964 SALVAGE CRYOABLATION OF PROSTATE CANCER USING 17 GAUGE CRYONEEDLES TECHNOLOGY 7 YEAR EUROPEAN EXPERIENCE

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The ProtecT trial - evaluating the effectiveness of treatments for clinically localised prostate cancer Lane J.A.1, Donovan J.L.1, Neal D.E.2, Hamdy F.C.3, ProtecT study group University of Bristol, Dept. of Social Medicine, Bristol, United Kingdom, 2Addenbrokes’ Hospital, Oncology Centre, Cambridge, United Kingdom, 3University of Oxford, Nuffield Dept. of Surgery, Oxford, United Kingdom

1

Introduction & Objectives: Prostate cancer is a significant public health problem with 30,000 new cases and 10,000 deaths (14% male cancer deaths) in the UK in 2004. Intense debate surrounds the advisability of prostate cancer screening in the UK, in part because the optimum treatment has not been determined by RCTs. Material & Methods: The ProtecT study is a UK multi-centre randomised controlled trial of the effectiveness, cost-effectiveness and acceptability of treatments for clinically localised prostate cancer preceded by case finding in general practices. The trial compares three treatments: active monitoring by PSA (prostate specific antigen), radical prostatectomy and radical conformal radiotherapy. Unselected men aged 50-69 years from 9 centres are invited to enter the study and have a PSA test. The primary outcome is survival at 10 years with secondary outcomes of disease progression, treatment complications, urinary symptoms, sexual function, QoL and health service utilisation. Results: ProtecT recruitment The study commenced in 1999 and will complete recruitment by the end of 2008 from nine centres across the UK. Currently over 109,748 men have attended the recruitment clinics (48 % of those invited by letter) and 10,152 have a raised PSA test (11.0%). Clinical characteristicsThere are 3,064 men with prostate cancer, of whom 2,512 have clinically localised disease (30% of those with a raised PSA) and 324 have locally advanced disease (11%). Participants eligible for randomisation (clinically localised disease) generally have favourable risk characteristics (Table 1). Randomisation and follow-up1593 men have been randomised (63% of those eligible) giving over 500 participants in each treatment group. Follow-up by research schedule and participant questionnaires at six months is currently 89%. Subsequent follow-up rates at 12 months and then annually is over 90% for research schedules and 89% for participant questionnaires.Table 1 Clinical characteristics of participants eligible for randomisation Characteristic Age (years)

PSA (ng/ml)1 Gleason score

Categories 50-54 55-59 60-64 65-69 3-5.99 6-9.99 10-19.99 6 7-10

Eligible cases (%) (1593) 148 (9.4%) 353 (22.5%) 494 (31.5%) 574 (36.6%) 1070 (68.2%) 341 (21.7%) 1 53 (9.8%) 1215 (74.4%) 352 (22.4%)

Particpants with a PSA less than 3.0 ng/ml are not biopsied within the trial and those with a PSA of 20 ng/ml and above are ineligible for randomisation.

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Testing the most stringent criteria for active surveillance: An analysis based on pathological features at radical prostatectomy Suardi N.1, Briganti A.1, Gallina A.1, Salonia A.1, Manuela M.1, Bianchi M.1, Passoni N.M.1, Cestari A.1, Karakiewicz P.I.2, Rigatti P.1, Montorsi F.1 1 Vita-Salute University San Raffaele, Dept. of Urology, Milan, Italy, 2University of Montreal Health Sciences, Cancer Prognostics and Health Outcomes Unit, Montreal, Canada

Introduction & Objectives: Active surveillance represents one of the treatment options for low-risk prostate cancer patients. Many different criteria have been proposed for the selection of patients potentially suitable for this approach. However, high rates of misclassification have been reported. We tested the most stringent proposed criteria for selecting patients potentially candidates to active surveillance in a large of population of patients treated with radical prostatectomy (RP). Material & Methods: The study population was represented by 874 contemporary patients treated with RP at a single institution between January 2002 and September 2008. All patients had complete clinical and pathological data. We evaluated pathological characteristics of patients who could have been selected for active surveillance according to the criteria proposed by Van den Bergh et al. (cT1c/T2, PSA≤10, PSA density <0.2 ng/ml per ml, Gleason score≤3+3, ≤2 positive biopsy cores) and Carter et al.(cT1, PSA density ≤15 ng/ml/cm3, Gleason score ≤3+3 with no pattern 4 or 5, ≤2 positive cores, ≤50% of anyone core involved with cancer). We analyzed the rates of advanced disease in these patients, defined as presence of extracapsular extension (ECE), seminal vesicle invasion (SVI), high grade pathologic Gleason score (defined as pathological Gleason score ≥8-10) and lymph node invasion (LNI). Results: Of 874 patients, 85 (9.7%) and 61 (6.9%) patients could have been selected for active surveillance according to the criteria proposed by Van den Bergh et al. and Carter et al, respectively. When testing the criteria suggested by Van den Bergh et al., ECE, SVI, LNI and high Gleason sum (8-10) was noted in 5.9, 1.2, 1.2 and 1.2% of patients respectively. When testing the criteria suggested by Carter et al., ECE, SVI, LNI and high Gleason sum (8-10) was noted in 3.3, 0.0, 3.3 and 0.0% of patients, respectively. The overall rate of unfavourable prostate cancer characteristics (one of the above mentioned disease parameters) was 7.1 and 3.3% of patients when the criteria by Van den Bergh et al. and Carter et al were tested, respectively. However, when Gleason sum 7 was considered as a proxy for unfavourable prostate cancer characteristics, 28.2 and 27.9% of patients showed unfavourable disease characteristics, respectively.

Conclusions: This large randomised trial focuses on an area of clinical uncertainty around the most appropriate treatment for localised prostate cancer. The trial has achieved its accrual target and is the largest trial comparing prostate cancer treatments worldwide. The clinical characteristics of participants eligible for randomisation are comparable to those of other screen-detected populations such as ERSPC. The trial results will inform UK policy for prostate cancer treatment and screening.

Conclusions: The criteria proposed by Van den Bergh et al. and Carter et al. represent valid tools to select patients for active surveillance. However, according to our patient population, active surveillance can be offered only to 6.9-9.7% of prostate cancer patients when the mentioned criteria are applied. Nevertheless, 3.3-7.1% of patients still risk to be misclassified. Whether these rates are acceptable needs to be discussed in the clinical decision making process.





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Prediction of 30-day mortality after channel transurethral resection for prostate cancer Jeldres C.1, Bhojani N.1, Isbarn H.2, Capitanio U.2, Baillargeon-Gagne S.1, Briganti A.3, Tutolo M.3, Gallina A.3, Salonia A.3, Scattoni V.3, Montorsi F.3, Karakiewicz P.I.2 University of Montreal Health Center, Dept. of Urology, Montreal, Quebec, Canada, 2 Cancer Prognostics and Health Outcomes Unit, Dept. of Urology, Montreal, Canada, 3 Vita-Salute San Raffaele, Dept. of Urology, Milan, Italy 1

Introduction & Objectives: About 8% of patients diagnosed prostate cancer (PCa) and are treated with androgen deprivation therapy (ADT) have to undergo transurethral resection of the prostate (TURP) at some date of the disease. However, little is known about the peri-operative mortality of such patients undergoing TURP. The objectives of this study were to examine the 30-day mortality rate after TURP of patients diagnosed PCa and exposed to ADT and to identify risk factors of 30-day mortality after TURP. Material & Methods: The study cohort consisted of overall 651 assessable patients from the Quebec Health Plan database. The effects on 30-day mortality of age, comorbidity (coded according to the Charlson Comorbidity Index [CCI]), annual surgical volume, number of previous TURPs of each patient, previous radiation therapy, usage of antiandrogens, type of ADT (either in the form of orchiectomy or in the form of LHRHa), duration of ADT until TURP, and time from diagnosis until TURP were tested in univariable and multivariable logistic regression models. Clinical parameters such as duration of surgery, gland size, or PSA-level were not available. Results: In the entire cohort of 651 patients, 31 deaths occurred during the initial 30 days after TURP (4.8%). Of all variables tested, CCI and precious radiation therapy were statistically significant and independent predictors for 30-day mortality after TURP (p<0.05). The remaining variables failed to reach statistical significance. Conclusions: Patients with diagnosed PCa and exposure to ADT have a substantial risk of 30-day mortality. CCI and previous radiation therapy are significant predictors of 30-day mortality after TURP. Our model can be used for purpose of informed consent prior to TURP, since no other predictive tool is currently available to predict the risk of death after TURP in patients with PCa.

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Salvage Cryoablation of prostate cancer using 17 gauge cryoneedles technology 7 year European experience Witzsch U.K.F., Skriapas K., Hieronymi S., Becht E.W. Krankenhaus Nordwest, Dept. of Urology and Pediatric Urology, Frankfurt Am Main, Germany Introduction & Objectives: Therapeutic options after failure of first line therapy for localized prostate cancer are limited. Mostly unsatisfying results are combined with severe side effects. Improvements in transrectal ultrasound (TRUS) technology and the introduction of the 17 gauge cryoneedles (Galil-Medical, USA) have made it possible for an urologist to monitor and precisely control ice formation during the prostate gland cryoablation. We show our experience of the last 7 years. Material & Methods: Between 9/2001 and 2/2008, 165 prostate cryoablation procedures were performed in our institution. 102/165 had been treated for salvage therapy. Indication for salvage therapy was: 1)Rising PSA after radiation therapy (either seed implantation, HDR Brachytherapy (n=10) or external beam radiation therapy n=40 local 2)recurrance after radical prostatectomy n=24 3)rising PSA after initial hormone therapy n=17 4)recurrence after cryotherapy n=10 5)recurrance after HIFU n=1 Pts. were classified as “favourable” if they had PSA <10ng/ml, Gleason <7, Tumour stage < T3, 10 pts. were patients with favourable characteristics. Pts. were classified as “unfavourable” if they did not met all three of the stated parameters. In this series 41 of the patients were salvage patients with unfavourable characteristics. However 50 patients were failures after any kind of radiation therapy. Median PSA was 5,6 ng/ml and median Gleason score was 8. All pts. had positive biopsies and negative metastatic work up prior to the cryoablation. From 9 to 19 17-gauge, cryoneedles were percutaneously placed in the prostate under transrectal ultrasound guidance. Two cryoneedles and a thermo sensor were placed in the area between the rectal wall and Denonvillier’s fascia for temperature monitoring and active thawing. During the freezing process rectal temperature was closely monitored and when a reading of below 20° C was noted, rectal warming was activated simultaneously. A “pull back” (of 15 mm median) was done for prostates longer than 35 mm (32pts.) Median treatment time was 115 minutes. Results: PSA % years 1 2 3 3 5 6

<0,1 ng/ml

>0,1- <0,5

>0,5 ng/ml

median

38% 34% 45% 37% 31% 30%

15% 14% 18% 26% 25% 20%

46% 52% 36% 37% 44% 50%

0,1 0,3 0,1 0,1 0,3 0,4

Patients after radiation therapy are suffering from a higher rate of irritative symptoms. Patients after radical prostatectomy remain low in PSA and side effects. No incontinence was observed. The minority of the remaining salvage patients stay on low PSA levels. This might be due to occult metastasis at the time of restaging. Except one fistula no SAE occurred. If the seminal vesicles are treated intermittent ureteral obstruction is probable. Conclusions: Although most of the pts. were at high risk for progression, the results are encouraging. Third generation cryoablation of the prostate is a minimally invasive alternative for pts. who had failed other therapeutic options for localized prostate cancer.

Eur Urol Suppl 2009;8(4):361