Objective: The therapeutic benefits of poly(ADP-ribose) polymerase inhibitors highlight the need to evaluate BRCA1/2 defects in tubal/ovarian cancer (OC). We sought to determine the pattern and disease characteristics associated with tumor BRCA1/2 mutations and BRCA1 methylation in women with OC. Methods: We obtained 111 OC specimens from 2 university hospitals and assessed BRCA1/2 mutations and BRCA1 methylation in tumor DNA. The frequency and pattern of BRCA1/2 defects were examined. Associations between patient/disease characteristics and BRCA1/2 defects were ascertained (Fisher’s exact test). Platinum-free interval (PFI), progression-free survival (PFS), and overall survival (OS) based on the underlying BRCA1/2 defect were determined (Kaplan-Meier analysis [log-rank test]). Results: We observed a BRCA1/2 dysfunction rate of 40% (28/70) in high-grade serous tubal/ovarian cancer (HGSC), including 14.3% BRCA1 methylation (n=10), 7.1% BRCA1 mutation (n=5), and 18.6% BRCA2 mutation (n=13). Defects in BRCA1/2 genes were associated with stage III/IV HGSC (BRCA1 methylation: P=0.005 [stage III/IV] and P=0.004 [HGSC]; BRCA1/2 mutation: P=0.03 [stage III/IV] and P<0.001 [HGSC]). Patients with BRCA1/2-mutated cancers showed improved OS (hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.43–0.99; P=0.045) and a trend toward improved PFI (HR, 0.48; 95% CI, 0.22–1.06; P=0.07) and PFS (HR, 0.72; 95% CI, 0.51–1.03; P=0.07). No survival differences were observed between BRCA1-methylated and BRCA1/2 wild-type non-BRCA1-methylated cancers. Conclusion We observed a high tumor BRCA1/2 dysfunction rate in HGSC with a unique predominance of BRCA2 over BRCA1 mutations. While BRCA1/2 mutations conferred survival benefits in OC, no such association was observed with BRCA1 methylation.

Objective: The therapeutic benefits of poly(ADP-ribose) polymerase inhibitors highlight the need to evaluate BRCA1/2 defects in tubal/ovarian cancer (OC). We sought to determine the pattern and disease characteristics associated with tumor BRCA1/2 mutations and BRCA1 methylation in women with OC. Methods: We obtained 111 OC specimens from 2 university hospitals and assessed BRCA1/2 mutations and BRCA1 methylation in tumor DNA. The frequency and pattern of BRCA1/2 defects were examined. Associations between patient/disease characteristics and BRCA1/2 defects were ascertained (Fisher’s exact test). Platinum-free interval (PFI), progression-free survival (PFS), and overall survival (OS) based on the underlying BRCA1/2 defect were determined (Kaplan-Meier analysis [log-rank test]). Results: We observed a BRCA1/2 dysfunction rate of 40% (28/70) in high-grade serous tubal/ovarian cancer (HGSC), including 14.3% BRCA1 methylation (n=10), 7.1% BRCA1 mutation (n=5), and 18.6% BRCA2 mutation (n=13). Defects in BRCA1/2 genes were associated with stage III/IV HGSC (BRCA1 methylation: P=0.005 [stage III/IV] and P=0.004 [HGSC]; BRCA1/2 mutation: P=0.03 [stage III/IV] and P<0.001 [HGSC]). Patients with BRCA1/2-mutated cancers showed improved OS (hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.43–0.99; P=0.045) and a trend toward improved PFI (HR, 0.48; 95% CI, 0.22–1.06; P=0.07) and PFS (HR, 0.72; 95% CI, 0.51–1.03; P=0.07). No survival differences were observed between BRCA1-methylated and BRCA1/2 wild-type non-BRCA1-methylated cancers. Conclusion We observed a high tumor BRCA1/2 dysfunction rate in HGSC with a unique predominance of BRCA2 over BRCA1 mutations. While BRCA1/2 mutations conferred survival benefits in OC, no such association was observed with BRCA1 methylation.

Objective: SHAPE (Simple Hysterectomy And PElvic node assessment) was an international phase III trial demonstrating that simple hysterectomy was non-inferior to radical hysterectomy for pelvic recurrence risk, but superior for quality of life and sexual health.The objective was to conduct a cost-effectiveness analysis comparing simple vs. radical hysterectomy for low-risk early-stage cervical cancer. Methods: Markov model compared the costs and benefits of simple vs. radical hysterectomy for early cervical cancer over a 5-year time horizon. Quality-adjusted life years (QALYs) were estimated from health utilities derived from EQ-5D-3L surveys. Sensitivity analyses accounted for uncertainty around key parameters. Monte Carlo simulation estimated complication numbers according to surgical procedure. Results: Simple hysterectomy was more effective and less costly than radical hysterectomy. Average overall costs were $11,022 and $12,533, and average gains were 3.56 and 3.54 QALYs for simple and radical hysterectomy, respectively. Baseline health utility scores were 0.81 and 0.83 for simple and radical hysterectomy, respectively. By year 3, these scores improved for simple hysterectomy (0.82) but not for radical hysterectomy (0.82). Assuming 800 early cervical cancer patients annually in Canada, the model estimated 3 vs. 82 patients with urinary retention, and 49 vs. 86 patients with urinary incontinence persisting 4 weeks after simple vs.radical hysterectomy, respectively. Results were most sensitive to variability in health utilities after surgery, but stable through wide ranges of costs and recurrence estimates. Conclusion Simple hysterectomy is less costly and more effective in terms of quality-adjusted life expectancy compared to radical hysterectomy for early cervical cancer.

Objective: SHAPE (Simple Hysterectomy And PElvic node assessment) was an international phase III trial demonstrating that simple hysterectomy was non-inferior to radical hysterectomy for pelvic recurrence risk, but superior for quality of life and sexual health.The objective was to conduct a cost-effectiveness analysis comparing simple vs. radical hysterectomy for low-risk early-stage cervical cancer. Methods: Markov model compared the costs and benefits of simple vs. radical hysterectomy for early cervical cancer over a 5-year time horizon. Quality-adjusted life years (QALYs) were estimated from health utilities derived from EQ-5D-3L surveys. Sensitivity analyses accounted for uncertainty around key parameters. Monte Carlo simulation estimated complication numbers according to surgical procedure. Results: Simple hysterectomy was more effective and less costly than radical hysterectomy. Average overall costs were $11,022 and $12,533, and average gains were 3.56 and 3.54 QALYs for simple and radical hysterectomy, respectively. Baseline health utility scores were 0.81 and 0.83 for simple and radical hysterectomy, respectively. By year 3, these scores improved for simple hysterectomy (0.82) but not for radical hysterectomy (0.82). Assuming 800 early cervical cancer patients annually in Canada, the model estimated 3 vs. 82 patients with urinary retention, and 49 vs. 86 patients with urinary incontinence persisting 4 weeks after simple vs.radical hysterectomy, respectively. Results were most sensitive to variability in health utilities after surgery, but stable through wide ranges of costs and recurrence estimates. Conclusion Simple hysterectomy is less costly and more effective in terms of quality-adjusted life expectancy compared to radical hysterectomy for early cervical cancer.

Objective: SHAPE (Simple Hysterectomy And PElvic node assessment) was an international phase III trial demonstrating that simple hysterectomy was non-inferior to radical hysterectomy for pelvic recurrence risk, but superior for quality of life and sexual health.The objective was to conduct a cost-effectiveness analysis comparing simple vs. radical hysterectomy for low-risk early-stage cervical cancer. Methods: Markov model compared the costs and benefits of simple vs. radical hysterectomy for early cervical cancer over a 5-year time horizon. Quality-adjusted life years (QALYs) were estimated from health utilities derived from EQ-5D-3L surveys. Sensitivity analyses accounted for uncertainty around key parameters. Monte Carlo simulation estimated complication numbers according to surgical procedure. Results: Simple hysterectomy was more effective and less costly than radical hysterectomy. Average overall costs were $11,022 and $12,533, and average gains were 3.56 and 3.54 QALYs for simple and radical hysterectomy, respectively. Baseline health utility scores were 0.81 and 0.83 for simple and radical hysterectomy, respectively. By year 3, these scores improved for simple hysterectomy (0.82) but not for radical hysterectomy (0.82). Assuming 800 early cervical cancer patients annually in Canada, the model estimated 3 vs. 82 patients with urinary retention, and 49 vs. 86 patients with urinary incontinence persisting 4 weeks after simple vs.radical hysterectomy, respectively. Results were most sensitive to variability in health utilities after surgery, but stable through wide ranges of costs and recurrence estimates. Conclusion Simple hysterectomy is less costly and more effective in terms of quality-adjusted life expectancy compared to radical hysterectomy for early cervical cancer.