Adoption of NACT lowers all-cause mortality in advanced ovarian cancer
Use of neoadjuvant chemotherapy (NACT) for advanced epithelial ovarian cancer in rapidly adopting regions has considerably reduced mortality within 3 years after diagnosis, according to a recent study. This appears to be facilitated by decreased postoperative morbidity and mortality.
“We observed that a rapid increase in the use of NACT between 2011 and 2012 in New England and east south central census districts led to a reduction in mortality assessed through 3 years after diagnosis,” researchers said. “In contrast, we found no difference in mortality in regions that did not increase NACT use.”
During 2011 and 2012, a total of 1,156 women received treatment with NACT for advanced epithelial ovarian cancer in the two rapidly adopting regions and 4,878 women in the three control regions.
Patients treated in 2012 vs 2011 in the New England and east south central regions had a mortality hazard ratio (HR) of 0.81 (95 percent CI, 0.71‒0.94) after adjusting for mortality time trends. On the other hand, there was no difference in control regions (HR, 1.02; 0.93‒1.12). [BMJ 2018;360:j5463]
Patients in rapidly adopting regions vs control regions also had greater reductions in 90-day surgical mortality (7.0‒4.0 percent vs 5.0‒4.3 percent; p=0.01) and in the proportion of women not receiving surgery and chemotherapy (20.0‒17.4 percent vs 19.0‒19.5 percent; p=0.04). Cross-sectional analysis confirmed that adoption of NACT correlated with lower mortality (p=0.001).
“These findings should reassure clinicians and policymakers who have greeted increasing acceptance of NACT with some concern,” researchers said.
However, the survival benefit seen in this study does not support the findings of some observational studies that have compared survival among women who received NACT with those who underwent primary surgery. [Gynecol Oncol 2016;140:436-442; Gynecol Oncol 2014;134:462-467; J Clin Oncol 2016;34:3854-3863; JAMA Oncol 2017;3:76-82]
According to researchers, these observational studies comparing survival among women assigned to these treatment modalities are subject to selection bias since patients with poor performance status and high disease burden are preferentially treated with NACT. [J Clin Oncol 2016;34:3827-3828]
“[O]ur findings do not indicate that all patients with advanced epithelial ovarian cancer will benefit from NACT,” researchers said. “The survival benefit measure in this study is [a] consequence of expanded adoption of NACT, which occurred selectively among older patients and those with stage 3 disease.” [Gynecol Oncol 2016;143:236-240]
“Furthermore, if the mechanism of benefit for NACT observed in this study is reduction in postoperative morbidity and mortality, NACT may be less beneficial in the context of expert centres that achieve better than average surgical outcomes,” they added.
In this quasi-experimental fuzzy regression discontinuity design and cross-sectional analysis, women (n=6,034) with a diagnosis of stage 3C or 4 epithelial ovarian cancer from regions that rapidly adopted use of NACT from 2011 and 2012 (27-percent increase in the New England and east south central regions) or remained unchanged (control regions, south Atlantic, west north central and east north central regions) were included.
All-cause mortality within 3 years of diagnosis was the primary outcome measure. Mortality differences between rapidly adopting regions and controls were compared using Kaplan-Meier curves and proportional hazard models.
“Future research may elucidate how patients who may benefit most can be identified and selected to receive NACT,” researchers noted.