Development of an evidence-based algorithm for the management of ovarian cancer

Objective: To describe the management of ovarian cancer to be undertaken by a gynaecologist and to describe the highest level of primary research evidence supporting it.

Design: Use of regional guidelines and semi-structured interviews with gynaecological oncologists to devise a flow-chart algorithm for management. Use of an algorithm to identify the key research questions and to define search strategies for primary research, which was assessed using pre-defined criteria for validity.

Main outcome measures: Highest level of evidence for each research question based on the design of the valid studies.

Results: Prospective cohort studies (level II-2A) support the algorithm's diagnostic procedures. The evidence for accurate staging is derived from case series data (level II-2B). Preserving the uterus in young women wishing to maintain fertility is supported by prospective cohort studies (level II-2A) and by case series data (level IV) for women with germ cell tumours. Prospective cohort studies (level II-2A) support surgical management with hysterectomy, bilateral oophorectomy and debulking. The evidence for chemotherapy comes from randomised controlled trials (level I), except for germ cell tumours where the evidence was from case series data (level IV).

Conclusions: The management of ovarian cancer and the level of evidence supporting it can be described using a flow-chart algorithm. Evaluations of whether this presentation helps consultants follow guidelines are required.

Ovarian cancer; Clinical algorithm; Evidence-based medicine

[1] Berrino F., Berrino F, Sant M., Verdecchia A. et al. (eds.): "Survival of Cancer Patients in Europe: The Eurocare Study". Lyon, International Agency for Research on Cancer, 1995.

[2] Wolfe C. D., Tilling K., Raju K. S.: "Management and survival of ovarian cancer patients in south east England". Eur. J. Cancer, 1997, 33 (11), 1835.

[3] Sackett D. L., Richardson W. S., Rosenberg W., Haynes R.: "Evidence Based Medicine: How to Practice and Teach EBM". London, Churchill-Livingstone, 1997.

[4] Guterman J. J., Mankovich N. J., Weinstein S.，Picken B.: "Structured knowledge representation: an improved methodology for communication of hospital policy. Proceedings - the Annual Symposium on Computer Applications in Medical Care, 1995, 733.

[5] Griffin N. L.: "Four models for imparting decision making information". Am. J. Occup. Ther., 1975, 29 (6), 349.

[6] Franklin R. C. G., Spiegelhalter D. J., Macartney F. J., Bull K.: "Evaluation of a diagnostic algorithm for heart disease in neonates". Br. Med. J., I 991, 302, 935.

[7] Aitchison T. C., Sire! J. M., Watt D. C., MacKie R. M.: "Prognostic trees to aid prognosis in patients with cutaneous malignant melanoma". Br. Med. J., 1995, 311, 1536.

[8] Darbar D., Gillespie N., Choy A.-M., Lang C. C., Pringle S. D., Pringle T. H. et al.: "Diagnosing left ventricular dysfunction after myocardial infarction: the Dundee algorithm". Quarterly Journal of Medicine, 1997, 90 (11), 677.

[9] Marsden A. K., Ng A. G., Dalziel K., Cobbe S. M.: "When is it futile for ambulance personnel to initiate cardiopulmonary resuscitation?". Br. Med. J., 1995, 311, 49.

[10] McKibbon K. A., Walker-Dilks C. J.: "Beyond ACP Journal Club: How to harness MEDLINE for diagnostic problems". A. C. P. Journal Club 1994, 121 (Suppl. 2) (2), AJO.

[11] McKibbon K. A., Walker-Dilks C. J., Haynes R. B., Wilczynski N., Beyond A. C. P. Journal Club: "How to harness MEDLINE for prognosis problems". A. C. P. Journal Club 1994, 121 (Suppl. 1) (1),Al 2.

[12] McKibbon K. A., Walker-Dilks C. J., Beyond A. C. P. Journal Club: "How to harness MEDLINE for therapy problems". A. C. P Journal Club 1994, 121 (Suppl. 1) (1), AIO.

[13] NHS Centre for Reviews & Dissemination. Undertaking systematic reviews of research on effectiveness: CRD guidelines for those carrying out or commissioning reviews. York, York Publishing Services, 1996.

[14] Schutter E. M., Kenemans P., Sohn C., Kristen P., Crombach G., Westermann R. et al.: "Diagnostic value of pelvic examination, ultrasound, and serum CA 125 in postmenopausal women with a pelvic mass. An international multicenter study". Cancer, 1994, 74(4), 1398.

[15] Maggino T., Gadducci A., D'Addario V., Pecorelli S., Lissoni A., Stella M. et al.: "Prospective multicenter study on CA 125 in postmenopausal pelvic masses". Gynecol. Oneal., 1994, 117.

[16] Kreuzer G. F., Paradowski T., Wurche K. D., Flenker H.: "Neoplastic or nonneoplastic ovarian cyst? The role of cytology". Acta Cytol., 1995, 39 (5), 882.

[17] Larsen T., Torp-Pedersen S. T., Ottesen M., Bostofte E., Sehested M., Rank F. E., Holm H. H.: "Abdominal ultrasound combined with histological and cytological fine needle biopsy of suspected ovarian tumors". Eur. J. Obst. Gynecol. Reprod. Biol., 1993, 50(3), 203.

[18] International Federation of Gynecology and Obstetrics. Pettersson F., Creasman W. T., Shepherd J. et al. (eds.): "Annual report on the results of treatment in gynaecological cancer". Stockholm, International Federation of Gynecology and Obstetrics, 1994.

[19] Schueler J. A., Trimbos J.B., Burg M., Cornelisse C. J., Hermans J., Fleuren G. J.: "DNA index reflects the biological behavior of ovarian carcinoma Stage I-Ila". Gynecol. Oneal., 1996, 59.

[20] Mayer A. R., Chambers S. K., Graves E., Holm C., Tseng P. C., Nelson B. E., Schwartz P. E.: "Ovarian cancer staging: does it require a gynecologic oncologist?". Gynecol. Oneal., 1992, 47 (2), 223.

[21] Zanetta G., Chiari S., Rota S., Bratina G., Maneo A., Torri V., Mangioni: "Conservative surgery for stage I ovarian carcinoma in women of childbearing age". Br. J. Obstet. Gynaecol., 1997, 104 (9), 1030.

[22] Lund B., Williamson P.: "Prognostic factors for outcome of and survival after second-look laparotorny in patients with advanced ovarian carcinoma". Obstet. Gynecol., 1990, 76 (4), 617.

[23] de] C. J., Felip E., Rubio D., Vidal R., Bermejo B., Colomer R., Zan on: "Long-term survival in advanced ovarian cancer after cytoreduction and chemotherapy treatment". Gynecol. Oneal., 1994, 53 (1), 27.

[24] Baker T. R., Piver M. S., Hempling R. E.: "Long term survival by cytoreductive surgery to less than I cm, induction weekly cisplatin and monthly cisplatin, doxorubicin, and cyclophospharnide therapy in advanced ovarian adenocarcinoma". Cancer, 1994, 74 (2), 656.

[25] Warwick J., Kehoe S., Earl H., Luesley D., Redman C., Chan K. K.: "Long-term follow-up of patients with advanced ovarian cancer treated in randomised clinical trials". Br. J. Cancer, 1995, 72 (6), 1513.

[26] Hoskins W. J., Bundy B. N., Thigpen J. T., Omura G. A.:'The influence of cytoreductive surgery on recurrence-free interval and survival in small-volume stage III epithelial ovarian cancer: a Gynecologic Oncology Group study". Gynecol. Oncol., 1992, 47 (2), 159.

[27] Trope C., Andersson H., Bjorkholm E., Frankendal B., Himmelman A., Hogberg et al.: "Doxorubicin-melphalan with and without cisplatin in advanced ovarian cancer-ten-year survival results from a prospective randomized study by the Swedish Cooperative Ovarian Cancer Study Group". Acta Oneal., 1996, 35 Suppl. 8, 109.

[28] Neijt J. P., ten Bokkel Huinink W.W., van der Burg M. E., van O. A., Willemse P. H., Vermorken J. B. et al.: "Long-term survival in ovarian cancer". Mature data from The Netherlands Joint Study Group for Ovarian Cancer, 1991.

[29] Bolis G., Colombo N., Pecorelli S., Torri V., Marsoni S., Bonazzi C. et al.: "Adjuvant treatment for early epithelial ovarian cancer: results of two randomised clinical trials comparing cisplatin to no further treatment or chromic phosphate (32P)". G.I.C.O.G.: Gruppo lnterregionale Collaborativo in Ginecologia Oncologica. Annals Oncol., 1995, 6 (9), 887.

[30] Williams S., Blessing J. A., Liao S. Y., Ball H., Hanjani P.: "Adjuvant therapy of ovarian germ cell tumors with cisplatin, etoposide, and bleomycin: a trial of the Gynecologic Oncology Group". J Clin. Oncol., 1994, 12 (4), 701.

[31] Peccatori F., Bonazzi C., Chiari S., Landoni F., Colombo N., Mangioni C.: "Surgical management of malignant ovarian germ-cell tumors: 10 years' experience of 129 patients". Obstet. Gynecol., 1995, 86 (3), 367.

[32] Scott J. S.: "Management of ovarian cancer: current clinical practices".1 ed., 1991.

[33] Melville A., Eastwood A., Kleijnen J., NHS CRD, (ed.): "Guidance on Commissioning Cancer Services: Improving Outcomes in Gynaecological Cancers". The Research Evidence, London, NHS Executive, 1999.

[34] Sainz d!C., Goff B. A., Fuller A. F. J., Nikrui N., Eichhorn J. H., Rice L. W.: "Prognostic importance of intraoperative rupture of malignant ovarian epithelial neoplasms". Obstet. Gynecol., 1994, 84 (1), 1.

[35] Ahmed F. Y., Wiltshaw E., A'Hern R. P., Nicol B., Shepherd J., Blake P. et al.: "Natural history and prognosis of untreated stage I epithelial ovarian carcinoma". J. Clin. Oncol., 1996, 14 (11), 2968.

[36] Heintz A. P., van 0. A., Trimbos J. B., Schaberg A., Van der Velde E. A., Nooy M.: "Th e treatment of advanced ovarian carcinoma (I): clinical variables associated with prognosis". Gynecol. Oncol., 1988, 30 (3), 347.