Tag Archive for: multicentre study


Article of the week: Out of the COLD: cryoablation for locally advanced PCa

Every week the Editor-in-Chief selects the Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an accompanying editorial written by a prominent member of the urological community. This blog is intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation.

If you only have time to read one article this week, it should be this one

Cryoablation for locally advanced clinical stage T3 prostate cancer: a report from the Cryo-On-Line Database (COLD) Registry

John F. Ward, Christopher J. DiBlasio*, Christopher Williams, Robert Given and J. Stephen Jones

§The University of Texas MD Anderson Cancer Center, Houston, TX, *Urology, Mount Sinai School of Medicine, Huntington, NY, Urology, University of Florida and Shands Medical Center, Jacksonville, FL, Urology, Eastern Virginia Medical School, Norfolk, VA, and §Urology, Cleveland Clinic Lerner College of Medicine, Cleveland, OH, USA


• To assess the oncological and functional outcomes of primary prostate cryoablation for men with clinical stage T3 (cT3) prostate cancer, as although radical prostatectomy (RP) or external beam radiotherapy (EBRT) are the standard treatments for locally advanced cT3 prostate cancer some patients opt for nonextirpative prostate cryoablation instead.


• The Cryo-On-Line Database (COLD) Registry was queried to identify patients with cT3 prostate cancer treated with whole-gland cryoablation (366 patients).

• We assessed biochemical disease-free survival (bDFS) using the Phoenix definition and determined reported rates of urinary incontinence and retention, sexual activity, and rectourethral fistulisation after treatment.

• Patients were subsequently assessed according to whether they were administered neoadjuvant androgen-deprivation therapy or not (ADT; 115 patients, 31.4%).


• For the entire cohort, the 36- and 60-month bDFS rates were 65.3% and 51.9%, respectively.

• Patients who received neoadjuvant ADT had statistically nonsignificantly higher 36- and 60-month bDFS rates (68.0% and 55.4%, respectively) than patients who did not receive neoadjuvant ADT (55.3% and 36.9%, respectively).

• The after treatment urinary incontinence rate was 2.6%; urinary retention rate, 6.0%; sexual activity rate, 30.4%; and rectourethral fistulisation rate, 1.1%.


• Cryoablation for patients with cT3 prostate cancer leads to less favourable bDFS than that after RP or RT for the same group of men.

• The after treatment rectourethral fistulisation rates for patients with cT3 disease are higher than in those with organ-confined prostate cancer treated with cryoablation; however, urinary dysfunction and sexual activity rates are similar for men with cT3 to those reported from this same registry in men with cT2 disease.

• The addition of neoadjuvant ADT (though not studied prospectively here) should be strongly considered if a patient with cT3 prostate cancer is to be treated with cryoablation.


Editorial: Cryosurgery for clinical T3 prostate cancer

There are limited data available on the outcomes of cryosurgery for clinical T3 prostate cancer, and as such, the role of cryosurgery for clinical T3 disease is currently undetermined [1]. Modern cryosurgery of the prostate, utilizing gas-based third-generation technology, a real-time monitoring system with ultrasonography and thermocouples, is associated with a low complication rate [7], although comparative outcomes of the different treatment modalities and long-term follow-up data remain to be seen.

Several aspects of cryosurgery can make it difficult to adequately control locally advanced prostate cancer. First, cryosurgery for clinical T3 cancer requires unique surgical expertise to control local disease while minimizing side-effects. Secondly, staging of locally advanced prostate cancer is challenging – it is difficult to accurately identify the extent of extracapsular extension, seminal vesicle involvement and/or lymph node metastasis. Thirdly, challenges in managing clinical T3 disease include the requirement of a more extensive ablation technique to appropriately target the extraprostatic disease and seminal vesicle involvement as well as treatment for possible microscopic metastasis, which might not be clinically detectable.

Two recent randomized trials compared outcomes of external beam radiation therapy with those of cryosurgery (including cT3 diseases with use of neo-adjuvant androgen deprivation therapy [ADT]), with contrasting results [2, 3]. Chin et al. [2] reported superiority of biochemical disease-free survival favouring external beam radiation therapy in relatively more advanced (bulky) disease, while Donnelly et al. [3] reported significantly fewer positive biopsy rates favouring cryosurgery in the relatively less advanced disease. These findings could suggest that more advanced bulky cases that require wider local control of bulky extraprostatic diseases are not suitable for cryosurgery, while in appropriately selected cases with fewer extraprostatic diseases, cryosurgery is an acceptable option (when combined with neo-adjuvant ADT). Although appropriately extended cryo-lesions that achieve lethal temperatures can control extraprostatic disease, there is a certain limitation in the extension of cryo-lesions without injury to vital peri-prostate organs, such as the urinary sphincter, rectal wall, bladder wall and ureters.

Evolving accuracy of preoperative diagnostic imaging to assess extraprostatic disease can enhance outcomes, and staging tissue sampling from suspected extraprostatic disease could also identify actual microscopic extension of the extraprostatic disease [4]. A recently updated nomogram predicting lymph node invasion [5] suggests that the probability of lymph node invasion in patients with cT3, PSA level >10 ng/mL, and biopsy primary Gleason grade 4 is 20% or greater. Clearly, the preoperative risk assessment of lymph node involvement using such a modern calculator is pertinent for appropriate patient selection. Finally, management decision should be made by a multidisciplinary team.

When combined with radiotherapy, neo-adjuvant ADT for high-risk and locally advanced prostate cancer has been associated with clinical benefit; however, when combining neo-adjuvant ADT with prostatectomy, there is pathological down-staging and reduction in the surgical positive margin but minimal improvement in overall or disease-free survival [6]. The role of neo-adjuvant and adjuvant ADT when combined with cryosurgery is still unknown. Clearly, a prospective study is needed to determine the optimal duration and method of ADT (whether to use LHRH analogue or combined blockade) and to analyse the side-effects, the quality of life and the cost-effectiveness of a combination of cryosurgery with ADT for cT3a and cT3b prostate cancer.

Osamu Ukimura, Andre Luis de Castro Abreu, Andrew J. Hung and Inderbir S. Gill
USC Institute of Urology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA


  1. Babaian RJ, Donnelly B, Bahn D et al. Best practice statement on cryosurgery for the treatment of localized prostate cancer. J Urol 2008; 180: 1993–2004
  2. Chin JL, Al-Zahrani AA, Autran-Gomez AM, Williams AK, Bauman G. Extended followup oncologic outcome of randomized trial between cryoablation and external beam therapy for locally advanced prostate cancer (T2c-T3b). J Urol 2012; 188: 1170–1175
  3. Donnelly BJ, Saliken JC, Brasher PM et al. A randomized trial of external beam radiotherapy versus cryoablation in patients with localized prostate cancer. Cancer 2010; 116: 323–330
  4. Ukimura O, Coleman JA, de la Taille A et al. Contemporary role of systematic prostate biopsies: indications, techniques, and implications for patient care. Eur Urol 2013; 63: 214–230
  5. Briganti A, Larcher A, Abdollah F et al. Updated nomogram predicting lymph node invasion in patients with prostate cancer undergoing extended pelvic lymph node dissection: the essential importance of percentage of positive cores. Eur Urol 2012; 61: 480–487
  6. Shelley MD, Kumar S, Wilt T, Staffurth J, Coles B, Mason MD. A systematic review and meta-analysis of randomised trials of neo-adjuvant hormone therapy for localised and locally advanced prostate carcinoma. Cancer Treat Rev 2009; 35: 9–17
  7. Ward JF, DiBlasio CJ, Williams C, Given R, Jones JS. Cryoablation for locally advanced clinical stage T3 prostate cancer: a report from the Cryo-On-Line Database (COLD) Registry. BJU Int 2014; 113: 714–718


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