UroToday - Prostate Cancer Progression in the Presence of Undetectable or Low Serum Prostate-Specific Antigen Level

Prostate Cancer Progression in the Presence of Undetectable or Low Serum Prostate-Specific Antigen Level

Tuesday, 10 April 2007

BERKELEY, CA (UroToday.com) - Patients treated with definitive therapy for prostate cancer (CaP) are reassured that a low or undetectable PSA means the absence of metastatic disease. However, exceptions to this can occur, as documented in a study from M.D. Anderson Cancer Center that appears in the online edition of Cancer.

Between 1999 and 2004, 4,145 patients diagnosed with prostate cancer were enrolled in the database at M.D. Anderson Cancer Center. A total of 100 patients were identified who had disease progression with a PSA level <2ng/ml. Disease progression was defined as metastasis in >1 of the following sites: bone, viscera or retroperitoneal lymph nodes above the aortic bifurcation. Forty-six men, representing 1.1% of all patients who were entered into the database had appropriate criteria for analysis.

Overall, 10 (22%) had undetectable serum PSA levels and 30 patients (65%) had PSA of less than 1ng/ml at the time of disease progression. Of the 25 men who had undergone radical prostatectomy, 7 were hormone naïve at the time of progression. The median increase in PSA was 0.25ng/ml at the time of progression. In 19 patients, there was no increase in PSA from the nadir level at the time of progression. The median PSA doubling time for the cohort was 7.6 months.

Atypical variants of CaP were identified in 21 of 46 patients; including 9 with ductal CaP, 8 with small cell variant, 2 with neuroendocrine tumors and 2 men with sarcomatoid tumors. Metastatic progression was most commonly in the bones, followed by liver, retroperitoneal lymph nodes and lungs. Progression was identified by bone scans, CT or MRI.

In patients with CaP variants, monitoring in addition to PSA may have value.

Dan Leibovici, Philippe E. Spiess, Piyush K. Agarwal, Shi-Ming Tu, Curtis A. Pettaway, Kate Hitzhusen, Randall E. Millikan, Louis L. Pisters

Cancer 2006;109(2): 198-204

UroToday.com Prostate Cancer Section

Written by Christopher P. Evans, MD, a Contributing Editor with UroToday.

Reader Comments

Written by This email address is being protected from spam bots, you need Javascript enabled to view it on 2007-05-04 11:16:03

I have read the full paper by Leibovici et al. The authors used a definition of undetectable PSA as < 0.1. Numerous peer-reviewed papers indicate that in the setting after RP, this is not a sufficient threshold to eliminate PC activity (see refs below). Moreover, there is established literature to indicate that as the Gleason score increaess the PSA leak into serum decreases significantly (Aihara M, Lebovitz RM, Wheeler TM, et al: Prostate specific antigen and gleason grade: an immunohistochemical study of prostate cancer. J Urol 151:1558-64, 1994.)and that reliance on PSA diminishes greatly in the context of high Gleason scores (8-10). In fact, Leibovici et al had 85% of their patients with Gleason scores of 7 or higher. Moreover, in any assessment of high Gleason score PC (GS 8-10), other biomarkers must be used as indicators of disease activity. These include CEA, CGA, NSE and PAP. Lastly, we have shown in an abstract presented at the PC Symposium in Orlando in 2007 that a PSA nadir of < 0.05 was most significantly correlated with the development of bone metastases (full paper in press in Urology). Therefore, again, the definition of undetectable is crucial in this context as is the completeness of the evaluation with other biomarkers to assess disease status.

References:
Doherty AP, Bower M, Smith GL, et al: Undetectable ultrasensitive PSA after radical prostatectomy for prostate cancer predicts relapse-free survival. Br J Cancer 83:1432-6, 2000.

Haese A, Huland E, Graefen M, et al: Ultrasensitive detection of prostate specific antigen in the followup of 422 patients after radical prostatectomy. J Urol 161:1206-11, 1999.

Shen S, Lepor H, Yaffee R, et al: Ultrasensitive serum prostate specific antigen nadir accurately predicts the risk of early relapse after radical prostatectomy. J Urol 173:777-80, 2005. PMID 15711268

Witherspoon LR, Lapeyrolerie T: Sensitive Prostate Specific Antigen measurements identify men with long disease-free intervals and differentiate aggressive from indolent cancer recurrences within 2 years after radical prostatectomy. J Urol 157:1322-1328, 1997.

Stephen B. Strum, MD
Medical Oncologist Specializing in PC

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