Fewer than half of women with locally advanced cervical cancer in the United States receive the recommended standard-of-care protocol of combination chemoradiation and brachytherapy, and overall survival (OS) is directly related to how comprehensively women are treated, a new analysis of the National Cancer Database (NCDB) indicates.
Of 15,194 patients with locally advanced cervical cancer registered with NCDB between 2004 and 2012, only 44.3% of patients received standard-of-care treatment consisting of external-beam radiation therapy (EBRT), chemotherapy, and brachytherapy.
The remaining patients received some of the treatments from that protocol, but not all, as follows: 2350 patients (15.5%) received EBRT alone, 4622 (30.4%) patients received EBRT with chemotherapy, and 1498 (9.9%) patients received EBRT with brachytherapy, but without chemotherapy.
The study was published in the November issue of Gynecologic Oncology.
"These findings build on prior studies that have shown that the use of brachytherapy is declining and highlight an alarming finding in practice patterns for locally advanced cervical cancer — that just under half of patients in the United States are receiving [standard of care] treatment," the authors comment.
"It is surprising to see that many women in the US are being undertreated, which negatively impacts survival," senior author Christine M. Fisher, MD, MPH, University of Colorado Cancer Center, Aurora, told Medscape Medical News in an email.
"The critical findings from this study are that all components of care are important to cure these patients, including brachytherapy, and patients and their primary care doctors should advocate for experienced oncologists to treat this uncommon cancer," she said.
Approached for his thoughts on the study by Medscape Medical News, Linus Chuang, MD, MPH, professor of gynecologic oncology, Icahn School of Medicine at Mount Sinai in New York, pointed out that the study highlights the importance of brachytherapy as an important part of the treatment protocol for locally advanced cervical cancer.
"Clinicians should either include brachytherapy as part of the treatment or refer their patients to centers where brachytherapy can be provided," Dr Chuang added.
"Not doing so affects adversely survival outcomes of these patients," he warned.
National Cancer Database
"This study re-emphasizes the survival benefit for brachytherapy, and builds on prior studies by highlighting an alarming finding that about 25% of all treated patients in our cohort received no radiotherapy boost at all. Further we show that patients treated with [standard of care] concurrent chemoradiation therapy including a brachytherapy boost have far superior outcomes to patients treated with alternative approaches, yet in our cohort only 44.3% of patients are treated in this manner," the authors write.
The American Brachytherapy Society states that all patients being treated with radiation for cervical cancer should receive brachytherapy as a component of their care unless they have a documented medical contraindication, the authors note.
However, their analysis found that 6972 (45.9%) patients were treated with EBRT alone, whereas 8222 (54.1%) patients received EBRT and brachytherapy.
Of the group who received EBRT alone, more than half (58%, 4067 of 6972 patients) did not receive a documented boost.
A total of 3609 patients treated with brachytherapy did receive an EBRT boost, including intensity-modulated radiation therapy or stereotactic body radiation therapy.
"We next stratified patients by chemotherapy," write the authors, led by Tyler P. Robin, MD, PhD, from the Department of Radiation Oncology at the University of Colorado Cancer Center.
Stratified by concomitant chemotherapy, Dr Robin and colleagues found that 15.5% received EBRT alone, 30.4% received EBRT plus chemotherapy, and 9.9% received both EBRT and brachytherapy but no chemotherapy.
Overall Survival vs Treatment
Overall, patients who received brachytherapy had significantly improved overall survival compared with patients treated with EBRT alone (median survival, 93.04 months vs 32.95 months; P< .001), the team reports.
Next, the authors stratified the patients who did not receive a boost vs patients who received an EBRT-only boost. They found improved overall survival for patients who received an EBRT-only boost compared with those who did not receive a radiotherapy boost at all, but both groups had substantially inferior overall survival compared with the group that received brachytherapy (median survival, 27.63, 47.05, and 94.03 months, respectively; P < .001).
Finally, the team used Kaplan-Meier curves and log-rank comparison to evaluate the role of chemotherapy in these patients. They found that the mean survival was 20.34 months in patients treated with EBRT alone, 43.74 months in patients treated with EBRT with concurrent chemotherapy, 56.18 months in patients treated with EBRT with brachytherapy without concurrent chemotherapy, and 105.23 months in patients who received the standard-of-care protocol of EBRT with concurrent chemotherapy and brachytherapy.
In multivariate analysis, brachytherapy was associated with a significant 38% improvement in overall survival (P < .001), Dr Robin and colleagues point out.
"The lack of brachytherapy cannot be made up by the addition of chemotherapy or sophisticated external beam radiation planning," the authors warn.
"All patients treated for cervical cancer with definitive intent radiotherapy should be treated with EBRT with brachytherapy and concurrent chemotherapy unless medically contraindicated," they emphasize.
In her comments to Medscape Medical News, Dr Fisher pointed out that brachytherapy is such a critical component of the cervical cancer treatment protocol because it allows oncologists to deliver very high doses of radiation directly to the tumor.
"It is this that really allows us to cure these patients, even those who have very large cervical cancers," she said in a statement.
Dr Robin and colleagues also found that patients treated at high-volume centers, academic centers, and comprehensive community cancer centers all were more likely to receive standard-of-care treatment.
Women with private insurance and those in a higher income bracket were similarly more likely to receive optimal care, while black patients were less likely to receive this, the authors report.
Patients with lower incomes, those treated at noncomprehensive community cancer centers, and those treated at centers with the lowest volume of cancer patients were also most likely not to receive any radiation boost, as were patients insured by Medicaid.
"Cervical cancer is a disease that overwhelmingly affects those without access to the healthcare system, which is disproportionately those with lower socioeconomic status, particularly the uninsured or underinsured, and disparities in care for cervical cancer unfortunately extend from screening and access to primary prevention — vaccination — as well as secondary prevention — early detection and treatment of preinvasive lesions," Dr Fisher commented.
"But this is a preventable cancer and essentially all women should have access to screening through local, county, and state-funding sources," she added.
Dr Fisher also emphasized that vaccination against the human papillomavirus, which causes most cervical cancers in the United States, should eventually help eradicate the malignancy.
In the meantime, she advises women who develop cervical cancer to seek expertise at a high-volume center, such as an academic or university hospital, where chances of cure are best through receipt of optimal treatment.
Gynecol Oncol. 2016;143:319-325