Abstract: We included only one comparison of whole gland cryotherapy versus external beam radiotherapy, which was informed by two trials with a total of 307 randomised participants. The median age of the included studies was around 70 years. The median follow-up of included studies ranged from 100 to 105 months. Primary outcomes: we are uncertain about the effect of whole gland cryotherapy compared to radiation therapy on time to death from prostate cancer; hazard ratio (HR) of 1.00 (95% confidence interval (CI) 0.11 to 9.45; 2 trials, 293 participants; very low QoE); this would correspond to zero fewer death from prostate cancer per 1000 men (95% CI 85 fewer to 520 more). We are equally uncertain about the effect of quality of life-related urinary function and bowel function (QoL) at 36 months using the UCLA-Prostate Cancer Index score for which higher values (range: 0 to 100) reflect better quality of life using minimal clinically important differences (MCID) of 8 and 7 points, respectively; mean difference (MD) of 4.4 (95% CI −6.5 to 15.3) and 4.0 (95% CI −73.96 to 81.96), respectively (1 trial, 195 participants; very low QoE). We are also uncertain about sexual function-related QoL using a MCID of 8 points; MD of −20.7 (95% CI −36.29 to −5.11; 1 trial, 195 participants; very low QoE). Lastly, we are uncertain of the risk for major adverse events; risk ratio (RR): 0.91 (95% CI 0.47 to 1.78; 2 trials, 293 participants; very low QoE); this corresponds to 10 fewer major adverse events per 1000 men (95% CI 58 fewer to 86 more). Secondary outcomes: we are very uncertain about the effects of cryotherapy on time to death from any cause (HR 0.99, 95% CI 0.05 to 18.79; 2 trials, 293 participants; very low QoE), and time to biochemical failure (HR 2.15, 95% CI 0.07 to 62.12; 2 trials, 293 participants; very low QoE). Rates of secondary interventions for treatment failure and minor adverse events were either not reported in the trials, or the data could not be used for analyses. We found no trials that compared whole gland cryotherapy or focal cryotherapy to other treatment forms such as radical surgery, active surveillance, watchful waiting or other forms of radiotherapy. Based on very low quality evidence, primary whole gland cryotherapy has uncertain effects on oncologic outcomes, QoL, and major adverse events compared to external beam radiotherapy. Reasons for downgrading the QoE included serious study limitations, indirectness due to the use of lower doses of radiation in the comparison group than currently recommended, and serious or very serious imprecision.

Plain-language summary: We searched the medical literature for evidence from trials up to 6 March 2018. We found two randomised trials that compared freezing of the whole prostate to radiation treatment. These included 307 randomised men with prostate cancer (cryotherapy 154 men, radiation 153 men). Their average age was around 70 years. These studies followed men for eight to nine years after treatment. We did not find any studies that compared freezing the prostate to surgery. Also, we did not find randomised trials that compared freezing of parts of the prostate (focal cryotherapy) to radiation, surgery or no treatment. We are uncertain of the effects of freezing of the whole prostate compared to radiation treatment on the time to death from prostate cancer, quality of life for urinary, bowel, and sexual function and serious unwanted treatment reactions. The quality of evidence was very low for all outcomes meaning that the real effect of whole gland cryotherapy may differ a lot from the findings in this review. Further research is very likely to change these findings.