Frailty may be a better predictor of poor surgical outcomes in patients with ovarian cancer than age, according to two studies reported at the Society of Gynecologic Oncology (SGO) 2021 Virtual Annual Meeting on Women’s Cancer. Researchers found that frail patients are less likely to undergo surgery, have more complications when they do, and have worse survival—though treatment at a high-volume center can ameliorate some of these risks.
As one of the researchers, Katelyn F. Handley, MD, explained, studies have correlated older age with worse outcomes in ovarian cancer, but the question remains: is age alone a sufficient prognostic and screening tool?
“Or can we do better with an assessment of frailty?” she asked.
In her study, frail patients were often denied surgery (and even laparoscopic assessment), and when they did undergo surgery, their procedures were often more complex and their clinical outcomes worse—including more postoperative morbidity and 30-day mortality, and worse progression-free and overall survival (Abstract ID 10463).
“Frailty was a better predictor of outcomes than age in this population,” said Dr. Handley, a postdoctoral fellow at The University of Texas MD Anderson Cancer Center. “While frailty does seem to correlate with increased age, it is not synonymous with age.”
A second study found that the proportion of frail patients with ovarian cancer in the population has increased over time, but outcomes for frail patients have improved—though not to the level of their nonfrail counterparts (Abstract ID 11016).
As reported by Morcos Nakhla, MS, a medical student at the David Geffen School of Medicine at the University of California, Los Angeles (UCLA), the presence of frailty increased the odds of dying, of developing postoperative complications, and of having a non-home discharge—but treatment at a high-volume center reduced mortality risk. The study’s senior author was Joshua G. Cohen, MD, of UCLA Health.
Adverse Outcomes by Modified Frailty Index
Dr. Handley and colleagues used the Modified Frailty Index (mFI), a sum of 10 components indicative of frailty, to evaluate associations between frailty and outcomes in 591 patients with stage II to IV ovarian cancer treated at MD Anderson between 2013 and 2017. In their cohort, 57% of patients had an mFI of 0 (least frail), 29% had an mFI of 1 (moderately affected), and 14% had an mFI of ≥ 2 (frailest).
“We saw that patient age does correlate with mFI, but if you look at the age ranges in each category, there are patients as young as age 47 with mFI ≥ 2 and some as old as age 89 with an mFI of 0,” she said.
The frailest patients (mFI ≥ 2), relative to least frail (mFI 0), were:
- Less likely to be offered laparoscopic assessment to determine resectability: 28% vs 49% (P < .0004)
- More likely to have a predictive index value ≥ 8, by laparoscopic assessment (ie, modified Fagotti score): 58% vs 34% (P = .038)
- Less likely to proceed to primary debulking surgery: 17% vs 34% (P = .015)
- Less likely to undergo any tumor reductive surgery: 59% vs 85% (P < .001)
- More likely to have an extensive procedure, including splenectomy (20% vs 6%, P = .001) and small bowel resection (14% vs 3%, P = .006)
- More likely to have postoperative complications: 64% vs 44% (P = .014)
- More likely to die within 30 days postoperatively: 9% vs 0.4% (P = .005).
Compared to the least frail patients, worse progression-free and overall survival were also observed for the frailest patients. In the multivariate analysis, which controlled for age, stage, BRCA status, and tumor reductive surgery, hazard ratios (relative to mFI 0) were 1.50 (P = .017) for progression-free survival and 1.57 (P = .047) for overall survival, Dr. Handley reported.
In this model, frailty was a better predictor of both progression-free and overall survival than age, which was not significantly associated with these important outcomes.
Frailty should play a role in clinical and surgical decision-making in patients with advanced ovarian cancer...Moving forward, consideration should be given to adding formal frailty assessments to our new [patients with] advanced ovarian cancer.— Katelyn F. Handley, MD
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Findings From the Inpatient Sample Database
Mr. Nakhla and colleagues identified 198,820 patients with ovarian cancer within the National Inpatient Sample database from 2005 to 2017, finding 12,085 (6.1%) who were considered frail according to the multidimensional Johns Hopkins Adjusted Clinical Groups (ACG) frailty-defining diagnosis indicator.
They determined that the proportion of frail patients undergoing surgery increased significantly throughout the study period, from 4% in 2005 to 10% in 2017 (P < .001), though, interestingly, their overall rate of in-hospital mortality fell over time, from 8% to approximately 3% (P < .001).
In the multivariate analysis, frailty was associated with a threefold risk of dying (P < .001); a 3.4-fold chance of non-home discharge; and a risk for respiratory, infectious, and renal complications that was 1.8 to 2.2 times higher (P < .001) than nonfrail patients. Frailty was also associated with a 4-day longer hospitalization (P < .001), possibly explaining the $12,000 increase in these patients’ hospital cost of care (P < .001), he said.
“After adjusting for relevant variables, such as age, we found that frailty predicts a significantly higher probability of mortality in patients with older age at a cutoff that seems to be in the fifth decade,” explained Mr. Nakhla. “We also found that while the probability of mortality was still significantly higher for frail patients each year, it decreased throughout the study period.”
Finally, the research team looked at surgical volume in the centers where care was received. While frail patients were less likely to be treated at centers with high surgical volume, treatment at such centers significantly reduced their risk for mortality. For example, for frail patients, in-hospital mortality was approximately 3% at centers performing only about 50 ovarian cancer surgeries a year but dropped to about 1.5% at centers performing 450 or more.
“In the future, we hope to understand the biological changes associated with frailty and explore efforts to mitigate its impacts, Mr. Nakhla said.
The findings reinforce the need to better assess frailty and act on the findings, the speakers said.
“Frailty should play a role in clinical and surgical decision-making in patients with advanced ovarian cancer,” concluded Dr. Handley. “Moving forward, consideration should be given to adding formal frailty assessments to our new [patients with] advanced ovarian cancer.”
Disclosure: Mr. Nakhla and Dr. Handley had no relevant disclosures.
