Ultrasensitive detection of prostate specific antigen in the followup of 422 patients after radical prostatectomy

Purpose: We validated our ultrasensitive prostate specific antigen (PSA) as say based on lyophilization and 4-fold concentration of patient sera with t he clinical long-term followup and according to histopathological character istics of 422 patients treated with radical retropubic prostatectomy for pr ostate cancer. Materials and Methods: Each serum sample was divided into 2 aliquots for st andard and 4-fold concentrated (ultrasensitive) detection. Samples were ana lyzed by the same unmodified DPC-Immulite* PSA assay. Biochemical relapse w as defined as an increase of at least 0.10 ng./ml. in native serum (equival ent to 0.025 ng./ml. in concentrated serum). Mean followup was 449 days (ra nge 29 to 2,057). Kaplan-Meier analysis of standard and ultrasensitive dete ction results was done, and findings were correlated with pathological stag e, Gleason grade, total cancer volume, Gleason grade 4 cancer volume and ma rgin status. Significance of earlier detection in ultrasensitive versus sta ndard detection was calculated with the log rank (Mantel-Cox) test with p < 0.05 considered significant. Results: Of 442 patients 88 (20.8%) experienced biochemical recurrence. Of this cohort 28 (31%) demonstrated early failure on the ultrasensitive assay which was later confirmed on the standard assay, 37 (42%) had failure simu ltaneously on both assays and 23 (26%) had failure on the ultrasensitive bu t remained disease-free on the standard assay. Average time for ultrasensit ive assay detection of recurrence was 288 days (standard 555). Kaplan-Meier analysis revealed significant advantages in earlier detection of recurrenc e with the ultrasensitive assay, and close correlation with pathological st age, Gleason grade, margin status and Gleason grade 4 cancer volume. Time a dvantages of ultrasensitive versus standard detection were greater for adva nced cancers (pT3a/b or greater, Gleason 3 + 4 or greater) than for small, low grade tumors. All patients who had positive results on the standard ass ay had a previous (28) or simultaneous (37) positive ultrasensitive result. With standard detection 25% of all relapses were evident within the first year of surgery and with ultrasensitive detection the percentage increased to 85.7%. On both assays 334 patients remained free of biochemical recurren ce. Conclusions: Our ultrasensitive PSA assay is useful for early detection of biochemical relapse after radical retropubic prostatectomy. It not only pro vides the same accuracy as conventional PSA assays but also offers the adva ntage of detecting recurrence about 300 days earlier. Thus, long-term resul ts of radical retropubic prostatectomy series can be calculated sooner. The clinical impact of this assay will be obvious once curative treatment opti ons are available ii. applied at the earliest time of evident tumor recurre nce.