Effect on Survival of Androgen Deprivation Therapy Alone Compared to Androgen Deprivation Therapy Combined with Concurrent Radiation Therapy to the Prostate in Patients with Primary Bone Metastatic Prostate Cancer in a Prospective Randomised Clinical Trial: Data from the HORRAD Trial.

BACKGROUND: The cornerstone of standard treatment for patients with primary bone metastatic prostate cancer (mPCa) is androgen deprivation therapy (ADT). Retrospective studies suggest a survival benefit for treatment of the primary prostatic tumour in mPCa, but to date, no randomised-controlled-trials (RCTs) have been published addressing this issue. OBJECTIVE: To determine whether overall survival is prolonged by adding local treatment of the primary prostatic tumour with external beam radiation therapy (EBRT) to ADT. DESIGN, SETTING, AND PARTICIPANTS: The HORRAD trial is a multicentre RCT recruiting 432 patients with prostate-specific antigen (PSA) >20ng/ml and primary bone mPCa on bone scan between 2004 and 2014. INTERVENTION: Patients were randomised to either ADT with EBRT (radiotherapy group) or ADT alone (control group). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary endpoint was overall survival. Secondary endpoint was time to PSA progression. Crude and adjusted analyses were applied to evaluate treatment effect. RESULTS AND LIMITATIONS: Median PSA level was 142ng/ml and 67% of patients had more than five osseous metastases. Median follow up was 47 mo. Median overall survival was 45 mo (95% confidence interval [CI], 40.4-49.6) in the radiotherapy group and 43 mo (95% CI: 32.6-53.4) in the control group (p=0.4). No significant difference was found in overall survival (hazard ratio [HR]: 0.90; 95% CI: 0.70-1.14; p=0.4). Median time to PSA progression in the radiotherapy group was 15 mo (95% CI: 11.8-18.2), compared with 12 mo (95% CI: 10.6-13.4) in the control group. The crude HR (0.78; 95% CI: 0.63-0.97) was statistically significant (p=0.02). CONCLUSIONS: The current RCT comparing ADT to ADT with EBRT to the prostate in patients with primary bone mPCa did not show a significant difference in overall survival, although the CI cannot exclude a substantial survival benefit. Further research is needed to confirm our findings. PATIENT SUMMARY: This study investigated the effect of adding radiation therapy to the prostate to hormonal therapy in prostate cancer patients with metastasis to the bone at diagnosis. In our patient group, additional radiotherapy did not improve overall survival. Further research is needed to confirm our findings. TWITTER SUMMARY: Adding radiotherapy to the prostate in patients with bone metastatic prostate cancer does not improve overall survival.

[Necrotic bladder following radiotherapy for cervical carcinoma]. / Blaasnecrose na radiotherapie voor cervixcarcinoom.

BACKGROUND: In contrast to proctitis, vaginitis and acute radiation cystitis are late complications of pelvic radiation therapy, rare, more severe and irreversible. CASE DESCRIPTION: A 66-year-old patient presented with progressive renal failure ten years after radiotherapy for carcinoma of the cervix. Ultrasound investigation revealed a bilateral hydroutereronefrosis (grade 4), with narrowing of the ureterovesical junctions and a diffuse thickening of the urinary bladder wall. Biopsy of the bladder wall showed extended necrosis. The diagnosis was a necrotic bladder with bilateral ureteral stenosis without local symptoms. Lifelong renal urinary drainage was indicated. CONCLUSION: Late obstructive urological complications, such as bladder necrosis and urethral obstruction, are rare following radiotherapy for cervical carcinoma. Ultrasound follow-up can contribute to the early detection of these complications and intervention can prevent further loss of renal function; however, this would not be cost-effective because of the low incidence rate and because these complications appear in the long term.

Repeat transobturator tape after failed mid-urethral sling procedure: follow-up with questionnaire-based assessment.

OBJECTIVE: To determine if repeat transobturator tape (TOT) is feasible after failed initial synthetic mid-urethral sling (MUS) for stress urinary incontinence, and to ascertain objective physician-determined outcome as well as subjective questionnaire-based outcome for this procedure. PATIENTS AND METHODS: Between February 2005 and February 2008, a total of 21 patients underwent repeat TOT procedure after failed sling treatment. Initial sling procedures were all synthetic MUS, i.e. tension-free vaginal tape in 5 cases and TOT in 16 cases. RESULTS: At a mean follow-up of 16 months, physician-determined cure was achieved in 55% of patients, improvement in 15% and failure in 30%. Outcome deduced from the International Consultation on Incontinence Questionnaire at a mean follow-up of 17 months showed 53% of patients to be cured and 5% of patients to be improved, but failure was noted in 42% of patients. CONCLUSIONS: Repeat TOT after failed synthetic MUS treatment is a feasible procedure with minor morbidity. Repeat TOT provides a reasonable physician-determined success rate, but a lower patient self-reported success rate can be deduced from questionnaires. The transobturator approach seems to show poorer outcomes than the retropubic approach in repeat sling surgery.

Carcinoid tumours of the testis.

OBJECTIVE: To review previous reports of carcinoid (an endocrine tumour mostly of the gastrointestinal tract) tumours of the testis. METHODS: Carcinoid tumours of the testis are rare and can be divided into primary carcinoid (group 1), testicular metastasis from another location (group 2) and carcinoid within a testicular teratoma (group 3). A case of testicular carcinoid within our clinic prompted us to review previous reports; all the cases found were assessed for patient and tumour characteristics, diagnostic tools used, treatment and prognosis. RESULTS: In all, 62 cases were assessed and divided into groups 1 (44 patients), 2 (six) and 3 (12), respectively. Seven patients in group 1 developed metastases. A wide variety of diagnostic tools was used to search for other tumour sites. All patients were treated with orchidectomy. Three patients with a primary carcinoid were treated with adjuvant chemotherapy (two) or radiotherapy (one), with unknown results. All but one of the nine patients who died were known to have metastasis, either from a primary testicular carcinoid or testicular metastases from an intestinal carcinoid. CONCLUSION: When a testicular carcinoid tumour is discovered, other tumour sites should be excluded. The most useful diagnostic tools for this purpose seem to be urinary 5-hydroxyindoleacetic acid measurement, somatostatin receptor scintigraphy, computed tomography and video-capsule endoscopy. Localized testicular carcinoid tumours have an excellent prognosis after orchidectomy.

Female sexual function after surgery for stress urinary incontinence: transobturator suburethral tape vs. tension-free vaginal tape obturator.

INTRODUCTION: The transobturator suburethral tape (TOT) and tension-free vaginal tape obturator (TVT-O) procedures are relatively new incontinence treatment procedures. Studies on the influence on sexual function as a result of these procedures are limited. AIM: The influence of TOT or TVT-O for the surgical treatment of stress urinary incontinence (SUI) on female sexual function. METHODS: We evaluated 77 sexually active patients after TVT-O (N = 34, mean age 53.2 years) and TOT (OB-TAPE, Porges) (N = 44, mean age 52.0 years) placement for SUI based on the responses to a mailed questionnaire 3 months after the operation. MAIN OUTCOME MEASURE: Difference in postoperative sexual complaints related to the TVT-O (inside-out) and TOT (outside-in) procedure. RESULTS: Postoperative TOT and TVT-O: There was almost no difference in frequency of sexual intercourse and an improvement of the continence during intercourse; continence was reported in 33 patients (42.3%) before and 67 patients (78.4%) after operation. The appreciation of sexual intercourse was improved in 15 patients (19.2%) and worsened in eight patients (10.3%). Postoperative TVT-O vs. TOT: No difference was seen in lost of lubrication, clitoral tumescence reduction, and clitoral sensibility reduction between both procedures. Pain because of vaginal narrowing was seen significantly more in the TOT procedure group. CONCLUSION: Overall, in this study, the technique of TOT gave rise to more sexual dysfunction than TVT-O. However, because of the successful outcome on incontinence, both procedures had, overall, a positive effect on sexual function. The cause of significant more pain during intercourse as a result of vaginal narrowing in the TOT procedure requires further investigation. Like other studies, this study demonstrated that incontinence surgery can have a positive and negative outcome on sexual function. It is important to put this issue in the informed consent.

Is the efficacy of hormonal therapy affected by lymph node status? data from the bicalutamide (Casodex) Early Prostate Cancer program.

OBJECTIVES: To report an exploratory subgroup analysis assessing the extent to which the overall benefit found in the Early Prostate Cancer program is dependent on lymph node status at randomization. The program is ongoing, and the overall survival data are immature. The first combined analysis of the bicalutamide (Casodex) Early Prostate Cancer program at 3 years' median follow-up showed that bicalutamide, 150 mg once daily, plus standard care (radical prostatectomy, radiotherapy, or watchful waiting), significantly reduced the risk of objective progression and prostate-specific antigen (PSA) doubling in patients with localized/locally advanced prostate cancer. METHODS: Men (n = 8113) with localized/locally advanced disease received bicalutamide 150 mg or placebo once daily, plus standard care. The time to event data (objective progression, PSA doubling) was analyzed by lymph node status at randomization. RESULTS: Compared with standard care alone, bicalutamide significantly reduced the risk of objective progression, irrespective of lymph node status, with the most pronounced reduction in patients with N+ (hazard ratio [HR] 0.29; 95% confidence interval [CI] 0.15 to 0.56) compared with those with N0 (HR 0.59; 95% CI 0.48 to 0.73) and Nx (HR 0.60; 95% CI 0.50 to 0.72) disease. The largest decrease in risk of PSA doubling with bicalutamide was observed in N+ disease (HR 0.16; 95% CI 0.09 to 0.29), with significantly reduced risks seen in N0 (HR 0.45; 95% CI 0.40 to 0.51) and Nx (HR 0.38; 95% CI 0.33 to 0.44) disease. CONCLUSIONS: The greatest reduction in the risk of objective progression and PSA doubling with bicalutamide was seen in patients with N+ disease. However, bicalutamide also provided a statistically significant benefit in those with N0 and Nx disease.

Bicalutamide as immediate therapy either alone or as adjuvant to standard care of patients with localized or locally advanced prostate cancer: first analysis of the early prostate cancer program.

PURPOSE: We determine the efficacy and tolerability of bicalutamide as immediate therapy, either alone or as adjuvant to treatment of curative intent, in patients with clinically localized or locally advanced prostate cancer. MATERIALS AND METHODS: This international program consists of 3 ongoing, randomized, double-blind, placebo controlled clinical trials (trials 23, 24, and 25). Men with localized or locally advanced (T1-T4, Nx/N0, M0) prostate cancer were randomized to receive 150 mg. bicalutamide daily or placebo, in addition to standard care with radical prostatectomy, radiotherapy or watchful waiting. Primary end points are time to objective progression and overall survival. In this first analysis data from the trials were combined in a single overview analysis according to protocol. RESULTS: Data are available for 8,113 patients (4,052 randomized to bicalutamide, 4,061 to standard care alone) at a median followup of 3.0 years. Treatment with bicalutamide provided a highly significant reduction of 42% in the risk of objective progression compared with standard care alone (9.0% versus 13.8%, hazards ratio 0.58; 95% confidence interval 0.51, 0.66; p <<0.0001). The overall result was reflected in 2 of the 3 trials (trials 24 and 25) with trial 3 (trial 23) showing a nonsignificant difference at this time. Reductions in the risk of disease progression were seen across the entire patient population, irrespective of primary treatment or disease stage. Overall survival data are currently immature and longer followup will determine if there is also a survival benefit with bicalutamide. The most frequently reported side effects of bicalutamide were gynecomastia and breast pain. CONCLUSIONS: Immediate treatment with 150 mg. bicalutamide daily, either alone or as adjuvant to treatment of curative intent, significantly reduces the risk of disease progression in patients with localized or locally advanced prostate cancer. This benefit must be balanced with the morbidity associated with long-term hormonal therapy. Followup is ongoing to determine potential survival benefits of this treatment approach.