ASCO has updated its guidelines on the role of neoadjuvant chemotherapy for patients newly diagnosed with advanced ovarian cancer, underscoring key considerations in selecting patients for treatment and where to go from there.1
Since ASCO’s previous guidelines were published in 2016, there has been a major shift in the upfront treatment of advanced ovarian cancer in the United States.2 Data from the National Cancer Database showed that between 2010 and 2021, the proportion of patients with stage III or IV ovarian cancer who underwent primary cytoreductive surgery fell from 70.1% to 37.2%. Meanwhile, the proportion receiving neoadjuvant chemotherapy followed by interval surgery more than doubled, from 16.6% to 40.8%.3
Those trends followed the publication of several clinical trials demonstrating the noninferiority of neoadjuvant chemotherapy/interval surgery compared with primary cytoreductive surgery in terms of survival and a reduction in perioperative complications.
Stéphanie Gaillard, MD, PhD
“We wanted to revisit the data,” said Stéphanie Gaillard, MD, PhD, of Johns Hopkins University, who co-chaired the guideline Expert Panel. “We wanted to see if there have been updates in the studies that support the shift we’re seeing, to see whether there’ve been new studies that support that shift, and to remind physicians about best practice for patients with newly diagnosed ovarian cancer.”
In total, the panel reviewed 61 studies, including 9 randomized clinical trials, published between March 2015 and February 2024.
Initial Evaluation
Like the 2016 guidelines, the ASCO update stresses the importance of involving a gynecologic oncologist in the initial assessment to determine whether a patient is a good fit for upfront surgery. It also points to the various tools available for that assessment, noted Expert Panel Co-Chair William P. Tew, MD, of Memorial Sloan Kettering Cancer Center, New York.
William P. Tew, MD
At a minimum, patients should receive CA-125 blood testing and CT of the pelvis, abdomen, and chest. When the feasibility of optimal cytoreduction is unclear, further evaluation with laparoscopy, or additional imaging such as MRI, FDG-PET, or ultrasound, may be beneficial. In addition, an endometrial biopsy may be warranted to exclude the possibility of advanced endometrial cancer. This is critical, Dr. Tew noted, because first-line treatment of that disease has recently changed to include immunotherapy with chemotherapy.
The update also highlights separate ASCO guidelines on germline and somatic testing, which recommend that all patients with ovarian cancer be offered testing at the time of diagnosis or as soon as possible thereafter.4 One reason for this, Dr. Tew noted, is to identify those who would be eligible for PARP inhibitors as maintenance therapy after completion of chemotherapy.
“We’re stressing the point that testing be done early because, unfortunately, many patients aren’t being offered germline and somatic testing,” Dr. Tew said.
Choosing Upfront Treatment
For patients who are medically fit and have a high likelihood of complete cytoreduction with acceptable morbidity, primary cytoreductive surgery remains the recommended approach. Neoadjuvant chemotherapy followed by interval surgery is recommended for patients who are deemed unlikely to have complete cytoreduction, as well as those who have a high perioperative risk profile.
Those recommendations are in line with the 2016 guidelines, as longer-term data have provided more supporting evidence for them. “The difference between now and 2016 is that neoadjuvant chemotherapy is now in wide use,” Dr. Tew noted. “So, we did want to highlight the role of primary surgery for the appropriate patients.”
When neoadjuvant chemotherapy is the choice, the update advises that all patients should first have histologic confirmation of an invasive ovarian, fallopian tube, or peritoneal cancer, with a core biopsy strongly preferred. “Fine-needle aspirants are not sufficient,” Dr. Gaillard said.
Next Steps
As in the 2016 guidelines, platinum/taxane doublet remains the neoadjuvant regimen of choice. As for the timing of interval surgery, the update recommends it be performed after four or fewer chemotherapy cycles. A total of at least six cycles is recommended, though the number of postsurgery cycles can be adjusted based on patient factors and response to treatment.
“We’ve also learned that we shouldn’t wait too long after interval surgery to restart chemotherapy,” Dr. Gaillard said. Based on studies finding poorer outcomes with delays in adjuvant chemotherapy after primary cytoreductive surgery, the update recommends resuming chemotherapy within 4 to 6 weeks of interval surgery, if feasible.
In a case where a patient has progressive disease during neoadjuvant chemotherapy, the update says that a repeat biopsy is warranted. Ovarian cancer usually responds to chemotherapy, Dr. Gaillard noted, “so it is imperative we make sure the diagnosis is correct.”
A Role for HIPEC
Since 2016, new data have emerged on the efficacy of adding hyperthermic intraperitoneal chemotherapy (HIPEC) at the time of interval cytoreductive surgery. The OVHIPEC-1 trial found that HIPEC (with one-time perfusion of cisplatin) improved disease-free and overall survival among patients with advanced ovarian cancer vs interval surgery without HIPEC.5
At the same time, Dr. Tew said, HIPEC is resource-intensive, limiting its availability, and patients need to be medically fit for it based on factors such as renal function and performance status. “So we’re not endorsing HIPEC for all patients,” Dr. Tew said. “But we feel it’s something that can be offered to some.”
In sum, the update largely reinforces the recommendations of the original guideline and emphasizes the role of the gynecologic oncologist in determining whether a patient is a candidate for primary cytoreductive surgery, Dr. Gaillard said. “We hope this update provides physicians with the best practice recommendations as they navigate neoadjuvant chemotherapy decisions for patients newly diagnosed with ovarian cancer,” she said.
DISCLOSURE: For full disclosures of all authors, visit https://ascopubs.org/doi/10.1200/JCO-24-02589.
REFERENCES
1. Gaillard S, Lacchetti C, Armstrong DK, et al: Neoadjuvant chemotherapy for newly diagnosed, advanced ovarian
cancer: ASCO guideline update. J Clin Oncol. January 22, 2025 (early release online).
2. 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 34:3460-3473, 2016.
3. Bercow A, Stewart T, Bregar AJ, et al: Utilization of primary cytoreductive surgery for advanced-stage ovarian cancer. JAMA Netw Open 7: e2439893, 2024.
4. Konstantinopoulos PA, Lacchetti C, Annunziata CM: Germline and somatic tumor testing in epithelial ovarian cancer: ASCO guideline summary. JCO Oncol Pract 16:e835-e838, 2020.
5. Aronson SL, Lopez-Yurda M, Koole SN, et al: Cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy in patients with advanced ovarian cancer (OVHIPEC-1): Final survival analysis of a randomised, controlled, phase 3 trial. Lancet Oncol 24:1109-1118, 2023.
Originally published in ASCO Daily News. © American Society of Clinical Oncology. ASCO Daily News, January 22, 2025. All rights reserved.
