BERKELEY, CA (UroToday.com) -
Investigations of the role of (-2)ProPSA serum and DNA content Biomarker to Predict Failure Among Active Surveillance Prostate Cancer Patients.
The Fisher Biomarker Biorepository Laboratory (FBBL) has been involved in a search of biomarkers that can predict disease progression among men with low grade, low stage prostate cancer (PCa) enrolled in Active Surveillance (AS) program.(1-4) The Johns Hopkins Hospital (JHH) AS program was initiated by Dr. Ballentine Carter in 1995 to prevent over-diagnosis and over-treatment of PCa. Patients were enrolled if they met inclusion criteria i.e. nonpalpable tumor on digital rectal examination (stage T1c tumors), PSA Density ≤0.15 ng/ml/cm3 and favorable diagnostic needle biopsy characteristics (Gleason score ≤6, ≤2 cores involved with cancer, ≤50% of any core involved with cancer). Patients were followed-up semi-annually with serum total PSA, free PSA and DRE, annually with at least 12 cores surveillance biopsy examination. Curative intervention is triggered by unfavorable biopsy conversion (Gleason score ≥7 or any Gleason pattern 4/5 or ≥3 cores involved with cancer or >50% of any core involved with cancer) on annual surveillance biopsy examination.
We evaluated several biomarkers in diagnostic biopsy tissue and serum samples of 71 men enrolled in AS program to predict unfavorable biopsy conversion (i.e. recommendation for curative intervention) on annual surveillance biopsy examination. Thirty-nine patients developed unfavorable biopsies while 32 patients maintained favorable biopsies on annual surveillance biopsy examination (median follow-up: 3.72 years). Figure 1 shows Kaplan-Meier plots of Prostate Health Index (phi), [-2]proPSA/%fPSA, DNA content in Benign-adjacent tumor area (BA Excess of OD) and cancer tissue area (CA StdDev of OD) to predict unfavorable biopsy conversion.
In the current study, we showed that prostate health index (or proPSA/%fPSA) when combined with biopsy tissue DNA content had accuracy of ~70% to predict, at the time of diagnosis, which patients would eventually fail surveillance and would require treatment for PCa. In the past we were not able to make such a prediction and were dependent on annual surveillance biopsies to monitor disease progression. Currently, there are no parameters to predict small indolent PCa without some risk of missing high grade cancers. We are currently evaluating a larger cohort for these biomarkers to validate our findings. The final solutions will necessitate application of molecular biomarkers in serum, urine and/or tissue to identify men with ‘indolent’ PCa that can safely elect AS.
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- Makarov DV, Isharwal S, Sokoll LJ, Makarov DV, Marlow C, Epstein JI, Partin AW, Carter HB, and Veltri RW. proPSA Measurements in Serum and Tissue are Associated with Treatment Necessity Among Men Enrolled in Expectant Management for Prostate Cancer. Clin Cancer Res 2009; 15(23):7316–21.
- Isharwal S, Makarov DV, Carter HB, Epstein JI, Partin AW, Landis P, Marlow C, and Veltri RW. DNA content in the diagnostic biopsy benign-adjacent and cancer tissue areas predicts the need for treatment in men with T1c prostate cancer undergoing surveillance in an expectant management program. BJUI, 105, 2009; 329 – 333.
- Isharwal S, Makarov DV, Sokoll L, Landis P, Marlow C, Epstein JI, Partin AW, Carter HB, and Veltri RW: ProPSA and diagnostic biopsy tissue DNA content combination improves accuracy to predict the need for prostate cancer treatment among men enrolled in a proactive surveillance program. Urology, 2011; doi:10.1016/j.urology.2010.07.526.
Sumit Isharwal, MD and Robert W. Veltri, PhD as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.