Cryosurgical ablation therapy for prostate cancer.

Adenocarcinoma of the prostate in the most common malignancy in men and still the leading cause of death from cancer in American men. Current data and published reports indicate that cryotherapy for clinically localized prostate cancer can be an effective treatment method in selective patients. Since 1993, 643 cryosurgical procedures have been performed, including 68 patients who failed radiation therapy, and 20 patients who failed initial cryotherapy. Recently developed targeted cryotherapy techniques, using 6-8 probes, shows promising initial results. The complication rates are also compared favorably to the established therapies for prostate cancer. It is a minimally invasive procedure with a high patient's acceptance rate. It is a highly operator-dependant procedure with a steep learning curve coupled with constantly evolving technology.

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.

Patient-reported complications after cryoablation therapy for prostate cancer.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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 or 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. CONCLUSIONS: Patient-reported complications for cryoablation 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.

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.

The role of TRUS-guided biopsies for determination of internal and external spread of prostate cancer.

This study hopes to define local extent of newly diagnosed prostate cancer by comparing sextant biopsies with transrectal ultrasound-guided diagnostic and staging biopsies. The study group consists of 110 men with sextant biopsy proven prostate cancer who presented for an opinion for prognosis and treatment options. All patients were rediagnosed and staged by transrectal ultrasound-guided and staging biopsies. Tumor diagnosis was substantiated in 94.5% (104 of 110). For the 5.4% (6 of 110) not detected by transrectal ultrasonography, review of their outside slides revealed 83.3% (5 of 6) with cancer < or =2 mm with a Gleason score of < or =6. These have the criteria of latent cancers. For the remaining 104 patients with transrectal ultrasound proven cancer, 30% (31 of 104) had extracapsular extension. Sextant and directed biopsy confirmed stage T3 in 3.8% (4 of 104). For clinical stages T1c and T2, 19% and 30%, respectively, had extracapsular extension. Perineural invasion was 1.9 times greater for directed biopsies than sextant biopsies (P < .001. The mean Gleason score was greater for directed biopsies than sextant biopsies, although no statistical difference was found (P > .05). For these 104 patients, 50% (52 of 104) had perineural invasion, of which 38.5% (20 of 52) had proven extracapsular extension. In our hands, transrectal ultrasound-directed and staging biopsies afford more substantive results than sextant biopsies for detecting extracapsular extension. For our cohort of sextant T1-T2 diagnosed cancer (n = 100), 27% were upstaged to T3-T4 by transrectal ultrasound-directed staging biopsy. Thus, transrectal ultrasound-directed staging biopsy has the ability to diagnose unsuspected extracapsular extension and objectifies prognosis and choice of definitive treatment.

Cryosurgery of prostate cancer. Use of adjuvant hormonal therapy and temperature monitoring--A one year follow-up.

OBJECTIVE: To determine the clinical outcomes at one year of Stages T2-T3 prostate cancer by cryosurgery utilizing pretreatment with total androgen ablation therapy and temperature monitoring to control the freezing process. Study Group To date, 347 patients have had 356 cryosurgical procedures, 280 have reached one year post treatment. Of these 131 had re-evaluation with prostatic biopsy and serum PSA. METHODS: Transrectal ultrasound (TRUS) measurement of tumor size and biopsy of extraprostatic space was used to stage patients into two main groups: confined (66.6%) versus nonconfined (19.3%). Radiation failures (14.1%) formed a separate group. Failure rates for the 131 men include all cancer diagnosed during the one year period following cryosurgery. RESULTS: The one year failure rate for the study group was 19.8% (26/131). For stages T2a, T2h C, T3 and radiation failures, the rates of positive biopsies were 13.9%, 12.9%, 33.3% and 35%, respectively. For those with local control of cancer (negative biopsy), 80% had prostate specific antigen (PSA) levels of < 0.5 ng/ml. The statistical variables for persistent cancer with prostate specific antigen > 0.5 ng/ml were: sensitivity of 66.7%, PPV of 16.7%, NPV of 98% and specificity of 83.7%. A statistically significant difference exist between stages T2 vs T3 and radiation failures (p = < 0.5). Major complications of rectal fistula and total incontinence for previously non-treated cancer versus radiation failures were 0.33% and 8.7% respectively, a 26 times greater risk. CONCLUSION: Results of cryosurgery for all stages of prostate cancer at one year are encouraging, being 80% free of disease (biopsy and prostate specific antigen). The morbidity of the previously non-treated cancers from this procedure for us was minimal with high patient acceptance. For radiation failures a local control rate of 65% was achieved. However, early in our experience significant morbidity did occur and our enthusiasm for attempted salvage was initially tempered.

An algorithm for predicting nonorgan confined prostate cancer using the results obtained from sextant core biopsies with prostate specific antigen level.

PURPOSE: We determined the enhanced ability to predict nonorgan confined prostate cancer using several histopathological and quantitative nuclear imaging parameters combined with serum prostate specific antigen (PSA). MATERIALS AND METHODS: Several independent pathological and quantitative image analysis variables obtained from sextant biopsy specimens, as well as preoperative PSA were used. The study population included 210 patients with pathologically staged disease (192 with PSA). All variables were examined by univariate and multivariate logistic regression analyses to assess ability to predict disease organ confinement status. RESULTS: Univariate logistic regression analysis demonstrated that, in decreasing order, quantitative nuclear grade, preoperative PSA, total percent tumor involvement, number of positive sextant cores, preoperative Gleason score and involvement of more than 5% of a base and/or apex biopsy were significant (p < or = 0.006) for prediction of disease organ confinement status. Backward stepwise logistic regression was applied to these univariately significant variables, including deoxyribonucleic acid ploidy, to calculate a multivariate model for prediction of disease organ confinement status. This algorithm had a sensitivity of 85.7%, specificity 71.3%, positive predictive value 72.9%, negative predictive value 84.7% and area under the receiver operating characteristic curve 85.9%. CONCLUSIONS: Information from pathological study of sextant prostate biopsies, preoperative PSA blood test and a new image analysis variable termed quantitative nuclear grade can be combined to create a multivariate algorithm that can predict more accurately nonorgan confined prostate cancer compared to previously reported methods.

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.

Prostate cancer: US-guided percutaneous cryoablation. Work in progress.

PURPOSE: To present early results of cryosurgical ablation of prostate cancer with an ultrasound-guided percutaneous technique. MATERIALS AND METHODS: Cryosurgery was performed in 210 patients; near complete 3- and 6-month follow-up data were available for 130. Androgen ablation therapy was used to decrease the size of the prostate gland for optimal freezing. Prostate-specific antigen (PSA) and prostatic biopsy studies were performed at 3, 6, and 12 months. RESULTS: Gland volume decreased from 29 cm3 +/- 14.1 to 20.4 cm3 +/- 8.4 (P < .0001) after androgen ablation. Rates of positive biopsy findings at 3, 6, and 12 months were 7.7%, 3.3%, and 2.3%, respectively. Serious complications were minimal and included no deaths, urethrorectal fistulas in five patients, and total incontinence in three. Mean PSA levels decreased from 12.6 +/- 16.1 preoperatively to 0.35 +/- 0.75 at 3 months, 0.54 +/- 1.1 at 6 months, and 0.43 +/- 0.78 at 12 months (persistent cancers excluded). CONCLUSION: These preliminary results demonstrate that cryosurgery can cause necrosis of prostate cancer. Long-term results and randomized trials are necessary to determine if this means longer disease-free intervals and increased patient survival compared with results of current therapeutic methods.

US-guided percutaneous cryoablation of prostate cancer.

A tailored approach to cryosurgery of prostate cancer is presented. The authors have performed 214 cryoprocedures to date with use of this protocol. The technique requires pretreatment with androgen ablation therapy, preoperative diagnosis and staging with ultrasound (US)-guided biopsies, and detailed knowledge of prostate and rectal anatomy. Five cryoprobes are placed in the prostate under US guidance in a configuration that depends on tumor location, sites of extracapsular extension, the size of the tumor, and gland geometry. Freezing starts anteriorly to keep from obstructing the ultrasound beam. Two freezes are performed at the known cancer site, and additional freezes are performed, if necessary, to include the remainder of the gland. Thermosensors enable monitoring of the cryosurgical ice ball and determination of the number of freezes. Cryosurgery is always performed by a urologist and a radiologist working together.

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.