PSA Density, PSA Velocity and Family History of Prostate Cancer are Predictors of Progression in Patients with Low Risk Prostate Cancer on Active Surveillance Protocol Using a 20-Core Saturation Biopsy Technique
Ignacio F. San Francisco, MD1, Glenn Bubley, MD2, Marc B. Garnick, MD2, William C. DeWolf, MD2.
1Beth Israel Deaconess Medical Center and Pontificia Universidad Catolica de Chile, Boston, MA, USA, 2Beth Israel Deaconess Medical Center, Boston, MA, USA.
BACKGROUND: Active surveillance (AS) is a reasonable form of treatment for patients with low risk prostate cancer. However, there are no validated safety criteria for entering, monitoring, and then triggering active intervention. We present an update of our prospective study cohort of active surveillance in 111 patients with low risk prostate cancer using a 20-core saturation biopsy technique.
METHODS: The study population consisted of 111 consecutive patients who were prospectively enrolled with low risk prostate cancer with intent to cure from January 2003 to January 2009 by one urologist (WCD). All patients were followed with 20-core saturation biopsy technique. The inclusion criteria were clinically localized cancer (T1c-T2), less than 3 positive cores, Gleason score 6 or less, and no more than 50% of core involved. The criteria for progression, and therefore treatment were: ≥ 3 positive cores, increase in grade (Gleason score ≥ 7) and ≥ than 50% of any core involved with cancer. Patients were monitored with an office visit every 6 months and restaging 20-core saturation biopsy every 12-18 months. Definitive treatments as RRP or Radiotherapy were performed in patients who progressed.
RESULTS: From the 111 patients who fit the entering criteria, 3 withdrew the protocol before an endpoint was reached. Therefore 108 patients were analyzed in the final cohort. The mean age of the study group at the time of the first biopsy was 62 years. The median time of follow-up was 25 months. The median number of total biopsies was 2 (range, 1-5). Ninety five patients had at least one saturation re-biopsy. The progression rate was 26% (28/108). Fifty one patients (54%) had a negative first re-biopsy. Of the patients who progressed 54% did so due an increase number of positive cores. Univariate analyses revealed PSA density, using cut point the median value 0.08 ng/ml/cc (p=0.0048), PSA velocity (p=0.01) and family history of prostate cancer (p=0.01) were predictors of progression. PIN and atypia were non predictors of progression. Most of the patients who progressed did so at second biopsy (17 patients). The median time to progression was 24 months. Of the patients who progressed 11 underwent RRP. Of those 10 patients (91%) had organ confined, low volume disease with negative margins, 4 had Gleason 3+4 and one patient had a T3b disease. Interestingly, 2 of 4 (50%) patients who had Gleason 7 as criteria of progression on needle biopsies had Gleason 6 on the final RP specimens.
CONCLUSIONS: In our study PSA density, PSA velocity and family history of prostate cancer are predictors of progression in univariate analysis. Most of the first re-biopsies (54%) had no cancer. In the group of patients with negative first re-biopsy there was still subsequent progression revealing a 30 months lead time bias as noted by Kaplan Meier curves. Of the patients who progressed and underwent RP, 91% had a final pathology with organ-confined and low volume disease. In our setting AS with delayed intervention appears to be a safe and viable option in selected men with low risk prostate cancer.