Haese A, Huland E, Graefen M, Hammerer P, Noldus J, Huland H
Department of Urology, University Clinic Eppendorf, Hamburg, Germany.
J Urol. 1999 Apr;161(4):1206-11.
We validated our ultrasensitive prostate specific antigen (PSA) assay based on lyophilization and 4-fold concentration of patient sera with the clinical long-term followup and according to histopathological characteristics of 422 patients treated with radical retropubic prostatectomy for prostate cancer.
Each serum sample was divided into 2 aliquots for standard and 4-fold concentrated (ultrasensitive) detection. Samples were analyzed by the same unmodified DPC-Immulite PSA assay. Biochemical relapse was defined as an increase of at least 0.10 ng./ml. in native serum (equivalent to 0.025 ng./ml. in concentrated serum). Mean followup was 449 days (range 29 to 2,057). Kaplan-Meier analysis of standard and ultrasensitive detection results was done, and findings were correlated with pathological stage, Gleason grade, total cancer volume, Gleason grade 4 cancer volume and margin status. Significance of earlier detection in ultrasensitive versus standard detection was calculated with the log rank (Mantel-Cox) test with p <0.05 considered significant.
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 simultaneously on both assays and 23 (26%) had failure on the ultrasensitive but remained disease-free on the standard assay. Average time for ultrasensitive assay detection of recurrence was 288 days (standard 555). Kaplan-Meier analysis revealed significant advantages in earlier detection of recurrence with the ultrasensitive assay, and close correlation with pathological stage, Gleason grade, margin status and Gleason grade 4 cancer volume. Time advantages of ultrasensitive versus standard detection were greater for advanced 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 assay 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 recurrence.
Our ultrasensitive PSA assay is useful for early detection of biochemical relapse after radical retropubic prostatectomy. It not only provides the same accuracy as conventional PSA assays but also offers the advantage of detecting recurrence about 300 days earlier. Thus, long-term results of radical retropubic prostatectomy series can be calculated sooner. The clinical impact of this assay will be obvious once curative treatment options are available if applied at the earliest time of evident tumor recurrence.
我们基于冻干和患者血清4倍浓缩技术验证了超敏前列腺特异性抗原（PSA）检测方法，并通过对422例行耻骨后根治性前列腺切除术治疗前列腺癌患者的临床长期随访以及组织病理学特征进行分析。
每份血清样本分为2份用于标准检测和4倍浓缩（超敏）检测。样本通过相同未改良的DPC免疫发光PSA检测法进行分析。生化复发定义为天然血清中PSA至少增加0.10 ng/ml（相当于浓缩血清中0.025 ng/ml）。平均随访时间为449天（范围29至2057天）。对标准检测和超敏检测结果进行Kaplan-Meier分析，并将结果与病理分期、Gleason分级、肿瘤总体积、Gleason 4级肿瘤体积和切缘状态相关联。通过对数秩（Mantel-Cox）检验计算超敏检测与标准检测相比早期检测的显著性，p<0.05被认为具有显著性。
442例患者中，88例（20.8%）发生生化复发。在该队列中，28例（31%）在超敏检测中显示早期失败，随后在标准检测中得到证实；37例（42%）在两种检测中同时失败；23例（26%）在超敏检测中失败，但在标准检测中仍无疾病复发。超敏检测复发的平均时间为288天（标准检测为555天）。Kaplan-Meier分析显示，超敏检测在复发早期检测方面具有显著优势，且与病理分期、Gleason分级、切缘状态和Gleason 4级肿瘤体积密切相关。晚期癌症（pT3a/b或更高，Gleason 3+4或更高）超敏检测与标准检测相比的时间优势大于小的低级别肿瘤。所有在标准检测中呈阳性结果的患者之前（28例）或同时（37例）超敏检测结果也为阳性。标准检测中，25%的复发在手术后第一年内明显，而超敏检测中这一比例增至85.7%。两种检测中，334例患者未发生生化复发。
我们的超敏PSA检测方法有助于耻骨后根治性前列腺切除术后生化复发的早期检测。它不仅提供与传统PSA检测相同的准确性，还具有提前约300天检测复发的优势。因此，可以更快地计算耻骨后根治性前列腺切除术系列的长期结果。一旦有治愈性治疗方案，若在肿瘤复发最早阶段应用该检测方法，其临床影响将很明显。
