clinical trials, there seems to be an emerging consensus that 0.03 ng/ml is the optimal uPSA cutoff. Using a lower cutoff for early salvage or adjuvant RT will lead to overtreatment, and there seems to be no risk attached to waiting for it. Provisionally, I believe it should be viewed as a surrogate for the traditional BCR definition.