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LiFE re
Literature for ENYGO
Screening for ovarian and fallopian tube cancer
Editor Lucas Minig
Descriptive summary
The first survival outcomes from the largest ovarian cancer screening
trial to date, the UKCTOCS protocol (UK Collaborative Trial of Ovarian
Cancer Screening) have recently been published.
The aim of the study was to compare different methods of screening.
A total of 200,000 postmenopausal women volunteers were randomi-
sed into 3 arms: 100,000 to no screening, 50,000 to annual transva-
ginal ultrasound (TVS), and 50,000 to multi-modal screening (MMS),
with a follow-up of 15 years.
The MMS strategy includes annual measurement of CA 125, not con-
sidering outliers, but individual variability over the years. The research
team developed the ROCA (Risk of Ovarian Cancer Algorithm) tool,
which considers the age of the patient, family history risk, and CA 125
values over time. Based on that result, women were categorised as
normal, intermediate or high risk. CA 125 determination was perfor-
med annually in women at normal risk (always recalculating risk). In
the intermediate-risk patients, CA 125 was repeated every 3 months;
in high-risk patients, a new CA 125, transvaginal ultrasound, and
surgery (in case of persistent abnormal results) were performed within
the following 6 weeks.
The study requires some considerations:
T he analysis with ROCA was centralised, and the values were not
considered by the usual cut-off of 35, but changed over time.
T he transvaginal ultrasound was to be reported according to a strict
protocol, which was modified during the study (e.g., simple ovarian
cyst size om imaging was changed from 5 to 10 cm for the indicati-
on of surgery).
Previous reports of this study showed that the specificity of MMS was
similar to TVS (99 %), a sensitivity of 88 % vs. 63 %, a positive predic-
tive value of 24 vs. 4 %, and the number of operations performed by
case detected was 4 vs. 25. By using MMS, they also showed a higher
Relevant articles retrieved Nov 2015 - Feb 2016
No Title
1 Ovarian cancer screening and mortality in the UK Collaborative Trial of Ovari- Jacobs IJ et al.
an Cancer Screening (UKCTOCS): a randomised controlled trial.
2 Quality assurance and its impact on ovarian visualization rates in the
multicenter United Kingdom Collaborative Trial of Ovarian Cancer Screening
(UKCTOCS).
3 Lavage of the Uterine Cavity for Molecular Detection of Müllerian Duct
Carcinomas: A Proof-of-Concept Study.
International Journal of Gynecological Cancer, Volume 26, Supplement #1
OVARIAN CANCER
percentage of patients with early-stages (I/II), 39 vs. 33 % (this ratio
was equal between low- and high-grade tumours).
The study failed to show whether these differences between the
methods translated into decreased mortality: The MMS and TVS bran-
ches showed no statistically significant decrease in mortality of 15
% (95 % CI: -3, 30) and TVS 11 % (-7, 27) respectively, in comparison
with the no-screening group.
For every 10 women who died in the follow-up arm, two could have
been saved with MMS. There was a more pronounced reduction in
mortality after long-term follow-up and after exclusion of prevalent
cases. The reduction in mortality during the first seven years was 8 %
and 2 % for MMS and TVS, respectively, but between in year 7-14, the
estimated mortality for MMS reduction was 23 % (95 % CI: 1 to 46)
and 21 % (95 % CI: - 2 to 42) for TVS. In conclusion, it would appear
that finally a screening program in ovarian cancer could have an
impact on survival. However, long-term follow-up is needed before any
final conclusion in this regard.
There is evidence that müllerian duct cancers (i.e., ovarian or endo-
metrial cancers). One study investigated 65 women (27 with benign
lesions of genital organs, 30 with ovarian cancer, 5 with endometrial
cancer and 3 with other cancers) to see if uterine lavage could detect
malignant cells. Next generation sequencing was able to identify
specific mutations in 24 (80 %) women with ovarian cancer, all 5
patients with endometrial cancer and 8 (29.6 %) women with benign
diseases, including KRAS. The main mutations in ovarian cancer pati-
ents included TP53, KRAS and PIK3CA. One occult ovarian cancer was
detected in an asymptomatic woman with BRCA-1 mutation submitted
for risk-reduction salpingo-oophorectomy. Limitations include the small
sample size, the inclusion of mainly advanced ovarian cancers and the
detection of mutations also in the samples of patients with benign
disease. Data regarding tolerability is also needed.
Authors Journal Link to abstract
Lancet
http://www.ncbi.nlm.nih.gov/
Ultrasound Obstet Gyehcol pubmed/26707054
Sharma A et al., http://www.ncbi.nlm.nih.gov/
pubmed/26095052
Maritschnegg E et al. J Clin Oncol http://www.ncbi.nlm.nih.gov/
pubmed/26552420
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