Advances in imaging and image-guided biopsies have resulted in a better understanding of the characteristics of recurrences within the prostate gland, which are often restricted to select parts of the gland, and therefore amenable to whole-gland or focal salvage cryo-ablation, as one of the possible therapeutical options.
The mechanisms behind cryotherapy entail tissue destruction initiated by very low temperatures. This was first detailed by Baust and Gage as a combination of cell membranes injury, micro-vascular damage and initiation of apoptosis.4 This cascade results in tissue necrosis followed by cicatrisation from the margins of the ablated mass. In animal models, a temperature of -20°C in one cycle of freezing is sufficient to drive prostate tissue necrosis5. However, in the clinical world, it is recommended to perform two cycles of freezing (10 min each) interspaced by passive thawing to achieve best results.
A successful cryoablation is represented by effective and complete destruction at the center of the target mass, counterbalanced at the edge by the dynamic recruitment of angiogenesis, and cell division that support cicatrisation. Thus, the major limitations of cryotherapy include the risk of injury of neighboring organs driven by too low a temperature or by impaired cicatrisation; and the risk of leaving some intact foci of neoplastic tissues at the margins.
Before referring the patient to undergo this procedure, we must answer several questions:
- What are the odds that local recurrence may be on the long term detrimental to the patient
- What is the extent of the recurrence within the prostate gland and the neighboring structures?
- How likely is it that the recurrence is only restricted to the gland.
1. General health status: WHO/ECOG status, predicted life expectancy, comorbidities, and geriatric evaluation
2. Local evaluation: Digital rectal examination (DRE), multiparametric MRI, image-guided biopsies of
any suspicious area in the prostate
3. Metastatic evaluation: TNM initial stage, time to recurrence, PSA kinetics, mpMRI results (involvement of regional nodes), Whole body CT-scan, metabolic (PET-Choline) and molecular imaging (PET-PSMA).
Lastly, preoperative transrectal ultrasonography will verify that the TRUS probe can be inserted in the rectum, it will also be used to evaluate the risks of local complications by measuring the distance between the prostate capsule and the rectal wall (usually ~2mm), and the presence of an hyper-echoic crescent of protective fat (Figure 1).
The main risk of the procedure includes injury the rectal wall (2%), which may lead to urethrorectal fistula, a serious complication that is hardly amenable to surgical correction in the context of previous radiotherapy, and is usually treated by permanent colostomy.
Few series of salvage cryoablation are available. However, Williams et al. showed in a relatively large historical series of 176 patients that two criteria, PSA<5 and Gleason score <7 at presentation, could be used to select a population more likely to have favorable prognosis.6
Figure 1 – Cryotherapy:
Speaker: Bernard Malavaud, MD, PhD at Univeristé Paul Sabatier Toulouse, France
Written By: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre @GoldbergHanan at The 15th Meeting of the EAU Section of Oncological Urology ESOU18 - January 26-28, 2018 - Amsterdam, The Netherlands
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2. Roach M, 3rd, Hanks G, Thames H, Jr., et al. Defining biochemical failure following radiotherapy with or without hormonal therapy in men with clinically localized prostate cancer: recommendations of the RTOG-ASTRO Phoenix Consensus Conference. Int J Radiat Oncol Biol Phys. 2006;65(4):965-74.
3. Jones JS. Radiorecurrent prostate cancer: an emerging and largely mismanaged epidemic.
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4. Baust JG, Gage AA. The molecular basis of cryosurgery. BJU Int. 2005;95(9):1187-91.
5. Gage AA, Baust JM, Baust JG. Experimental cryosurgery investigations in vivo. Cryobiology. 2009;59(3):229-43.
6. Williams AK, Martinez CH, Lu C, Ng CK, Pautler SE, Chin JL. Disease-free survival following salvage cryotherapy for biopsy-proven radio-recurrent prostate cancer. Eur Urol. 2011;60(3):405-10.