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There is a paucity of information in the contemporary literature that would permit assessment of the urologist's ability to endoscopically discriminate between benign and malignant lesions of the bladder or to predict the grade and stage of papillary neoplasms. This prospective study evaluates the correlation between cystoscopic impression of urothelial lesions and final histologic diagnoses. Sixty-four patients with 68 urothelial abnormalities requiring formal biopsy or endoscopic resection were evaluated prospectively. At the time of endoscopy, treating urologists completed questionnaires documenting the surgeon's endoscopic impression of disease type and extent and performed standard biopsy or resection of all suspicious lesions. Specimens were submitted for routine histopathologic analysis, and the results were correlated with the questionnaire data. Endoscopic evaluation correctly discriminated between dysplastic/malignant and benign/reactive lesions in this study with a sensitivity of 100%, specificity of 100%, and positive and negative predictive values of 100%. Urologists could not readily distinguish between low- and high-grade papillary urothelial lesions and were frequently unable to determine if a tumor was invasive, particularly if the degree of invasion was microscopic. Endoscopic impression at the time of bladder biopsy or resection is accurate and discriminates between the presence and absence of cancer. Endoscopic impression alone is a relatively poor staging tool with respect to extent of invasive disease and must be coupled with careful histopathologic analysis of biopsy material, bimanual examination when appropriate, and axial imaging for complete assessment of a given tumor.

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PURPOSE: Cure from malignancy is commonly defined as a disease-free state lasting 5 years after treatment. We analyzed clinical and biochemical progression rates after radical prostatectomy for men with clinically localized prostate cancer with particular attention to recurrence beyond 5 years. Annual hazard rates of progression were calculated to determine the probability of recurrence at specific intervals following surgery. MATERIALS AND METHODS: The records of 2,782 men with clinically localized prostate cancer (cT1-T2) undergoing radical prostatectomy between 1987 and 1993 were reviewed. All patients were treated in the prostate specific antigen (PSA) era so that serial followup PSA values were available from the time of surgery. Analysis was limited to patients who did not receive adjuvant treatment within 90 days of radical prostatectomy. Disease progression was defined as documented local recurrence, systemic progression and/or PSA 0.4 ng./ml. or greater. Lymph node positive cases were eliminated from analysis since almost all received adjuvant hormonal therapy. Annual hazard rates for progression were calculated using the formula: [No. events / No. patients at risk] x 100. Progression-free survival probabilities were determined using the Kaplan-Meier method. RESULTS: Pathological stage was pT2a-b, N0 (68%), pT3a, N0 (21%) and pT3b, N0 (11%). Biochemical progression-free survival at 5 and 10 years was 76% and 59%, respectively, for the entire study population while those with pathologically organ confined (pT2, N0) cancers had progression-free survival rates of 82% and 68% at 5 and 10 years, respectively. A total of 819 patients (29%) eventually had disease progression, including 160 (6%) with progression after 5 years. Annual hazard rates were highest during the first 2 years after radical prostatectomy for the entire population. Patients with adverse prognostic features (pT3b, PSA 10 ng./ml. or greater, Gleason score 8-10 and nondiploid cancers) had high initial hazard rates that decreased with time to lower levels. Those with pathologically organ confined cancer had low but constant hazard rates throughout followup. CONCLUSIONS: Although progression after radical prostatectomy usually occurs early, reflecting the impact of clinical under staging, a significant number of men, including those with organ confined cancers, will continue to have disease progression after 5 years. Patients undergoing radical prostatectomy should be subjected to long-term followup to allow the option of early intervention should progression occur.

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PURPOSE: We assessed retrospectively the outcome after bilateral pelvic lymphadenectomy and radical prostatectomy for pathological pTxN+ adenocarcinoma of the prostate when treated with or without adjuvant androgen ablation therapy. MATERIALS AND METHODS: A total of 790 men treated with radical prostatectomy for prostatic adenocarcinoma were found to have pTxN+ disease and treated further with or without androgen ablation therapy. Mean patient age was 64 years (range 40 to 79). Mean followup was 6.5 years, (range up to 25). Clinical stages were T2 or less in 60% of the cases, T3 in 38% and N+ in 2%. Gleason scores were 6 or less in 31% and 7 or greater in 69%. Deoxyribonucleic acid ploidy was diploid in 43%, tetraploid in 39% and aneuploid in 18%. Of the patients 96 (12%) received no androgen ablation therapy, with the remainder getting androgen ablation therapy within 90 days of radical prostatectomy. RESULTS: Of the patients 186 (24%) died, with 109 (14%) dying of prostatic anedocarcinoma. Overall (and cause specific) survival probabilities at 5, 10 and 15 years were 87 (91), 69 (79) and 39% (60%), respectively. Patients with diploid tumors had better cause specific survival than those with nondiploid tumors (p = 0.009). Patients with diploid tumors were less likely to have progression biochemically, locally or systemically than those with nondiploid tumors (p = 0.038). Androgen ablation therapy had no effect on cause specific survival in nondiploid patients. Diploid patients treated with androgen ablation therapy for up to 10 years had no improvement in disease specific survival compared to those with no androgen ablation therapy. However, cancer death was significantly reduced after 10 years (p <0.002). The local control rate of pTxN+ cases that receive radical prostatectomy and androgen ablation therapy at 15 years is virtually identical to that of stage pT2c cases at our institution (79 +/- 3.0 versus 80% +/- 3.5%, respectively). There were no deaths secondary to radical prostatectomy, and complications were within the experience of that seen in patients with localized disease. CONCLUSIONS: Radical prostatectomy with androgen ablation therapy is a viable option for patients with pTxN+ disease, particularly in view of excellent local control rates and low morbidity. Patients with diploid tumors have a more favorable outcome than those with nondiploid tumors when treated with androgen ablation therapy.

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BACKGROUND: A proposed pathologic (pTNM) classification system for prostate carcinoma was analyzed for its impact on survival outcome in the prostate specific antigen (PSA) era. The impact of margin status on the survival outcome of patients with otherwise organ-confined disease (i.e., without extraprostatic extension or seminal vesicle involvement) was assessed. METHODS: Among 5467 patients, the original pathologic classification was T2 in 2094 patients; those with evidence of positive margins, extraprostatic extension, or seminal vesicle involvement were initially classified as having pT3 disease (2920 patients) or pT4 residual disease (211 patients). According to the proposed pTNM system, 1512 patients for whom margin status was considered independent of T classification were reclassified. RESULTS: After reclassification, 803 specimens had been down-classified to pT2, resulting in 2932 (54%) with pT2N0 organ-confined disease and a margin positivity rate of 27%; originally, only 38% of patients had been classified as pT2N0. When the old and new classifications were compared, 5-year progression free survival to the combined endpoint of clinical and/or PSA progression (< or = 0.2 ng/mL) was 86% versus 84% and 70% versus 67% for disease classified as pT2N0 and pT3N0, respectively. Multivariate analysis assessed the effect of margin status on 2334 pT2N0 patients (classified according to the proposed pTNM system) who did not receive adjuvant therapy; adjustments were made for Gleason grade, preoperative PSA, and DNA ploidy. In this analysis, the relative risk (with 95% confidence interval) associated with positive margins was 1.65 (1.24-2.18); this was significant for the combined endpoint of clinical/PSA progression. The 5-year survival, free of clinical/PSA progression, was 86% for those without versus 75% for those with positive margins. CONCLUSIONS: This analysis supports the adoption of the proposed pTNM system, which will allow for uniform reporting of pathologic data on prostate carcinoma. For patients with organ-confined disease, positive margins are associated with higher rates of PSA progression. Accordingly, patients should be stratified based on margin positivity in addition to pT classification.

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Despite a heightened focus of the medical and research community on prostate cancer, many important questions about this disease remain unanswered. These include questions about the possible prevention of prostate cancer, as well as the optimal treatment approaches for localized, locally advanced, metastatic, and hormone-refractory disease. A whole host of prospective, well-designed clinical trials are currently in progress that should answer many of these questions. This review briefly explores some of these unresolved issues and describes ongoing trials designed to address them.

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PURPOSE: Whether androgens down regulate the androgen receptor during penile development is controversial. We investigated the effects of androgens on penile androgen receptor expression. MATERIALS AND METHODS: We injected prepubertal hypogonadotropic hypogonadal microphallic rats with testosterone or dihydrotestosterone. Specimens were obtained at 3 (prepuberty), 9 (puberty to early postpuberty) and 12 weeks (late postpuberty). At necropsy we compared penile size and androgen receptor expression of these animals to those of age matched nontreated hypogonadotropic hypogonadal and normal controls. RESULTS: At age 3 weeks prepubertal androgens up regulated androgen receptor expression and significantly increased penile size compared to normal and untreated hypogonadotropic hypogonadal controls. By 9 weeks the normal down regulation of androgen receptor that occurs with maturation was present. Prepubertal androgens failed to accelerate or exaggerate the normal maturational loss of the androgen receptor. At 9 weeks penile size of normal controls and prepubertal androgen treated animals was identical. Interestingly despite down regulation of the penile androgen receptor, normal animals continued to have increases in penile size between 9 and 12 weeks, while the prepubertal androgen treated animals had no penile growth. CONCLUSIONS: Prepubertal androgen administration in hypogonadotropic hypogonadal animals resulted in diminutive penises in adulthood. However, the decrease in penile size was not associated with an accelerated or exaggerated down regulation of the androgen receptor. This finding coupled with continued growth of the normal control penises after androgen receptor down regulation suggests that cessation of penile growth may not be solely related to down regulation of the penile androgen receptor.

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PURPOSE: The majority of impalpable prostate cancers (state T1c) are biologically significant. We report the interim results in 257 patients with stage T1c prostate cancer treated with radical prostatectomy. MATERIALS AND METHODS: Prostate specific antigen progression-free survival was assessed by the Kaplan-Meier method. Multivariate analyses were performed to determine which clinical and pathological variables independently correlated with progression. Comparisons among the various clinical substages (T1a to T2b/c) were calculated. RESULTS: Of the patients with stage T1c cancers 51% had stage pT2c or less and 91% had clinically significant tumors on the basis of pathological grade, deoxyribonucleic acid ploidy and tumor volume. High preoperative prostate specific antigen, poorly differentiated tumors and nondiploid status were strong independent predictors of progression. The 5-year survival rate free of progression was 84%. Patients with clinical stage T1c cancers had a significant progression-free survival advantage compared to those with clinical stage T2b/c disease (p = 0.0005). CONCLUSIONS: Impalpable tumors should not be regarded as insignificant or innocuous on the basis of pathological analysis. Disease-free survival in the stage T1c group was similar to that in the clinical stages T1a to T2a group but significantly better than that in the T2b/c group.

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PURPOSE: The in vitro effects of the fluoroquinolone antibiotics ciprofloxacin and ofloxacin upon 3 human transitional cell carcinoma cell lines were investigated at concentrations that are attainable in the urine of patients taking these drugs orally. MATERIALS AND METHODS: Cell lines TCCSUP, T24, and J82 were exposed in culture to either ciprofloxacin or ofloxacin at concentrations ranging from 0 to 800 micrograms./ml. and at durations ranging from 24 to 120 hours. Inhibition of proliferation and DNA synthesis were assessed via MTT and tritiated thymidine assays, respectively. RESULTS: From the MTT assay ciprofloxacin, at concentrations of 25 to 800 micrograms./ml., produced proliferation inhibition in the TCCSUP line ranging from 8.1% to 90.2% at 24 hours, 25.1% to 94.9% at 72 hours, and 53.8% to 96.9% at 120 hours. Inhibition of proliferation for the T24 line ranged from 8.0% to 85%, 31.5% to 96.5%, and 27.3% to 98.2%. Inhibition of proliferation of the J82 line ranged from 20.8% to 84.8%, 22.8% to 92.7%, and 37.4% to 97.1%. Inhibition of DNA synthesis (due to ciprofloxacin at the concentrations above) as measured by the tritiated thymidine assay was also significant for each of the 3 cell lines. Inhibition of proliferation and DNA synthesis due to ofloxacin was lower but not overall statistically different from that due to ciprofloxacin. In a separate experiment, enhanced cytotoxicity was observed at lower concentrations of ciprofloxacin when the initial media pH was approximated to 5.5. CONCLUSIONS: Ciprofloxacin and ofloxacin inhibit proliferation and DNA synthesis of these 3 human TCC lines in vitro. Inhibition occurred in a concentration- and time-dependent manner. The concentrations that were assessed are attainable in the urine of patients taking these agents orally.

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PURPOSE: We determined whether bladder neck sparing radical prostatectomy may leave prostate tissue in the unresected bladder neck. MATERIALS AND METHODS: We intraoperatively evaluated the presence of prostate tissue in bladder neck biopsy specimens from 73 consecutive patients undergoing bladder neck sparing radical prostatectomy. RESULTS: Of the 73 specimens 14 (19%) contained prostate tissue: 9 (12%) were positive for prostate cancer and 5 (7%) contained benign prostate tissue. All patients with a positive bladder neck biopsy had a positive margin at another site. CONCLUSIONS: We recommend routine bladder neck biopsies for patients undergoing a bladder neck sparing procedure.

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Although historical data generally attest to a relatively benign course for stage A1 prostate cancer, at least some recent studies suggest that with prolonged followup patients have a significant risk of disease progression. This study was done with the hypothesis that such disease progression is a function of patient age and close, prolonged followup, and not the mere presence of stage A1 disease. A total of 304 patients who underwent transurethral resection of the prostate for histologically confirmed benign prostatic hyperplasia was reviewed, with a minimum followup of 8 years. Of 269 patients with full followup data 187 (70%) are alive without prostate cancer and 61 (23%) died without development of the disease. A total of 21 patients (7.8%) had clinically apparent prostate cancer at a mean of 7.0 years following transurethral resection, of whom 3 (14%) died of prostate cancer and 1 died of other causes. These data suggest that the risk of progression and death from prostate cancer may not be significantly greater in patients with stage A1 disease than in those reported to have benign disease at transurethral prostatectomy.

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