Is Postoperative Chemotherapy Necessary for Intermediate-Risk Cervical Cancer?

Why Are Cervical Cancer Treatment Strategies Being Reconsidered?

Cervical cancer is one of the most common gynecological cancers worldwide. Although surgery can achieve high cure rates when diagnosed early, some patients are advised to receive additional (adjuvant) treatment according to pathological risk factors. One of the most debated questions is whether patients at intermediate risk should receive chemotherapy in addition to radiotherapy .

Two important new studies have reignited the debate and questioned whether adjuvant chemoradiotherapy is truly necessary in this group. The studies showed that chemotherapy causes harm rather than benefit for these patients.

Phase 3 GOG 0263 Study: Adding Chemotherapy Does Not Improve Outcomes

The NRG-GOG 0263 phase 3 study, conducted in the United States and presented at the Society of Gynecologic Oncology (SGO) annual meeting, evaluated 316 women with intermediate-risk early-stage cervical cancer. All had undergone radical hysterectomy.

The study tested whether addingcisplatin-based chemotherapy to postoperative radiotherapy improved recurrence-free survival . However, the findings were contrary to expectations:

• The 5-year recurrence-free survival rate did not differ significantly between radiotherapy alone and chemoradiotherapy.
• Moreover, toxicity (side effects) in the chemotherapy group was substantially higher.

These findings indicated that, in intermediate-risk cervical cancer, chemotherapy provides no additional benefit and may instead cause greater harm.

What Do Treatment Guidelines Say?

The United States National Comprehensive Cancer Network (NCCN) recommends radiotherapy as the first-line approach for this group, while presenting chemotherapy as a category 2B option supported by weaker evidence. These findings may require NCCN guideline updates.

By contrast, United States National Cancer Institute (NCI) guidance still gives chemotherapy priority, increasing inconsistency and confusion between guidelines.

JAMA Oncology Study: The Same Result in More Patients

Another study, published in March 2025 in JAMA Oncology , reported similar findings. Led by Dr. Núria Agustí Garcia at the MD Anderson Cancer Center in Texas, it analyzed data from 1116 women.

• The 5-year overall survival rate in patients receiving chemoradiotherapy versus radiotherapy alone was identical: 87%
• Patients given chemotherapy had larger tumors and nonsquamous histology.
• However, even with propensity score matching , the chemotherapy group showed no additional survival advantage.

Statistical results:

• HR = 0.85 (95% confidence interval, 0.59–1.23; P = 0.38)

This indicates that adding chemotherapy does not provide a statistically significant benefit and may cause unnecessary adverse effects.

Which Patients Are Defined as “Intermediate Risk”?

The intermediate-risk patients in these studies generally had clinical stages according to the FIGO 2009 classification of IB1 – IIA1 . However, risk classification is based not only on stage but also on postoperative pathological findings .

Who Are Intermediate-Risk Patients?

• Patients who have undergone radical hysterectomy and pelvic lymph node dissection
• With lymph node metastasis, parametrial invasion, or positive surgical margins absent (meaning they are not “high risk”)

But with one or more of the following Sedlis criteria:

• Tumor diameter >4 cm
• Deep stromal invasion (%>1/3 – %2/3)
• Lymphovascular space invasion (LVSI)

This group is defined as having intermediate-risk cervical cancer, and postoperative radiotherapy is usually recommended. Until now, however, strong evidence of a clear benefit from adding chemotherapy was lacking . The studies presented here clarify this question.

Why Was Chemotherapy So Widely Used Previously?

In the late 1990s, cisplatin-containing chemoradiotherapy was shown to substantially improve survival in advanced cervical cancer. These favorable findings were extrapolated to intermediate-risk patients. That approach now appears to be “an incorrect inference” .

These patients have no parametrial involvement or lymph node metastases and may therefore behave biologically differently from advanced-stage disease.

Are Modern Radiotherapy Techniques More Effective?

Modern radiotherapy techniques (IMRT, IGRT) appear particularly to reduce additional problems  associated with treatment, but without a major effect on overall survival.

Radiation is highly effective, particularly for microscopic disease. Additional chemotherapy may therefore be unnecessary in these patients.

Chemotherapy's ability to control systemic disease also remains limited in this group.

Why Are Larger Tumors and Nonsquamous Histology Associated With Chemotherapy?

The authors of both studies explain this as follows: Patients with larger tumors and different histological subtypes are perceived as high risk by doctors and directed toward more aggressive treatment. In terms of survival, however, this choice has no positive effect.

Are Changes in Clinical Practice Expected?

These two studies suggest that some guidelines need updating. In current practice, however, most centers already use radiotherapy alone as the standard approach for intermediate-risk patients.

With these data, we now clearly know that radiotherapy alone is the best approach for intermediate-risk patients rather than giving chemotherapy.

We should avoid chemotherapy when there is no evidence-based benefit. This improves quality of life and prevents overtreatment within the healthcare system.

Conclusion: Adjuvant Chemotherapy Is Truly Unnecessary

New evidence shows that adding chemotherapy in intermediate-risk cervical cancer neither improves survival nor reduces recurrence . Instead, it increases the risk of adverse effects. Therefore:

• In intermediate-risk cervical cancer, standard treatment should be radiotherapy alone.
• Chemotherapy should be reserved for high-risk or advanced-stage cases .
• Clinical guidelines also need to be reviewed in light of these findings.