By David A. Levy, MD; Ahmed El-Shafei, MD; and J. Stephen Jones, MD, FACS
Cleveland Clinic is a non-profit academic medical center. Advertising on our site helps support our mission. We do not endorse non-Cleveland Clinic products or services Policy
Although whole-gland cryosurgical ablation to treat clinically localized prostate cancer is recognized as a safe procedure, there are no established biochemical standards defining treatment success, as exist for radiation therapy and prostatectomy.
We have conducted numerous studies during the past six years in an effort to identify an evidence-based definition of treatment success for prostate cryoablation. We have utilized the national Cryo On-Line Database (COLD) Registry as well as data from Cleveland Clinic patient populations to achieve our goal. A recent publication from the COLD Registry represents the culmination of our efforts to date.
Methodology for Evaluating PSA Endpoint
From the COLD Registry we reviewed hormone-naive patients who underwent primary whole-gland cryoablation, all of whom had a minimum of five years of follow-up data. None of the cohort received adjuvant therapy of any kind during the follow-up period.
We studied variables of interest including age, prostate specific antigen (PSA) level at time of diagnosis, Gleason score, clinical T stage and all postoperative PSA values.
Patients were stratified according to the D’Amico risk criteria. We studied biochemical progression-free survival (BPFS) at 0.1 ng/mL PSA increments for the intermediate risk category (471 men), aiming to identify a statistically significant PSA endpoint of biochemical success. We plotted Kaplan-Meier estimates of five-year BPFS using the Phoenix definition. Cohort demographics are listed in Table 1. We determined hazard ratios (HR) based on 0.1 ng/mL nadir PSA increments and analyzed failure rates.
Table 1. D’Amico risk-stratified biochemical progression-free survival.
Results and Survival Impact
A total of 891 (74.25 percent) of 1,111 patients achieved a nadir PSA < 0.4 ng/mL, which correlated with five-year BPFS rates of 90.4 percent, 81.1 percent and 73.6 percent for low, intermediate and high risk, respectively (Figure 1).
Figure 1. Five-year biochemical progression-free survival (BPFS) comparing nadir PSA < 0.4 ng/mL and nadir PSA ≥ 0.4 ng/mL.
As shown in Table 1, 24-month biochemical failure rates in patients who had a PSA nadir > 0.4 ng/mL were significant, regardless of risk group. Moreover, patients who had a nadir PSA < 0.3 ng/mL had similar outcomes compared with those who had a PSA nadir < 0.4 ng/mL, with five-year BPFS rates of 92.2 percent, 81 percent and 77 percent for low-, intermediate- and high-risk patients, respectively (Table 1).
Our analysis failed to reveal a statistically superior PSA nadir endpoint compared with the < 0.4 ng/mL value (HR 5.649 [95 percent confidence interval (CI) 4.33-7.38], p < 0.0001).
PSA Nadir Guides Ongoing Treatment
To the best of our knowledge, our results convey the first evidence-based study for definition of biochemical success in patients who underwent primary whole-gland cryoablation of the prostate. A nadir PSA < 0.4 ng/mL is the best cutoff point for biochemical success, with no statistical advantage of using a lower PSA nadir.
Patients with a nadir PSA > 0.4 ng/mL showed unacceptable biochemical progression at 24 months in all risk categories, which precludes using a higher-nadir PSA endpoint. Consideration of post-treatment biopsy in patients whose PSA fails to reach that nadir may help direct management to either salvage local therapy or evaluation of possible metastasis if local control is confirmed.
Dr. Levy is a staff member of Cleveland Clinic Glickman Urological & Kidney Institute’s Department of Urology. Dr. El-Shafei is a research fellow in Cleveland Clinic’s Education Institute. Dr. Jones is President, Cleveland Clinic Regional Hospitals and Family Health Centers, Professor of Surgery at Cleveland Clinic Lerner College of Medicine and holds the Leonard Horvitz and Samuel Miller Distinguished Chair in Urological Oncology Research.