No Benefit With CRT Versus RT in Cervical Cancer After Radical Hysterectomy

The addition of concurrent cisplatin chemotherapy to adjuvant radiation therapy (CRT), versus RT alone, couldn’t move the needle on outcomes in patients with cervical cancer who had intermediate risk factors after radical hysterectomy and lymphadenectomy.

While the outcomes for recurrence-free survival (RFS) and overall survival (OS) suggested a trend towards a benefit in favor of CRT, they fell short of statistical significance in the phase III trial, reported Sang Young Ryu, MD, of the Korea Cancer Center Hospital in Seoul.

Specifically, 3-year recurrence-free survival (RFS) estimates for the CRT and RT arms were 88.5% and 85.4%, respectively (HR 0.6976, 95% CI 0.408-1.192, P=0.0927), while estimated 3-year OS rates for the CRT and RT arms were 97.2% and 90.3%, respectively (HR 0.586, 95% CI 0.286-1.199, P=0.0695).

Thus, “there is no survival benefit in terms of recurrence-free survival and overall survival,” Ryu said in a presentation at the Society of Gynecologic Oncology (SGO) annual meeting in Seattle.

However, there was a substantial increase of toxicity with CRT. Grade 3 or 4 adverse events (AEs) occurred much more frequently in the CRT group, particularly hematological toxicities, such as neutropenia (27 grade 3/4 AEs in the CRT arm vs two in the RT arm), and leukopenia (45 vs three, respectively).

The NRG Oncology/GOG-263 study was conducted between 2010 and 2022 and involved 316 eligible patients with early-stage disease and intermediate-risk factors, including a combination of histopathologic factors such as capillary lymphatic space involvement, stromal invasion, and tumor size.

Patients had a median age of 46, 52.5% were Asian, 38% white, and 5.4% Black. Most had an ECOG performance score of 0, and most had FIGO (2009) stage IB1 (56%) and IB2 (34%) disease, along with squamous cell carcinoma histology (74%).

Patients randomized to the RT arm received external-beam RT using four-field “standard” RT or intensity-modulated RT. In the CRT arm, a dose of cisplatin 40 mg/m² was administered weekly, six cycles during RT.

The majority of patients (almost 92%) had 28 fractions of RT with median dosage of 50.4 Gy and duration of 39 days, and 91% of the patients in CRT arm received at least four cycles of weekly cisplatin.

In an accompanying SGO presentation, Alexandra Smick, MD, of the University of California Los Angeles, reported on patient-reported outcomes (PRO) and quality of life (QoL) from GOG-263, which she said was the first U.S.-based clinical trial on early-stage high-risk cervical cancer that collected PRO/QoL data prospectively.

Patients completed QoL assessments at baseline and follow-up at 3, 7, and 36 weeks. These assessments were completed at rates of 98%, 90%, 88% and 81%, respectively, and showed “an overall decrease in health-related quality of life for all patients approximately 3 weeks after beginning treatment,” Smick reported. “This was significantly worse for patients in the cisplatin plus radiation arm compared to radiation alone.”

However, all patients recovered to their baseline QoL at 9 months.

Patient-reported AEs for gastrointestinal categories of abdominal pain, food digestion, diarrhea, and bowel control “were surprisingly similar between the two groups,” Smick said, with both groups experiencing a worsening of symptoms by 3 weeks with a gradual improvement up to 7 weeks, with a return to pretreatment level by 9 months. The same pattern held true for genitourinary symptoms.

“While there was no difference between the two treatment arms for any of these GI symptoms, it is important to note that all patients did experience some worsening of GI symptoms, no matter what the intervention was,” Smick said.

Patient-reported neuropathy showed that all patients reported a gradual worsening of their neuropathy symptoms from baseline to 36 weeks, with no significant difference between the two groups at 9 months, while all patients reported a worsening of pain between 3 and 7 weeks after treatment, but had returned to baseline by 9 months.

“We know from this study and from prior studies that adding cisplatin to radiation does have increased toxicities, and we now see that this correlates with a worsening quality of life for all patients between 3 and 7 weeks, and this is really regardless of the intervention arm,” Smick said.

Also, “there are differences in timelines when mentioning PROs and treatment toxicities,” she observed. “Change in laboratory abnormalities may not correlate with a patient’s experience on a cancer treatment. This is why it is important to continue to integrate PRO data collection in the clinical trial data so that we can better understand the patient’s perspective on their cancer treatment and ultimately improve their care.”

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