Fakulteit Geneeskunde en Gesondheidswetenskappe • Faculty of Medicine and Health Sciences Screening for Endometrial Cancer Haynes van der Merwe 21 March 2017
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Fakulteit Geneeskunde en Gesondheidswetenskappe •
Faculty of Medicine and Health Sciences
Screening for Endometrial Cancer
Haynes van der Merwe 21 March 2017
Declaration of interests
• None
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Introduction
• EC more common in industrialized countries: • North America ASR 16.4 per 100 000 • Africa ASR 2.6 per 100 000
• Disease of predominantly PM women: • 93% in women >50 years of age • Peaks in early 70’s
• Incidence risen in recent years: • Greatest increases 60-79 year age group
• Risk factors: unopposed estrogen key driver
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ACS Guidelines for the Early Detection of Cancer
• The American Cancer Society recommends that at the time of menopause, all women should be told about the risks and symptoms of endometrial cancer. Women should report any unexpected vaginal bleeding or spotting to their doctors.
• Some women – because of their history – may need to consider having a yearly endometrial biopsy. Please talk with a health care provider about your history.
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Screening for EC
• Screening not advocated in low-risk population: • 95% become symptomatic • Still early stage and curable
• Abnormal vaginal bleeding most common presentation
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Appropriate management of women presenting with postmenopausal bleeding to allow early detection of EC
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Postmenopausal bleeding
• Definition • How common is PMB? • Is it important?
Smith-Bindman R, Kerlikowske K, Feldstein V, et al. JAMA 1998;280:1510-7. Tabor A, Watt HC, Wald NJ. Obstet Gynecol 2002;99:663-70.
Gupta JK, Chien PF, Voit D, et al. Acta Obstet Gynecol Scand 2002;81:799-816. Smith-Bindman R, Weiss E, Feldtsein V. Ultrasound Obstet Gynecol 2004;24:558-65.
• What is the aim of assessment?
Differential diagnosis
• Systemic • Bleeding disorders • Exogenous estrogens • Endogenous estrogens
• Local • Benign • Malignant/Premalignant
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Clinical assessment
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How did we manage 30 years ago?
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How did we manage 30 years ago?
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Dilatation and curettage
• 10% of lesions missed • Incomplete sampling of endometrial cavity • Invasive • Risk of complications
Word B, Gravlee LC, Widemon GL. Obstet Gynecol 1958;12:642-5. Stock RJ, Kanbour A. Obstet Gynecol 1975;45:537-41.
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TVUS
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TVUS
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Office sampling
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Saline infusion sonohysterography
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SIS
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Office hysteroscopy
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TVUS
• Exclude endometrial cancer (EC) • Introduced mid 1980’s • Endometrial thickness (EL) ≈ histology • EL ≤5mm = inactive endometrium • Only 1 cancer with EL = 5mm
Nasri MN, Coast GJ. Br J Obstet Gynaecol 1989;96:1333-8. Goldstein SR, Nachtigall M, Snyder JR, Nachtigall L. Am J Obstet Gynecol 1990;163:119-23.
Varner RE, Sparks JM, Cameron CD, et al. Obstet Gynecol 1991;78:195. Granberg S, Wikland M, Karlsson B, et al. Am J Obstet Gynecol 1991;164:47-52.
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TVUS – Meta-analysis
• 35 studies • 2x2 tables: measured EL against
presence/absence of EC • 5mm threshold:
• Sensitivity 96% • Specificity 61%
• Post-test probability for EC 1% Smith-Bindman R, Kerlikowske K, Feldstein V, et al. JAMA 1998;280:1510-7.
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TVUS – Meta-analysis
• 9 studies (original data supplied) • Median EL per center • Results comparable to previous meta-
analysis • Conclusion: 4% false-negative rate
unacceptable Tabor A, Watt HC, Wald NJ. Obstet Gynecol 2002;99:663-70.
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TVUS – Meta-analysis
• 57 studies • 8890 patients • 1243 cases of EC • 4mm threshold:
• 1.2% post-test probability of EC • 5mm threshold:
• 2.3% post-test probability of EC Gupta JK, Chien PF, Voit D, et al. Acta Obstet Gynecol Scand 2002;81:799-816.
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TVUS – Meta-analysis
• Combined individual patient data • Threshold ≤4mm:
• Sensitivity of 95% • Specificity of 47% • Post-test probability 1.2%
• Threshold ≤3mm: • Sensitivity of 98% • Specificity of 35% • Post-test probability 0.7%
• LR for negative test result of 0.06 Timmermans A, Opmeer BC, Khan KS, et al. Obstet Gynecol 2010;116(1):160–7.
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TVUS - Technique
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TVUS - Technique
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TVUS in asymptomatic PM women
• EL >4.5mm in 10-17% of PM women Berliere M, Radikov G, Galant C, et al. Eur J Cancer 2000;6:S35-S36.
Garuti G, Cellani F, Centinaio G, et al. Gynecol Oncol 2005;98:63-67. Dreisler E, Sorensen SS, Ibsen PH, Lose G. Ultrasound Obstet Gynecol 2009;33: 344-348.
• EL thicker in first year after LMP • EC 1.3-1.7/1000 • PPV ≤3.3% for detection of EC • High false positive rate
Vuento MH, Pirhonen JP, Mäkinen JI, et al. BJOG 1999;106:14–20. Ciatto S, Cecchini S, Bonardi R, et al.Tumori 1995;81:334–7.
Fleischer AC, Wheeler JE, Lindsay I, et al.Am J Obstet Gynecol 2001;184:70–5.
• 1.3-3.6% risk of serious complications with removal of polyps
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Office endometrial sampling
• Pipelle on 40 patients with EC • Sensitivity of 97.5%
Stovall TG, Photopulos GJ, Poston WM, et al. Obstet Gynecol. 1991;77:954-6
• Three meta-analysis early 2000’s: • Sensitivity for EC ≈ 99% • Sensitivity for hyperplasia ≈ 80% • D & C as reference standard
Dijkhuizen FP, Mol BW, Brolmann HA, Heintz AP. Cancer 2000;89:1765-72. Clark TJ, Mann CH, Shah N, et al. Acta Obstet Gynecol Scand 2001; 80: 784-793
Clark TJ, Mann CH, Shah N, et al. Br J Obstet Gynaecol 2002;109:313–21.
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Office endometrial sampling
• Hysteroscopy with histology as reference standard
• Sensitivity: • EC 90% • Atypical hyperplasia/EC 82% • Any endometrial pathology 39%
• Specificity 98-100% Van Hanegem N, Prins MMC, Bongers MY, et al. Eur J Obstet Gynecol Reprod Biol 197
(2016) 147-155
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Office sampling
• “Non-diagnostic” test: • Inadequate tissue • Procedure failure • 5-20% atypical hyperplasia/EC
Nagele F, O’Connor H, Baskett TF, et al. Fertil Steril 1996 Jun;65(6):1145-50. Gordon SJ, Westgate J. Aust N Z J Obstet Gynaecol 1999 Feb;39(1):115-8.
Giusa-Chiferi MG, Gonçalves WJ, et al. Int J Gynaecol Obstet 1996 Oct;55(1):39-44. Van Doorn HC, Opmeer BC, Burger CW, et al. Int J Gynaecol Obstet 2007
Nov;99(2):100- 4.
• Fail to identify focal pathology Epstein E, Ramirez A, Skoog L, et al. Acta Obstet Gynecol Scand 2001 Dec;80(12):1131-6.
Gebauer G, Hafner A, Siebzehnrübl E, Lang N. Am J Obstet Gynecol 2001 Jan;184(2):59-63. Angioni S, Loddo A, Milano F, et al. J Minim Invasive Gynecol 2008 Jan-Feb;15(1):87-91.
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16-50%
Saline infusion sonohysterography
• Sensitivity of 95% • Specificity of 88% • No calculations for EC • Not separately described for pre- and
postmenopausal women • Success rate 87%
De Kroon CD, De Bock GH, Dieben SW, Jansen FW. BJOG 2003; 110:938–947.
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Office hysteroscopy
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Office hysteroscopy
• Accuracy in diagnosis of hyperplasia and EC: • + result increase EC probability to 71.8% • - result reduce EC probability to 0.06%
Clark TJ, Voit D, Gupta JK, et al. JAMA 2002; 288:1610–1621.
• Accuracy in diagnosis of hyperplasia and endometrial abnormalities: • Sensitivity of 96% • Specificity of 90 % • + result increase post-test probability to
93% Van Dongen H, De Kroon CD, Jacobi CE, et al. BJOG 2007; 114: 664-675.
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Office hysteroscopy
• Success rate 95.6-96.9% Van Dongen H, De Kroon CD, Jacobi CE, et al. BJOG 2007; 114: 664-675.
Clark TJ, Voit D, Gupta JK, et al. JAMA 2002; 288:1610–1621.
• Low complication rate Van Dongen H, De Kroon CD, Jacobi CE, et al. BJOG 2007; 114: 664-675.
•Unreliable without biopsy Lewis BV. J R Soc Med 1984; 77:235–237.
Downes E, Al-Azzawi F. Br J Obstet Gynaecol 1993; 100:1148–1149.
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Conclusions
• TVUS accurate to exclude EC • Best threshold – 3/4/5mm? • Sequence of tests dependent on many
factors: • Cost-effectiveness • Prevalence of EC • Local logistics • Doctor and patient preferences
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Thank you very much for your attention
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