EURURO-4420; No. of Pages 9 E U R O P E A N U R O L O G Y X X X ( 2 0 1 2 ) X X X – X X X ava ilable at www.sciencedirect.com journa l homepage: www.europeanurology.com Platinum Priority – Prostate Cancer Editorial by XXX on pp. x–y of this issue Focal Cryotherapy for Clinically Unilateral, Low-Intermediate Risk Prostate Cancer in 73 Men with a Median Follow-Up of 3.7 Years a,b a a a b Duke Bahn , Andre Luis de Castro Abreu , Inderbir S. Gill , Andrew J. Hung , Paul Silverman , a a a, Mitchell E. Gross , Gary Lieskovsky , Osamu Ukimura * a Institute of Urology, Hillard and Roclyn Herzog Center for Prostate Cancer Focal Therapy, Keck School of Medicine, University of Southern California, Los b Angeles, CA, USA; Prostate Institute of America, Community Memorial Hospital, Ventura, CA, USA Article info Abstract Article history: Background: Evolution of cryotherapy for prostate cancer is likely to result in parenchyma-sparing modifications adjacent to the urethra and neurovascular bundle. Accepted March 5, 2012 Results of initial series of focal therapy to minimize cryosurgery-related morbidity Published online ahead of without compromising oncologic control have been encouraging, but limited in short- print on March 20, 2012 term outcomes. Objective: To retrospectively report (1) median 3.7-yr follow-up experience of primary Keywords: focal cryotherapy for clinically unilateral prostate cancer with oncologic and functional outcomes, and (2) matched-pair analysis with contemporaneous patients undergoing Prostatic neoplasms radical prostatectomy (RP). Cryotherapy Design, setting, and participants: Over 8.5 yr (September 2002 to March 2011), focal Biopsy cryoablation (defined as ablation of one lobe) was performed in 73 carefully selected Ultrasound patients with biopsy-proven, clinically unilateral, low-intermediate risk prostate cancer. All patients underwent transrectal ultrasound (TRUS) and Doppler-guided sextant and Prostate-specific antigen targeted biopsies at entry. Outcome measurements and statistical analysis: Post-therapy follow-up included mea- suring prostate-specific antigen (PSA) level every 3–6 mo; TRUS biopsies at 6–12 mo and yearly, as indicated; and validated symptom questionnaires. Matched-pair analysis compared oncologic outcomes of focal cryotherapy and RP (matched for age, PSA, clinical stage, and biopsy Gleason score). Results and limitations: Complete follow-up was available in 70 patients (median follow-up: 3.7 yr; range: 1–8.5 yr). No patient died or developed metastases. Pre- cryotherapy mean PSA was 5.9 ng/ml and Gleason score was 6 (n = 30) or 7 (n = 43). Postcryotherapy mean PSA was 1.6 ng/ml (70% reduction compared to precryotherapy; p < 0.001). Of 48 patients undergoing postcryotherapy biopsy, 36 (75%) had negative biopsies; positive biopsy for cancer (n = 12) occurred in the untreated contralateral (n = 11) or treated ipsilateral lobe (n = 1). Complete continence (no pads) and potency sufficient for intercourse were documented in 100% and 86% of patients, respectively. Matched-pair comparison of focal cryotherapy and RP revealed similar oncologic outcome, defined as needing salvage treatment. Conclusions: Primary focal cryoablation for low-intermediate risk unilateral cancer affords encouraging oncologic and functional outcomes over a median 3.7-yr follow- up. Close surveillance with follow-up whole-gland biopsies is mandatory. # 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved. * Corresponding author. Institute of Urology, Hillard and Roclyn Herzog Center for Prostate Cancer Focal Therapy, Keck School of Medicine, University of Southern California, 1441 Eastlake Ave., Ste. 7416, Los Angeles, CA 90089, USA. Tel. +1 323 865 3700; Fax: +1 323 865 0120. E-mail address: [email protected] (O. Ukimura). 0302-2838/$ – see back matter # 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved. doi:10.1016/j.eururo.2012.03.006 Please cite this article in press as: Bahn D, et al. Focal Cryotherapy for Clinically Unilateral, Low-Intermediate Risk Prostate Cancer in 73 Men with a Median Follow-Up of 3.7 Years. Eur Urol (2012), doi:10.1016/j.eururo.2012.03.006 EURURO-4420; No. of Pages 9 2 E U R O P E A N U R O L O G Y X X X ( 2 0 1 2 ) X X X – X X X cryoablation [7]. At 70-mo follow-up, a 96% negative 1. Introduction follow-up biopsy rate, 89% preservation of erectile function, With prostate-specific antigen (PSA) testing widely used, and 100% continence rate were documented, with no rectal more men are diagnosed with localized prostate cancer of injury. lower volume and grade. Such cancers may not adversely In this paper, we report follow-up (median: 3.7 yr) affect the individual’s overall survival, allowing conserva- experiences with focal cryosurgery in 73 carefully selected tive management with active surveillance as a treatment men with clinically unilateral low- to intermediate-risk option [1]. Alternatively, if targeted focal therapy could cure prostate cancer, with an emphasis on our technique of or acceptably control such low-grade prostate cancer, it sextant and targeted mapping biopsies and subsequent may become an appealing option for men who otherwise image-guided intervention. would be suitable candidates for active surveillance but who wish to use some form of therapy against their cancer 2. Materials and methods [2]. According to Turpen and Rosser [3], ‘‘As defined by the International Task Force on Prostate Cancer and the Focal After obtaining institutional review board approval, retrospective Lesion Paradigm, the goal of focal therapy for prostate analysis was performed of 73 men who had undergone focal cancer would be to ‘selectively ablate(s) known disease and cryoablation (from September 2002 to July 2010) for biopsy-proven, preserve(s) existing functions, with the overall objective of clinically unilateral, low-intermediate risk (PSA 20, Gleason minimizing lifetime morbidity without compromising life score 7, clinical stage T1-T2b) prostate cancer (Fig. 1; Table 1). expectancy.’’’ Focal cryoablation was defined as ablation of one lobe of the prostate. Evolution of cryotherapy as a minimally invasive All patients gave preoperative consent after detailed discussion of treatment option for men with clinically localized prostate limitations and benefits of focal cryoablation for the known clinically cancer is likely to result in modifications of the established unilateral prostate cancer. At study entry, all 73 patients (100%) underwent transrectal surgical technique, including parenchyma-sparing modifi- ultrasound (TRUS)–Doppler evaluation (Type EUB-6500; Hitachi Medi- cations adjacent to the urethra and neurovascular bundle. In cal Systems America, Inc., Tarrytown, NJ, USA) followed by entry-staging 2008, the American Urologic Association released its best biopsy. TRUS-suspicious regions were schematically represented on a practices statement on cryosurgery for the treatment of worksheet, documenting lesion size, location, and vascularity (Fig. 2). localized prostate cancer [4]. The report outlined the long- Entry biopsies (median: 7; range: 6–9) were performed in a random, term outcomes in 370 patients with prostate cancer who systematic, sextant template; additionally, one targeted biopsy was underwent whole-gland cryosurgery and showed that, performed per TRUS-visible suspicious lesion (Table 1; Fig. 2). Exclusion according to Kaplan-Meier analysis, the biochemical criteria by entry biopsy included (1) clinically bilateral cancer, (2) disease-free survival rate at 10 yr was 80.6% and 74.2% Gleason score 8, and (3) biopsy-proven extraprostatic extension of for low- and moderate-risk groups, respectively [5]. In a cancer. Among the 93 potential candidates who were interested in focal cryotherapy and underwent the entry-staging biopsy in our institution, randomized trial of whole-gland cryosurgery (n = 122) 20 patients (21.5%) met the exclusion criteria. Patients with PSA >10 ng/ versus external radiation therapy (n = 122), more patients ml or Gleason score 7 disease underwent metastatic evaluation with in the radiotherapy arm had a positive follow-up biopsy abdominopelvic computed tomography and bone scintigraphy. (28.9%) compared with patients in the cryosurgery arm Any androgen deprivation therapy (ADT) and/or 5a-reductase (7.7%) at 36 mo [6]. Importantly, results of initial clinical inhibitors (5-ARI) that had been given by referring physicians at the series of cryosurgery as a focal treatment modality for outside institution was discontinued at study entry. During the entire prostate cancer to further minimize cryosurgery-related follow-up period after focal cryoablation, no patients received any ADT morbidity without compromising oncologic control have and/or 5-ARI. been encouraging [7–9]. We have previously reported short- Focal cryoablation of the entire ipsilateral lobe was performed using an term data of our initial experience (n = 28) with focal argon/helium gas-based system (Endocare, HeathTonics Inc., Austin, TX, 51% (36/70) 1.5% (1/70) 4% (3/73) 31% (22/70) 1.5% (1/70) Negave biopsy Posive biopsy in Lost follo w -up No follow-up biopsy Hormonal blockade (benign) treated side 11% (8/70) Acve surveillance 73 Paents 3% (2/70) Repeated focal cryoablaon 17% (12/70) 16% (11/70) 96% (70/73) 69% (48/70) Posive biopsy Posive biopsy in 1.5% (1/70) Follo w -up Follow - up biopsy (cancer) untreated side Brachy + IMRT Fig. 1 – Schematic tree of study cohort. Brachy = brachytherapy; IMRT = intensity-modulated radiation therapy. Please cite this article in press as: Bahn D, et al. Focal Cryotherapy for Clinically Unilateral, Low-Intermediate Risk Prostate Cancer in 73 Men with a Median Follow-Up of 3.7 Years. Eur Urol (2012), doi:10.1016/j.eururo.2012.03.006 EURURO-4420; No. of Pages 9 E U R O P E A N U R O L O G Y X X X ( 2 0 1 2 ) X X X – X X X 3 Table 1 – Demographics and intraoperative data of 73 patients indicated.