Is there a role for ovarian cancer screening? O&G Dept CME 29 Nov 2013 Dr Voon Hian Yan Supervisor: Dr Sim Wee Wee
Dec 05, 2014
Is there a role for ovarian cancer screening?
O&G Dept CME29 Nov 2013
Dr Voon Hian YanSupervisor: Dr Sim Wee Wee
What do they have in common?
7 Commandments on ScreeningAdapted by WHO after Wilson and Jungner
Significant prevalance and severityFixed spectrum of symptomsTests which are simple and acceptable to the patientAccurate screening testConfirmatory test availableTreatable diseaseFavourable cost/benefit ratio
Screening is done where direct diagnostic tests are costly/invasive / requires specialised personnel or equipment / greater risk to patient
Burden of Ovarian cancer
2nd most common cancer of the female genital tract 5th most common cancer in females 7000 women in the UK are diagnosed with ovarian cancer/yr8 in 10 are diagnosed in women >50yrs old
Incidence: 17 in 100,000 Lifetime risk: 1 in 71
No identifiable premalignant stages ex CIN5yr survival 94% if detected in Stage I (15% )Majority 60% are detected late with 5 yr survival 28%
Incessant ovulationInflammation
How and who to screen?HOWTumor markers: Ca-125 -only 50% stage I and II epithelial ovarian cancers -only 80% of epithelial ovarian cancers
-false +ve esp in younger women
Imaging : TVS (patient acceptability, skilled operator)
WHOPost-menopausal womenGeneral population vs high risk groups
Is there a role of Ca125 or Ultrasound screening?
Effect of Screening on Ovarian Cancer Mortality: The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Randomized Controlled Trial
JAMA. 2011;305(22):2295-2303. doi:10.1001/jama.2011.766
Target groupPostmenopausal women
PLCO: Ovarian cancer mortality
cancers deaths
Mortality rates were similar between both groups
Intervention group (screened) 118 deaths3.1 er 10,000 person years
Usual care group 100 deaths2.6 per 10,000 person years
(mortality RR, 1.18; 95% CI, 0.91-1.54 [unadjusted] )(mortality RR, 1.18; 95% CI, 0.82-1.71 [sequentially adjusted])
Stage at detection, histology of ovarian cancers detected and
treatment needed did not differ
Screening-related harms: Minor
Bruising or Fainting
58.3 in 10,000 Ca1253.3 in 10,000 TVS
Screening-related harms
3285 false positive (5%),1080 (33%) of whom needed surgeryMajor complication rate of 20/100 (some women had >1 complication)Oophrectomy rates were 33% higher in intervention (85/10000) vs control (64/10,000)
Author's conclusion
"Annual screening for ovarian cancer as performed in the PLCO trial with simultaneous CA-125 and transvaginalultrasound does not reduce disease-specific mortality in women at average risk for ovarian cancer but does increase invasive medical procedures and associated harms"
Other population cohorts
UKTOCS Shizuoka Cohort Study of ovarian cancer screening
N 200,000 (largest) ;50-74yrs old 70,000 (=PLCO); median 58yrs
Screening strategies
Multimodal (annual Ca125 +/- TVS)
Annual TVS
Control
Annual TVS+CA125
Control
Preliminary results
Multimodal= 42 cancers
Annual TVS= 45 cancers *Overall 48% detected in stage I or II, no difference in stage distribution in both groups
*Results from controls not released yet
Significant withdrawal rate 5% in USS and 1% in MMS group?Acceptability of TVS as a screening modality
Intervention= 35 cancers detected after a mean period of 9yrs
Control= 32 cancers
Mortality benefit Pending (trial completes in 2014) Pending (trial completed)
Screening in the high risk population
Before and after
BRCA-1/BRCA-2/HNPCC
BRCA1-/BRCA-2
Prophylactic BSO reduces lifetime risk of ovarian cancer from 40% to 1-2%Reduces risk of breast cancer by 50%Reduces risk of recurrent breast cancer if previously diagnosedRisk of primary peritoneal cancer reduced 1% per year to 0.2% per year(4% up to 20yrs after BSO)
Rarer famillial ovarian cancer syndromes
Muir-Torre syndrome (MTS)- sebaceous skin tumorss, colorectal, ovarian, endometrial
Turcot syndrome-colorectal, CNS tumors, endometrial, ovarian
UKFOCSSUK Familial Ovarian Cancer Screening Study
2002-2010
Overview-Over 3500 women between 35-75 yrs old -> 10% lifetime risk of developing ovarian cancer-yearly Ca125 and TVS
Results-14 of 37 women (38%) diagnosed with Stage I or II -23 of 37 women (62%) diagnosed with Stage III or IV
ConclusionGap between screening may have impact on stage at diagnosis. Interval > 1 year more likely to have advanced cancer at diagnosis
Phase II UKFOCSS
Will increased screening interval improve stage at detection?
4 monthly screening
So............... is there a role in Ovarian Cancer Screening?
1) Low risk population-Does not increase the detection of early stage ovarian cancer or alter treatment rendered
- No statistically significant change in mortality
- Increased intervention (33% more oophrectomies) and complications (1 in 5), especially in false positive cases
2) High risk population-Awaiting outcome of Phase II UKFOCSS
-Genetic screening instead?
Is there a role for OvarianCancer screening?
3) Type of tumor markersNested trials within the PLCO did not show any increase in sensitivity with
-HE4 -transthyretin-CA15.3 / CA72.4-apolipoprotein A1 -transferrin-hepcidin-beta-2 microglobulin -connective tissue activating protein III-inter-alpha-trypsin inhibitor heavy-chain
4) Serial rather than single Ca125 value?"Ca125 trajectory"
HE-4
Raised in 50% of epithelial ovarian tumours that do not express Ca125
Highly specific, allowing it to differentiate benign from malignant tumors
Greater sensitivity than with Ca125 alone in detecting early stage ovarian cancers
References
Sueblinvong T, Carney ME. Current of risk factors for ovarian cancer. Current Treatment Options in Oncology 2009;10:67-81
Devlin LA and PJ Morrison PJ. Inherited gynaecological cancer syndromes.TOG 10.1576/toag.10.1.009.27371 2008;10:9–15
Darnforth KN et al. Addendum to Screening for Ovarian Cancer: Evidence Update for the U.S. Preventive Services Task Force Reaffirmation Recommendation Statement. AHRQ Publication No. 12-05165-EF4April 2012
Buys SS, Partridge E, Black A, et al. Effect of screening on ovarian cancer mortality: the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Randomized Controlled Trial. JAMA. 2011;305(22):2295-303
References
Menon U, Gentry-Maharaj A, Hallett R, et al. Sensitivity and specificity of multimodal and ultrasound screening for ovarian cancer, and stage distribution of detected cancers: results of the prevalence screen of the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS). Lancet Oncol. 2009;10(4):327-40.
THANK YOU
Limitations PLCO
The trial was powered for a 35% mortality reduction based on a predicted number of mortality events (n = 226) that was essentially met. However, from a public health point of view, smaller effect sizes are still potentially worthwhile to detect.
The sequentially adjusted lower 95% CI for the mortality RR was 0.82, indicating at most an 18% relative benefit within the limits of reasonable probability. ( Ci was 0.82-1.71)
Additionally, the data collected on treatment were somewhat limited. The PLCO trial neither abstracted the type of systemic therapy used, nor the type of surgeon who performed the oophorectomy (eg, gynecologic oncologist or not); both factors have been shown to be related to ovarian cancer survival. However, we have no reason to suppose that these factors differed by study group.