Reliability of PSA circulating cells as markers of metastatic prostate cancer

We read with great interest the article published in the SJCLI by Lintula et al. [1]. To investigate the influence of prostatic surgery and endocrine treatment on prostatic cells in the circulation of 56 patients undergoing biopsy, radical prostatectomy, transurethral resection of the prostate (TURP), orchiectomy, or androgen blockade they developed a quantitative reverse transcription-polymerase chain reaction (RT-PCR) method for detecting prostate specific antigen (PSA) mRNA in peripheral blood (PB) samples before, during, and up to 26 weeks after these procedures. PSA mRNA levels increased after RP, TURP, or orchiectomy and became undetectable within 1 – 3 days. No significant correlation was found between PCR positivity and the clinical characteristics of the patients, serum PSA, stage, or grade. The investigators conclude that the increased levels of PSA mRNA in PB after prostatic surgery indicate temporary dissemination of prostatic cells. Published data nevertheless suggest that increasing levels of PSA mRNA in PB after prostatic surgery do not necessarily indicate temporary dissemination of prostatic cells; nor can RT-PCR PSA-positive cells help in gauging the extent of disease progression after radical prostatectomy for prostate cancer [2]. Our study reporting PSA circulating cells in PB from 1 of 11 untreated patients with apparently localized cancers, without recurrent disease developed within 24 months after RP, support these proposals. In a preliminary study, designed to investigate these matters, we amplified cDNA (250 ng) in PB from 42 patients with treated or untreated prostate carcinoma (CaP) and with benign prostatic hyperplasia (BPH) (controls) by RT-PCR, using the following primers: sense, located in exon 2: 5’TGTCCGTGACGTGGATTGGTG3’; antisense, located in exon 4: 5’CATGGAGGTCCACACACTGAA3’ using 40 cycles 40 (94‡C for 30@, 65‡C for 30 min and 72‡C for 60 s) of PSA [3] and as control sense, located in exon 1: 5’AGCACAGAGCCTCGCCTTTG3’; antisense located in exon 4: 5’TGGCCATCTCTTGCTCGAAG3’ using 30 cycles (94‡C for 30 min, 56‡C for 30 min and 72‡C for 60 s) for human b-actin [4]. We studied three clinical groups: 11 patients with CaP who underwent androgen ablation (AA) followed by retropubic radical prostatectomy (RP) (2 tumors were Gleason score sum 4, 7 Gleason sum 7, and 2 Gleason sum 8; 7 tumors were organ-confined diseases (T2N0) and 4 were extra-prostatic diseases (T3b). Follow-up after treatment ranged from 3 to 84 months (mean 27 months). At the time of venipuncture for PB, we distinguished two subgroups: patients who responded to the first 24 months of treatment without clinical progression; and patients who received neoadjuvant androgen deprivation therapy because recurrent disease developed within 24 months after RP. The second subgroup comprised 11 patients with elevated serum PSA levels (more than 4.0 ng/mL), who had been given a diagnosis of CaP based on TRUS-guided prostate biopsy (1 tumor was Gleason sum 6 and 10 were Gleason sum 7). All 11 patients had organ-confined disease. In patients treated for CaP, PB samples were obtained 27 to 84 months (mean 55 months) after treatment ended; in patients who had received a diagnosis of CaP based on clinical and biochemical evidence of malignancy, PB samples were obtained before biopsy and before treatment began. The control group comprised 20 men aged 50 years or older with no known malignancy, with a histologic Scand J Clin Lab Invest 2004; 64: 687–690