Balancing Benefit and Toxicity in Adjuvant Therapy for Cervical Cancer

After a radical hysterectomy and pelvic lymphadenectomy for early-stage cervical cancer, patients often face decisions about whether to pursue adjuvant therapy. The goal of adjuvant treatment—typically, radiation therapy (RT) alone or combined with chemotherapy (CRT)—is to reduce the risk of cancer recurrence.

However, these treatments are not without adverse effects (AEs). Patients may experience fatigue, nausea, and hematologic changes such as anemia and neutropenia. Gastrointestinal symptoms, including diarrhea, cramping, or changes in bowel habits, are also common during radiation therapy due to the radiation site’s proximity to the gastrointestinal tract. Bladder irritation may occur, leading to increased frequency, urgency, or mild discomfort with urination. In addition, changes in sexual health, such as vaginal dryness, narrowing, or discomfort during intercourse, can affect intimacy and emotional wellbeing.

Beyond physical AEs, many women experience emotional distress and disruptions in their daily routines. Anxiety about recurrence, frustration with lingering fatigue, and difficulty returning to work or family responsibilities can weigh heavily during recovery. For example, a young, active mother undergoing adjuvant chemoradiation found that even mild nausea and fatigue made it difficult to keep up with work and family responsibilities. She worried about missing days on the job and felt guilty for relying on others at home, which added to her emotional stress.

Exploring Adjuvant Therapy Options for Intermediate-Risk Cervical Cancer

Historically, RT alone has been the standard approach for patients meeting intermediate-risk criteria, defined by tumor size, depth of stromal invasion, and lymphovascular space involvement, also known as Sedlis criteria. To explore whether outcomes could be improved, the NRG Oncology/GOG-0263/KGOG 1008 trial (NCT01101451) evaluated the addition of weekly cisplatin-based CRT compared with RT alone, according to findings published in Annals of Oncology.

This open-label, phase 3 randomized trial enrolled adults with stage IB–IIA cervical cancer and intermediate-risk features. Eligible histologies included squamous cell carcinoma, adeno-squamous carcinoma, and adenocarcinoma.

Patients were randomized 1:1 to receive either adjuvant RT alone (n = 158) or CRT (n = 158), with RT delivered via conventional 3D conformal therapy or intensity-modulated radiation therapy (IMRT) at a total dose of 50.4 Gy over 28 fractions. CRT patients received weekly cisplatin at 40 mg/m².

Baseline labs ensured adequate hematologic, renal, and hepatic function, and patients with high-risk features, prior chemotherapy or RT, or recent malignancies were excluded. Follow-up included physical exams, Pap tests, imaging, and quality-of-life (QOL) assessments using the FACT-Cx questionnaire. The primary end point was recurrence-free survival (RFS), with overall survival (OS) and QOL as secondary end points.

A total of 316 eligible patients were analyzed, with a median age of 46 years. Most had stage IB1 cervical cancer and squamous cell carcinoma (56.0%; P = .83). Nearly all patients in the RT-only group (99.4%) finished their planned therapy, and 84.8% of patients receiving CRT completed all planned treatment.

After a median follow-up of 76.5 months (IQR, 50.3-107.7), the estimated 3-year RFS was slightly higher in the CRT group at 88.5% (95% CI, 82%-93%) compared with 85.4% (95% CI, 79%-90%) in the RT-only group, though this difference was not statistically significant (hazard ratio [HR], 0.698, P = .09).

OS also trended in favor of CRT but did not reach statistical significance (HR, 0.586; P = .07). Recurrence patterns were similar between the 2 groups. Subgroup analyses suggested that CRT might be more beneficial than RT alone for patients receiving conventional conformal RT, while IMRT appeared to favor RT-only treatment. Patients in the CRT group experienced significantly higher rates of more severe (grade 3–4) hematologic AEs (42.9%), such as neutropenia, leukopenia, and thrombocytopenia, compared with the RT arm (15.3%; P <.01). PROs indicated a temporary decline in quality of life during CRT, which generally returned to baseline by 36 weeks.

Nursing Considerations

In the case of our young mother, the results of this trial helped provide context about the potential benefits and risks of her treatment. The study showed that adding weekly cisplatin to RT offered a modest improvement in 3-year recurrence-free survival and a trend toward better overall survival, though these differences were not statistically significant. At the same time, CRT is associated with more severe hematologic AEs and a temporary decline in quality of life.

Using this information, nurses could tailor supportive care and education to her needs. For example, they could closely monitor blood counts, proactively manage nausea, and provide strategies for fatigue management. Nurses might also assist in planning work flexibility and family support, normalizing the emotional impact of treatment and reassuring her that temporary disruptions in daily routines are common. By applying study data to her situation, nurses help patients make informed decisions, anticipate challenges, and feel supported throughout treatment and recovery.

References

Ryu SY, Deng W, Albuquerque K, et al. Randomized phase III trial of adjuvant radiation versus chemoradiation in intermediate-risk, early-stage cervical cancer following radical hysterectomy and lymphadenectomy: results from NRG Oncology/GOG-263/KGOG 1008. Ann Oncol. Published online September 12, 2025. doi:10.1016/j.annonc.2025.09.003