Evolutions in the management of advanced ovarian cancer

Advanced ovarian cancer has the lowest survival rates and cure rates remain dismal; as a result it remains the most challenging gynaecological cancer to manage. All multidisciplinary specialities involved in the management of advanced ovarian cancer are fighting tirelessly to expedite evolutions that would transform the course of this ruthless disease towards simply a chronic condition. Allowing patients affected to live longer, even if repeated sequences of therapies are required.

Our series “Evolutions in the Management of Advanced Ovarian Cancer” is designed to provide all interested readers with a thorough and comprehensive understanding of areas of evolution taking place, throughout the patient journey. A number of comprehensive and narrative reviews have been included in this series.

Different factors determine triaging patients with advanced ovarian disease to either primary debulking surgery (PDS) or neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS). Inappropriate upfront laparotomies, have a negative impact on survival. The role of staging laparoscopy (S-LPS) in clinical practice has increased significantly as a pre-operative assessment tool, and the evidence of such practice in surgical planning for ultra-radical surgery, is undoubtedly in the patient’s best interest (1-7).

As confirmed by evidence from different published studies, maximal survival benefit is reached when the surgical target of zero residual disease (also known as R0) is achieved. To balance the best favourable oncologic outcome without deranging the morbidity profile, mastery of dissection techniques in the upper abdomen is mandatory. The principles of safe and efficacious upper abdominal surgery should be something gynaecological oncological surgeons are fully familiar with (8-14).

Among the surgical challenges in advanced ovarian cancer management is the frequent need for multiple bowel resections (MBRs) to achieve complete cytoreduction (R0). The resulting post-operative morbidity and mortality were very high until NACT was used as a successful strategy to reduce the aggressiveness of debulking surgery (especially in frail patients) without affecting the overall survival (15-19).

The vast majority of patients with advanced ovarian cancer have multiple co-morbidities. When they then need to undergo major open and extended surgeries, these patients represent a significant challenge for anaesthetists. The challenges faced, strategies to overcome, and effectiveness of these strategies aiming to improve recovery and potentially long-term outcomes have been reviewed (20,21).

It is also well known that the majority of newly diagnosed patients with stage III/IV ovarian cancer will relapse, despite the optimum upfront treatment given. A literature review of the challenges and opportunities in ovarian cancer relapse, including second- and third-line chemotherapy, recent clinical trials and the role of surgery in prolonging survival in relapsed disease are all thoroughly discussed in our series (22-25).

The challenges faced by histopathologists with chemotherapy response score (CRS) reporting for measuring response to NACT in IDS specimens or after full chemotherapy, and its utility in determining progression-free and overall survival rates, have been covered in an interesting written mini-review by Sanjiv Manek.

Through greater understanding of ovarian cancer biology, with further advances in molecular diagnostics, and by identification of new molecular pathways, evolutions in chemotherapeutic treatment occurred over the last decade, that changed the global view and approach to ovarian cancer management.

We hope that all interested and involved individuals in the management of advanced ovarian cancer will find our series comprehensive and elaborative, covering evolutions in different aspects of the multidisciplinary management of this complex and challenging disease.

Acknowledgments

Funding: None.

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, Gynecology and Pelvic Medicine for the series “Evolutions in the Management of Advanced Ovarian Cancer”. The article did not undergo external peer review.

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://gpm.amegroups.com/article/view/10.21037/gpm-23-14/coif). The series “Evolutions in the Management of Advanced Ovarian Cancer” was commissioned by the editorial office without any funding or sponsorship. HSM served as the unpaid Guest Editor of the series and serves as an unpaid editorial board member of Gynecology and Pelvic Medicine from June 2020 to May 2024. The authors have no other conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Soleymani Majd H, Ferrari F, Gubbala K, et al. Latest developments and techniques in gynaecological oncology surgery. Curr Opin Obstet Gynecol 2015;27:291-6. [Crossref] [PubMed]
2. Bristow RE, Tomacruz RS, Armstrong DK, et al. Survival effect of maximal cytoreductive surgery for advanced ovarian carcinoma during the platinum era: a meta-analysis. J Clin Oncol 2002;20:1248-59. [Crossref] [PubMed]
3. du Bois A, Reuss A, Pujade-Lauraine E, et al. Role of surgical outcome as prognostic factor in advanced epithelial ovarian cancer: a combined exploratory analysis of 3 prospectively randomized phase 3 multicenter trials: by the Arbeitsgemeinschaft Gynaekologische Onkologie Studiengruppe Ovarialkarzinom (AGO-OVAR) and the Groupe d'Investigateurs Nationaux Pour les Etudes des Cancers de l'Ovaire (GINECO). Cancer 2009;115:1234-44. [Crossref] [PubMed]
4. Tozzi R, Hardern K, Gubbala K, et al. En-bloc resection of the pelvis (EnBRP) in patients with stage IIIC-IV ovarian cancer: A 10 steps standardised technique. Surgical and survival outcomes of primary vs. interval surgery. Gynecol Oncol 2017;144:564-70. [Crossref] [PubMed]
5. Hall M, Savvatis K, Nixon K, et al. Maximal-Effort Cytoreductive Surgery for Ovarian Cancer Patients with a High Tumor Burden: Variations in Practice and Impact on Outcome. Ann Surg Oncol 2019;26:2943-51. [Crossref] [PubMed]
6. Querleu D, Planchamp F, Chiva L, et al. European Society of Gynaecologic Oncology Quality Indicators for Advanced Ovarian Cancer Surgery. Int J Gynecol Cancer 2016;26:1354-63. [Crossref] [PubMed]
7. Fotopoulou C, Hall M, Cruickshank D, et al. British Gynaecological Cancer Society (BGCS) epithelial ovarian/fallopian tube/primary peritoneal cancer guidelines: recommendations for practice. Eur J Obstet Gynecol Reprod Biol 2017;213:123-39. [Crossref] [PubMed]
8. Tozzi R, Gubbala K, Majd HS, et al. Interval Laparoscopic En-Bloc Resection of the Pelvis (L-EnBRP) in patients with stage IIIC-IV ovarian cancer: Description of the technique and surgical outcomes. Gynecol Oncol 2016;142:477-83. [Crossref] [PubMed]
9. Tozzi R, Ferrari F, Nieuwstad J, et al. Tozzi classification of diaphragmatic surgery in patients with stage IIIC-IV ovarian cancer based on surgical findings and complexity. J Gynecol Oncol 2020;31:e14. [Crossref] [PubMed]
10. Addley S, Yao DS, Soleymani Majd H. Primary diaphragmatic closure following diaphragmatic resection and cardiophrenic lymph node dissection during interval debulking surgery for advanced ovarian malignancy. Gynecol Oncol Rep 2021;36:100744. [Crossref] [PubMed]
11. Pinelli C, Morotti M, Casarin J, et al. The Feasibility of Cardiophrenic Lymphnode Assessment and Removal in Patients Requiring Diaphragmatic Resection During Interval Debulking Surgery for Ovarian Cancer. J Invest Surg 2021;34:756-62. [Crossref] [PubMed]
12. Soleymani Majd H, Ferrari F, Manek S, et al. Diaphragmatic peritonectomy vs. full thickness resection with pleurectomy during Visceral-Peritoneal Debulking (VPD) in 100 consecutive patients with stage IIIC-IV ovarian cancer: A surgical-histological analysis. Gynecol Oncol 2016;140:430-5. [Crossref] [PubMed]
13. Addley S, Morotti M, Pinelli C, et al. Transdiaphragmatic resection of enlarged cardiophrenic lymph node during interval debulking surgery for advanced ovarian cancer. Gynecol Oncol Rep 2021;37:100807. [Crossref] [PubMed]
14. Fotopoulou C. Intrathoracic surgery as part of primary cytoreduction for advanced ovarian cancer: The evolution of a "pelvic" surgeon. Gynecol Oncol 2023;170:A1-3. [Crossref] [PubMed]
15. Tozzi R, Casarin J, Baysal A, et al. Morbidity of multiple bowel resection compared to single bowel resection after debulking surgery for ovarian cancer. Eur J Obstet Gynecol Reprod Biol 2019;240:215-9. [Crossref] [PubMed]
16. Tozzi R, Casarin J, Baysal A, et al. Bowel resection rate but not bowel related morbidity is decreased after interval debulking surgery compared to primary surgery in patents with stage IIIC-IV ovarian cancer. J Gynecol Oncol 2019;30:e25. Erratum in: J Gynecol Oncol 2019;30:e101. [Crossref] [PubMed]
17. Tozzi R, Traill Z, Garruto Campanile R, et al. Porta hepatis peritonectomy and hepato-celiac lymphadenectomy in patients with stage IIIC-IV ovarian cancer: Diagnostic pathway, surgical technique and outcomes. Gynecol Oncol 2016;143:35-9. [Crossref] [PubMed]
18. Tozzi R, Traill Z, Campanile RG, et al. Diagnostic flow-chart to identify bowel involvement in patients with stage IIIC-IV ovarian cancer: Can laparoscopy improve the accuracy of CT scan? Gynecol Oncol 2019;155:207-12. [Crossref] [PubMed]
19. Tozzi R, Casarin J, Garruto-Campanile R, et al. Morbidity and reversal rate of ileostomy after bowel resection during Visceral-Peritoneal Debulking (VPD) in patients with stage IIIC-IV ovarian cancer. Gynecol Oncol 2018;148:74-8. [Crossref] [PubMed]
20. Fotopoulou C. How to predict treatment failure in frail patients with advanced epithelial ovarian cancer: strategies to personalize surgical effort. J Gynecol Oncol 2020;31:e26. [Crossref] [PubMed]
21. Liu YL, Filippova OT, Zhou Q, et al. Characteristics and survival of ovarian cancer patients treated with neoadjuvant chemotherapy but not undergoing interval debulking surgery. J Gynecol Oncol 2020;31:e17. [Crossref] [PubMed]
22. Fotopoulou C, Sehouli J, Aletti G, et al. Value of Neoadjuvant Chemotherapy for Newly Diagnosed Advanced Ovarian Cancer: A European Perspective. J Clin Oncol 2017;35:587-90. [Crossref] [PubMed]
23. Wright AA, Bohlke K, Armstrong DK, et al. Neoadjuvant Chemotherapy for Newly Diagnosed, Advanced Ovarian Cancer: Society of Gynecologic Oncology and American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol 2016;34:3460-73. [Crossref] [PubMed]
24. Vergote I, Tropé CG, Amant F, et al. Neoadjuvant chemotherapy or primary surgery in stage IIIC or IV ovarian cancer. N Engl J Med 2010;363:943-53. [Crossref] [PubMed]
25. Kehoe S, Hook J, Nankivell M, et al. Primary chemotherapy versus primary surgery for newly diagnosed advanced ovarian cancer (CHORUS): an open-label, randomised, controlled, non-inferiority trial. Lancet 2015;386:249-57. [Crossref] [PubMed]