Detection of prostate cancer relapse with prostate specific antigen monitoring at levels of 0.001 to 0.1 microG./L.

PURPOSE: The development of prostate specific antigen (PSA) assays with detection limits of approximately 0.001 microgram./l. is technically feasible. We examined if serum PSA changes of 0.001 to 0.1 microgram./l. for up to 3 years after radical prostatectomy have any clinical value.

MATERIALS AND METHODS: We studied 148 patients with a postoperative PSA of less than 0.1 microgram./l. by a conventional PSA assay. At least 3 serial serum samples were collected per patient along with detailed clinicopathological features. Serial serum samples were analyzed for PSA with the ultrasensitive method. Associations between increase in serum PSA and clinicopathological features were analyzed with the unconditional logistic regression model.

RESULTS: After establishing a set of interpretative criteria, we divided the patients into 51 with biochemical relapse, 93 who were free of relapse and 4 with equivocal status. Between the groups with and without relapse there was no difference in year of surgery, age at operation or length of followup. Compared to patients without relapse, those with biochemical relapse were likely to have positive surgical margins (p < 0.01), larger tumor volumes (p < 0.01), greater preoperative PSA (p = 0.03) and disease extending outside the prostate (p = 0.02). The relative risks for biochemical relapse estimated by a univariate logistic regression model were 3.1 (95% confidence interval 1.39 to 6.82, p < 0.01) for positive surgical margin, 3.4 (95% confidence interval 1.46 to 8.13, p < 0.01) for tumor volume, 2.3 (95% confidence interval 1.08 to 5.02, p = 0.03) for high preoperative PSA and 2.7 (95% confidence interval 1.12 to 6.26, p = 0.03) for extraprostatic tumor extension. At multivariate analysis with the same model the associations between positive surgical margins and biochemical relapse (relative risk 2.95, p = 0.04) and tumor volume (relative risk 3.36, p = 0.03) remained significant. These associations were still observed when we analyzed a subset of patients classified as having biochemical relapse based on PSA changes of 0.001 to 0.08 microgram./l.

CONCLUSIONS: Increases in postoperative serum PSA at levels of 0.001 to 0.1 microgram./l. after radical prostatectomy are associated with clinicopathological features of poor prognosis. Monitoring postoperative cases with a highly sensitive PSA assay (detection limit 0.001 microgram./l.) could offer a simple and effective means of detecting clinically important biochemical relapse early after radical prostatectomy. These patients may be suitable for early intervention when effective treatments for relapse become available.