Leave it in the Past: Primary Treatment Should Not Preclude Secondary Surgery in Ovarian Cancer

Leave it in the Past: Primary Treatment Should Not Preclude Secondary Surgery in Ovarian Cancer

Patients with high-grade epithelial ovarian cancer with recurrence after neoadjuvant chemotherapy followed by interval debulking surgery (NACT-IDS) had similar outcomes following secondary cytoreduction surgery (SCS) compared to patients with recurrence after primary debulking surgery (PDS), according to a retrospective study by Memorial Sloan Kettering Cancer Center (MSK) Team Ovary. The paper was recently published online ahead of print in Gynecologic Oncology(1)

“Our results indicate that the primary treatment modality should not be used to exclude patients from secondary surgery,” said MSK gynecologic oncology fellow Beryl Manning-Geist, MD, co-lead author of the study together with gynecologic oncology fellow Tiffany Sia, MD. “Patient selection should be based on other factors, including age, operative risk, disease burden, and time between the end of first-line chemotherapy and secondary surgery.”

“MSK Team Ovary is the only group in the U.S. solely dedicated to the surgical treatment of all types and stages of ovarian cancer,” said senior study author gynecologic surgeon Dennis Chi, MD, FACOG, FACS, Head of the Section of Ovarian Cancer Surgery, the Ronald O. Perelman Chair in Gynecologic Surgery, and Deputy Chief of the Gynecology Service at MSK. “We perform hundreds of procedures annually and are committed to advancing ovarian cancer research through retrospective studies of our experience at MSK and clinical trials testing new treatment strategies for improving patient outcomes.”

High-Grade Epithelial Ovarian Cancer

Standard treatment for high-grade epithelial ovarian cancer (EOC) includes cytoreductive surgery and chemotherapy. Patients with advanced disease at presentation are offered PDS or NACT-IDS. (2) (3) (4) NACT is usually selected for patients who are older, have more extensive disease, and/or have comorbidities that elevate their surgical risk. (5)

Advanced ovarian cancer recurs after initial treatment in about 80% of patients. Results from two randomized trials have demonstrated that SCS provides a survival benefit compared to chemotherapy alone, especially for patients with no gross residual disease. (6) (7)

Selecting appropriate patients for SCS is essential, and several models for predicting the success of complete gross resection have been published, including the MSK SCS Team Ovary Criteria. (8) However, these models were primarily built and/or validated in patients with EOC who received PDS rather than NACT-IDS.

About 25% to 45% of patients with EOC receive up-front NACT-IDS. (9) (10) (11) (12)There are limited data from three recent randomized controlled trials evaluating the best treatment modality for platinum-sensitive recurrent EOC for informing the benefit of SCS. This patient population was not well represented in the DESKTOPIII (5) and SOC-1 (6) studies, and the proportion of patients who received NACT was not reported in the GOG-0213 trial. (13)

Study Design

The investigators analyzed electronic medical records for 374 patients with high-grade EOC who underwent SCS after primary surgery at MSK between February 2004 and October 2021. (1)

The research team collected clinical characteristics, including age at diagnosis, time of SCS, self-reported race and ethnicity, histology, stage at diagnosis, presence of BRCA1/2 germline mutations, performance status, preoperative CA-125 level at the time of cancer recurrence, type of preoperative imaging, number of sites imaged, and reason for NACT. (1)

They also collected surgical data, including the mode of abdominal access for SCS, the amount of residual disease after PDS, IDS, and SCS, and complete gross resection (CGR) status at primary surgery (CGR1) and SCS (CGR2). Optimal and suboptimal debulking were defined as one centimeter or greater than one centimeter or more of visible residual disease, respectively. (1)

Finally, the investigators included treatment characteristics, including postoperative and maintenance chemotherapy after PDS, IDS, and SCS, and time from the end of first-line chemotherapy to SCS. (1)

Study Results

Among 374 patients with high-grade EOC who underwent SCS at least 180 days after primary surgery, 312 or 83% had received primary treatment with PDS, and 62 (17%) had received NACT-IDS. (1)

The median age for patients undergoing SCS was 60 years. Most patients, 335 (90%), had high-grade serous adenocarcinoma. At diagnosis, 22 patients (6%) had stage 1 disease, 36 (10%) had stage 2, 238 (64%) had stage 3, and 78 (21%) had stage 4. A total of 92 patients (25%) had a germline BRCA1 or BRCA2 mutation. (1)

Overall, 257 (69%) of patients achieved CGR, and 90 (24%) had an optimal resection at the time of primary surgery. All patients had chemotherapy after their first surgery. (1)

Despite being older, having higher-grade EOC, and more comorbidities and metastatic disease at presentation, the proportions of patients achieving CGR after SCS were similar between the PDS group and NACT-IDS group, with CGR2 rates of 84% and 88%, respectively. (1)

Progression-free survival (PFS) and overall survival (OS) after SCS were also similar between groups. The median PFS after SCS was 1.7 years for the PDS cohort and 1.4 years for the NACT-IDS cohort. Median OS after SCS was 7.1 years for the PDS group and 6.2 years for the NACT-IDS group. (1)

Learn More

Watch this video to hear Dr. Manning-Geist summarize the study results presented at the 2023 Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer.

Advancing Ovarian Cancer Care

The MSK Section of Ovarian Cancer Surgery is a highly specialized program for women with advanced ovarian cancer. Surgeons have different areas of focus and expertise and collaborate closely with other specialists to provide patients with individualized treatment plans.

MSK is conducting 25 clinical trials of new treatment approaches for patients with ovarian cancer. For example, our team is currently recruiting patients for a phase 3 randomized clinical trial investigating whether adding hyperthermic intraperitoneal chemotherapy to surgery is more effective than surgery alone in patients with advanced ovarian cancer (NCT03772028).

MSK Team Ovary study authors included Aaron Praiss, MDYukio Sonada, MD, FACOG, FACSRachel Grisham, MDYing Liu, MD, MPHVance Broach, MD; Oliver Zivanovic, MD; Kara Long Roche, MD, MSc, FACOG; and Ginger Gardner, MD, FACOG.

The study was partly funded by the National Institutes of Health/National Cancer Institute Support Grant P30 CA008478. Dr. Manning-Geist reported no conflicts of interest. Dr. Chi reported personal fees from Apyx Medical, Verthermia Inc., Biom ‘Up, and AstraZeneca, as well as recent or current stock/options ownership of Apyx Medical, Verthemia, Intuitive Surgical, Inc., TransEnterix, Inc., Doximity, Moderna, and BioNTech SE. Refer to the paper for disclosures by other authors.

Refer a Patient
Call our dedicated clinician access number at 646-677-7440 or click the link below, and one of our care advisors will assist you with your referral needs.
  1. Sia TY, Manning-Geist BL, Ehmann S, et al. Leave it in the past - primary treatment modality for high-grade epithelial ovarian cancer is not associated with secondary cytoreduction outcomes: A Memorial Sloan Kettering Cancer Center Team Ovary study [published online ahead of print, 2023 Jul 14]. Gynecol Oncol. 2023;176:69-75.
  2. Fagotti A, Ferrandina MG, Vizzielli G, et al. Randomized trial of primary debulking surgery versus neoadjuvant chemotherapy for advanced epithelial ovarian cancer (SCORPION-NCT01461850). Int J Gynecol Cancer. 2020;30(11):1657-1664.
  3. Vergote I, Coens C, Nankivell M, et al. Neoadjuvant chemotherapy versus debulking surgery in advanced tubo-ovarian cancers: pooled analysis of individual patient data from the EORTC 55971 and CHORUS trials. Lancet Oncol. 2018;19(12):1680-1687.
  4. 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(28):3460-3473.
  5. Meyer LA, Cronin AM, Sun CC, et al. Use and Effectiveness of Neoadjuvant Chemotherapy for Treatment of Ovarian Cancer. J Clin Oncol. 2016;34(32):3854-3863.
  6. Harter P, Sehouli J, Vergote I, et al. Randomized Trial of Cytoreductive Surgery for Relapsed Ovarian Cancer. N Engl J Med. 2021;385(23):2123-2131.
  7. Shi T, Zhu J, Feng Y, et al. Secondary cytoreduction followed by chemotherapy versus chemotherapy alone in platinum-sensitive relapsed ovarian cancer (SOC-1): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2021;22(4):439-449.
  8. Chi DS, McCaughty K, Diaz JP, et al. Guidelines and selection criteria for secondary cytoreductive surgery in patients with recurrent, platinum-sensitive epithelial ovarian carcinoma. Cancer. 2006;106(9):1933-1939.
  9. Melamed A, Hinchcliff EM, Clemmer JT, et al. Trends in the use of neoadjuvant chemotherapy for advanced ovarian cancer in the United States. Gynecol Oncol. 2016;143(2):236-240.
  10. Matsuo K, Matsuzaki S, Nusbaum DJ, et al. Possible candidate population for neoadjuvant chemotherapy in women with advanced ovarian cancer. Gynecol Oncol. 2021;160(1):32-39.
  11. Hinchcliff E, Melamed A, Bregar A, et al. Factors associated with delivery of neoadjuvant chemotherapy in women with advanced stage ovarian cancer. Gynecol Oncol. 2018;148(1):168-173.
  12. Melamed A, Rauh-Hain JA, Gockley AA, et al. Association Between Overall Survival and the Tendency for Cancer Programs to Administer Neoadjuvant Chemotherapy for Patients With Advanced Ovarian Cancer. JAMA Oncol. 2021;7(12):1782-1790.
  13. Coleman RL, Spirtos NM, Enserro D, et al. Secondary Surgical Cytoreduction for Recurrent Ovarian Cancer. N Engl J Med. 2019;381(20):1929-1939.