Original article Predicting biopsy-proven prostate cancer recurrence following cryosurgery Jorge R. Caso, M.D., M.P.H. 1 , Matvey Tsivian, M.D., Vladimir Mouraviev, M.D., Ph.D. 1 , Thomas J. Polascik, M.D.* Division of Urologic Surgery, Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA Received 23 February 2010; received in revised form 2 April 2010; accepted 3 April 2010 Abstract Objectives: Prostate cancer (CaP) cryosurgery utilizes PSA nadir level and radiotherapy criteria as surrogates for success. We attempted to correlate PSA doubling time (PSAdt) and time of undetectable PSA (TUPSA) with biopsy-proven cancer recurrence (BPR) in men treated with primary third-generation cryotherapy for clinically localized CaP. Materials and methods: Demographic, clinical, and pathologic data was retrieved including age, race, use of preoperative hormones or 5- reductase inhibitors (5-ARIs), initial biopsy PSA, biopsy Gleason score, cT stage, prostate volume, presence/absence median lobe, and follow-up. Post-cryotherapy biopsy was considered for PSA levels  0.5 ng/ml. PSAdt was determined by the log-slope method. TUPSA was defined as time from surgery to a PSA value  0.2ng/ml or most recent follow-up if undetectable. Results: Ninety-seven patients were identified. Preoperative hormonal manipulation was used in 25 (26%); 5 (5%) were using a 5-ARI. Twenty-seven (29%) underwent post-cryotherapy biopsy, 12 (12%) had a BPR. In 41 (42%), PSAdt was calculated (median 11.9 months, IQR 6.6 –34.8); no significant difference between patients with BPR and without CaP was found (P = 0.46). TUPSA was a median of 4.9 months (IQR 3.2–9.9) vs. 15.6 months (IQR 6.1–30.3) for BPR or no CaP, respectively (P = 0.005). On proportional hazards regression, TUPSA was the only independent predictor of BPR (P = 0.03, OR 0.91). Conclusions: Post-cryosurgery PSAdt does not appear to be associated with BPR risk, whereas TUPSA reduces the risk of BPR by 9% per month. This may help guide management if local failure is suspected. © 2012 Elsevier Inc. All rights reserved. Keywords: Prostate cancer; Prostate-specific antigen; Recurrence; Cryosurgery 1. Introduction From the pioneering days of modern cryosurgery in the early 1960s, various technological advances and improvements led to the development of third generation cryoprobes introduced in the late 1990s. This technology found a natural application for pros- tate cancer (CaP) with the relative ease of percutaneous insertion of sharp-tipped cryoneedles and real time monitoring of the ice ball by means of transrectal ultrasound (TRUS) [ 1,2]. Given the brief history, there are few established clinical parameters in the postoperative follow-up of patients receiving this therapy to define oncologic success. A meta-analysis of localized prostate cancer treatments did not include cryosurgery given the paucity of long- term data, leading to the later release in 2008 of a best practice statement from the American Urologic Association for its use [ 3]. Since cryoablation is an in-situ therapy similar to brachy- therapy, the American Society for Therapeutic Radiology and Oncology (ASTRO) criteria to define biochemical recurrence (BCR) has been adopted as a surrogate endpoint by several cryosurgeons [4–8]. In order to reduce the necessary time of follow-up, there have also been attempts at correlating nadir post-therapy PSA values with biochemical disease-free sur- vival (BDFS) [7]. However, most studies have not further evaluated the association between BCR and biopsy-proven recurrence (BPR). In this study, we attempt to define post- therapy PSA kinetics and the attendant risk of a BPR in a cohort of CaP patients receiving cryosurgery as primary ther- apy. PSA kinetics were calculated with doubling times (PSAdt) and the time of undetectable PSA (TUPSA). * Corresponding author. Tel.: +1-919-684-4946; fax: +1-919-684- 5220. E-mail address: polas001@mc.duke.edu (T.J. Polascik). 1 These authors were supported by research funds from the Committee for Urologic Research, Education, and Development (CURED) of Duke University. Urologic Oncology: Seminars and Original Investigations 30 (2012) 391–395 1078-1439/$ – see front matter © 2012 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.urolonc.2010.04.001