Robert A. Badalament

Targeted cryoablation of the prostate: 7-year outcomes in the primary treatment of prostate cancer

The efficacy and safety of the long-term experience with targeted cryoablation of prostate cancer (TCAP) at a community hospital is retrospectively reviewed. A series of 590 consecutive patients who underwent TCAP as primary therapy with curative intent for localized or locally advanced prostate cancer from March 1993 to September 2001 were identified. Patients were stratified into 3 risk groups according to clinical characteristics. Biochemical disease-free survival (bDFS), post-TCAP biopsy results, and post-TCAP morbidity were calculated and presented. The mean follow-up time for all patients was 5.43 years. The percentages of patients in the low-, medium-, and high-risk groups were 15.9%, 30.3%, and 53.7%, respectively. Using a prostate-specific antigen (PSA)-based definition of biochemical failure of 0.5 ng/mL, results were as follows: (1) the 7-year actuarial bDFS for low-, medium-, and high-risk patients were 61%, 68%, and 61%, respectively; (2) the bDFS probabilities for a PSA cutoff of 1.0 ng/mL for low-, medium-, and high-risk patients were 87%, 79%, and 71%, respectively; and (3) the bDFS probabilities for low-, medium-, and high-risk patients using the American Society for Therapeutic Radiology and Oncology (ASTRO) definition of biochemical failure (3 successive increases of PSA level) were 92%, 89%, and 89%, respectively. The rate of positive biopsy was 13%. After a positive biopsy, 32 patients underwent repeat cryoablation. For those patients who underwent repeat cryoablation, 68%, 72%, and 91% remain bDFS using definitions of 0.5 ng/mL, 1.0 ng/mL, and the ASTRO criteria, respectively, after a mean follow-up time since repeat cryoablation of 63 months. The rates of morbidity were modest, and no serious complications were observed. TCAP was shown to equal or surpass the outcome data of external-beam radiation, 3-dimensional conformal radiation, and brachytherapy. These 7-year outcome data provide compelling validation of TCAP as an efficacious treatment modality for locally confined and locally advanced prostatic carcinoma.

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

OBJECTIVESnTo describe and assess the efficacy for increased glandular destruction by using 6 to 8 cryoprobes in place of the traditional 5 probes.nnnMETHODSnIn 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.nnnRESULTSnThe 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.nnnCONCLUSIONSnA 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.

Treatment of superficial bladder cancer with intravesical chemotherapy

Proper care of patients with superficial bladder cancer requires the assessment of multiple factors, including an understanding of the natural history of this disease, accurate clinical staging, and the expected efficacy of each drug. The pharmacology of intravesical mytomycin C is discussed in detail, as many of this drugs pharmacological principles are applicable to all intravesical chemotherapeutic agents, including doxorubicin, thiotepa, bacillus Calmette-Guérin, epirubicin, and ethoglucid. The bladder wall, bladder cavity, chemical properties of intravesical chemotherapeutic agents, and tumor considerations are discussed. Suggestions based on pharmacological studies are presented to optimize the efficacy of intravesical chemotherapy.

In treating localized prostate cancer the efficacy of cryoablation is independent of DNA ploidy type.

While the prognostic value of DNA ploidy has been well established for radical prostatectomy, external beam radiation, brachytherapy and androgen deprivation therapy its role as a survival outcome predictor for prostate cancer patients treated with cryoablation has not yet been examined. Anecdotal evidence suggesting that cryoablation may be independent of DNA ploidy type led to the implementation of the current study. Retrospective analysis of data including flow digital cytometry was performed on 447 archival specimens taken from patients who had undergone cryosurgical ablation of primary prostate cancer. Five-year biochemical disease free survivals (bDFS) (defined as PSA thresholds of 0.5 and 1.0 ng/ml) were determined with Kaplan-Meier analysis. Patients were grouped according to DNA ploidy types then stratified by Gleason grade, risk group, pre-surgical PSA level, and disease stage. Mean and median age of the cohort was 65 and 64.6 years. Mean follow-up was 65.7 months. The DNA ploidy status of the population was found to be 59% diploid, 13% tetraploid, and 28% aneuploid. Using PSA < 1.0 ng/ml criterion, the bDFS rates for diploid, tetraploid, and aneuploid were 78%, 75%, and 79% respectively. The bDFS rates using a PSA < 0.5 ng/ml criterion were 67%, 59%, and 69% for diploid, tetraploid, and aneuploid groups. No significant outcome differences were found in stratified analysis. This investigation demonstrates that the efficacy of cryoablation is independent of DNA ploidy type.

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 cancers detected during 5α-reductase inhibitor use are smaller, de-differentiated, but confined when compared to controls

Rationale: To compare cancers detected during use of 5α-reductase inhibitors (5αRI) with cancers detected in untreated controls stratified for tumor size. Methods: Prostate biopsies were performed on 235 consecutive patients “for cause” (elevated or rising PSA, positive digital rectal examination, or focal hypoechoic lesion). Fifty patients were excluded for a prior diagnosis of cancer, leaving 185 as the study group (5αRI=41, control=144). Patients in the 5αRI group had been treated for a mean of 3.5 years. Cancer was ultimately diagnosed in 114/185 patients. Results: Cancer was diagnosed in 31/41 (76%) of patients treated with 5αRI and 83/144 (58%) of the control group (p=0.04). Control tumors were larger (14.3 mm) than those in 5αRI treated patients (9.4 mm, p=0.0007). No differences in mean PSA or PSA kinetics were detected between groups. For tumors less than 1.0 cm, the proportion of high grade cancers (Gleason 7-10 and Gleason 4+3-10) was higher in 5αRI subjects than in controls (p<0.05). Fewer 5αRI patients had proven extracapsular extension than controls, but this difference did not reach statistical significance (p=0.13). Normal DNA ploidy was more likely to be diagnosed in the 5αRI group versus controls, but this difference was not statistically significant (81% vs. 65%, p=0.14). Conclusions: Cancers diagnosed in patients presenting “for cause” treated with 5αRI drugs are more likely to be de-differentiated compared to controls. However, these tumors are also smaller and less likely to have extracapsular extension and abnormal DNA ploidy than controls.