Frailty is a better predictor than age of poor outcomes in patients with ovarian cancer, according to 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 this risk.
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.
“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
Tweet this quote
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 survival and overall survival.1
“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 their outcomes have also improved—though not to the level of their nonfrail counterparts.2
Morcos Nakhla, MS
Joshua G. Cohen, MD
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, developing postoperative complications, and having a nonhome 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 (see sidebar on page 6), 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 an 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 (ie, modified Fagotti score) by laparoscopic assessment: 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 postoperative complications: 64% vs 44% (P = .014)
- More likely to die within 30 days postoperatively: 9% vs 0.4% (P = .005).
Compared with the least frail patients, worse progression-free survival 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 an mFI of 0) were 1.50 (P = .017) for progression-free survival and 1.57 (P = .047) for overall survival, she reported.
In this model, frailty was a better predictor of both progression-free and overall survival than was age, which was not significantly associated with these important outcomes. Additional analyses are ongoing.
Findings From the Inpatient Sample Database
Mr. Nakhla and colleagues identified 198,820 patients with ovarian cancer within the National Inpatient Sample database of 2005 to 2017, finding 12,085 (6.1%) who were considered frail according to the multidimensional Johns Hopkins Adjusted Clinical Groups 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 nonhome discharge; and a risk for respiratory, infectious, and renal complications that was 1.8 to 2.2 times higher (P < .001) relative to nonfrail patients. Frailty was also associated with a 4-day longer hospitalization (P < .001), possibly explaining the $12,000 increase in their hospital cost of care (P < .001), he said.
KEY POINTS
- Studies show that frailty is a better predictor than age of poor outcomes in patients with ovarian cancer.
- 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.
- Surgery at a high-volume center reduces the excess mortality risk seen in frail patients in general.
“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,” he said. “We also found that, although 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 where care was received. Although frail patients were less likely to be treated at centers with high surgical volume, treatment at such centers significantly reduced their risk of dying. For example, for frail patients, in-hospital mortality was approximately 3% at centers performing 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 biologic changes associated with frailty and explore efforts to mitigate its impacts,” Mr. Nakhla said.
MODIFIED FRAILTY INDEX
- In the study by Handley et al, the Modified Frailty Index (mFI) was calculated based on 10 comorbidities: chronic obstructive pulmonary disease or recent pneumonia, congestive heart failure, myocardial infarction, coronary artery disease, diabetes, hypertension, peripheral vascular disease, cerebrovascular disease (CVA), CVA with neurologic deficit, and Eastern Cooperative Oncology Group status 3 or 4, with each item receiving a score of 1 if present.
- Patients with an mFI ≥ 2 were classified as high frailty.
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,” Dr.Handley concluded. “Moving forward, consideration should be given to adding formal frailty assessments to our new patients with advanced ovarian -cancer.”
DISCLOSURE: Dr. Handley and Mr. Nakhla reported no conflicts of interest.
REFERENCES
1. Handley KF, Sood AK, Dal Molin GZ, et al: Frailty repels the knife: The impact of frailty index on surgical intervention and outcomes. Society of Gynecologic Oncology 2021 Virtual Annual Meeting on Women’s Cancer. Abstract 31. Presented March 20, 2021.
2. Nakhla M, Mandelbaum A, Salani R, et al: Higher surgical volume is associated with better outcomes for frail patients undergoing surgery for ovarian cancer. Society of Gynecologic Oncology 2021 Virtual Annual Meeting on Women’s Cancer. Abstract 30. Presented March 20, 2021.
