Top Line: What is the best approach to adjuvant therapy for resected cervical cancer with adverse features?
The Study: Patients with adverse features after hysterectomy typically receive either radiation alone or chemoradiation (CRT) depending on their risk. However, a sequential chemo → radiation → chemo approach has also been proposed. The Chinese phase 3 STARS trial randomized over 1000 women with FIGO IB-IIA cervical cancer post-radical hysterectomy with at least one adverse pathologic feature to one of three treatment arms:  pelvic radiation,  radiation with concurrent weekly cisplatin, or  sequential chemo (cisplatin and paclitaxel) given in two cycles before and then two cycles after radiation. For reference, the Sedlis and Peters studies each enrolled < 300 patients. Intermediate risk factors (think Sedlis) were LVSI and deep stromal invasion. High risk factors (think Peters) were nodal disease, parametrial invasion, and positive margins. Any of those factors bought enrollment, and they were equally balanced among treatment arms. The primary endpoint of disease-free survival at 3 years was significantly improved with sequential CRT (90%) compared to concurrent CRT (85%) and radiation alone (80%). The difference between concurrent CRT and RT alone was not significant. Sequential CRT also improved cancer-specific survival 88→ 92% compared to RT alone. The benefit with sequential CRT was maintained in subgroup analyses, even among women with intermediate-risk factors. As expected, grade 3-4 toxicity was less with RT alone (13%) than with concurrent (29%) or sequential CRT (25%) due to heme toxicity—with the small difference between the latter two due to more GI toxicity with concurrent CRT.
TBL: When compared to the current standards of adjuvant radiation and chemoradiation, sequential/sandwiched chemo and radiation for resected intermediate- or high-risk cervical cancer improves disease free survival. | Huang, JAMA Oncol 2021