New Neoadjuvant Chemotherapy in Epithelial Ovarian Cancer

Ovarian cancer is the leading cause of death for gynecologic cancer, and epithelial ovarian cancer (EOC), which develops in the outer surface tissue of the ovaries or fallopian tubes, makes up 85-90% of all ovarian cancer diagnoses. Primary debulking surgery (PDS) and adjuvant chemotherapy are the standard of care for most cases. However, for advanced disease cases when complete cytoreduction is unlikely, care teams and patients are increasingly considering an alternative approach using neoadjuvant chemotherapy (NACT) to shrink tumor size before interval debulking surgery (IDS).

As a referring physician, understanding Moffitt's expertise in this innovative treatment strategy should encourage you to promptly refer eligible patients, potentially improving their chances for optimal outcomes.

NACT Efficacy

NACT in epithelial ovarian cancer has been shown to simplify surgery, reduce complications, shorten hospital stays, and enable quicker transition to follow-up chemotherapy.

While the standard treatment course is preferred for primary debulking surgery (PDS), NACT can be an effective treatment for those with Stage III-IV EOC with extensive tumor dissemination and a low possibility of removing all visible cancer through surgery. A NACT approach should also be considered for cases with a significant risk of surgical complications. Initial evaluation by a Gynecologic Oncologist to determine the resectability for primary debulking surgery (PDS) is a crucial step toward better patient outcomes.

For example, studies have shown that older women with ovarian cancer often receive less aggressive treatment than younger patients, leading to poorer outcomes. NACT offers a less invasive initial approach, which can be more tolerable for older individuals. Additionally, NACT has been associated with lower perioperative morbidity and mortality, making it a viable option for elderly patients who might not withstand the rigors of primary cytoreductive surgery.

However, it's important to note that while NACT can make surgery more feasible and reduce immediate surgical risks, it may also delay definitive surgical intervention and could potentially increase the risk of local recurrence. Therefore, the decision to use NACT should be individualized, considering the patient's overall health, comorbid conditions, and personal preferences. A multidisciplinary team approach, involving oncologists, geriatricians, and surgeons, is essential to optimize treatment outcomes for older patients with ovarian cancer.

According to Dr. Jing-Yi Chern, a gynecologic oncologist in the Gynecologic Oncology Program at Moffitt, “More than half of newly diagnosed ovarian cancer patients are women older than 65. With increasing age, comorbidities, and potential complications such as polypharmacy, drug interactions, assistance with daily activities, cognitive decline, frailty, poor nutritional status, limited social support, and access to resources become more prevalent. Addressing these needs is crucial, as they can impact treatment and outcomes during chemotherapy and the perioperative period.”

As part of our assessment of older patients, we conduct a comprehensive geriatric evaluation to assess a patient’s functional status, medical conditions, cognitive status, nutritional health, and psychosocial support. This is integrated into our rehabilitation program. Our Gynecologic Oncologists collaborate closely with Senior Adult Oncology specialists, social workers, nutrition consultants, and our behavioral outcomes team to optimize care for patients undergoing NACT for newly diagnosed ovarian cancer. Our goal is to enhance patient’s fitness to minimize chemotherapy-related toxicities and reduce major postoperative complications following cytoreductive surgery.

Treatment Regimen

When NACT is initiated, it usually consists of three or four chemotherapy cycles followed by surgery and another three cycles of platinum-based chemotherapy. Moffitt’s multidisciplinary team closely manages patients considering or undergoing neoadjuvant therapy. On a case-by-case basis, we carefully consider the benefits and drawbacks, including potential evidence of little to no difference in primary survival outcomes between PDS and NACT. We tailor each treatment plan to each unique patient, considering age, histology, cancer stage, surgical resectability, and performance status. We also monitor treatment response, understanding that IDS is not viable for patients who do not respond adequately to NACT. In these cases, patients should be treated as platinum-refractory, and the course of action will be changed.

Moffitt’s nuanced expertise in treating ovarian cancer is a critical differentiator that can enhance the patient’s outcomes and quality of life. For healthcare providers with patients suspected of having epithelial ovarian cancer, Moffitt should be the first referral choice, as it gives patients the best chances of survival.

Outcomes and Advancements

Studies investigating the effectiveness of NACT and IDS vs. PDS have shown some conflicting results for survival outcomes. While some studies found that patients experienced prolonged overall survival (OS) following NACT, others observed little to no improvements in OS. However, researchers have also seen several clear positive outcomes across the board. Clinically meaningful differences in favor of NACT were reported concerning:

• Fewer postoperative serious adverse effects (6% NACT vs. 29% PDS)
• Reduced need for stoma formation (5.9% NACT vs. 20.4% PDS)
• Reduced risk of necessary bowel resection during surgery (13% NACT vs. 36.6% PDS)
• Reduced postoperative mortality (0.6% NACT vs 3.6% PDS)

Further studies are needed to evaluate less common subtypes of EOC, study how NACT combined with PARP inhibitors and immunotherapy impacts outcomes, and address the reason for impaired long-term survival of patients who undergo NACT. Additionally, existing trials have faced questions about study design and surgery quality deficiencies, so further clinical trials should carefully consider these factors.

Moffitt is currently involved in studying the efficacy of a single intraperitoneal injection of Radspherin (a radiopharmaceutical treatment that uses microparticles to emit radiation to localized tissue and minimizes radiation exposure to healthy tissue) in patients with high-grade EOC scheduled to undergo NACT and IDS. Community healthcare providers with patients eligible for this clinical trial should refer them to Moffitt for pre-screening.

Why Moffitt?

Moffitt’s Gynecologic Oncology Program comprises a multispecialty team, including medical oncologists, radiation oncologists, surgeons, fertility specialists, and other experts specializing in treating ovarian cancer. Working together closely on tumor boards, our care team develops individualized treatment plans informed by each patient’s unique disease and characteristics. As the only Florida cancer hospital designated as a Comprehensive Cancer Center by the National Cancer Institute, Moffitt provides the highest level of care, giving each patient the best chance of survival. We’re dedicated to exploring the efficacy of new and innovative treatment methods, including NACT and IDS for patients with high-grade EOC. Moffitt patients may qualify for certain treatments through clinical trial research that aren’t readily available to cancer patients anywhere else.

We encourage you to refer patients to Moffitt's Gynecologic Oncology Program for the best chance of beating cancer.  Please complete our online form or contact a physician liaison for assistance. As part of our efforts to shorten referral times as much as possible, online referrals are typically responded to within 24 - 48 hours.