Definitive pelvic radiotherapy was associated with longer survival in stage IVB cervical cancer

Median survival was 25 versus 18 months with chemotherapy plus definitive pelvic radiotherapy after propensity matching in stage IVB cervical cancer.

KEY POINTS

  • JROSG22-1/JGOG1088S was a nationwide Japanese multicenter retrospective study of 343 patients with newly diagnosed FIGO 2018 stage IVB cervical cancer treated from 2016–2020. Patients received chemotherapy alone (n=137) or chemotherapy plus definitive-dose pelvic radiotherapy (n=206).
  • Definitive pelvic RT was defined as pelvic EBRT ≥40 Gy, brachytherapy, or both. Among patients with available dosimetry, median total EQD2 was 65.4 Gy at point A and 70.3 Gy to CTVHR D90; 67% of the pelvic-RT group received brachytherapy and 78% received concurrent chemoradiotherapy.
  • After 1:1 propensity-score matching, 103 patients per group were compared. Median overall survival was 25.0 months with pelvic RT versus 18.0 months with chemotherapy alone, corresponding to HR 0.58 (95% CI 0.42–0.79; P<.001); two-year survival was 50.3% versus 31.0%.
  • Progression-free survival also favored pelvic treatment, although the absolute median difference was modest: 9 versus 8 months, HR 0.65 (95% CI 0.48–0.87; P=.002). Sensitivity analyses using inverse-probability weighting and a six-month landmark analysis continued to show a significant survival association.
  • Pelvic disease control improved substantially. In the overall cohort, the first progression was local in 19% with pelvic RT versus 34% with chemotherapy alone (P=.003), while any pelvic first progression occurred in 22% versus 41% (P<.001).
  • The survival association was seen across most metastatic patterns but was absent in patients with T1–2 disease, HR 1.11 (95% CI 0.64–1.92), with a significant interaction by T stage (Pinteraction=.008). Even among patients with organ metastases, the matched analysis favored pelvic RT, HR 0.66 (95% CI 0.46–0.95).
  • Brachytherapy emerged as an important treatment-associated factor within the pelvic-RT cohort: on multivariable analysis it was associated with better overall survival, HR 0.48 (95% CI 0.33–0.71; P<.001), and progression-free survival, HR 0.66 (95% CI 0.47–0.93; P=.016). Median survival was 38 months with pelvic RT plus brachytherapy, 23 months with EBRT alone and 18 months with chemotherapy alone in the overall cohort.
  • Treatment intensification came with greater gastrointestinal morbidity. In the matched cohort, late grade ≥3 gastrointestinal toxicity occurred in 13.6% with pelvic RT versus 4.9% with chemotherapy alone (P=.030); grade ≥3 genitourinary toxicity was similar at 5.8% versus 4.9%. Importantly, the cohort predates contemporary first-line checkpoint-inhibitor therapy.

CLINICAL TAKEAWAY

Definitive treatment of the pelvis may matter even when cervical cancer is already metastatic: pelvic RT was associated with a seven-month median survival advantage and substantially less pelvic progression, with the strongest signal when brachytherapy was incorporated. This is compelling real-world evidence, but selection bias, non-standardized systemic therapy and the absence of modern immunotherapy mean pelvic RT cannot yet be considered a proven survival-improving standard for unselected stage IVB disease.

SOURCE

Radiotherapy and Oncology