Athens, Greece (UroToday.com) Cryoablation involves freezing of the targeted prostate tissue in two cycles, reaching minus 40 degrees Celsius, with the following histological changes:
- Protein denaturation
- Direct rupture of cell membranes by crystal formation
- Vascular stasis and secondary microthrombi formation
- Ischemic cell death
- Coagulative necrosis
Ten-year data of whole-gland cryoablation in 370 patients with a follow-up of 12.55 years have shown a biochemical disease-free survival rate at 10 years of 80.56%, 74.16%, 45.54% for low-, intermediate-, and high-risk disease, respectively.1 The 10-year negative biopsy rate was 76.96%. These patients maintain relatively high continence and potency rates compared to radical definitive therapies.
Patient selection is critical to achieving a high success rate in focal therapy. The ideal patient is a patient who has a disease which is between Gleason grade group 1 and 2, who is not an ideal candidate for active surveillance, such as a patient with Gleason grade group 1 with multiple positive cores, with a high percentage of core involvement, and a high PSA density. A patient with low volume Gleason grade 2 who desires to undergo this treatment is also a good candidate.
Prior to treatment with focal therapy all patients need to undergo a mpMRI and systematic and targeted biopsies. The index lesion needs to be localized accurately. Posterior tumors may be amenable to better results using treatment with high intensity ultrasound (HIFU) treatment, but anterior lesions should be treated with cryotherapy.
In a large systematic review of all focal therapy modalities published in 2017, the functional outcomes of focal cryoablation were detailed to be as followed: serious adverse events occur in 2.5% of cases, continence is kept in 98% of men, potency remains in 69-88%, and the rate of fistula development is very low with 0-0.3%. When analyzing the oncologic outcomes of cryotherapy, in a posttreatment biopsy clinically significant prostate cancer was found in only 5.4% of cases.2
Lastly, Dr. Abreu discussed the comparison of focal cryoablation to active surveillance. A large study compared 33 cryotherapy treated patients with 189 active surveillance (AS) – treated patients. All patients had at least one follow-up prostate biopsy between 2002 and 2014.3 The primary endpoint of this study was pathological progression-free survival, and the secondary endpoint was radical treatment-free survival. The pathological progression free-survival and radical treatment-free survival are shown in Figure 1 and figure 2, respectively, showing a clear advantage for patients treated with focal therapy. This study was limited by its retrospective nature, and a small number of patients.
Figure 1 – Pathological progression free survival in cryoablation vs. active surveillance:
Figure 2 – Radical treatment free survival in cryoablation vs. active surveillance:
The last topic that was discussed was focal cryoablation for intermediate or high-risk prostate cancer patients. Dr. Abreu presented a study of 122 patients with 87 having intermediate risk disease and 35 having high-risk disease.4 These patients underwent focal cryotherapy of all MRI visible tumors, with anterior tumors consisting of 65.5% of tumors. The median follow-up was 27.8 months with follow-up biopsy taking place in 24% of patients. The primary outcome was failure free survival.
Adverse events were reported in 27.8% of cases, with urinary retention, urinary tract infection, penile numbness, and osteomyelitis of the pubic bone occurring in 4.1%, 9%, 9.8%, and 0.8%, respectively. The potency rate at the end of follow-up was 84% with no reported incontinence. The overall failure free survival at 36 months was 90.5%.
In conclusion, Dr. Abreu believes that cryotherapy is safe and feasible, reproducible, with good oncological and functional outcomes. Larger multicenter cohorts are still required in order to obtain more data. The utilization of this modality for high risk disease is still not clear, and we need a much longer follow-up to better understand the long-term outcomes.
Presented by: Andre Abreu, MD, Assistant Professor of Clinical Urology, University of Southern California, Los Angeles, California, USA
Written by: Hanan Goldberg, MD, Urology Department, SUNY Upstate Medical University, Syracuse, New-York, USA @GoldbergHanan at the 39th Congress of the Société Internationale d'Urologie, SIU 2019, #SIUWorld #SIU2019, October 17-20, 2019, Athens, Greece
- Cohen JK, Miller RJ, Jr., Ahmed S, Lotz MJ, Baust J. Ten-year biochemical disease control for patients with prostate cancer treated with cryosurgery as primary therapy. Urology 2008; 71(3): 515-8.
- Valerio M, Cerantola Y, Eggener SE, et al. New and Established Technology in Focal Ablation of the Prostate: A Systematic Review. Eur Urol 2017; 71(1): 17-34.
- Ashrafi A, Tafuri A, Shakir A, et al. MP78-09 FOCAL CRYOABLATION IS ASSOCIATED WITH IMPROVED PATHOLOGICAL PROGRESSION-FREE COMPARED TO ACTIVE SURVEILLANCE IN GLEASON 6 PROSTATE CANCER. Journal of Urology 2019; 201.
- Shah TT, Peters M, Eldred-Evans D, et al. Early-Medium-Term Outcomes of Primary Focal Cryotherapy to Treat Nonmetastatic Clinically Significant Prostate Cancer from a Prospective Multicentre Registry. Eur Urol 2019; 76(1): 98-105.