Cryotherapy for Prostate Cancer
Cryotherapy (cryosurgery/cryoablation) is a minimally invasive treatment that uses extreme cold to freeze and destroy prostate cancer tissue, recommended as an alternative option for low- and intermediate-risk localized prostate cancer in patients who cannot undergo surgery or radiation due to comorbidities, but with the critical caveat that erectile dysfunction is an expected outcome and long-term mortality data remain insufficient. 1
What Cryotherapy Is
Cryotherapy is a specific type of ablation that achieves tumor destruction through local freezing by introducing probes directly into the prostate 2, 3. The procedure uses third-generation or higher argon-based cryosurgical systems to create ice balls that kill malignant cells 1. This is distinct from other ablation techniques like radiofrequency or microwave ablation 2.
Clinical Indications and Patient Selection
Consider whole gland cryosurgery specifically for: 1
- Low- and intermediate-risk localized prostate cancer (stages T1c-T2c)
- Patients unsuitable for radical prostatectomy due to:
- Morbid obesity
- Prior pelvic surgery
- Significant comorbidities
- Patients with contraindications to radiotherapy including:
- Previous pelvic radiation
- Inflammatory bowel disease
- Rectal disorders
- Life expectancy >10 years despite comorbidities 1
Relative contraindications include: 1
- Defects from prior transurethral resection of the prostate (TURP) due to increased risk of urethral sloughing
Oncologic Efficacy
Biochemical Control Rates
The AUA/ASTRO/SUO guidelines report that cryosurgery demonstrates similar progression-free survival to non-dose escalated external beam radiation therapy (EBRT) with neoadjuvant hormonal therapy in low- and intermediate-risk disease 1. However, conclusive comparison of mortality is lacking due to insufficient sample sizes and follow-up duration 1.
Recent case series data show: 4, 5, 6
- Biochemical progression-free survival (BPFS) of 67-70% for low- and intermediate-risk groups at 5 years
- BPFS of 96.4% for low-risk, 91.2% for intermediate-risk, and 62.2% for high-risk patients in prospective studies
- Cancer-specific survival of 94-98% at 5 years
- Overall survival of 89-94% at 5 years
One completed RCT showed cryosurgery had a lower rate of persistent primary cancer on biopsy at 36 months (8% versus 29% for EBRT), though this study was underpowered for mortality outcomes 1.
Predictors of Success
PSA nadir is the strongest predictor of biochemical control 4, 7. Patients achieving an undetectable PSA (<0.1 ng/mL) post-cryotherapy have significantly better outcomes than those who do not (73% versus 30% biochemical recurrence-free survival) 7.
Adverse Effects and Quality of Life Impact
Sexual Function
Erectile dysfunction is an expected outcome that patients must be counseled about before proceeding 1. The AUA/ASTRO/SUO guidelines emphasize this as a clinical principle, with rates of 47-100% reported across studies 3, 6. Whole gland cryosurgery is associated with worse sexual side effects than radiotherapy 1.
Urinary Function
- Continence is maintained in 95% of patients 4
- Incontinence occurs in 1.3-19% of cases 3, 6
- Urinary obstructive symptoms can be exacerbated, similar to brachytherapy 1
- Acute urinary retention in 8.5%, typically resolved conservatively 4
- Urethral sloughing in 3.9-85% (wide range reflects evolution of technique) 3
Other Complications
- Bowel/rectal side effects similar to radiotherapy 1
- Perineal pain in 11-26% 4, 3
- Urinary tract infection in 9-17.5% 4, 3
- Prostatorectal fistula in 0-2% (rare but serious) 3, 6
- Bladder neck obstruction and strictures in 2-55% 3
Most patients are discharged within 1-4 days 3.
Role of Androgen Deprivation Therapy
The benefit of concurrent ADT with cryosurgery has not been formally established 1. While ADT can reduce prostate size to facilitate treatment (particularly for prostates 40-60cc), it is unclear whether it improves cancer control 1, 4. This contrasts with radiotherapy where ADT has proven survival benefits in high-risk disease 1.
Technical Considerations
Third-generation or higher argon-based cryosurgical systems should be utilized 1. Studies using temperature monitoring with thermocouples report better outcomes (71-89% progression-free survival) compared to those without temperature monitoring (17-28% positive biopsies post-treatment) 3.
Evidence Limitations and Clinical Context
The major limitation is the paucity of randomized controlled trials 1. Only two RCTs have been reported, both comparing cryosurgery to EBRT with neoadjuvant ADT. One multicenter RCT was aborted before reaching half its accrual goal, and the completed single-center study was underpowered for mortality outcomes 1. A 2007 Cochrane review found no randomized trials comparing cryotherapy with other primary therapies 3.
Because of this limited evidence, the NCCN does not recommend cryotherapy as routine primary therapy, citing lack of long-term comparative data 1. The AUA/ASTRO/SUO guidelines provide only a conditional recommendation (Evidence Level Grade C) 1.
Salvage Cryotherapy
Cryotherapy is also used as salvage treatment for local recurrence after radiation therapy 1. In this setting, biochemical recurrence-free survival rates of 66-79% at 12 months have been reported, with PSA nadir <0.1 ng/mL being the strongest predictor of success 7.
Clinical Decision-Making Algorithm
For patients with low- or intermediate-risk localized prostate cancer:
First-line options remain radical prostatectomy or radiotherapy for surgical candidates with >10 year life expectancy 1
Consider cryotherapy when:
- Patient has prohibitive surgical risk (morbid obesity, prior pelvic surgery, significant comorbidities) AND
- Contraindications to radiotherapy exist (prior pelvic radiation, inflammatory bowel disease, rectal disorders) AND
- Life expectancy >10 years 1
Mandatory patient counseling must include: 1
- Erectile dysfunction is expected (near-universal)
- Similar progression-free survival to non-dose escalated EBRT but lacking mortality data
- Similar urinary and bowel side effects to radiotherapy
- Requirement for third-generation argon-based systems
Avoid cryotherapy if: 1
- Prior TURP defects present (increased urethral sloughing risk)
- Patient unwilling to accept near-certain erectile dysfunction
- High-risk disease where proven therapies (surgery + adjuvant radiation or EBRT + long-term ADT) have established survival benefits
The critical clinical caveat: While cryotherapy offers a minimally invasive option with competitive short-to-intermediate term biochemical control rates, the absence of long-term randomized data comparing mortality outcomes means patients must understand they are choosing a treatment with less robust evidence than standard therapies 1, 3.