Gynecologic cancer illustration: © Crystal Light – stock.adobe.com
A retrospective study has corroborated recent research showing that there is no survival benefit with adjuvant therapy after hysterectomy in women with early-stage, intermediate-risk cervical cancer, according to findings from the Dutch, Danish and Swedish Gynaecological Oncology (DANDELION) research group.1
In the international, population-based, retrospective cohort study, there was not a significant difference in 5-year overall survival (OS) rates between patients receiving adjuvant therapy (AT) post-hysterectomy and those receiving no further treatment (NFT arm): 87.7% vs. 91.9%, respectively (HR, 1.58; 95% CI, 1.04–2.39; P =.031). Similarly, there was no significant difference in 5-year recurrence-free survival (RFS) rates at 82.6% vs 79.8%, respectively (HR, 0.86; 95% CI, 0.62–1.19; P =.358).
This lack of an OS or RFS benefit with AT was also observed in a subgroup analysis restricted to women with postoperative intermediate-risk factors of having a tumor size ≥4 cm or a tumor size of 2 cm to 3.9 cm along with the presence of lymphovascular space invasion (LVSI). Also of note, tumor size and LVSI were predictive indicators of worse survival outcomes.
“Adjuvant therapy after radical hysterectomy was not associated with a survival benefit in women with [early-stage] cervical cancer. These findings corroborate earlier findings on the role of adjuvant therapy for cervical cancer with intermediate-risk factors and support de-escalation to avoid radiation harm for this patient population,” the DANDELION researchers wrote.
Study Rationale and Design
The researchers noted that they decided to conduct their analysis because despite several prior studies and analyses, “AT based on intermediate-risk factors remains controversial.”
The study assessed women with early-stage cervical cancer from 3 European population-based registers: the Danish Gynaecological Cancer Database, the Swedish Quality Registry for Gynaecologic Cancer, and the Netherland Cancer Registry. Overall, the analysis included data from 976 women with FIGO 2018 stages IB2 to IIA2 cervical cancer whose tumors were at least 20 mm and whose lymph nodes were negative.
Between 2010 and 2017, the patients had received hysterectomy followed by NFT (667 women) or AT with either radiotherapy or chemoradiotherapy (309 women). Among the women who received AT, 220 (71%) were treated with chemoradiotherapy, 88 (28%) received radiotherapy, and 1 was given chemotherapy.
The median patient age was 46 years (range, 21–84) in the AT arm and 44 years (range, 24–84) in the NFT arm. Histological subtypes included squamous cell carcinoma (69% in AT vs 61% in NFT), adenocarcinoma (26% vs 35%), and adenosquamous carcinoma (5% vs 4%).
Patients in the AT group generally presented with more advanced or severe disease factors, including a higher percentage of patients with tumors ≥40 mm (28% vs 12%); a higher rate of LVSI (64% vs 35%); and a greater depth of tumor invasion (11-20 mm: 53% vs 31%; >20 mm: 7% vs 2%).
The researchers noted that the main limitation of their study is its observational design.
In their concluding remarks, the study authors reiterated, “Our result contributes to a growing body of evidence [including a 2022 meta-analysis2] suggesting that AT may not provide meaningful oncological advantages in this context. Safely de-escalating primary treatment for cervical cancer is of importance, as the long-term consequences of radiation therapy can be devastating.”
Regarding next steps, they wrote, “An ongoing prospective trial is expected to shed further light on the indications for adjuvant therapy and in the meantime, a critical reassessment of the use of AT in early-stage cervical cancer with intermediate-risk factors is warranted.”