Prognostic significance of 5-year PSA value for predicting prostate cancer recurrence

PURPOSE: To analyze the prognosis and outcomes of patients who remain free of biochemical failure during the first 5 years after treatment.

METHODS AND MATERIALS: Between 1991 and 2002, 742 patients with prostate cancer were treated with brachytherapy alone (n = 306), brachytherapy and hormonal therapy (n = 212), or combined implantation and external beam radiotherapy (with or without hormonal therapy; n = 224). These patients were free of biochemical failure (American Society for Therapeutic Radiology and Oncology [ASTRO] definition) during the first 5 post-treatment years and had a documented 5-year prostate-specific antigen (PSA) value. The median follow-up was 6.93 years.

RESULTS: The actuarial 10-year freedom from PSA failure rate was 97% using the ASTRO definition and 95% using the Phoenix definition. The median 5-year PSA level was 0.03 ng/mL (range, 0-3.6). The 5-year PSA value was 0.01-0.10 in 31.1%, >0.10-0.2 in 10.2%, >0.2-0.5 in 7.82%, and >0.5 in 3.10%. The 5-year PSA value had prognostic significance, with a PSA value of or=0.2 ng/mL (n = 81; p < .0001). The treatment regimen had no effect on biochemical failure. None of the 742 patients in this study developed metastatic disease or died of prostate cancer.

CONCLUSION: The results of this study have shown that the prognosis for patients treated with brachytherapy and who remain biochemically free of disease for >or=5 years is excellent and none developed metastatic disease during the first 10 years after treatment. The 5-year PSA value is prognostic, and patients with a PSA value <0.2 ng/mL are unlikely to develop subsequent biochemical relapse

Stock RG, Klein TJ, Cesaretti JA, Stone NN.
Department of Radiation Oncology, Mount Sinai Hospital, New York, NY 10029, USA

Characteristics and outcome of prostate cancer with PSA <4 ng/ml at diagnosis: a population-based study

Division of Radiation Oncology, Geneva University Hospitals, Geneva, Switzerland.

This population-based study aims to assess prognosis of prostate cancer diagnosed with prostate-specific antigen (PSA) levels <4 ng/ml in routine care. Materials and methods We compared prostate cancer patients with low PSA values (n=59) with other prostate cancer patients (n=1330) by logistic regression and the Cox model using data from the Geneva Cancer Registry. Results Patients with low PSA values more frequently had early-stage and well differentiated tumours. Nevertheless, 35% presented with aggressive tumour characteristics or metastases. After adjustment for other prognostic factors, prostate cancer-specific mortality was similar for both groups (hazard ratio: 1.1; 95%CI: 0.6-2.2). Conclusion We conclude that cancer with low PSA values at diagnosis is not indolent.

Strategy for sensitive and specific detection of molecular forms of PSA based on 2DE and kinetic analysis: A step towards diagnosis of prostate canc

Clin Chim Acta. 2008 Dec 3.
Kumar V, Hassan MI, Singh AK, Dey S, Singh TP, Yadav S.

BACKGROUND: Prostate specific antigen (PSA) present in human seminal fluid exists in many isoforms due to different sequence, glycosylation pattern and polypeptide length. Its presence in various stages of cancer has already been reported. METHODS: We identified 8 forms of Prostate specific antigen followed by purification of 3 forms. We compared their binding affinities to designed synthetic peptides, by using surface plasmon resonance (SPR). PSA forms were purified using various chromatographic procedures and characterized by 2D gel electrophoresis (2DE), matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). RESULTS: The heterogeneity of purified PSA was demonstrated by 2DE analysis. The peptides were designed on the basis of cleavage map of insulin-like growth factor binding protein 3 (IGFBP-3) subsequently, these peptides showed the binding affinities in the range of 10(-5) to 10(-12) M. Out of 7 peptides, VLLH showed maximum affinity to intact PSA, while FLSYK showed maximum affinity to cleaved forms of PSA. On the other hand, FLSYK in the presence of zinc showed higher affinity to intact PSA. These peptides showed higher affinity to PSA compared to zinc, which is a known inhibitor of PSA. CONCLUSIONS: This study reports purification and characterization of 3 forms of PSA simultaneously. Furthermore, we have reported specific peptides for different forms of PSA which are either responsible for prostate cancer (PCa) or benign prostatic hyperplasia (BPH). Our study aids the existing information on categorizing the molecular heterogeneity of PSA

Prostate-specific antigen detection by using a reusable amperometric immunosensor based on reversible binding and leasing of HRP-anti-PSA from phenylb

Background
In recent years, many automated immunoassay analyzers have been developed for accurate diagnosis of various disease states and to improve effective drug administration. Amperometric immunoassay has been increasingly applied to laboratory medicine due to its ease in automation, rapid speed and low detection limits. It is important to develop reusable immunologically-sensitive elements for prostate-specific antigen (PSA) detection.

Methods
The strategy for the immunosensor construction is based on the enzyme-conjugated prostate-specific antibody (HRP-anti-PSA) reversible binding with a self-assembled phenylboronic acid monolayer on gold.

Results
After incubating an HRP-anti-PSA modified electrode in a prostate-specific antigen (PSA) solution, a decrease in the electrocatalytic response of the HRP-anti-PSA modified electrode to the reduction of H2O2 is observed. The photometric activity assays show that this decrease of the electrocatalytic response arises from the formation of immunocomplexes of HRP-conjugated anti-PSA and its antigen, not from the loss of bound HRP-anti-PSA from the electrode surface. Analytical performances and optimal conditions of the described immunosensor are also investigated. Under the optimal conditions, the amperometric immunosensor shows a linear increase of the relative intensity in 2 PSA concentration range from 2 to 15 ng/ml and 15 to 120 ng/ml, respectively.

Conclusion
This method could be used for rapid analysis of prostate-specific antigen (PSA) and potentially other antigens.

ARTICLE

Negative influence of changing biopsy practice patterns on the predictive value of prostate-specific antigen for cancer detection on prostate biopsy.

BACKGROUND: A correlation between prostate specific antigen (PSA) level and positive prostate biopsy rate was established in an era when biopsy practice patterns were different from what they are today. We evaluated if changes in biopsy practice patterns have affected the ability of PSA to predict cancer detection on prostate biopsy in the current era.

METHODS: Of 3634 prostate biopsies performed from 1993-2005, 1607 met criteria for analysis. Biopsy data were divided into 3 time-cohorts (1993-1997, 1998-2001, and 2002-2005) to assess for practice patterns shifts and correlation between PSA and biopsy results.

RESULTS: Significant changes in biopsy practice patterns included an increase in biopsy cores and more frequent use of PSA 2.5-3.99 ng/mL as a biopsy indication. In men with normal DRE, a moderate correlation between PSA and positive biopsy rate did exist from 1993-1997, but was subsequently lost. On multivariate analysis, prostate specific antigen (PSA) was not a significant predictor of biopsy result in men with normal DRE.

CONCLUSIONS: Early in the PSA era, the predictive power of PSA depended on multiple factors: high prevalence of disease, higher prevalence of high-grade disease, and low likelihood of prostate cancer diagnosis in men with low PSA. Now, beyond the culling effect of increased biopsy incidence and with shifted biopsy practice patterns, the correlation between PSA and biopsy result is lost in men with normal DRE. Diagnosing a higher proportion of tumors in men with a PSA between 2.0-4.0 ng/mL has negatively influenced the predictive value of prostate specific antigen (PSA) for cancer detection.