Age is predictive of immediate postoperative urinary continence after radical retropubic prostatectomy.

INTRODUCTION: Immediate continence is a goal to take into consideration for better patient satisfaction after radical prostatectomy. Factors predicting urinary continence at catheter removal were investigated. MATERIALS AND METHODS: We evaluated preoperative, operative, clinical, hormonal and pathological variables in a homogeneous series of radical retropubic prostatectomies (RRPs) following the principles of urinary sphincter restoration technique. RESULTS: The study included 201 patients who underwent RRP. The overall immediate continence rate at catheter removal was 67.7% (136 patients); 28.8% (58 patients) were using one protective pad daily and 3.5% (7 patients) were incontinent. At 6-month follow-up incontinence had reached the lowest level of 2.5% (5 patients) and at 12 months the patients using one pad daily had decreased to 11.9% (24 patients). Multivariate logistic analysis showed that the only two factors independently associated with immediate continence were age <65 years (OR = 2.63, 95% CI 1.13-5.88, p = 0.02) and potency (OR = 3.6, 95% CI 1.2-10.7, p = 0.01) adjusting for D'Amico risk group, surgical margins, extracapsular extension, clinical stage, PSA, testosterone, LH and FSH. No significant association was noted for PSA, hormonal levels, hospital stay, prostate size, clinical stage, risk group, TNM stage, pathological Gleason score or extracapsular extension. CONCLUSIONS: In our series age <65 years was associated with immediate continence after RRP. Moreover, patients who were immediately continent had a 3.6-fold probability to be potent within 12 months.

Diagnosis, Treatment Response, and Prognosis: The Role of 18F-DOPA PET/CT in Children Affected by Neuroblastoma in Comparison with 123I-mIBG Scan: The First Prospective Study.

Our purpose was to evaluate the diagnostic role of 18F-3,4-dihydroxyphenylalanine (DOPA) PET/CT at the time of staging in children with neuroblastoma and to investigate its ability to assess treatment response. We also investigated the prognostic value of 18F-DOPA PET/CT at the same time points. Methods: We enrolled children with neuroblastoma at onset. Before and after induction chemotherapy, all patients underwent 18F-DOPA PET/CT and 123I-metaiodobenzylguanidine (MIBG) scanning plus SPECT/CT. 18F-DOPA PET/CT results were compared with those of 123I-MIBG whole-body scanning (WBS). For each modality, patient-based analysis and lesion-based analysis were performed and sensitivity was calculated. We applied scoring systems to 123I-MIBG scanning and 18F-DOPA PET/CT (i.e.,123I-MIBG WBS score and whole-body metabolic burden [WBMB], respectively) and evaluated the association between these parameters, the principal neuroblastoma risk factors, and outcome. Results: We enrolled 16 high-risk and 2 intermediate-risk neuroblastoma patients. On patient-based analysis, sensitivity in detecting primary tumors, soft-tissue metastases, and bone or bone-marrow metastases was 83%, 50%, and 92%, respectively, for 123I-MIBG WBS versus 94%, 92%, and 100%, respectively, for 18F-DOPA PET/CT. On lesion-based analysis, the sensitivity of 18F-DOPA PET/CT in detecting soft-tissue and bone or bone-marrow metastases was 86% and 99%, respectively-significantly higher than that of 123I-MIBG WBS, at 41% and 93%, respectively. After therapy, on patient-based analysis, the sensitivity in detecting primary tumors, soft-tissue metastases, and bone or bone-marrow metastases was 72%, 33%, and 38%, respectively, for 123I-MIBG WBS versus 83%, 75% and 54%, respectively, for 18F-DOPA PET/CT. On lesion-based analysis, the sensitivity of 18F-DOPA PET/CT in detecting soft-tissue and bone or bone-marrow metastases was 77% and 86%, respectively-significantly higher than that of 123I-MIBG WBS, at 28% and 69%, respectively. During follow-up, 8 cases of disease progression and 5 deaths occurred. On multivariate analysis, only posttherapeutic 18F-DOPA WBMB (>7.5) was associated with progression-free survival. Conclusion:18F-DOPA PET/CT is more sensitive than 123I-MIBG WBS in staging neuroblastoma patients and evaluating disease persistence after chemotherapy. In a time-to-event analysis, posttherapeutic 18F-DOPA WBMB remained the only risk factor associated with disease progression.

Randomized Placebo Controlled Trial of Low-Dose Tamoxifen to Prevent Local and Contralateral Recurrence in Breast Intraepithelial Neoplasia.

PURPOSE: Tamoxifen administered for 5 years at 20 mg/d is effective in breast cancer treatment and prevention, but toxicity has limited its broad use. Biomarker trials showed that 5 mg/d is not inferior to 20 mg/d in decreasing breast cancer proliferation. We hypothesized that a lower dose given for a shorter period could be as effective in preventing recurrence from breast intraepithelial neoplasia but have a lower toxicity than the standard dose. PATIENTS AND METHODS: We conducted a multicenter randomized trial of tamoxifen, 5 mg/d or placebo administered for 3 years after surgery in women with hormone-sensitive or unknown breast intraepithelial neoplasia, including atypical ductal hyperplasia and lobular or ductal carcinoma in situ. The primary end point was the incidence of invasive breast cancer or ductal carcinoma in situ. RESULTS: Five hundred women 75 years of age or younger were included. After a median follow-up of 5.1 years (interquartile range, 3.9-6.3 years), there were 14 neoplastic events with tamoxifen and 28 with placebo (11.6 v 23.9 per 1,000 person-years; hazard ratio, 0.48; 95% CI, 0.26 to 0.92; P = .02), which resulted in a 5-year number needed to treat of 22 (95% CI, 20 to 27). Tamoxifen decreased contralateral breast events by 75% (three v 12 events; hazard ratio, 0.25; 95% CI, 0.07 to 0.88; P = .02). Patient-reported outcomes were not different between arms except for a slight increase in frequency of daily hot flashes with tamoxifen (P = .02). There were 12 serious adverse events with tamoxifen and 16 with placebo, including one deep vein thrombosis and one stage I endometrial cancer with tamoxifen and one pulmonary embolism with placebo. CONCLUSION: Tamoxifen at 5 mg/d for 3 years can halve the recurrence of breast intraepithelial neoplasia with a limited toxicity, which provides a new treatment option in these disorders.

Prognostic Significance of VEGF after Twenty-Year Follow-up in a Randomized Trial of Fenretinide in Non-Muscle-Invasive Bladder Cancer.

Non-muscle-invasive bladder cancer (NMIBC) may progress to muscle-invasive disease, but no effective preventive treatments are available. In addition, no reliable prognostic biomarkers have been identified. We assessed the long-term effect of the oral retinoid fenretinide and the prognostic value of circulating VEGF levels. We updated through the Tumor Registry the vital status of 99 patients with resected Ta/T1 bladder tumors who were recruited in a randomized trial of 2 years of fenretinide or no treatment in 1993-1994. Serum VEGF levels measured at baseline and 12 months were available in a subgroup of 62 patients. After a median of 20.5 years, 54 subjects died, 35 of any cancer and 14 of bladder cancer. Neither overall survival (OS), nor cancer survival (CS) or bladder cancer survival (BCS) was affected by fenretinide (log-rank P ≥ 0.2). DNA aneuploidy in bladder washing was associated with shorter OS (P = 0.02), CS (P = 0.05), and BCS (P = 0.09). Subjects with baseline VEGF levels in the top quintile (≥350 pg/mL) had a significantly shorter OS (P = 0.01), CS (P = 0.02), and BCS (P = 0.008). The trend across quintiles of VEGF was significant for BCS (P = 0.007). Multivariate analyses showed that, in addition to smoking status, VEGF level in the top quintile was an independent prognostic factor for OS (HR = 2.7; 95% CI, 1.1-6.5), CS (HR = 3.3; 95% CI, 1.1-9.4) and BCS (HR = 8.9; 95% CI,1.3-61). Fenretinide did not affect the long-term outcome of patients with NMIBC. High serum VEGF level was a significant predictor of overall and cancer death and may help to identify high-risk subjects who may benefit from a preventive therapy. Cancer Prev Res; 9(6); 437-44. ©2016 AACR.

Association of Biomarkers with Serious Cardiac Adverse Events during Abiraterone Acetate Treatment in Castration Resistant Prostate Cancer.

BACKGROUND: Abiraterone acetate is an effective drug for castration-resistant prostate cancer, but cardiac serious adverse events (SAEs) may occur. We studied their association with N-terminal pro-brain natriuretic peptide (NT-proBNP) and troponin T (TnT) during abiraterone therapy. PATIENTS AND METHODS: In a single institution, 17 patients were treated with abiraterone acetate 1 g daily with concomitant prednisone and then switched to dexametasone plus canrenone. Blood samples for PSA, NT-proBNP, and TnT were obtained at baseline and after 1, 3, and 6 months. RESULTS: Five patients (29.4%) experienced G3 to 4 cardiac SAEs after a median of 13 weeks (range, 9-32), including pulmonary edema, heart failure, acute coronary syndrome, sinus bradycardia with syncope, and pulmonary edema. At baseline, 4 weeks, and 3 months, median NT-proBNP and TnT levels were higher in patients with subsequent cardiac SAEs (P= .03 and P= .04 for NT-proBNP and TnT at 3 months, respectively). After switching to dexametasone and introducing canrenone, no additional cardiac SAEs were noted. Overall response rate was 67%. CONCLUSIONS: Our study suggests a higher than expected risk of cardiac SAEs during abiraterone treatment which may well be due to the small sample size and the unrestricted entry criteria. However, baseline and frequent NT-proBNP and TnT monitoring predicted a higher risk for cardiac SAE. Larger studies should confirm our findings.

An observational study of nasal cavity toxicity in cancer patients treated with bevacizumab.

BACKGROUND: The nasal cavity is a vulnerable zone which may be damaged by vascular disorders. We systematically assessed the frequency and severity of nasal cavity alterations during bevacizumab treatment, to determine its clinical relevance and factors contributing to its onset. PATIENTS AND METHODS: We conducted a hospital-based cohort study in 47 consecutive patients with advanced cancers who were on treatment with chemotherapy and bevacizumab at different doses. All patients underwent otolaryngology (ENT) examination at the time of study initiation. RESULTS: The mean number of cycles at first ENT examination was 16 (standard deviation = 14). A total of 45 patients (96%) showed nose mucosal lesions, of whom 30% had erosions and 62% had grade 1 - 2 epistaxis. One patient had septal perforation. Grades 1 - 4 sinus disorders were noted in 60%. There was a significant trend to a higher risk of grade ≥ 2 nasal events for bevacizumab doses > 7.5 mg/kg, concomitant taxane use and digital nasal self-manipulation. CONCLUSIONS: We found a high incidence of nasal cavity lesions in patients receiving bevacizumab, with evidence for a dose-related effect. Most cases were low grade and manageable without drug interruption, but severe toxicity may rarely occur. Oncologists should be aware of this unusual event.

A case series of low dose bevacizumab and chemotherapy in heavily pretreated patients with epithelial ovarian cancer.

BACKGROUND: The addition of bevacizumab to standard chemotherapy prolongs progression free survival in the first line treatment of epithelial ovarian cancer (EOC), but its cost/effectiveness is debated. We assessed the safety and activity of a lower dose of bevacizumab in pretreated advanced stage EOC. METHODS: We treated 15 patients, mostly with platinum resistant EOC, who had received a median of four prior cytotoxic regimens, with bevacizumab 5-7.5 mg/kg q21 days in combination with either carboplatin (n = 8), oral cyclofosfamide (n = 5) or weekly paclitaxel (n = 2). Bevacizumab was administered until disease progression. Tumor response was assessed by CA125 and fusion 18 F-FDG PET/contrast enhanced CT. RESULTS: The median number of bevacizumab cycles was 21 (range 3-59). The median baseline CA125 was 272 U/ml and decreased to 15.2 U/ml at nadir. Tumor response was 4 complete response (CR) (26.7%) and 7 partial response (PR) (46.7%) by chemotherapy (CT), with an overall response rate of 73.4% (95% CI, 51.0 - 95.8) according to Response Evaluation Criteria In Solid Tumors (RECIST), and 6 CR (40%) and 4 PR (26.7%) by PET, for an overall metabolic response rate of 67% (95%CI, 42.8 - 90.6) according to PET Response Criteria in Solid Tumors (PERCIST). Median progression free survival (PFS) was 21 months and median overall survival (OS) was 24 months. Grade 3 adverse events related to bevacizumab were hypertension (n = 2), proteinuria (n = 1) and epistaxis (n = 5). Treatment was delayed in five patients for nasal bleeding or uncontrolled hypertension. CONCLUSIONS: Low-dose bevacizumab and chemotherapy was well tolerated and active in a heavily pretreated population of advanced EOC. Further studies should assess the activity of low dose bevacizumab in EOC.