# Radiation Oncology/Prostate/Cryotherapy

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Cryotherapy (Cryosurgery)

## RT vs Cryotherapy

* University of Calgary (1997-2003) -- EBRT vs Cryotherapy
** Randomized. Trial closed prematurely due to slowing patient accrual. 244 patients of 480 planned, localized prostate cancer (T2-T3N0, PSA <=20 ng/ml, volume <=60 ml), PLND if GS 8+. Excluded clinically bulky patients. Neoadjuvant ADT 3 or 6 months. Arm 1) EBRT (median dose 68 Gy, max 73.5 Gy) using 4F box vs Arm 2) cryoablation using argon/helium and 2 freeze/thaw cycles. Early cryotherapy failures (within 6 months) were not scored as protocol failure, and underwent salvage cryotherapy. QoL assessment. Primary endpoint was failure rate at 3 years
** 2010 PMID 19937954 -- "A Randomized Trial of External Beam Radiotherapy Versus Cryoablation in Patients With Localized Prostate Cancer" (Donnelly BJ, Cancer. 2010 Jan 15;116(2):323-30. Published Online: 24 Nov 2009) Median F/U of surviving patients 8.3 years
*** Outcome: 3-year failure rate (using nadir+2) cryo 17% vs. EBRT 13% (NS); 5-year rate 25% vs. 25% (NS); 7-year rate 27% vs. 32% (NS); 5-year DSS 96% vs. 96% (NS); 5-year OS 90% vs 88% (NS). Biopsy (+) cryo 8% vs EBRT 29%
*** Toxicity: GI Grade 3-4 cryo 3% vs. EBRT 7%; GU Grade 3-4 cryo 9% vs. EBRT 6%; intercourse 4% vs. 26%
*** Conclusion: Essentially no difference, but with long-term follow up, trend favors cryotherapy
*** Editorial (Lee WR, Duke) PMID 19924796: Noninferiority design, 10% margin, concern about patients with early failure and salvage cryotherapy with 6 months as "nonfailure". Overall, cryotherapy not likely to be a lot worse than EBRT
** 2009 PMID 19691092 -- "A randomized trial of external beam radiotherapy versus cryoablation in patients with localized prostate cancer: quality of life outcomes." (Robinson JW, Cancer. 2009 Oct 15;115(20):4695-704.)
*** Outcome: Cryotherapy more acute GU dysfunction (SS), no difference in late GU dysfunction. Cryotherapy worse sexual function at 3 months (SS) and 3 years (SS)
*** Conclusion: No long term QoL difference, except worse sexual function after cryoablation
** Comment: low RT dose
* University of Western Ontario -- EBRT vs cryotherapy
** Randomized. Trial stopped prematurely due to slow accrual. 64 of planned 150 patients, cT2c-T3b. Neoadjuvant ADT for 6 months. Arm 1) EBRT vs. Arm 2) cryotherapy
** 2008 PMID 17579613 -- "Randomized trial comparing cryoablation and external beam radiotherapy for T2C-T3B prostate cancer." (Chin JL, Prostate Cancer Prostatic Dis. 2008;11(1):40-5. Epub 2007 Jun 19.)
*** Outcome: Treatment failure EBRT 45% vs. cryotherapy 64%. 4-year bPFS 47% vs. 13%. Mean bPFS 41 months vs 28 months. No difference in DSS and OS
*** Toxicity: Serious complications uncommon; EBRT more frequent GI toxicity
*** Conclusion: Low numbers, but cryotherapy is suboptimal primary therapy for locally advanced prostate cancer

## Cryotherapy for salvage after RT

See Radiation_Oncology/Prostate/Recurrence_after_RT#Cryotherapy

## Salvage RT after cryotherapy

* Allegheny General (Pittsburgh) (1990-99)
** 49 pts treated for isolated local recurrence after cryotherapy (rising PSA or positive biopsy; negative metastatic workup). 88% had high risk disease initially (PSA>10,G>=7,or >=T2b).
** RT was 3D-CRT in 45 of 49 pts, 64.8 Gy (median dose) to the P+SV.
** PMID 11068312, 2000 — "Salvage radiotherapy for prostate cancer recurrence after cryosurgical ablation." Burton S et al. Urology. 2000 Nov 1;56(5):833-8.
*** Median f/u 32 m. Biochemical control in 61%; associated with higher RT dose (> 64 Gy), lower pre-RT PSA.
*** No grade 3-4 acute GI or GU toxicity. 1 pt with urethral stricture. No pts with urinary incontinence.