Michael C. Large, MD
BASICS
DESCRIPTION
• Primary cryotherapy is an option for patients with clinically localized prostate cancer of low-, intermediate- or high-grade (1)[B]
• Especially suited for comorbid patients who cannot tolerate alternative therapy (extensive previous surgery, inflammatory bowel disease) (1)[B]
EPIDEMIOLOGY
Incidence
• Nearly 7,000 cryoablations for prostate cancer were performed in US in 2005 (2)[C]
– Usage projected to increase
RISK FACTORS
• For recurrence after primary cryotherapy:
– Larger glands make uniform freezing more difficult
– PSA >10 ng/mL
• For complications after primary cryotherapy:
– Prior TURP increases risk of urethral necrosis
PATHOPHYSIOLOGY
• Tissue destruction from cryotherapy multifactorial
– Induces apoptosis
– Intracellular ice formation and local hypoxia cause necrosis
– Maximum cell death with: Nadir temperature <−20°C, rapid freezing rate, slow thawing rate, multiple freeze/thaw cycles
– Urethral warming catheter protects urothelium but increases potential for preserving PSA-producing tissue
DIAGNOSIS
HISTORY
• History of prostate cancer treated by primary cryotherapy
– Recommend ≥3 mo elapse from primary treatment before testing for recurrence
PHYSICAL EXAM
• Digital rectal exam
– Findings may be difficult to interpret given previous therapy
DIAGNOSTIC TESTS & INTERPRETATION
Lab
• PSA spikes initially from necrosis of the prostate tissue
• Following cryotherapy PSA rechecked every 3 mo × 1 yr, then every 6 mo thereafter
• PSA may not decrease to undetectable
• PSA-based definition for biochemical recurrence is not standardized. Various parameters used:
– PSA >0.4 ng/mL, >0.5 ng/mL, >1.0 ng/mL,
– 3 consecutive increases (“ASTRO” definition)
– Nadir + 2 ng/mL (“Phoenix” definition)
Imaging
• Complete metastatic workup may include:
– CXR
– CT abdomen/pelvis
– Bone scan
– Endorectal MRI
Diagnostic Procedures/Surgery
• Transrectal biopsy
– Commonly performed post-cryotherapy
– Recommend waiting 6 mo for inflammation to resolve
– Negative biopsy reported in 75–95% (1)[B],(2)[C]
– Lower PSA nadir and lower clinical stage predict negative re-biopsy
DIFFERENTIAL DIAGNOSIS
• Necrosis, especially if within 3 mo of procedure
• Residual benign prostatic tissue
• Treatment failure
• Recurrent disease (local or metastatic)
TREATMENT
GENERAL MEASURES
Confirmation of recurrence via transrectal biopsy
MEDICATION
First Line
• No first-line medication therapy
– Consider androgen-deprivation therapy or clinical trial if metastatic disease
– No significant data on the use of androgen-deprivation after local cryotherapy failure
Second Line
N/A
SURGERY/OTHER PROCEDURES
• Salvage prostatectomy feasible but large series are lacking
• Reported techniques include:
– Open retropubic or perineal
– Laparoscopic or robotically assisted
• Salvage cystoprostatectomy with urinary diversion
– Option for extensive local recurrence with severe, treatment-refractory lower urinary tract symptoms
ADDITIONAL TREATMENT
Radiation Therapy
• Conformal or Intensity-modulated radiotherapy
– Largest series 49 patients, received conformal RT (3)[C]
– Mean preradiation PSA 2.4 ng/mL
– Mean RT dose 62.9 Gy
– At median follow-up 32 mo, biochemical-free survival rate 61%
Additional Therapies
• Repeat cryotherapy
– Largest series 32 patients (4)[C]
– Median follow-up 63 mo
22, 23, and 29 were biochemical disease free by definitions of 0.5 ng/mL, 1.0 ng/mL, and ASTRO definition
Complementary & Alternative Therapies
None widely studied
ONGOING CARE
PROGNOSIS
• Biochemical recurrence-free survival after primary cryotherapy (Phoenix definition)
– 5-yr estimates based on D’Amico risk category: (1)[B],(2)[C]
Low risk: 85–90%
Intermediate risk: 80%
High risk: 60–70%
– 10-yr estimates based on D’Amico risk category:
Low risk: 80%
Intermediate risk: 75%
High risk: 45%
COMPLICATIONS
• No large series following postcryotherapy salvage treatment
• Surgery:
– Intraoperative rectal injury
Small injury: 2-layer primary repair and omental interposition
Large injury, gross spillage, poor tissue viability: Primary repair and diverting colostomy
– Urinary incontinence, impotency
• Radiation
– Rectourethral fistula, urethral stricture, urinary incontinence, impotency, and bladder and rectal toxicities
• Repeat cryotherapy
– Rectourethral fistula, urethro-cutaneous fistula, urethral stricture, urinary incontinence, impotency, and bladder and rectal toxicities
FOLLOW-UP
Patient Monitoring
• No standards exist for postcryotherapy recurrence follow-up
• If biochemical disease untreated, may treat patient according to algorithms for (1) localized or (2) advanced prostate cancer outlined in prior chapters
• If patient has undergone salvage treatment after cryotherapy, no standards exist
– PSA often performed every 3 mo after salvage therapy
– Re-biopsy may be offered 6 mo after treatment, or if clinically indicated
Patient Resources
American Cancer Society http://www.cancer.org/cancer/prostatecancer/detailedguide/prostate-cancer-treating-cryosurgery
REFERENCES
1. Babaian RJ, Donnelly B, Bahn D, et al. Best practice statement on cryosurgery for the treatment of localized prostate cancer. J Urol. 2008;180:1993–2004.
2. Finley DS, Pouliot F, Miller DC, et al. Primary and salvage cryotherapy for prostate cancer. Urol Clin North Am. 2010;37:67–82.
3. Burton S, Brown DM, Colonias A, et al. Salvage radiotherapy for prostate cancer recurrence after cryosurgical ablation. Urology. 2000;56:833–838.
4. Bahn DK, Lee F, Badalament R, et al. Targeted cryoablation of the prostate: 7-yr outcomes in the primary treatment of prostate cancer. Urology. 2002;60(2A):3–11.
ADDITIONAL READING
AUA best practice policy statement on cryosurgery for the treatment of localized prostate cancer: http://www.auanet.org/content/media/cryosurgery08.pdf (Accessed July 22, 2014)
See Also (Topic, Algorithm, Media)
• Prostate Cancer, Biochemical Recurrence (elevated PSA) Following Radiation Therapy
• Prostate Cancer, Biochemical Recurrence (elevated PSA) Following Radical Prostatectomy
• Prostate Cancer, General
• PSA Elevation, General Considerations
• Reference Tables: TNM: Prostate Cancer
CODES
ICD9
• 185 Malignant neoplasm of prostate
• 790.93 Elevated prostate specific antigen [PSA]
• V10.46 Personal history of malignant neoplasm of prostate
ICD10
• C61 Malignant neoplasm of prostate
• R97.2 Elevated prostate specific antigen [PSA]
• Z85.46 Personal history of malignant neoplasm of prostate
CLINICAL/SURGICAL PEARLS
• An early rise in PSA after cryotherapy is normal, and further testing should be deferred until at least 3 mo following treatment.
• Various definitions of PSA failure after cryotherapy exist: >0.4 ng/mL, >0.5 ng/mL, >1.0 ng/mL, 3 consecutive rises, and nadir + 2 ng/mL.
• Prostate biopsy is useful in the workup of postcryotherapy biochemical recurrence.
• Postcryotherapy treatment of recurrent disease should be reserved for highly experienced surgeons and radiation oncologists.