Testosterone Therapy after Radiation Therapy for Low, Intermediate and High Risk Prostate Cancer.

PURPOSE: Limited literature exists regarding the safety of testosterone therapy in men treated for prostate cancer. We present multi-institutional data on testosterone therapy in hypogonadal men with prostate cancer treated with radiation therapy. MATERIALS AND METHODS: We retrospectively reviewed the records of hypogonadal men treated with testosterone therapy after radiation therapy for prostate cancer at 4 institutions. Serum testosterone, free testosterone, estradiol, sex hormone-binding globulin, prostate specific antigen, prostate specific antigen velocity and prostate biopsy findings were analyzed. RESULTS: A total of 98 men were treated with radiation therapy. Median age was 70.0 years (range 63.0 to 74.3) at initiation of testosterone therapy. Median baseline testosterone was 209 ng/dl (range 152 to 263) and median baseline prostate specific antigen was 0.08 ng/ml (range 0.00 to 0.33). In the cohort the tumor Gleason score was 5 in 3 men (3.1%), 6 in 44 (44.9%), 7 in 28 (28.6%), 8 in 7 (7.1%) and 9 in 4 (4.1%). Median followup was 40.8 months (range 1.5 to 147). Serum testosterone increased to a median of 420 ng/dl (range 231 to 711) during followup (p <0.001). Overall a nonsignificant increase in mean prostate specific antigen was observed from 0.08 ng/ml at baseline to 0.09 ng/ml (p = 0.05). Among patients at high risk prostate specific antigen increased from 0.10 to 0.36 ng/ml (p = 0.018). Six men (6.1%) met criteria for biochemical recurrence. CONCLUSIONS: Testosterone therapy in men following radiation therapy for prostate cancer was associated with a minor increase in serum prostate specific antigen and a low rate of biochemical recurrence.

Testosterone replacement for hypogonadism after treatment of early prostate cancer with brachytherapy.

BACKGROUND: Controversy and a notable paucity of published clinical data best characterize the current knowledge of testosterone-replacement therapy (TRT) for hypogonadism after treatment for early, localized prostate cancer. The objective of this study was to assess the risk of biochemical failure with TRT after treatment of early prostate cancer with permanent transperineal brachytherapy with or without external beam therapy in patients with low serum levels of testosterone and clinical symptoms of hypogonadism. METHODS: Patients who underwent prostate brachytherapy from 1996 to 2004 and received subsequent TRT for symptomatic hypogonadism were reviewed to detail cancer characteristics and treatment as well as pre- and post-TRT serum testosterone and prostate-specific antigen (PSA) values. RESULTS: Thirty-one men received TRT after prostate brachytherapy for 0.5 to 8.5 years (median, 4.5 years), with a follow-up that ranged from 1.5 years to 9.0 years (median, 5.0 years) postbrachytherapy. TRT was started from 0.5 years to 4.5 years (median, 2.0 years) after brachytherapy. Serum total testosterone levels ranged from 30 ng/dL to 255 ng/dL (median, 188 ng/dL) before TRT and rose to 365 ng/dL to 1373 ng/dL (median, 498 ng/dL) on TRT. Transient rises in PSA were observed in 1 patient. The most recent PSA level was <0.1 ng/mL in 23 patients (74.2%), <0.5 ng/mL in 30 patients (96.7%), and <1 ng/mL in 31 patients (100%). No patients stopped TRT because of cancer recurrence or documented cancer progression. CONCLUSIONS: For patients with low serum testosterone levels and symptoms of hypogonadism, TRT may be used with caution and close follow-up after prostate brachytherapy.

Use of a multitarget fluorescence in situ hybridization assay to diagnose bladder cancer in patients with hematuria.

PURPOSE: We evaluated the multitarget UroVysion fluorescence in situ hybridization assay for the diagnosis of bladder cancer in patients with hematuria and no history of bladder cancer. MATERIALS AND METHODS: A multicenter, blinded trial was performed to compare the sensitivity of the fluorescence in situ hybridization assay to that of voided cytology in patients with gross or microscopic hematuria. Confirmation of hematuria was required. Voided urine was sent to a central laboratory for each study before cystoscopy. Suspicious lesions on cystoscopy were biopsied or resected. A centrally reviewed histopathological interpretation was used to confirm cancer and assign grade and stage. RESULTS: A total of 497 patients were enrolled at 23 centers and in 473 (95.2%) fluorescence in situ hybridization and cytology results were interpretable. Bladder cancer was diagnosed histologically in 50 patients (10.1%) and ureteral cancer was diagnosed in 1. Fluorescence in situ hybridization assay detected 69% of cases and cytology detected 38% (95% CI 25 to 52). When low grade, low stage (TaG1) tumors were excluded, fluorescence in situ hybridization detected 25 of 30 cancers (84%), while cytology detected only 15 (50%). Of 265 current or past smokers with hematuria and positive fluorescence in situ hybridization assay findings bladder cancer was detected in 65% with a history of greater than 40 pack-years compared to 13.6% to 24.2% in those with no, less than a 20 or a 20 to 40-pack-year smoking history. CONCLUSIONS: The UroVysion fluorescence in situ hybridization assay is significantly more sensitive than voided cytology for detecting bladder cancer in patients evaluated for gross or microscopic hematuria for all grades and stages. Based on these data UroVysion was approved by the Food and Drug Administration for use in patients with hematuria.

A phase II clinical trial of oral bropirimine in combination with intravesical bacillus Calmette-Guérin for carcinoma in situ of the bladder: a Southwest Oncology Group Study.

OBJECTIVES: To estimate the probability of response when intravesical bacille Calmette-Guérin (BCG) is given in combination with oral bropirimine for bladder carcinoma in situ, and to evaluate toxicity when the 2 agents are combined. METHODS: A total of 51 patients with histologic evidence of carcinoma in situ and no prior treatment with BCG or bropirimine were enrolled in a cooperative group multicenter phase II trial. Initial treatment included Tice BCG 50 mg weekly for 6 weeks and oral bropirimine 3.0 g/day for 3 consecutive days each week for 12 weeks. Response was assessed after 12 weeks by cystoscopy, biopsy, and barbotage cytology. Most patients received a second course followed by an identical assessment. Toxicity was recorded according to the Southwest Oncology Group toxicity criteria. RESULTS: A total of 51 patients were enrolled and treated. There were 42 patients who were eligible and valuable for response and toxicity. There were 28 complete responders (67%, 50% to 80% 95% confidence interval). The 5-year progression-free survival estimate is 53%, and the 5-year survival estimate is 80%. There were no deaths, 2 patients had grade 4 toxicity, 14 grade 3 toxicity, 17 grade 2 toxicity, 6 grade 1 toxicity, and only 3 had no toxicity reported as their worst toxicity grade. CONCLUSIONS: The combination failed to show an estimated response higher than 80%. It is not recommended that further evaluation of this combination be conducted.

Urinary and rectal complications of contemporary permanent transperineal brachytherapy for prostate carcinoma with or without external beam radiation therapy.

BACKGROUND: Prostate brachytherapy is increasingly used to treat prostate carcinoma, alone or combined (combination therapy) with external beam radiation therapy (EBRT). This report cites the frequency and nature of urinary and rectal complications requiring unplanned interventions after contemporary brachytherapy with or without EBRT. METHODS: A total of 177 consecutive patients underwent either brachytherapy (100 patients [56.5%]) or combination therapy (77 patients [43.5%]) for clinical T1-2 prostate carcinoma between July 1998 and July 2000. All the patients were analyzed with regard to disease characteristics, treatment details, and complications requiring unplanned interventions in up to 48 months of follow-up. RESULTS: Catheter drainage for urinary retention was required for a median of 55 days (range, 3-330 days) in 36 patients (20%), including 24% after brachytherapy and 16% after combination therapy. Transurethral resection of the prostate (TURP) was performed at a median of 12 months (range, 8-18 months) after implantation in 5% of patients after brachytherapy and 14.5% of patients after combination therapy (P = 0.029). Colonoscopy with or without fulguration for rectal bleeding was performed in 37 of 158 patients (97 in the brachytherapy group and 61 in the combination therapy group) (23.4%) at a median of 17 months (range, 4-45 months), including 15 patients (15.5%) after brachytherapy and 22 patients (36%) after combination therapy (P = 0.002). Combination therapy resulted in fecal diversion in 6.6% of patients (P = 0.021), urinary diversion in 3.2% of patients (P = 0.148), and clean intermittent self-catheterization for recurrent stricture after multiple TURPs in 4.9% of patients (P = 0.055), none of which occurred after brachytherapy. Overall, 20.6% of patients underwent TURP or colonoscopy after brachytherapy, whereas 44.2% underwent those or more extensive unplanned procedures after combination therapy (P = 0.001). CONCLUSIONS: Complications requiring unplanned procedures may occur after brachytherapy, and may be increased significantly after brachytherapy combined with EBRT. These data reinforce the concept that quality assurance and technique are important in prostate brachytherapy, but, even when these are in place, complications can occur, especially when EBRT is added to brachytherapy.

Surgical factors influence bladder cancer outcomes: a cooperative group report.

PURPOSE: A randomized, cooperative group trial (Southwest Oncology Group 8710, Intergroup 0080) reported that neoadjuvant chemotherapy improved the survival of patients with locally advanced bladder cancer who were treated with radical cystectomy. We evaluated whether surgical factors from patients enrolled onto the study predicted bladder cancer outcomes. PATIENTS AND METHODS: Surgical and tumor factors were recorded from surgical and pathologic reports from 268 patients with muscle-invasive bladder cancer who received radical cystectomy. Cystectomies were performed by 106 surgeons in 109 institutions. Half of the patients received neoadjuvant methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) chemotherapy. Variables were tested in univariate and multivariate analyses for associations with postcystectomy survival (PCS) and local recurrence (LR) in all patients receiving cystectomy. RESULTS: Five-year PCS and LR rates were 54% and 15%, respectively. A multivariate model adjusted for MVAC (P =.97), age (P =.03), pathologic stage (P =.0002), and node status (P =.04) showed that surgical variables associated with longer PCS were negative margins (v positive; hazard ratio [HR], 0.37; P =.0007), and > or = 10 nodes removed (v < 10; HR, 0.51; P =.0001). These associations did not differ by treatment arms (P >.21 for all tests of interactions between treatment and surgical variables). Predictors of LR in a multivariate model adjusted for MVAC (P =.16), pathologic stage (P =.02), and node status (P =.37) were positive margins (v negative; odds ratio [OR], 11.2; P =.0001) and fewer than 10 nodes removed (v > or = 10; OR, 5.1; P =.002). CONCLUSION: Surgical factors influence bladder cancer outcomes after cystectomy, after adjustment for pathologic factors and neoadjuvant chemotherapy usage.

Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer.

BACKGROUND: Despite aggressive local therapy, patients with locally advanced bladder cancer are at significant risk for metastases. We evaluated the ability of neoadjuvant chemotherapy to improve the outcome in patients with locally advanced bladder cancer who were treated with radical cystectomy. METHODS: Patients were enrolled if they had muscle-invasive bladder cancer (stage T2 to T4a) and were to be treated with radical cystectomy. They were stratified according to age (less than 65 years vs. 65 years or older) and stage (superficial muscle invasion vs. more extensive disease) and were randomly assigned to radical cystectomy alone or three cycles of methotrexate, vinblastine, doxorubicin, and cisplatin followed by radical cystectomy. RESULTS: We enrolled 317 patients over an 11-year period, 10 of whom were found to be ineligible; thus, 154 were assigned to receive surgery alone and 153 to receive combination therapy. According to an intention-to-treat analysis, the median survival among patients assigned to surgery alone was 46 months, as compared with 77 months among patients assigned to combination therapy (P=0.06 by a two-sided stratified log-rank test). In both groups, improved survival was associated with the absence of residual cancer in the cystectomy specimen. Significantly more patients in the combination-therapy group had no residual disease than patients in the cystectomy group (38 percent vs. 15 percent, P<0.001). CONCLUSIONS: As compared with radical cystectomy alone, the use of neoadjuvant methotrexate, vinblastine, doxorubicin, and cisplatin followed by radical cystectomy increases the likelihood of eliminating residual cancer in the cystectomy specimen and is associated with improved survival among patients with locally advanced bladder cancer.

Clinical evaluation of a multi-target fluorescent in situ hybridization assay for detection of bladder cancer.

PURPOSE: The UroVysion fluorescence in situ hybridization assay (UroVysion Bladder Cancer Recurrence Kit, Vysis, Inc., Downers Grove, Illinois) is a multi-target assay that detects aneuploidy of chromosomes 3, 7 and 17, and loss of the 9p21 band in exfoliated cells in urine from patients with transitional cell carcinoma. We performed 2 multicenter trials. In 1 trial we compared the sensitivity of the FISH assay to the BTA Stat test (Bion Scientific, Redmond, Washington) and voided cytology in the detection of transitional cell carcinoma. In a separate study of healthy volunteers and patients with other (nontransitional cell carcinoma) conditions we determined the specificity of the FISH assay. MATERIALS AND METHODS: A total of 176 patients with transitional cell carcinoma in the previous 9 months provided voided urine before cystoscopy. Each specimen was split, preserved and shipped to a central laboratory where all 3 tests were performed. All sites were blinded to results. Sensitivity calculations were based on central pathology review of resected tissue. Specificity was determined by testing 275 volunteers who were healthy and with nontransitional cell carcinoma conditions. RESULTS: The 21 sites enrolled 176 patients with a history of transitional cell carcinoma, with 62 recurrences while undergoing surveillance. Overall sensitivities (with 95% CI) were FISH 71% (95% CI 58 to 82), BTA Stat test 50% (37 to 63) and cytology 26% (16 to 39). FISH was negative in 260 of the 275 healthy volunteers or patients with no history of transitional cell carcinoma (specificity 94.5%). CONCLUSIONS: Sensitivity of the FISH assay is superior to that of cytology and at least equivalent to the BTA Stat test in detecting recurrent transitional cell carcinoma. Its specificity approaches that of cytology. Further testing of its clinical use is warranted.