Duke Bahn

Five-year retrospective, multi-institutional pooled analysis of cancer-related outcomes after cryosurgical ablation of the prostate

OBJECTIVES To define the potential role of cryosurgical ablation of the prostate (CSAP) as a treatment option for patients with localized prostate carcinoma (PCA), we performed a retrospective outcomes analysis of a large database of patients undergoing CSAP constructed from five institutions and compared this with matching outcomes from contemporary reports of patient outcomes after radiotherapy. METHODS A total of 975 patients who underwent CSAP as primary therapy from January 1993 to January 1998 with sufficient outcomes data available were identified. Patients were stratified into three groups on the basis of their clinical features. Biochemical-free survival (BFS), post-CSAP biopsy results, and post-CSAP morbidities were calculated and recorded. RESULTS The median follow-up for all patients was 24 months. The percentages of patients in the low, medium, and high-risk groups were 25%, 34%, and 41%, respectively. For prostate-specific antigen thresholds of less than 0.5 and less than 1.0 ng/mL, the 5-year actuarial BFS ranged from 36% to 61% and 45% to 76%, respectively, depending on the risk category. Overall, the positive biopsy rate was 18%. Morbidities included impotence in 93%, incontinence in 7.5%, rectourethral fistula in 0.5%, and transurethral resection of the prostate in 13% of patients (10% approved warming catheters versus 40% nonapproved). CONCLUSIONS For each risk group, the 5-year BFS and positive biopsy rate after CSAP was comparable to matching outcomes reported after radiotherapy. Morbidities also seemed comparable, with impotence rates higher and rectal injury rates lower after CSAP than after radiotherapy. These data indicate that CSAP can be performed with low morbidity and can produce cancer-related results comparable to those reported for patients undergoing radiotherapy.

Best Practice Statement on Cryosurgery for the Treatment of Localized Prostate Cancer

Introduction The protracted natural history of clinically localized prostate cancer has confounded the development of a national consensus regarding the optimal treatment for this disease. In the AUA 2007 Guideline for the Management of Clinically Localized Prostate Cancer: 2007 Update, multiple treatment modalities are considered as options. This conundrum is further complicated by stage migration and lead time bias, both associated with PSA-based early detection strategies and the resultant increase in the detection of small volume clinically localized cancers. Since the majority of men currently diagnosed with prostate cancer are likely to have the disease eradicated by one of several treatment modalities, the clinical focus on HRQL associated with treatment has intensified. There are no published long-term data on the efficacy of cryosurgery on metastasis-free, prostate cancerspecific, or overall survival as there are with other more established forms of therapy; however, several large, single institution experiences, a pooled analysis, and several prospective evaluation studies report the efficacy and morbidity of cryosurgery of the prostate. Additionally, prostate cryosurgery has been found to result in acceptable HRQLbased outcomes with a reduced cost when compared to other local therapeutic options. Short-term PSA relapse-free survival outcomes following cryoablation of the entire prostate comparable to radiation therapy in men with intermediateand high-risk disease have been reported. Bio-

Group Consensus Reports from the Consensus Conference on Focal Treatment of Prostatic Carcinoma, Celebration, Florida, February 24, 2006

( EPORT OF CONSENSUS GROUP 1: ATHOBIOLOGY OF PROSTATE CANCER: MPLICATIONS FOR FOCAL THERAPY ocal ablative therapy may be reasonable for some atients with prostate cancer; selection factors include variety of clinical and pathologic factors in combiation with informed patient choice. Our group evalated 4 specific pathologic features that may influence his treatment decision. We reviewed the published iterature for applicable studies regarding the natural istory of prostate cancer, multifocality, cancer volme, and accuracy of cancer detection by current ethods. Results were as follows:

Cryosurgery for prostate cancer: improved glandular ablation by use of 6 to 8 cryoprobes

OBJECTIVES To describe and assess the efficacy for increased glandular destruction by using 6 to 8 cryoprobes in place of the traditional 5 probes. METHODS In April 1996, a revised method for cryosurgery was begun that uses 6 to 8 cryoprobes, and by July 1997, 81 men had been treated. This group was compared retrospectively to our last 82 cases done before April 1996 using 5 cryoprobes. All cases were consecutive. To ensure that the groups were similar, comparison was performed of entrance prostate-specific antigen (PSA), clinical stage, and Gleason score. Six months after cryosurgery, PSA and residual epithelial acini were compared between the two groups. RESULTS The two groups were comparable for all the above parameters (P >0.05). The degree of overall glandular kill was greater for the 6 to 8-probe method (P = 0.023). Complete glandular ablation for the 5-probe and 6 to 8-probe methods was 39% and 53%, respectively, and the difference was not significant (P = 0.072). However, when one combined the complete glandular ablation group with the none to few residual acini group, 67.5% for the 5-probe method and 88.9% for the 6 to 8-probe method, a significant difference was found (P = 0.001). The odds of having many remaining acini versus having none to few were 3.5 times greater in the 5-probe group than in the 6 to 8-probe group. The mean and median PSA for the 5- and 6 to 8-probe groups were 0.19 and 0.1 versus 0.11 and 0.07 ng/mL, respectively, a significant difference (P = 0.02). No difference was found in rates of tumor persistence or complications. CONCLUSIONS A revised method for cryosurgery using 6 to 8 cryoprobes has proved to be more effective for near-glandular ablation than the traditional 5-probe method. It was easily applied, had a wide margin of safety, and even shortened learning time. These innovations have permitted a closer approach to the goal of complete glandular destruction.

Patient-reported complications after cryoablation therapy for prostate cancer

To define the patient-reported complications after cryoablation therapy for prostate cancer and to compare these results to previously published patient-reported complications for radical prostatectomy and external beam irradiation. A questionnaire similar to previously published patient-reported complication studies was sent to the first 290 patients treated by cryoablation therapy at our Institution. The questionnaire was returned by 267 patients. Forty-four patients were excluded from analysis because of prior irradiation, transurethral prostatectomy, or cryoablation, resulting in a study group of 223 patients. Of the 208 patients with good urinary control preoperatively, 9 (4.3%) patients used incontinence pads after cryoablation. Seven of the 8 patients who used one pad daily reported leakage of only a few drops. Impotency, defined as an inability to obtain erections adequate for vaginal penetration, occurred in 85% of men who were potent preoperatively. Urethrorectal fistula occurred in 1 patient (0.4%). Bladder outlet obstruction caused by stricture of sloughed necrotic prostatic tissue required dilation or transurethral resection in 10% of patients. Scrotal swelling, penile tingling, and pelvic pain occurred in 18, 15, and 12% of patients, respectively; typically, these resolved spontaneously within 3 months. Patient-reported complications for cryoblation compared favorably to those reported for radical prostatectomy and external beam irradiation. Patient satisfaction was high; 96% of patients reported that they would choose cryosurgery as a treatment option again.

Focal Cryoablation of Prostate: A Review

Current treatment options for men with early localized prostate cancer are either some form of radical therapy or active surveillance. Radical therapy is usually associated with significant adverse effects that might jeopardize a mans quality of life. Some observers believe that PSA screening has resulted in the over diagnosis and over treatment of prostate cancer. Many men are being diagnosed with an early stage, small volume, unifocal or unilateral prostate cancer but are reluctant to accept watchful waiting or active surveillance. Focal cryoablation is the less than complete ablation of the gland with ice. Based on review of the limited amount of material available in the current literature, focal cryoablation can provide acceptable cancer control while preserving sexual potency and urinary continence. Focal cryoablation may fill a void in the therapeutic options available to patients with unifocal or unilateral prostate cancer who have a strong desire to maintain their quality of life.

Is radical prostatectomy primarily a surgical debulking procedure

Radical prostatectomy has been considered the gold standard for the curative treatment of clinically localized prostate cancer. After an extensive review of the literature, we concluded that surgery probably functions primarily as a tumor debulking procedure rather than a curative one. Morphometric studies suggest that the majority of patients undergoing surgery have tumors too large for cure. Histologic studies demonstrate that 55% of radical prostatectomy specimens show evidence of extraprostatic disease and approximately 15% have tumors so small that a clinical impact on longevity is unlikely. Thus, only 30% of patients have surgery that is clearly beneficial on a histopathologic basis. Given the rather long doubling time of prostate cancers, many patients with residual cancer following surgery die of other causes, giving the false impression of cure. However, long-term studies in men with positive surgical margins have demonstrated that the majority die from prostate cancer. Furthermore, using prostate specific antigen as a measure of progression, the biochemical disease-free survival rates are substantially lower than the cause-specific survival rates. Although radical prostatectomy may be the best tumor debulking procedure available, it is associated with substantial morbidity and cost. This information is important for both physician and patient when deciding on management of prostate cancer.

Nuclear scintigraphy in the evaluation of renal colic.

Forty patients with acute onset renal colic were studied using technetium-99m DTPA renal scintigraphy. Thirty-two were found to have varying degrees of obstruction. In the obstructed group the level was determined by the scan alone in 24 of 32 cases (75%). When the analysis included an abdominal radiograph, the level of obstruction was ascertained in 29 of 32 cases (91%). A delayed nephrogram, as evidenced by an “empty renal pelvis sign” at 5 minutes, was observed in all but one of the cases of obstruction (97%). Delayed clearance of activity from the pyelocalyceal system or ureter was also seen in 97%. In all cases of obstruction either one or both of these signs were observed. However, delayed clearance was found to be a nonspecific finding and was noted in 25% of nonobstructed cases. The finding of the “empty renal pelvis sign” at 5 minutes was found to be specific and was not seen in the nonobstructed group. The authors conclude that radionuclide renal scanning is an effective method for evaluating selected patients with suspected renal colic.

PD34-05 5-ALPHA REDUCTASE INHIBITORS IN PATIENTS ON ACTIVE SURVEILLANCE FOR PROSTATE CANCER: IMPACT ON DISEASE PROGRESSION AND CURATIVE INTERVENTION

INTRODUCTION AND OBJECTIVES: To report pathologic progression (PP) and curative intervention (CI) in 361 men on active surveillance (AS) in comparison between with and without use of 5alpha reductase inhibitors (5-ARI). METHODS: Total 361 patients were grouped: with use of 5-ARI (n1⁄4 119, 33%) or without use of 5-ARI (No 5-ARI), n1⁄4242 (67%). All the patients had at least two years of follow up and the median follow up time was 5.1 years for 5-ARI vs 5.3 years for No 5-ARI (p1⁄40.6). The AS protocol included PSA (6 monthly), multi-parametric transrectal ultrasound (TRUS) annually, and surveillance biopsy (2-3 yearly, or as indicated). PP was defined as upgrade on Gleason score, increase in cancer core length (>4mm) or percent (>25%), or clinical progression on the follow up. CI was defined as discontinuing AS to undergo any kind of curative or hormonal therapy. Clinical variables were compared between the two groups. Kaplan-Meier method was conducted to estimate survivals for PP and CI, and multivariable Cox regression for predictors of PP. RESULTS: At the entry, the two groups were similar: age (63 vs. 61yrs, p1⁄40.1), PSA (4.8 vs. 4.8ng/ml, p1⁄40.5), prostate volume on TRUS (41cc vs. 35cc, p1⁄40.1), clinical stage T1c/T2a (85%/13% vs. 90%/9%, p1⁄40.06), biopsy Gleason score (6/3þ4/4þ3 1⁄4 88%/10%/2% vs. 87%/11%/2%, p1⁄40.9), biopsy cancer core length (1.5mm vs. 1mm, p1⁄40.37) and percent (10% vs. 8.5%, p1⁄40.2) of index cancer, and number of positive cores (1 vs. 1, p1⁄40.1), respectively for 5-ARI vs No 5-ARI groups. Predictors of PP were: not taking 5-ARI (p1⁄40.017), entry PSA > 4ng/ml (p1⁄40.009) and Gleason pattern 4 in biopsy (p<0.001). In regression analyses, 5-ARI-group had lowered the risk of PP by 41%. Estimated probability of PP-free survival (Fig 1) and CI-free survival (Fig 2) are shown: CONCLUSIONS: The use of 5-ARI for selected patients on AS delayed PCa progression and curative intervention. Source of Funding: None

552 COMPLICATIONS OF SALVAGE CRYOSURGERY AFTER PRIMARY RADIATION THERAPY FOR PROSTATE CANCER: POOLED MULTICENTER ANALYSIS OF 798 PATIENTS

INTRODUCTION AND OBJECTIVES: Salvage prostate cryosurgery (SPC) following primary radiation therapy has been associated with substantial morbidity. We aimed to report the frequency of SPC related complications and to identify risk factors and time trends. METHODS: Clinical data, procedure related data, and complications were recorded retrospectively on 798 patients who had undergone SPC in 6 medical centers. The occurrence of mild/moderate and severe urinary incontinence (UI), urine retention, bladder neck contracture, urethral sloughing, gross hematuria, perineal pain, and rectourethral fistula were documented after SPC. Univariate analysis addressed risk factors. RESULTS: Of the patients with complete data, the following complications were reported: mild to moderate UI in 26.4%, severe UI in 15.6%, urine retention in 15.1%, bladder neck contracture in 7.2%, urethral sloughing in 17.4%, hematuria in 9.8%, perineal pain in 10.6%, and fistula in 2.5% of the patients. The risk for any complication was associated with the year of salvage cryosurgery (odds ratio [OR] 0.46; 95%CI 0.31, 0.69 for 2000-2005 versus 1992-1995), the cryosurgery device generation (OR 0.05 95%CI 0.01, 0.24 for generation 3 versus 1) and the number of freeze/thaw cycles (OR 0.23, 95%CI 0.06,0.33 for 2 versus 1 cycle). The following complications became significantly less frequent between the years 1996 to 1999 and 2000 to 2005 versus 1992-1995: mild to moderate UI (32.5% to 20.5%); urine retention (24.1% to 9.2%); bladder neck contracture (10.0% to 2.3%); urethral sloughing (27.9% to 9.8%); pelvic/perineal pain (18.5% to 7.1%). There was a non-significant trend towards less frequent occurrence of fistula from 3.7% to 1.7%. Because the year of SPC and device generation were interdependent no multivariate analysis was performed. CONCLUSIONS: Although SPC is associated with substantial complications most complications have become less frequent in recent years.