Esteemed Physician Humanitarian Distinguished Citizen Disclosure Ovarian Cancer The State of Ovarian Care in the US Why aren t we making more progress? Dr. Goff has indicated that she has no relevant financial relationships to disclose and that her discussion will not include mention of investigational or off-label usage. No other individuals in control of CME content have relevant financial relationships. Barbara Goff, MD Director, Gynecologic Oncology University of Washington 3 4 Educational Objectives Upon completion of this lecture, participants should be better able to: Discuss the current best practices for management of ovarian cancer. Identify barriers to appropriate care for patients in the United States. Explore possible solutions to overcome barriers to care. Ovarian Statistics 2015 22,260 cases/15,500 deaths estimated 20 30% present early, 70 80% advanced Survival: Disease Stage Cure Rate Early 70 90% Late: Optimal cytoreduction 30 40% (median survival >60 mos) Suboptimal cytoreduction 10 20% (median survival 36 mos) 5 6 1
Ovarian Statistics 2012 Ovarian Statistics 2013 Age-Adjusted Cancer Death Rates, Females (1930 2010) Cancer Incidence and Age Adjusted Death Rate per 100,000 Population 9 10 Goff BA. Gynecologic Oncology. Jan 2015; 136: 1-2. Ovarian Statistics 2013 Ovarian Statistics 2012 Trend in Five-Year Survival Rates (5) 1975-2009 Trends in 5-yr Relative Survival Rates 1975 2007 35% 38% 1975 77 1987 89 43% 2001 07 1975 77 African American 42% 34% 1987 89 2001 07 36% 1975 77 36% 38% 1987 89 44% 2001 07 12 13 Goff BA. Gynecologic Oncology. Jan 2015; 136: 1-2. Current International Standard of Care Fourth Ovarian Cancer Consensus Conference, June 25 27, 2010 Surgical Outcomes as a Prognostic Factor 100 % Optimal Cytoreduction ultimate goal New Definition: no macroscopic residual disease ProgressionFree Survival % PFS 75% Systemic Treatment A taxane and a platinum agent x 6 cycles Recommended Regimen: HR (95%CI) 50 % 0 mm 1-10 mm vs 0 mm: 2.52 (2.26-2.81) >10 mm vs 1-10 mm: 1.36 (1.24-1.50) 25% 1-10 mm log-rank: P <.0001 >10 mm 0% 0 12 24 36 48 60 72 84 96 108 120 132 14 4 Months 100% Paclitaxel 175 mg/m2 + IV Carboplatin (AUC) q 3 wks Overall Survival 99 months 99 months % OS 75% Acceptable additions/variations in dose, schedule, route of delivery: Dose-dense IV paclitaxel (JCOG 3016) Intraperitoneal chemotherapy with 1 cm residual disease (GOG 172) Biological agent: Bevacizumab (GOG 218, Arm 3) Each of these has been associated with improved OS in certain populations HR (95%CI) 0 mm 50% 36 months 36 months 25% 1-10mm 29.6 months 29.6 months >10 mm 1-10 mm vs 0 mm: 2.70 (2.37-3.07) >10 mm vs 1-10 mm: 1.34 (1.21-1.49) log-rank: P <.0001 0% 0 12 24 36 48 60 72 84 96 108 120 132 144 Months UW Medicine Thigpen TI et al. Int J Gynecol Cancer. 2011;21(4):756 62. 14 PFS, progression-free survival; OS, overall survival; HR, hazard ratio; CI, confidence interval. du Bois AI et al. Cancer. 2009;115(6):1234-1244. 2
Importance of Cytoreduction Stage IIIC Ovarian Cancer with Residual Disease <1 cm Optimal cytoreduction appeared to negate effect of tumor burden: Importance of Cytoreduction Stage IIIC Ovarian Cancer and Carcinomatosis The tendency of surgeons to perform radical surgery had a significant impact on survival outcomes, despite referral pattern and same access to services: Aletti, et al. Ob/Gyn 2006. 16 Aletti, et al. Ob/Gyn 2006. 17 Importance of Gyn Onc Importance of Gyn Onc Early Stage Disease 5-year OS Gyn Onc Gyn/GS p value Mayer 1992 83% 59% <0.05 Puls 1997 90% 68% 0.04 Engelen 2006 86% 70% 0.03 Hazard Ratio for Recurrence 2.42 (CI 1.09 6.32) Advanced Stage Disease Gyn or Gyn Onc Gen Surg p value Eisenkop 1992 35 mos 17 mos <0.001 Junor 1994 27% 19% <0.05 Junor 1999 18 mos 13 mos <0.005 Carney 2002 26 mos 15 mos <0.01 Tinulstad 2003 21 mos 12 mos 0.01 Earl 2006 HR 0.86 (CI 0.76 0.95) Engelen 2006 21% 13% 0.02 Chan 2007 31% 22% <0.001 Le 2002 18 19 Importance of Paclitaxel IP Chemotherapy Primary Approach to Systemic Therapy GOG-172: Survival Outcomes GOG-111 Cisplatin/Cyclophosphamide vs Cisplatin/Paclitaxel Firstline paclitaxel PFS and OS in advanced disease Proportion 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 PFS OS Paclitaxel / Cisplatin Cyclophos / Cisplatin Paclitaxel / Cisplatin Cyclophos / Cisplatin 0.0 0 6 12 18 24 30 36 42 48 Months After Entry into Study Proportion Progression-Free 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0 Progression-Free Survival Rx Group IV IP IV: 18 mos IP: 24 mos HR: 0.80, P = 0.05 IP/Optimal: 43 mos 0 12 24 36 48 60 Months on Study PF Failed Total 50 160 210 63 142 205 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0 Overall Survival IV: 50 mos IP: 66 mos HR: 0.75, P = 0.03 IP/Optimal: 110mo Rx Group IV IP Alive 93 117 Dead 117 88 0 12 24 36 48 60 Months on Study Total 210 205 McGuire WP, et al. N Engl J Med. 1996;334(1):1-6. 20 Armstrong DK, et al. N Engl J Med. 2006;354(11):34-43. 21 3
100 Dose Dense Chemotherapy Dose Dense: Survival Outcomes Progression-Free Survival Overall Survival 100 OS JGOG 3016: Long-term results of a randomised openlabel trial of dose-dense paclitaxel and carboplatin versus conventional paclitaxel and carboplatin in ovarian cancer Katsumata N. et.al. Lancet 2013 Patients Surviving Progression-Free (%) 80 60 40 20 0 HR 0.714 (95% CI 0.58-0.88) P = 0.001 Events Med PFS Dose dense 160 25.0 mo Conventional 200 17.2 mo 0 6 12 18 24 30 36 42 48 Months From Randomization Patients surviving (%) Katsumata N, et al. Lancet. 2009;374(9698):1351-1363. 80 60 40 20 0 HR 0.75 (95% CI 0.57-0.98) P = 0.03 Events 3-yr OS Dose dense 96 72.1% Conventional 124 65.1% 0 6 12 18 24 30 36 42 48 54 60 66 Months From Randomization 22 23 Importance of identifying mutations Impact of RRSO in BRCA1/2 Mutation Carriers Patterns of Care for Women in the US Review of 785 Women with Ovarian Cancer (from 1991) NCI Recommended Therapy Stage I/II 10% Stage III 71% Stage IV 53% Factors associated with NCI recommended therapy: Age, stage, comorbidity, race, teaching hospital Kauf ND and Barakat RR. J Clin Oncol July 10, 2007;25(20):2923. 24 Muñoz et al. J Clin Oncol 1997. 25 Patterns of Care for Women in the US Follow-up Study in 2003 816 women (from 1996) NCI Guideline Therapy Stage I 61.7% Stage II 38.4% Stage III/IV 62.3% Factors associated with lower rates guideline therapy: Age, stage, race, lack of private insurance Improvement from 1991 to 1996 Patterns of Ovarian Cancer Care Patterns of Surgical Care Across the US (2006) Predictors of Comprehensive Surgical Treatment in Patients with Ovarian Cancer (2007) CDC funded studies Hospital d/c data from 10,432 ovarian cancer patients Population-based, including 9 states 1999 2002 Harlan et al. J Clin Oncol 2003. 26 Goff et al. Gyn Oncol 2006. Goff et al. Cancer 2007. 27 4
Patterns of Care in the US Ovarian Cancer Treatment Across the US Overall, 67% of women had comprehensive surgery Significantly lower rates in vulnerable populations (non-caucasian, elderly, low socioeconomic status, rural areas) Factors independently associated with comprehensive surgery: Surgeon specialty (76% vs 37% vs 38%) Surgical volume Hospital volume Urban hospital location Early stage disease (only 40% adequately staged) Ovarian Cancer Surgery Across the US 25% of women with ovarian cancer have surgery by a surgeon who performs only 1 case/year 33% are treated in a low volume hospital (only 1 9 cases/year) In low volume settings, ~50% of women receive the correct surgery 28 29 Trends in Advanced EOC in Medicare Population Methods SEER Medicare Database (1995 2005) 8,211 women age 65+ with Stage III/IV ovarian cancer Results 58.8% primary debulking 75.8% chemo 24.6% primary chemo 32.2% surgery 16.6% no chemo or surgery Only 39.1% had surgery and 6 cycles of chemo 30 Thrall MM et al. Gynecol Oncol 2011;122:100 106. 31 Factors Associated with Odds of Receiving Both Surgery and 6 Cycles Chemo for Advanced Ovarian Cancer Time Trends in Medicare Claims in Treatment of Advanced Ovarian Cancer * indicates p<0.01 for category Thrall MM et al. Gynecol Oncol 2011; 122:100 106. 32 Thrall MM et al. Gynecol Oncol 2011;122:100 106. 33 5
Adherence to Guideline Therapy Ovarian Cancer Outcomes in California CR 1999 2006 13,321 women with ovarian cancer Evaluated by adherence to NCCN guidelines Only 37.2% of women had guideline appropriate care Non adherence to guideline care was associated with a significant decrease in disease specific survival (HR 1.33, 95% CI 1.26-1.41) Ovarian Cancer Outcomes in NCDB 1998 2007 96,802 women with ovarian cancer (EOC) Borderline and rare subgroups excluded Only 40% of women underwent surgery and completed 6 cycles of chemotherapy Improper or no surgery main reason for non-adherence Those receiving adherent care 44% more likely to be alive after 5 years Bristow et al. Gynecol Oncol 2103. 35 Cliby et al. Gynecol Oncol 2015. 36 30-Day Mortality After Primary Cytoreductive Surgery for Advanced Ovarian Cancer in the Elderly 5,475 women 65+ identified from SEER/Medicare database 30-day mortality 8.2% Elective admission 5.6% (251 of 4,517) Emergent admission 20.1% (168 of 835) Age, cancer stage and co-morbidity scores significantly associated with 30-day mortality Thrall MM et al. Obstet Gynecol 2011. 37 Thrall MM et al. Obstet Gynecol 2011;118(3):537 47. 38 Involvement of Gynecologic Oncologists in Treatment of Patients with Suspicious Ovarian Mass 3,200 primary care physicians surveyed in 2009 Vignette-based survey of a 57 year old with pain, bloating, suspicious right adnexal mass and ascites Referral to Gyn Onc: FP 39.3% IM 51.0% Gyn 66.3% 33.7% performed primary surgery Referrals/Consults for Ovarian Cancer by FPs or IMs Ovarian Multivariate Statistics Regression 2012 Afr Amer vs Cauc Private Ins vs Medicaid Average # Patients/wk: 1 60 vs 91 61 90 vs 91 Urban vs Rural Practice Female vs Male MD Int Med vs Fam Med Practice Type: Group vs Solo Other vs Solo Goff et al. Gynecol Oncol 2011. 39 40 6
Ovarian Cancer: Patterns of care Referral for Genetic Counseling Vignette: A woman presents for an annual exam VARIABLES Race black, white Age 35 vs 51 Insurance private or Medicaid Level of risk: Average: Mom had breast cancer age 70 HIGH: Personal hx breast cancer age 30 Paternal grandmother ovarian cancer Paternal 1 st cousin breast ca premenopausal Trivers KF et al. Cancer Dec 1, 2011;117(23): 5334. 41 Outcome: Referral to genetic counseling and/or offering BRCA1/2 testing (almost never, sometimes, almost always) 42 Patterns of Care for High Risk Women Referral for Genetic Counseling VIGNETTE Risk for Ovarian Ca Physicians Average HIGH Reported adherence 71% 41% to USPSTF guidelines Correctly 61% 47% identified risk Ovarian Cancer How do we do better? Standardization of care Process measures Outcome measures Registries Centers of Excellence 43 44 Measuring Quality NSQIP Story Historically, the 133 VA hospitals in the US had high observed rates mortality and complications VA-NSQIP created in 1994 to allow for risk adjusted comparison of all 133 VA hospitals Regular monitoring, reporting and comparison of outcome variables between VA Hospitals 27% in 30-day post op mortality 45% in post op complications 45 Outcome Measures NSQIP Complications Risk adjusted (30 day outcomes) Mortality Morbidity Cardiac complications Post-op pneumonia Re-intubation within 48 hours Unplanned intubations SSI PE/DVT Renal dysfunction Complications reported for each participating institution and rank compared to other institutions 46 7
Surgical Quality NSQIP in the Private Sector 2001: NSQIP piloted and shown to be successful in private sector 2004 2011: Multiple studies show participation in NSQIP results in morbidity and mortality Each hospital participating annually prevents 250 500 complications saves 12 36 lives reduces costs by millions of dollars 47 Surgical Quality NSQIP Gyn Module Added 5 preoperative variables Added 3 post-op measures Added 3 variables for cancer pts Surgery subspecialty # prior surgeries Endometriosis/PID Uterine weight Parity GI obstruction Fistula or anastomotic leak Urinary complication FIGO stage Gross residual disease Site of residual disease 48 Ovarian Cancer Measures SGO/ASCO-QOPI (Quality Oncology Practice Initiative) Staging for early stage ovarian disease Documentation of residual disease Offering taxane/platinum Offering IP chemo for optimal cytoreduction Antiemetic choice VTE prophylaxis Antibiotic prophylaxis Discontinuation of antibiotic prophylaxis Chemotherapy within 14 days of death Ovarian Cancer Measures Staging for Early Stage Disease Denominator: Numerator: Women taken to surgery with epithelial ovarian, fallopian tube or primary peritoneal cancer, subsequently diagnosed with Stage I/II/IIIA and IIIB disease Surgical staging included: lymphadenectomy (pelvic and paraaortic), peritoneal washings, and omentectomy (confirmed by path report) Surgical staging omitted at least one of the following: lymphadenectomy (pelvic or paraaortic), washings or omentectomy Surgical staging omitted at least one of the following: lymphadenectomy (pelvic or paraaortic), washings or omentectomy and reason documented in clinical record 49 50 Ovarian Cancer Measures NSQIP Residual Disease/SGO Optimal Cytoreduction Denominator: Numerator: NSQIP/SGO Women taken to surgery (primary or secondary) with epithelial ovarian, fallopian tube or primary peritoneal cancer Operative report does not clearly document amount of residual disease Operative report indicates 1 cm residual disease (suboptimal cytoreduction) Operative report indicates <1 cm residual disease visible Operative report indicates no visible tumor remaining Ovarian Cancer Quality Measures Evaluation of SGO Quality Measures Measure 1 Staging 74% Full staging 10% Documentation why not 15% Inadequate staging and no reason Measure 2 Documentation of cytoreduction 25% No documentation 75% Documentation: 40% Optimal, no visible 18% Optimal, 1 cm 18% Suboptimal, >1 cm 51 Gogoi, Urban, Goff. Gynecol Oncol 2012. 52 8
Conclusions A significant percentage of women with ovarian cancer in the US are not treated with basic guideline therapy Implementing process and outcome measures, with reporting and comparison between institutions, is needed To improve the quality of ovarian cancer care in the US, we need to make significant changes in how cancer care is delivered 53 Questions and Discussion THANK YOU! 54 9