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Purpose: Periodic Health Assessments have been mandated for United States Air Force servicemen since the mid 1990s. Thus, we determined whether United States Air Force prostate cancer incidence rates increased thereafter and how these tumors segregate into low and intermediate/high risk categories. We also identified treatment choices., Materials and Methods: We queried the Department of Defense Automated Central Tumor Registry for prostate cancer diagnosed in United States Air Force servicemen between 1991 and 2008 to determine incidence rates, disease risk category and treatments., Results: Age adjusted rates in white active duty servicemen diagnosed for the most recent period of 2005 to 2008 increased 3-fold relative to the rate in the earliest period of 1991 to 1994. A similar trend was evident in black servicemen. Relative to the Surveillance, Epidemiology and End Results population prostate cancer rates in active duty United States Air Force men between 1995 and 2008 were significantly increased for the 2 racial groups. A significantly greater proportion of active duty servicemen than retirees (62% vs 40%) presented with low risk disease, defined as prostate specific antigen less than 10 ng/ml, Gleason sum less than 7 and clinical stage T1a-T2a. Of those with low risk disease significantly more active duty servicemen elected curative surgery than retirees (93% vs 53%)., Conclusions: Prostate cancer incidence rates in United States Air Force servicemen have increased with time, exceeding rates in the Surveillance, Epidemiology and End Results population. While most cases are characterized as low risk, aggressive management is elected., (Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: We assessed whether dutasteride enhances the usefulness of total prostate specific antigen for diagnosing clinically significant prostate cancer., Materials and Methods: The 4-year REDUCE study evaluated the efficacy and safety of 0.5 mg dutasteride daily for prostate cancer risk reduction in men with a prostate specific antigen of 2.5 to 10.0 ng/ml and a negative prostate biopsy. Specificity, sensitivity, and positive and negative predictive values of prostate specific antigen for the diagnosis of prostate cancer were assessed., Results: Final prostate specific antigen before biopsy and change from month 6 to final prostate specific antigen performed better for the diagnosis of Gleason score 7-10 tumors in men who received dutasteride vs placebo as assessed by the area under the ROC curves (0.700 vs 0.650, p = 0.0491; and 0.699 vs 0.593, p = 0.0001, respectively). Increases in prostate specific antigen were associated with a higher likelihood of biopsy detectable, Gleason score 7-10 and clinically significant (modified Epstein criteria) prostate cancer. Percentage decreases in prostate specific antigen from baseline to month 6 in the dutasteride arm did not predict prostate cancer overall or Gleason score 7-10 cancer., Conclusions: In men with a previously negative prostate biopsy, prostate specific antigen performed better during the 4-year study as a marker of prostate cancer in men who received dutasteride vs placebo. The degree of prostate specific antigen increase after 6 months was a better indicator of clinically significant cancer in the dutasteride arm than in the placebo arm. Conversely, the initial decrease in prostate specific antigen in men taking dutasteride did not predict the likelihood of prostate cancer., (Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Purpose: We determine if histopathological factors of the primary penile tumor can stratify the risk of the development of inguinal lymph node metastases., Materials and Methods: Clinical records of 48 consecutive patients with squamous cell carcinoma of the penis who underwent resection of the primary lesion and either inguinal lymph node dissection or were observed for signs of recurrence (median followup 59 months) were reviewed. Parameters examined included pathological tumor stage, quantified depth of invasion and tumor thickness, histological and nuclear grade, percentage of poorly differentiated cancer in the primary tumor, number of mitoses and presence or absence of vascular invasion. Variables were compared in 18 lymph node positive and 30 lymph node negative cases., Results: Pathological tumor stage, vascular invasion and presence of greater than 50% poorly differentiated cancer were the strongest predictors of nodal metastasis on univariate and multivariate regression analyses. None of 15 pT1 tumors exhibited vascular invasion or lymph node metastases. Of 33 patients with pT2 or greater tumors 21 (64%) had vascular invasion and 18 (55%) had metastases. Only 4 of 25 patients (15%) with 50% or less poorly differentiated cancer in the penile tumor had metastases compared with 14 of 23 patients (61%) with greater than 50% poorly differentiated cancer (p = 0.001). No other variables tested were significantly different among the patient cohorts., Conclusions: Pathological stage of the penile tumor, vascular invasion and greater than 50% poorly differentiated cancer were independent prognostic factors for inguinal lymph node metastasis. Prophylactic lymphadenectomy in compliant patients with pT1 lesions without vascular invasion and 50% or less poorly differentiated cancer does not appear warranted.

Purpose: There has been a significant shift toward multimodality therapy to try to eradicate extracapsular disease better in patients with locally advanced prostate cancer. We assess the feasibility and complications of initial cryotherapy followed by radical prostatectomy, and evaluate the frequency and location of viable benign and malignant prostate tissue and positive surgical margins after this treatment combination., Materials and Methods: A total of 12 patients with clinical stage T3 cancer or clinical stages T1c to T2, Gleason score 8 to 10 cancer on the initial biopsy were treated with initial cryotherapy followed by open surgical exploration 2 to 8 days later. If pelvic lymph nodes were negative, radical prostatectomy was performed. Prostate specific antigen was measured approximately every 3 months postoperatively, and complications were assessed by retrospective chart review and a quality of life survey., Results: Radical prostatectomy was aborted in 5 patients with positive pelvic lymph nodes. Of the 7 patients who underwent prostatectomy 4 had no residual prostate cancer in the specimen (pathological stage pT0 disease). All 7 of these patients had focal areas of viable normal prostate glands. Only 1 of the 7 patients had a positive surgical margin and biochemical failure (mean followup 22.6 months). The main complications of cryotherapy followed by radical prostatectomy were urinary incontinence and impotence., Conclusions: Neoadjuvant cryotherapy achieved complete tumor destruction in 4 of 7 patients with locally advanced prostate cancer. Cryotherapy followed by radical prostatectomy was associated with substantial morbidity, mainly in terms of urinary incontinence.

Purpose: The prognosis of patients with advanced squamous cell carcinoma of genitourinary origin is poor. While single agent chemotherapy results mainly in partial responses of short duration, data on the efficacy of combination chemotherapy are extremely limited. We determined the response rate and toxicity of a combination of 3 of the most active agents, methotrexate, cisplatin and bleomycin, in patients with advanced genitourinary squamous cell carcinoma., Materials and Methods: Patients with metastatic or locally advanced genitourinary squamous cell carcinoma were eligible for study. Treatment consisted of 200 mg./m.2 methotrexate on days 1, 15 and 22, and 20 mg./m.2 cisplatin and 10 mg./m.2 bleomycin on days 2 through 6 during a 28-day cycle., Results: Of the 30 patients who enrolled in the trial 29 were evaluable for response. Objective response was achieved in 16 patients (55%, 95% confidence interval 36 to 72), 4 of whom achieved a complete response (14%). Median objective response duration was 4.7 months (range 1.9 to 39.5). Median survival of the entire group was 11.5 months (range 1.5 to 87.0). Of the patients 9 achieved disease-free status, including 6 following consolidation surgery or radiation therapy. Median survival of these 9 patients (34.4 months, range 9.6 to 87.0) was significantly greater (p = 0.0003) than that of patients who did not become disease-free (7.0 months, range 1.5 to 38.6). Grade III or IV hematological toxicity in 116 courses included neutropenia (13%) and thrombocytopenia (6%). Among 30 patients evaluable for toxicity serious nonhematological toxic effects included stomatitis (3%) and renal toxicity (7%). There was 1 death from neutropenic sepsis., Conclusions: Methotrexate, cisplatin and bleomycin combination chemotherapy for genitourinary squamous cell carcinoma results in a high but short lived overall response rate, and a low complete response rate with manageable toxicity. A multidisciplinary approach to achieve disease-free status may provide the best opportunity to effect survival and should be the focus of future trials.

Purpose: We compared the relationship of pathological features and preoperative prostate specific antigen (PSA) levels of a consecutive series of black patients to a stage matched cohort of white patients treated during the same period., Materials and Methods: The radical prostatectomy specimens of 40 black patients were reviewed and tumor volume was determined. Histopathological features (stage, grade, zonal distribution of cancer foci), tumor volume and prostate weight were correlated to pretreatment serum PSA levels. These parameters were compared with those of 148 white patients matched by pathological stage., Results: Black patients exhibited a significantly higher incidence of seminal vesicle involvement (p=0.03) and cancers with a Gleason score of 8 or more (p=0.02), and a trend toward decreased pathologically organ confined, margin negative disease (40% black versus 53% white men, p=0.13). Although the incidences of multifocal cancer were virtually identical (90 and 82%) in the 2 groups, black patients exhibited a higher incidence of transition zone cancer foci (p <0.001). Mean prostate tumor volume, total gland weight and serum PSA level among black and white patients with pathological stage pT2-, pT2+ and pT3- cancer were not significantly different. However, with advancing pathological stage (pT3+ and pT3c) disease black patients had higher preoperative serum PSA levels on univariate and multivariate analyses despite similar total gland weight and tumor volume., Conclusions: Black patients who underwent radical prostatectomy often exhibited adverse pathological features. Two novel findings were that the distribution of cancer foci within the prostate was significantly different between black and white patients, and that serum PSA levels in patients with locally advanced prostate cancer were higher in black than in white men, despite adjustment for known variables affecting PSA. These observations suggest that differences in the biology of prostate cancer between these 2 races may exist.

Purpose: We evaluated the presentation, methods of diagnosis and treatment of pelvic recurrence following radical cystectomy for transitional cell carcinoma of the bladder., Materials and Methods: We reviewed the records of 33 patients who underwent radical cystectomy for transitional cell carcinoma between May 1960 and August 1995 at our cancer center and who later had pelvic recurrence., Results: The majority of patients underwent cystectomy for clinically advanced transitional cell carcinoma. Median time from cystectomy to recurrence was 10 months. Of the patients 25 were symptomatic (76%) at the time recurrence was diagnosed. Recurrence was discovered by digital rectal examination in 4 asymptomatic patients (12%) and by routine pelvic imaging in 2. Treatment included chemotherapy, surgery or radiation (alone or in combination). Of the 33 patients 29 died of progressive disease with a median survival of 7 months from the time of recurrence, and 4 remained free of disease at 7, 14, 26 and 95 months after local recurrence. Despite the poor survival rate following treatment 11 of 14 patients had complete resolution of symptoms following chemotherapy., Conclusions: The prognosis of patients with local recurrence is poor regardless of therapy. These recurrences are often symptomatic but careful post-cystectomy tumor surveillance, including digital rectal examination and pelvic imaging, provides an opportunity to diagnose local recurrences when they may be amenable to therapy. Systemic chemotherapy offers excellent palliation for symptomatic patients.

Purpose: Orthotopic bladder reconstruction in women is the focus of considerable interest. To define suitable candidates for orthotopic reconstruction among women with bladder cancer, we reviewed the risk of secondary urethral, vaginal and cervical involvement by transitional cell carcinoma in patients who underwent radical cystectomy at our institution., Materials and Methods: We retrospectively reviewed the charts of women who underwent radical cystectomy for primary transitional cell carcinoma of the bladder between 1985 and 1995. These cases also were reviewed pathologically., Results: Of 115 patients who underwent radical cystectomy for transitional cell carcinoma of the bladder 9 (8%) also had secondary transitional cell carcinoma of the urethra, including 2 with concomitant involvement of the vagina or cervix. In 4 patients (3%) the vagina or cervix was involved but not the urethra. Vaginal and cervical invasion correlated with stages T3b and T4 disease (p = 0.04). By logistic regression analysis the sole significant risk factor for urethral involvement was bladder neck involvement (p = 0.0005). Unlike previous studies 2 of 9 patients with secondary urethral transitional cell carcinoma did not have apparent cancer at the bladder neck., Conclusions: We report secondary urethral involvement without apparent bladder neck involvement in women with transitional cell carcinoma. Women who are candidates for orthotopic reconstruction should undergo biopsies of the bladder neck and urethra as part of the preoperative evaluation. In patients with palpable masses (stage T3b) on bimanual examination, transvaginal biopsies should also be considered. Intraoperative frozen sections of the urethral and vaginal margins should be obtained.

Purpose: A phase I/II study was done to evaluate the efficacy and complications of salvage cryotherapy as a treatment for locally recurrent prostate cancer following full dose radiation therapy and/or systemic therapy. The efficacy of single and double freeze-thaw cycles was compared using posttreatment prostate specific antigen (PSA) levels and prostate biopsies as end points., Materials and Methods: A total of 150 patients with locally recurrent prostate cancer following radiation, hormonal therapy and/or systemic chemotherapy underwent salvage cryotherapy using a single (71 men, mean followup 17.3 months) or double (79 men, mean followup 10.0 months) freeze-thaw cycle. PSA was measured approximately every 3 months postoperatively and sextant biopsies were repeated 6 months postoperatively. Complications were assessed by retrospective chart review and a mailed quality of life survey., Results: Overall, 45 patients (31%) had persistently undetectable PSA. Patients with a history of radiation therapy only who underwent a double freeze-thaw cycle had a higher negative biopsy rate (93 versus 71%, p < 0.02) and lower biochemical failure rate (defined as an increase in serum PSA of 0.2 ng./ml. above the nadir value, 44 versus 65%, p < 0.03) than those who underwent a single freeze-thaw cycle. The main complications of salvage cryotherapy were urinary incontinence (73% of the patients), obstructive symptoms (67%), impotence (72%) and severe perineal pain (8%)., Conclusions: Salvage cryotherapy impacts local tumor control as evident by the high frequency of negative posttreatment biopsies. A double freeze-thaw cycle appears more effective than a single cycle. Like salvage prostatectomy, salvage cryotherapy causes significant morbidity.

Purpose: We determined whether an extended sentinel lymph node dissection is effective for staging penile squamous carcinoma associated with clinically negative inguinal lymph nodes., Materials and Methods: A retrospective review was done of 20 consecutive patients who underwent extended sentinel lymph node dissection between 1985 and 1994., Results: Of the patients 14 underwent bilateral extended sentinel lymph node dissection, and 6 underwent ipsilateral extended sentinel lymph node dissection plus contralateral inguinal or ilioinguinal lymphadenectomy. All lymph nodes included in the extended sentinel node dissection were negative for metastases. Five patients had inguinal metastases at a median of 10 months (range 3 to 21) after negative extended sentinel lymph node dissection., Conclusions: Although it is a more extensive procedure than sentinel lymph node biopsy, extended sentinel lymph node dissection is still associated with a significant false-negative rate (25%). Thus, its routine use can no longer be recommended.