Top

The management of early-stage cervical cancer with intermediate-risk factors following radical hysterectomy has historically relied on adjuvant radiotherapy (RT) alone as standard treatment. Intermediate-risk criteria (Sedlis criteria) include tumour size, depth of stromal invasion, and lymphovascular space involvement.

Whilst chemoradiation has become established as superior therapy for locally advanced cervical cancer and high-risk early-stage disease, evidence supporting the addition of chemotherapy to adjuvant radiation in intermediate-risk patients remained limited.

The landmark GOG-92 trial, conducted 25 years prior, demonstrated benefit from RT alone but did not include chemotherapy. Given advances in radiation techniques, imaging modalities, and supportive care, along with clinical equipoise regarding whether adding cisplatin chemotherapy could improve outcomes, this trial was designed to definitively answer whether chemoradiation provides superior efficacy to justify potential increased toxicity.
 

The NRG Oncology/GOG-263 (KGOG 1008) trial was an open-label, randomised phase III trial which aimed to determine whether adjuvant concurrent chemoradiation with weekly cisplatin improves recurrence-free survival compared with radiation therapy alone in patients with pathologically confirmed intermediate-risk, early-stage cervical cancer following radical hysterectomy and pelvic lymphadenectomy.

The trial enrolled 340 women with stage I-IIA cervical cancer who underwent radical hysterectomy with bilateral pelvic lymph node dissection and had at least two intermediate-risk pathological factors.

Patients were randomised to receive either RT alone (172 patients) or concurrent chemoradiation (168 patients) with weekly cisplatin at 40 mg/m² for up to six cycles. Intensity-modulated radiation therapy was permitted in both arms.

The efficacy analysis included 158 patients per arm with balanced baseline characteristics including performance status, histology, tumour grade, age (median 45-46.5 years), and ethnicity (50-55% Asian).

The trial demonstrated trends towards improved outcomes with chemoradiation that did not reach statistical significance.

Three-year recurrence-free survival was 88.5% with chemoradiation versus 85.4% with RT alone (HR 0.70, p=0.09). Three-year overall survival favoured chemoradiation at 97.2% versus 90.3% (HR 0.59, p=0.07). However, chemoradiation significantly increased grade 3-4 toxicities (43% vs 15%), particularly neutropenia (17% vs 1%) and leucopenia (28% vs 2%).

Approximately 91% of patients in the chemoradiation arm completed at least four cycles of weekly cisplatin.

Patient-reported outcomes indicated transient quality-of-life decrements with chemoradiation. Subgroup analyses suggested potential benefits with modern radiation techniques like IMRT.

Cervical cancer is the fourth most common cancer amongst women worldwide, with the highest incidence in low-income countries, particularly in sub-Saharan Africa, where almost 90% of cervical deaths occur in resource-constrained settings. Early cervical cancer screening can detect cervical intraepithelial neoplasia grades 2 or 3—precancerous lesions that, if detected, treated, and managed early, can prevent the development of invasive cervical cancer.

The findings from the NRG Oncology/GOG-263/KGOG 1008 trial hold particular significance for South Africa, where cervical cancer remains a critical public health challenge despite being largely preventable.

On February 2, 2026, the Department of Health launched the 2026 Human Papillomavirus (HPV) Vaccination drive targeting girls aged nine years and older, aiming to protect future generations from developing cervical cancer. This primary prevention initiative comes against the backdrop of alarming statistics: South Africa records over 5,700 new cervical cancer cases annually, with more than 3,000 women dying from cervical cancer-related complications each year.¹

South Africa's cervical cancer burden far exceeds global averages. The age-standardised incidence rate stands at 31.7 per 100,000 persons compared to 14.0 per 100,000 globally, whilst the age-standardised mortality rate reaches 18 per 100,000 women versus 6.8 per 100,000 internationally. Cervical cancer ranks as the second most common cancer amongst South African women and the leading cause of cancer death across all age groups. The disease disproportionately affects black women (82.7% of cases) and represents the most common malignancy in women aged 15-44 years. ^2,3

The HIV epidemic significantly compounds this burden, as cervical cancer was classified as an AIDS-defining illness in 1993. Women living with HIV face substantially higher risks of HPV-associated disease and more aggressive cervical cancer progression, making unvaccinated HIV-positive girls and women particularly vulnerable to serious health complications. The epidemic has also diverted limited healthcare resources away from preventive activities like cancer screening, exacerbating detection delays.^2,3

For the subset of South African women diagnosed with early-stage cervical cancer who undergo radical hysterectomy and are found to have intermediate-risk pathological features, the GOG-263 trial results provide crucial treatment guidance—but equally important is the question of whether adding chemotherapy to radiation is even practical in resource-constrained settings.

The finding that radiotherapy alone achieves outcomes comparable to more toxic chemoradiation has important resource implications for South Africa's healthcare system. In settings where managing chemotherapy-related complications (particularly severe neutropenia and leucopenia requiring supportive care, blood products, and antimicrobial therapy) poses significant logistical and financial challenges, evidence supporting RT alone as standard treatment offers a more feasible approach without compromising patient outcomes.
This is particularly relevant given that 43% of patients receiving chemoradiation experienced grade 3-4 toxicities compared to only 15% with RT alone.

However, the broader message remains clear: primary prevention through HPV vaccination and early detection through screening programmes represent the most effective strategies to reduce South Africa's disproportionate cervical cancer burden. The current vaccination campaign, combined with evidence-based treatment protocols for those who do develop disease, offers a comprehensive approach to addressing this preventable cause of premature death amongst South African women.
 

Back to top