Primary debulking surgery of advanced epithelial ovarian cancer in developing countries: challenges and expectations

Ovarian cancer often presents itself in advanced stages and can be accompanied by various comorbidities. Treatment options are primary debulking surgery (PDS) followed by adjuvant chemotherapy, or alternatively, neoadjuvant chemotherapy followed by interval debulking surgery (IDS). The option taken is based on several considerations. If the patient can be treated with PDS, the absence of macroscopic residual disease becomes an independent prognostic factor. However, achieving this outcome is a challenge for the gynaecologic oncologist since advanced stage ovarian cancer generally metastasizes into the peritoneum and the upper abdominal organs. Optimal outcomes are that surgery will be safe for the patient, no macroscopic residual disease is achieved, minimal postoperative complications are encountered, and a good survival rate is obtained. Developed countries, especially Europe, have well-recognized standards of care which are followed by developing countries; however, challenges with insurance coverage and inter-departmental cooperation are recognized hurdles in developing countries. Competency improvement along with good inter-departmental communication and collaboration are keys to optimal outcomes for PDS.

Ovarian cancer; Primary debulking surgery; Residual disease; Interdepartmental approach; Competency

[1] Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians. 2018; 68: 394-424.

[2] Surveillance, Epidemiology, End Results Program. Cancer stat facts: ovarian cancer. National Cancer Institute. 2020; 3: 111-117.

[3] Momenimovahed Z, Tiznobaik A, Taheri S, Salehiniya H. Ovarian cancer in the world: epidemiology and risk factors. International Journal of Women’s Health. 2020; 11: 287-299.

[4] Reid F, Bhatla N, Jones A, Adams TS, Benites A, Blank S, et al. The world ovarian cancer coalition atlas. The World Ovarian Cancer Coalition. 2018.

[5] Vergote I, du Bois A, Amant F, Heitz F, Leunen K, Harter P. Neoadjuvant chemotherapy in advanced ovarian cancer: on what do we agree and disagree? Gynecologic Oncology. 2013; 128: 6-11.

[6] Fagotti A, Ferrandina G, Vizzielli G, Fanfani F, Gallotta V, Chiantera V, et al. Phase III randomised clinical trial comparing primary surgery versus neoadjuvant chemotherapy in advanced epithelial ovarian cancer with high tumour load (SCORPION trial): final analysis of perioperative outcome. European Journal of Cancer. 2016; 59: 22-33.

[7] Onda T, Satoh T, Saito T, Kasamatsu T, Nakanishi T, Nakamura K, et al. Comparison of treatment invasiveness between up-front debulking surgery versus interval debulking surgery following neoadjuvant chemotherapy for stage III/IV ovarian, tubal, and peritoneal cancers in a phase III randomised trial: Japan Clinical Oncology Group Study JCOG0602. European Journal of Cancer. 2016; 64: 22-31.

[8] Wright AA, Bohlke K, Armstrong DK, Bookman MA, Cliby WA, Coleman RL, et al. Neoadjuvant chemotherapy for newly diagnosed, advanced ovarian cancer: society of gynecologic oncology and american society of clinical oncology clinical practice guideline. Journal of Clinical Oncology. 2016; 34: 3460-3473.

[9] den Ouden JE, The R, Myren BJ, Boll D, Driel WJV, Lalisang RI, et al. Development of a decision aid for primary treatment of patients with advanced-stage ovarian cancer. International Journal of Gynecologic Cancer. 2020; 30: 837-844.

[10] Holschneider CH, Berek JS. Cytoreductive surgery: principles and rationale. In Bristow RE and Karlan BY. (eds.) Surgery for ovarian cancer principles and practice (pp. 87-117). Andover, UK: Thomson Publishing Services. 2006.

[11] Schorge JO, McCann C, Del Carmen MG. Surgical debulking of ovarian cancer: what difference does it make? Reviews in Obstetrics and Gynecology 2010; 3: 111-117.

[12] Berek JS, Kehoe ST, Kumar L, Friedlander M. Cancer of the ovary, fallopian tube, and peritoneum. International Journal of Gynecology & Obstetrics. 2018; 143: 59-78.

[13] Colombo N, Sessa C, Bois AD, Ledermann J, McCluggage WG, McNeish I, et al. ESMO-ESGO consensus conference recommendations on ovarian cancer: pathology and molecular biology, early and advanced stages, borderline tumours and recurrent disease. International Journal of Gynecological Cancer. 2019; 0: 1-33.

[14] Mahner S, Trillsch F, Chi D, Harter P, Pfisterer J, Hilpert F, et al. The forefront of ovarian cancer therapy: update on PARP inhibiotrs. Oxford University Press. 2020; 27: i30-i32.

[15] Harter P, Sehouli J, Lorusso D, Reuss A, Vergote I, Marth C, et al. A randomized trial of lymphadenectomy in patients with advanced ovarian neoplasms. New England Journal of Medicine. 2019; 380: 822- 832.

[16] Querleu D, Planchamp F, Chiva L, Fotopoulou C, Barton D, Cibula D, et al. European Society of Gynaecological Oncology (ESGO) guidelines for ovarian cancer surgery. International Journal of Gynecologic Cancer. 2017; 27: 1534-1542.

[17] Vergote I, Tropé CG, Amant F, Kristensen GB, Ehlen T, Johnson N, et al. Neoadjuvant chemotherapy or primary surgery in stage IIIC or IV ovarian cancer. New England Journal of Medicine. 2010; 363: 943-953.

[18] Kehoe S, Hook J, Nankivell M, Jayson GC, Kitchener H, Lopes T, et al. Primary chemotherapy versus primary surgery for newly diagnosed advanced ovarian cancer (CHORUS): an open-label, randomised, controlled, non-inferiority trial. The Lancet. 2015; 386: 249- 257.

[19] Vergote I, Coens C, Nankivell M, Kristensen GB, Parmar MKB, Ehlen T, et al. Neoadjuvant chemotherapy versus debulking surgery in advanced tuboovarian cancers: pooled analysis of individual patient data from the EORTC 55971 and CHORUS trials. The Lancet Oncology. 2018; 19: 1680-1687.

[20] Vergote IB, Van Nieuwenhuysen E, Vanderstichele A. How to select neoadjuvant chemotherapy or primary debulking surgery in patients with stage IIIC or IV ovarian carcinoma. Journal of Clinical Oncology. 2016; 34: 3827-3828.

[21] Reuss A, du Bois A, Harter P, Fotopoulou C, Sehouli J, Aletti G, et al. TRUST: Trial of Radical Upfront Surgical Therapy in advanced ovarian cancer (ENGOT ov33/AGO-OVAR OP7). International Journal of Gynecological Cancer. 2019; 29: 1327-1331.

[22] Purbadi S, Tanamas G, Novianti L. Advanced stage ovarian cancer survival in Jakarta. European Journal of Gynaecological Oncology. 2020; 4: 587-590.

[23] Fagotti A, Scambia G. Neoadjuvant chemotherapy versus upfront debulking surgery in advanced tubo-ovarian cancer. The Lancet Oncology. 2018; 19: 1558-1560.

[24] Ashrafian, H. Surgical philosophy concepts of modern surgery paralleled to Sun Tzu’s ‘art of war’. Broken Sound Parkway, NW: CRC Press. 2016.

[25] Iyoke CA. Burden of gynaecological cancers in developing countries. World Journal of Obstetrics and Gynecology. 2013; 2: 1-7.

[26] Mulisya O, Sikakulya FK, Mastaki M, Gertrude T, Jeff M. The challenges of managing ovarian cancer in the developing world. Case Reports in Oncological Medicine. 2020; 2020: 1-4.

[27] Brand AH, DiSilvestro PA, Sehouli J, Berek JS. Cytoreductive surgery for ovarian cancer: quality assessment. Oxford University Press. 2017; 28: viii25-29.

[28] Priyanto H, Andrijono A. Relative effectiveness of neoadjuvant chemotherapy versus primary surgery in patients with advanced ovarian cancer. International Conference on Public Health. 2018.

[29] European Society of Gynaecological Oncology. Advanced Ovarian Cancer Surgery Quality Indicators. ESGO. 2016; 0: 1-264.

[30] Gilbody J, Prasthofer A, Ho K, Costa M. The use and effectiveness of cadaveric workshops in higher surgical training: a systematic review. The Annals of the Royal College of Surgeons of England. 2011; 93: 347-352.

[31] Ledermann JA. PARP inhibitors in ovarian cancer. Annals of Oncology. 2016; 27: i40-i44.

[32] Mirza MR, Coleman RL, González-Martín A, Moore KN, Colombo N, Ray-Coquard I, et al. The forefront of ovarian cancer therapy: update on PARP inhibitors. Annals of Oncology. 2020; 31: 1148-1159.