Baseball great Satchel Paige’s famous adage, “Age is a case of mind over matter. If you don’t mind, it don’t matter,” may also apply to candidates for ovarian cancer surgery. That’s because investigators have found that physical frailty is a better determinant of fitness for surgery than is calendar age.
Investigators conducted a retrospective analysis of 591 patients considered for primary resection of stage II to IV high-grade ovarian, fallopian tube, or peritoneal cancer. Results showed that a 10-item modified frailty index was better than patient age for predicting survival outcomes.
“Frailty does seem to correlate with age and increase with age, but it is not synonymous with age,” said investigator Katelyn F. Handley, MD, of the University of Texas MD Anderson Cancer Center in Houston.
“Frailty is a spectrum, and we can see patients of the same chronological age, but one may be a 76-year-old, ultra-distance triathlete, while another is in failing health and diminishing function,” Dr. Handley said at the Society of Gynecologic Oncology’s Virtual Annual Meeting on Women’s Cancer (Abstract 10463).
Dr. Handley cited a consensus definition of frailty, published in 2013, as “a medical syndrome with multiple causes and contributors that is characterized by diminished strength, endurance, and reduced physiologic function that increases an individual’s vulnerability for developing increased dependency and/or death.”
Ten-item score
To assess the effect of frailty in ovarian cancer patients on surgical procedures and outcomes, the investigators retrospectively applied a modified frailty index (mFI) to patients who were treated at MD Anderson Cancer Center from April 2013 through September 2017.
The index is a sum of 10 items: Chronic obstructive pulmonary disease or recent pneumonia, heart failure, myocardial infarction, coronary artery disease, diabetes, hypertension, peripheral vascular disease, cerebrovascular disease, cerebrovascular accident with neurologic deficit, and poor Eastern Cooperative Oncology Group performance status (3 or 4).
Of the 591 patients who met inclusion criteria, 57% had mFI scores of 0, indicating no frailty, 29% had one frailty factor, and 14% had two or more factors.
Patient age did significantly correlate with mFI scores. Patients with an mFI score of 0 had a median age of 62 years, the median age in those with a score of 1 was 69 years, and the median age for those with scores of 2 or higher was 70.5 years (P <. 001).
Charlson comorbidity index scores also significantly increased with age, with mean scores of 3.00, 3.83, and 5.14 in patients with mFI scores of 0, 1, or 2, respectively (P <. 001).
“But if you look at the age ranges in each category, you’ll notice that there are patients as young as 47 with an mFI of greater than or equal to 2, and as old as 89 with an mFI of 0,” Dr. Handley pointed out.
Higher scores, fewer assessments
The investigators found that patients with suspected ovarian cancer with frailty scores of 2 or higher were less likely to be offered laparoscopic assessment to determine primary resectability than were those with scores of 1 or 0 (28% vs. 43% and 49%, respectively, P = .004).
Among all patients who underwent laparoscopic assessment, the predictive index score (modified Fagotti score) was more likely to be 8 or higher in patients with high frailty scores (58%, 48%, and 34% for scores of 2 or greater, 1, and 0, respectively; P = .038).
Only 17% of the most frail patients went on to primary debulking surgery, compared with 26% of patients with a single frailty factor and 34% of those with none (P = .015).
Patients with higher frailty scores were less likely to undergo primary or interval tumor reductive surgery (59% vs. 74% for those with mFI scores of 1 and 85% for those with scores of 0; P <. 001). The frailest patients were significantly more likely to undergo splenectomy (20%, 3%, and 6%, respectively; P = .001) and small bowel resection (14%, 8%, and 3%, respectively; P = .006).
Two-thirds of the most frail patients (64%) had postoperative complications, primarily gastrointestinal and renal complications, compared with 56% and 44% of patients with mFI scores of 1 or 0, respectively (P = .014).
Frailty was predictive of 30-day postoperative mortality (P = .005) but not postoperative length of stay.
Frailer patients were more likely to receive neoadjuvant chemotherapy (P = .033) but less likely to receive adjuvant chemotherapy (P <. 001).
mFI scores of 2 or greater and 1 were both associated with significantly worse progression-free survival (P < .001 and P = .022, respectively), but only an mFI of 2 or greater was associated with significantly worse overall survival (P <. 001).
On multivariate analysis controlling for frailty, age, stage, BRCA status, and tumor reductive surgery status, high frailty was associated with worse progression-free survival (P = .009) and a trend toward worse overall survival (P = .079).
High frailty was better than age for predicting worse progression-free survival (hazard ratio, 1.50; P = .017) and overall survival (HR, 1.57; P = .047)
Volume counts
In a separate presentation during the same session, Morcos Nakhla, of the University of California, Los Angeles, reported finding similar associations between frailty and worse surgical outcomes for ovarian cancer patients (Abstract 11016).
Mr. Nakhla and colleagues found that frail patients had a twofold increase in the risk of postoperative complications, a threefold increase in the risk for non-home dismissal, and a threefold increased risk of death (P <. 001 for all).
The team also found, however, that mortality improved from 2005 through 2017, despite an increase in frail patients over that time period.
In addition, higher surgical volumes were associated with decreased mortality among frail patients undergoing ovarian cancer surgery.
Navigating treatment
“Frailty syndrome is a medical syndrome. It’s not a disability,” said Jamie N. Bakkum-Gamez, MD, of the Mayo Clinic in Rochester, Minn., the invited discussant. “No patient or human wants to be frail, but at some point, we may all be at risk for frailty syndrome, and as we navigate much-needed novel ways to treat this medical syndrome, it’s imperative that we listen to the voice of the customer and that our communication and technology doesn’t add unanticipated stress.”
Dr. Bakkum-Gamez emphasized the importance of shared decision-making, screening for frailty syndrome, referral to higher volume surgical centers when practical, and surgical alternatives such as neoadjuvant chemotherapy with or without interval debulking surgery and palliative care.
Interventions for ameliorating frailty may include exercise, high-protein calorie supplementation, reduction of polypharmacy, and vitamin D supplementation.
“Sometimes, shared decision-making means deciding not to operate,” Dr. Bakkum-Gamez said. “This is sometimes amongst the hardest decisions for a surgeon. We know when we make the wrong decision in operating if our patient experiences a major, life-shortening complication, but it’s less clear to know if we make the wrong decision to not operate.”
The study by Dr. Handley and colleagues was funded by the Gulf Coast Consortia, MD Anderson, National Institutes of Health, American Cancer Society, and GOG Foundation. Mr. Nakhla and colleagues did not disclose a funding source. Dr. Handley, Mr. Nakhla, and Dr. Bakkum-Gamez all reported no relevant conflicts of interest.