Appropriate evidence-based triage is vital to outcomes in advanced epithelial ovarian cancer

June 26, 2021

A recently published study by Mayo Clinic Gynecologic Oncology has found that while patients with advanced epithelial ovarian cancer (EOC) need aggressive therapy, they must receive careful triage from gynecologic oncologists to reduce morbidity and mortality. This most recent publication builds on and confirms other Mayo studies demonstrating the importance of identifying frail patients who are at highest risk of poor outcomes after major complications.

At diagnosis, 57% of women with EOC present with advanced-stage disease (stage 3 to 4), according to the National Cancer Institute's Surveillance, Epidemiology, and End Results Program (SEER). Advanced ovarian cancer prognosis is poor, according to SEER: Five-year survival is 31%, though it is improving as randomized trials and specialized centers now commonly report five-year survival over 50%. Aggressive surgical debulking plays an important role in the management of advanced disease.

Thus, a team led by William A. Cliby, M.D., and Carrie L. Langstraat, M.D., gynecologic oncologists at Mayo Clinic in Rochester, Minnesota, embarked on studies with the goal of extending survival and lowering serious complication rates. This research confirms that a one-size-fits-all treatment planning approach is not in patients' best interests. Rather, physicians need to follow a treatment planning algorithm and customize therapy for each patient with advanced EOC to "maximize benefit and minimize harm."

Fitness for aggressive surgery

In a study published in Gynecologic Oncology in March 2021, Drs. Cliby and Langstraat and colleagues demonstrate the necessity of assessing patients' underlying fitness for surgery using a validated triage algorithm. This strategy allows physicians to identify patients at highest risk of poor outcomes such as early death, inability to start chemotherapy or non-home discharge after a complex, aggressive primary debulking surgery (PDS). The Mayo Clinic triage algorithm pinpoints patients at highest risk of severe complications and death within 90 days after cytoreductive surgery. For these patients, triage to neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) is a safer approach.

Drs. Cliby and Langstraat note a shift nationally toward relegating patients with advanced EOC to NACT followed by IDS. They attribute this trend to high morbidity and mortality rates with aggressive primary surgery upfront (PDS) and the limited success many centers have in achieving complete resection in the PDS setting. The research team has attempted to reduce complication rates by focusing on appropriate patient selection and novel selective improvements in surgical technique. Doing so has reduced the 90-day mortality rate after aggressive surgery by more than half.

"This triage has reduced the frequency of very poor outcomes — for instance, dying within three months following surgery or a patient not being able to go on to initiate chemotherapy, which is essential," says Dr. Cliby. "We want to deliver aggressive surgery for patients with advanced-stage disease, but we need to define those patients — and it's a minority — who are unable to tolerate such procedures."

Investigators found that use of the triage system still allowed 70% of women to undergo complex aggressive surgical cytoreduction but with minimal risk of mortality or other serious poor outcomes. Aggressive surgery was associated with the lowest amounts of residual disease and thus improved overall survival.

In their study of 334 patients with EOC, 69.5% were triaged to PDS and 30.5% to NACT and IDS. Patients triaged to PDS underwent more-aggressive surgery, had similar rates of complications and lived longer.

Drs. Cliby and Langstraat consider use of a validated triage algorithm to individualize management crucial to the selection of PDS or NACT followed by IDS. "Outcomes for NACT are not the same as those for PDS. I would prefer PDS if possible and reserve NACT for those who are frail," says Dr. Langstraat. "The algorithm makes selection possible and evidence based."

Triage and sarcopenia at diagnosis

A retrospective, single-institution study by Mayo Clinic Gynecologic Oncology studied sarcopenia in patients with advanced EOC. The results underlined the importance of frailty in management of EOC. The study, published in the January 2021 issue of Gynecologic Oncology, found that sarcopenia is common in patients with advanced EOC triaged to NACT. Due to advanced EOC symptoms — bloating, early satiety and fatigue — women may experience a nutritional decline and become frail by the time of diagnosis. Frailty and sarcopenia go hand in hand, says Dr. Langstraat.

This study included 285 patients with advanced-stage EOC. All underwent axial CT 90 days before treatment. The researchers used body composition software to evaluate scans for skeletal muscle density, skeletal muscle index, skeletal muscle mass area and skeletal muscle gauge, the last measure being a unique one in this study. The investigators determined sarcopenia status based on the international consensus on female skeletal muscle index published by Fearon and colleagues in The Lancet Oncology in May 2011.

Of this group, 200 patients underwent PDS; 85 patients had NACT plus IDS. Treating physicians most often referred patients for NACT plus IDS due to low albumin. The investigators observed that more patients who met criteria and were triaged to NACT were sarcopenic than in the PDS group (40% vs. 28%). Drs. Cliby and Langstraat highlight that the higher rates of sarcopenia in the triaged patients underscore the value of the triage algorithm to identify patients who are unable to tolerate aggressive surgery and also identify potential strategies to begin to address frailty and sarcopenia. These strategies include pre-habilitation, with interventions for nutrition, physical fitness and mental strength, which may benefit NACT-triaged patients during chemotherapy.

"Sometimes patients are just so frail — even at age 60 — due to their cancer," says Dr. Langstraat. "Frailty is a marker for doing worse in treatment. We want to see what things we can do to improve their status and help them recover better from treatment."

The Mayo team's next step is a prehabilitation trial with exercise, nutrition and stress-reduction interventions for NACT-triaged patients, led by Amanika Kumar, M.D., a gynecologic oncologist at Mayo Clinic's campus in Rochester, Minnesota.

Thoughts to consider for physicians of patients with advanced EOC

The investigators in Mayo Clinic Gynecologic Oncology identify two challenges for physicians treating patients with advanced EOC:

  • Appropriate triage
  • Complexity of both PDS and NACT plus IDS

Both of these factors demonstrate the potential value of referring patients with suspected advanced EOC to a high-volume center such as Mayo Clinic to maximize surgical and postoperative therapy benefits while identifying patients for whom primary surgery may not be in their best interests.

Ideally, says Dr. Cliby, treatment planning is done by the Mayo Clinic Gynecologic Oncology team working along with the local oncologist: This collaboration requires patient referral early in the scenario. "We want to help comanage patients with referring physicians for the best outcomes," says Dr. Cliby. "Once a relationship is established, we have smooth handoffs from one to another, providing comprehensive care for the patient."

For more information

Cancer stat facts: Ovarian cancer. Surveillance, Epidemiology, and End Results Program. National Cancer Institute.

Narasimhulu DM, et al. Appropriate triage allows aggressive primary debulking surgery with rates of morbidity and mortality comparable to interval surgery after chemotherapy. Gynecologic Oncology. 160;2021:681.

Fadadu PP, et al. Patients triaged to neoadjuvant chemotherapy have higher rates of sarcopenia: An opportunity for prehabilitation. Gynecologic Oncology. 2021;160:40.

Fearon K, et al. Definition and classification of cancer cachexia: An international consensus. The Lancet Oncology. 2011;12:489.