Prostate Gland Lengths and Iceball Dimensions Predict Micturition Functional Outcome Following Salvage Prostate Cryotherapy in Men with Radiation Recurrent Prostate Cancer

Abstract

IntroductionTissue cryoablation is a potential curative option for solid malignancies, including radiation recurrent prostate cancer (RRPC). Case series of salvage cryotherapy (SCT) in RRPC have reported promising disease free survival (DFS) outcomes and acceptable toxicity profile. While many men receive SCT, no predictive factors for treatment induced side effects are known. The aim of this study is to validate the oncologic outcome of SCT in a large multi-centre patient cohort and to identify potential parameters associated with an increased risk of micturition symptoms.Patients and MethodsIn this retrospective analysis, we studied 283 consecutive patients with RRPC treated by SCT in three independent U.K. centres (between 2001 and 2011). Two freeze-thaw cycles of transperineal cryotherapy were performed under transrectal ultrasound guidance by a single surgeon in each of the 3 sites. We analysed clinico-pathological factors against tumour response. Functional outcomes were assessed by continence status and IPSS questionnaire. Predictive factors for SCT-induced micturition symptoms were analysed in a sub-group (n = 42) of consecutive cases.ResultsWe found that nadir post-SCT PSA levels strongly associated with DFS. The DFS rates at 12- and 36-month were 84% and 67% for the ≤1 ng/ml group and 56% and 14% for the >1 ng/ml group, respectively (p<0.001). Correlative analysis revealed highly significant association between patients' post-SCT micturition status with prostate gland and iceball lengths following SCT. Finally, in a reduction model, both gland length and maximal length of iceball were highly associated with patients' IPSS outcome (p<0.001).ConclusionWe report the largest European patient cohort treated with SCT for RRPC. Oncologic outcome guided by nadir PSA of <1 ng/ml is consistent with earlier single-centre series. For the first time, we identified physical parameters to predict micturition symptoms following SCT. Our data will directly assist on-going and future trial design in cryotherapy in prostate cancer.

Decision analytic cost-effectiveness model to compare prostate cryotherapy to androgen deprivation therapy for treatment of radiation recurrent prostate cancer

“…With regard to adverse events, previous studies of cryotherapy and ADT have found that short-term adverse events have very little effect on overall/long-term quality of life; 37 however, they may incur considerable additional costs in patient treatment, so it is important to capture any cost or quality of life impacts of any acute adverse events and how these may impact on model outcomes. Therefore, the model allowed for patients in the SC cohort to experience the seven most common SC-related adverse events (incontinence, retention, lower urinary tract symptoms, perineal pain, haematuria, urethra stricture and fistula), utilising the worst case estimates reported in recent literature 22 33 35 to ensure the base-case analysis was pessimistic towards cryotherapy. Persistent erectile dysfunction would be experienced by the majority of patients who have RRPC before undertaking cryotherapy or beginning ADT, as a result of prior treatment, 6 which is accounted for in the baseline utility level for all cohorts (as detailed in online supplementary material ).…”

“…6–8 The Markov model comprises four states: ‘pre-ADT’ which for post-SC patients is biochemical disease-free survival (BDFS), ‘BDFS with ongoing ADT’, ‘Progression’ and ‘Death’. Cryotherapy-associated adverse events (urinary incontinence, obstructive urinary symptoms/retention, lower urinary tract symptoms, perineal pain, haematuria, urethral stricture and fistula) will typically manifest within 3 months post-treatment, 22 and are assigned an additional cost and quality of life decrement for this time period. Patients with troublesome ADT-induced hot flushes may require additional antiandrogen treatment.…”

“…Patients who received SC will enter the Markov model with the nadir prostate-specific antigen (nPSA) level achieved, with nPSA <1 ng/mL being a good prognostic marker. 13 22 At the end of each monthly cycle, SC patients can experience death, remain in the pre-ADT state or develop biochemical recurrence 13 triggering first-line ADT (with patients entering the lower BDFS state). In the ADT arm, all patients enter the model in the BDFS with ADT state, receiving monthly treatment with goserelin as clinically recommended.…”

Treatment methods of prostate cancer recurrence after radiotherapy. Current treatment alternatives and our clinical experience

“…More recent Finley et al study analyzed up-to-date oncologic and functional outcomes, as well as complications of salvage cryotherapy for radiationrecurrent prostate cancer and reported 21.7% urinary incontinence rate [18]. Other new study reported even better results: long term incontinence rate was 12% (using 1 pad per day beyond 6 months post-salvage cryotherapy) and fistula rate of 1.8% [19].…”

Comparative morbidity of ablative energy-based salvage treatments for radio-recurrent prostate cancer

“…22,23 Ahmad and colleagues (CROP trial) in their cohort of 283 patients reported an incontinence rate of 12% (0-1 pad/ day). 22 In our experience we found a higher rate of mild-moderate incontinence (≤1 pad/day) 49%, 31% and 3% in Groups 1, 2 and 3, respectively; for severe incontinence (>2 pad/ day), we reported a similar rate (1.5% , 5% and 3%) for Groups 1, 2 and 3, respectively. Pisters and colleagues reported in a comparable sized series 4.4 % (defined as incontinence requiring use of pads), which is commensurate with our results.…”