Biomarkers in monitoring for efficacy of immunotherapy and chemoprevention of bladder cancer with dimethylsulfoxide.

This study correlated biomarkers expressed in tumor and epithelial field with clinical response and recurrence. Of 25 bladder cancer patients, 11 received 6 weeks of intravesical Bacille Calmette-Guerin (BCG), and 14 were treated weekly with intravesical dimethylsulfoxide (DMSO) for 4 weeks to further modulate biomarker expression. G-actin, DNA aneuploidy, and p300 tumor antigen were evaluated by quantitative fluorescence image analysis on uroepithelial cells from bladder wash samples prior to and immediately following treatment. Excluding patients who did not respond to BCG (and who had persistently abnormal p300 and DNA markers), recurrence correlated with persistent abnormal G-actin findings. Of patients who were G-actin negative following therapy, only 25% recurred during follow-up in contrast to 67% in patients who were positive (p < 0.03 by Fisher's exact test). The odds ratio for recurrence was 6.00 (95% confidence interval: 1.3-28.6). Cytosolic G-actin levels can be an important intermediate end point marker for chemoprevention.

Histological presence of viable prostatic glands on routine biopsy following cryosurgical ablation of the prostate.

PURPOSE: Cryosurgical ablation of the prostate has recently received much attention as a therapeutic alternative for the treatment of localized prostatic adenocarcinoma. Biopsies after treatment reveal a variety of dysplastic changes as well as unaltered prostatic glandular epithelial elements. Prostate specific antigen (PSA) remains undetectable in the majority of men. However, in some PSA increases without demonstrable local recurrence. MATERIALS AND METHODS: A total of 383 patients underwent 447 procedures between June 1990 and January 1994. Of 358 biopsies performed at our institution, 317 (2,075 cores) were available for review. Each core was examined for unaltered prostatic glandular epithelial elements and then scored for the percentage of epithelial glandular involvement according to a scale of: 0-no, 0.5-less than 10%, 1-10 to 25%, 2-25 to 50%, 3-50 to 75% and 4-76 to 100% unaltered prostatic glandular epithelial elements. RESULTS: Of 317 biopsies 158 (49.8%) contained no unaltered prostatic glandular epithelial elements, while 185 (58.3%) and 206 (65%) had 1 core containing 10% and 10 to 25%, respectively, of such elements. Of 262 cases (82.6%) with a mean of 10% unaltered prostatic glandular epithelial elements per core 22 (8.4%) were positive for residual carcinoma. Among 55 cases with more normal epithelium per core 24 (43.6%) were positive for residual carcinoma. Patients with a positive biopsy had a median PSA of 2.02 ng./ml. (average gland/core score 0.54). Median PSA for men with negative biopsies was 0.2 ng./ml. (gland/core score 0.124). CONCLUSIONS: Cryosurgical ablation of the prostate has the ability to ablate prostatic tissue completely, thus rendering it free of glandular elements as determined by biopsy. Increasing PSA can indicate residual glandular elements. Increases in unaltered prostatic glandular epithelial elements with time are not paralleled by increased rates of local disease recurrence. undetectable serum PSA has a low risk of residual unaltered prostatic glandular epithelial elements and localized carcinoma. Results as measured by unaltered prostatic glandular epithelial elements and PSA improve with the surgical experience.

Cryosurgical ablation of the prostate: two-year prostate-specific antigen and biopsy results.

OBJECTIVES: Percutaneous cryosurgical ablation of the prostate (CSAP) was performed on patients with localized or locally advanced adenocarcinoma of the prostate. To assess local disease control, post-treatment biopsy and serum prostate-specific antigen (PSA) levels were obtained at 3 and 24 months post-treatment. METHODS: From June 1990 through May 1994, CSAP was performed 448 times on 383 patients under Institutional Review Board protocols. A urethral warming catheter was used for all procedures. A total of 239 patients were followed for a minimum of 21 months after treatment. None of this group had received prior local treatment. The group consisted of patients who were newly diagnosed and treated solely with cryotherapy (virgin); the remainder had been on androgen deprivation therapy (ADT) prior to CSAP. RESULTS: Biopsies were obtained from 114 patients at 21 months or more after treatment. In the virgin group, 79% had a negative biopsy after one or more treatments, and 88% of the ADT group are negative after one or more treatments. Overall, 69% had a negative biopsy after one treatment and 82% had a negative biopsy following one or more CSAP treatments. Of a group of 163 patients, PSA data were evaluable at 21 months or more after treatment. In the virgin group, 60% had a PSA 0.4 ng/mL or less, and 77% had a PSA 1.0 ng/mL or less. In the ADT group, 40% had a PSA 0.4 ng/mL or less, and 69% had a PSA value of 1.0 ng/m Lor less. Complications were minimal, the most common one being urethral tissue sloughing, which occurred in 10% of patients. CONCLUSIONS: CSAP appears to be effective in obtaining local control as measured by biopsy and PSA 21 months or more post-treatment. When retrospectively comparing our results with recently published radiotherapy series, CSAP was more effective in obtaining nadir PSA values 1.0 ng/mL or less and negative biopsies at 21 months or more after treatment.

Predicting the patient at low risk for lymph node metastasis with localized prostate cancer: an analysis of four statistical models.

PURPOSE: Statistical models using preoperative Prostate-Specific Antigen, Gleason primary grade or score of the biopsy specimen, and clinical stage have been developed to predict those patients with clinically localized prostate cancer at low risk for lymph node metastasis. It has been recommended that these patients do not require pelvic lymph node dissections. Four such models were evaluated to assess their accuracy in identifying this subgroup of patients. METHODS AND MATERIALS: We reviewed the records of 214 patients with clinically localized prostate cancer who underwent pelvic lymph node dissections. Data from these patients were entered into the four models. RESULTS: Lymph node metastasis was detected in 14% of patients. The results showed the following for each of the proposed models respectively: 78, 50, 76, and 42% of the patients were identified as low risk and, hence, would be spared pelvic lymph node dissections. The false negative rates are 13 (7.8%), 5 (4.6%), 14 (8.6%), and 1 (1.1%). Sensitivities are 56.7, 83.3, 53.3, and 96.7%. CONCLUSIONS: While the pelvic lymph node dissection is the most accurate method of detecting occult nodal metastasis, statistical models can identify a cohort of low risk patients that may be spared lymphadenectomy.