What is cryotherapy/cryosurgery? Who is a candidate? What is the success rate? What are the risks?

Cryotherapy is a technique used for prostate cancer treatment that involves controlled freezing of the prostate gland. First-line cryotherapy treatment is an option, when treatment is appropriate, to men who have clinically organ-confined disease of any Gleason grade with a negative metastatic evaluation. The size of the prostate gland affects the ability to obtain uniform freezing of the prostate and individuals with large prostates may benefit from decreasing the size of the prostate by the use of pretreatment hormone therapy. This procedure is performed under anesthesia. Transrectal ultrasound evaluation, similar to that used with your prostate biopsy, is used throughout the procedure to visualize the prostate and to monitor the position of the freezing probes, which are placed through the perineal skin into the prostate (Figure 18). During the freezing, the transrectal ultrasound demonstrates an ice ball in the prostate. The freezing process kills both hormone-sensitive and hormone-insensitive cancer cells. Proper positioning of the probe may allow one to kill cancer cells even at the prostate capsule^[1]. During the freezing, a catheter is placed into the urethra, and a warming solution is run through the catheter to protect the urethra from freezing.

Figure 18. Placement of needles for cryoblation of the prostate.

Cryotherapy is a minimally invasive option when treatment is appropriate for men who either don't want or who are not good candidates for radical prostatectomy because of comorbidities, including obesity or a history of pelvic surgery.

Who is a candidate for cryotherapy?

Although more commonly used as a salvage^[2] therapy (a procedure intended to "rescue" a patient after a failed prior therapy) for men who fail to respond to EBRT or interstitial seeds, cryotherapy can be used as a first-line therapy in individuals who have clinically organ-confined disease of any grade with a negative metastatic evaluation. The size of the prostate gland is a factor in patient selection and outcome. The larger the prostate the more difficult it is to achieve a uniformly cold temperature throughout the gland. Thus, those men with large prostate glands may benefit from the addition of hormone therapy (LHRH analogues) to decrease the size of the prostate prior to cryotherapy. A relative contraindication to performing cryotherapy is a large TURP defect. Cryotherapy achieves the best results when the starting PSA is less than 10 ng/ml. Cryotherapy is a minimally invasive option when treatment is appropriate for men who either don't want or who are not good candidates for radical prostatectomy because of comorbidities, including obesity or a history of pelvic surgery. It may also be a reasonable option for men with a narrow pelvis or those who cannot tolerate EBRT, including those with previous nonprostatic pelvic irradiation, inflammatory bowel disease, or rectal disorders. For patients desiring minimally invasive therapy for intermediate disease prostate cancer, Gleason 7 and/or Gleason 8 with PSA > 10 ng/ml and < 20 ng/ml and/or clinical stage T2b, cryotherapy is also an option.

What is the success rate of cryotherapy?

In patients who have not responded locally to EBRT, approximately 40% who then undergo salvage cryotherapy have an undetectable PSA level after cryotherapy, and 78% have negative prostate biopsy results. It appears that a drop in the PSA to 0.5 ng/mL after cryotherapy is associated with a good prognosis. In men with post-cryotherapy PSA levels > 0.5 ng/mL, there is a higher likelihood that the PSA will increase or that the prostate biopsy result will be positive. When cryotherapy is used as the initial primary therapy, a PSA lowest value of < 0.5 ng/mL is associated with a better prognosis.

In studies with long-term data ranging from 5-10 years postcryotherapy, the 5-year biochemical disease-free survival rates for low-, intermediate-, and high-risk cases range from 65-92%, 69-89%, and 48-89%, respectively. A multi-center registry (the Cyroablation online database registry) of primary cryotherapy (no prior procedures surgical or radiation-based) reported pooled 5-year biochemical disease-free progression outcomes noting that:

85% of low-risk patients are disease free at 5 years.

73.4% of intermediate-risk patients were disease free at 5 years.

75% of high-risk patients were disease free at 5 years, using the old ASTRO definition of biochemical recurrence/progression which was defined as three consecutive rises in PSA.

Using the "Phoenix biochemical disease free" definition of nadir PSA plus 2 ng/ml, the following results were achieved:

91% biochemical disease-free rate in low-risk patients

78% biochemical disease-free rate in intermediate-risk patients

62% biochemical disease-free rate in high-risk patients

What are the side effects/complications of cryotherapy?

Common side effects of cryotherapy include perineal pain, transient urinary retention, penile and/or scrotal swelling, and hematuria. Urinary retention occurs in roughly 3% of individuals. Anti-inflammatories seem to help, but individuals may require a catheter or suprapubic tube for a few weeks post-treatment. Penile and/or scrotal swelling is common in the first or second post-procedure weeks and usually resolves within 2 months of cryotherapy. Penile paraesthesia may occur and usually resolves within 2 to 4 months postprocedure. Long-term complications of cryotherapy include fistula formation, incontinence, erectile dysfunction, and urethral sloughing. The risk of permanent incontinence (i.e., need to wear a pad) is reported to range from < 1 to 8%. However, in individuals undergoing salvage cryotherapy after radiation failure, the incidence of urinary incontinence may be as high as 43%. Similarly, with total prostate gland cryotherapy, the ice ball extends beyond the capsule of the prostate and in most cases encompasses the neurovascular bundles and can cause erectile dysfunction. The incidence of erectile dysfunction after cryotherapy in the literature ranges from 49 to 93% at 1 year post-cryotherapy. The risk of fistula formation, a connection between the prostate and the rectum, occurs in 0 to 0.5% of individuals undergoing cryotherapy for prostate cancer and is highest in those men undergoing salvage cryotherapy after failed radiation therapy (EBRT). Urethral sloughing occurs less frequently with use of the urethral warming catheter. Urethral sloughing may cause dysuria and urinary retention. The incidence of urethral sloughing after cryotherapy with use of the urethral warming catheter ranges from 0 to 15%. Symptomatic patients may require transurethral resection of the necrotic tissue.

• [1] A fibrous outer layer that surrounds the prostate.
• [2] A procedure intended to "rescue" a patient after a failed prior therapy, e.g., a salvage radical prostatectomy after failed external-beam therapy.