The Need for Survivorship Care in Genitourinary Cancers: Considerations from SUO and LUGPA.

INTRODUCTION: A quarter of American cancer survivors have genitourinary malignancies that are largely managed by urologists. We explored urologist perceptions about survivorship care for genitourinary malignancies. METHODS: A total of 701 SUO (Society of Urologic Oncology) and 1,746 LUGPA (Large Urology Group Practice Association) members were invited to complete a web based survey composed of 5 domains, including 1) demographics, 2) current survivorship care practices, 3) perceived barriers, 4) accessibility to survivorship resources and 5) perceptions of advocacy groups. RESULTS: Of 191 respondents 137 (72%) had no training in survivorship care. Of the 174 respondents 129 (74%) practiced shared care models while 45 (26%) preferred pure specialized followup care. Only 39 of 129 respondents (30%) with a shared care model always provided a written care plan. These plans infrequently included information on lifestyle modifications and educational resources. Routine patient referral to advocacy organizations was highest for prostate cancer at 40% followed by bladder, testicular and kidney cancers at 17%, 10% and 8%, respectively. Lack of time/resources and practice guidelines were considered the 2 most important barriers to survivorship care by 31% and 30% of participants, respectively. Web based information on advocacy groups and best practice guidelines were selected as the most important initiatives to promote survivorship care. CONCLUSIONS: Despite the low response rate this study highlights important practice gaps in survivorship care for patients with genitourinary malignancies. In collaboration with advocacy organizations professional societies should initiate programs to better educate and train their members in survivorship care guidelines and consensus best practices.

Loss of androgen receptor expression is not associated with pathological stage, grade, gender or outcome in bladder cancer: a large multi-institutional study.

OBJECTIVE: • To investigate androgen receptor (AR) expression in a large series of patients with bladder cancer (BC) because data on a limited number of patients showed that loss of AR expression was associated with invasive BC. PATIENTS AND METHODS: • A total of 472 patients with urothelial bladder carcinoma (UBC) from two institutional centres (Toronto and Dallas) were analysed. Tissue microarrays comprising both non-muscle-invasive UBC (n= 167) and muscle-invasive UBC (n= 305) were accrued and immunohistochemical staining for AR was performed. • We used bright-field microscopy imaging coupled with advanced colour detection software to detect, classify and count stained cellular objects and manual scoring. • Results obtained in Dallas were blindly reviewed and validated in Toronto and samples randomly chosen were further analysed in Rochester, NY, USA. RESULTS: • The AR were positively expressed in 61/472 (12.9%) bladder tumours. No statistically significant difference in AR expression between men and women was observed. • Only 9.0% of non-muscle-invasive BC expressed the AR compared with 15.1% of muscle-invasive tumours (P= 0.059). The highest percentage of AR positivity (28.9% of cases) was found in T2 tumours. • There was no statistically significant difference in death from BC, time to death, or time to recurrence between AR-positive and AR-negative cases. CONCLUSION: • In contrast to previous reports, based on our large BC series, we did not observe a decrease in AR protein expression in bladder tumours with increased pathological stage. Our data do not suggest that loss of AR expression is gender-related nor is it associated with invasive BC.

Effect of medical castration on CYP3A4 enzyme activity using the erythromycin breath test.

PURPOSE: Testosterone administration can lead to increased antipyrine clearance in humans. Medical or surgical castration is a standard treatment of progressive prostate carcinoma, but the effect of the subsequent fall of testosterone concentrations upon drug metabolism has not been reported. METHODS: Eleven men with a biopsy-proven diagnosis of progressive prostate cancer were enrolled after providing informed consent. CYP3A4 activity was determined using the erythromycin breath test (EBT) in each patient prior to their beginning with an LHRH-agonist (leuprolide or goserelin). No patients had elected to undergo orchiectomy during the period of subject accrual. Each subject underwent a second EBT 2 months after beginning LHRH suppression. Blood samples were collected at these time points to determine changes in testosterone and leutinizing hormone. RESULTS: All subjects had a predictable drop in serum testosterone concentrations over the 8-week course of the study, but concentrations in three did not fall below castrate levels (<50 ng/dl). There was no statistically significant change in CYP3A4 activity using the EBT method (p = 0.88). The extent and direction of changes in CYP3A4 activity was highly variable, with three subjects experiencing an increase in activity, and five demonstrating a decrease in activity. CONCLUSION: There is no clinically significant change in CYP3A4 activity after medical castration. No changes in the clearance of docetaxel or other CYP3A4 substrates are likely during and after medical castration. Although similar findings are expected after orchiectomy, we were not able to test this presumption because of patient preference for medical castration.