2294 - Breaking the Ceiling of Local Therapy: Evolutionary Trajectories and Systemic Bottlenecks In Anal Cancer from the 2D/3D to IMRT Era

03:00pm - 04:00pm ET

Poster Hall - Exhibit Hall A

Screen: 20

Presenter(s)

YangMei Zhou, MD - National Cancer Center/Cancer hospital & Shenzhen Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Shenzhen, Guangdong

Y. Zhou¹, Q. Xiao¹, and J. Jin^1,2; ¹National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital and Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, Shenzhen, China, ²State Key Laboratory of Molecular Oncology and Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China

Purpose/Objective(s):

The standard chemotherapy for anal squamous cell carcinoma (ASCC) remains unchanged for decades, but radiotherapy (RT) has evolved from 2D/3D to IMRT. Modern RT has significantly enhanced locoregional control (LRC), yet its translation into improved long-term overall survival (OS) remains controversial. This study quantified the impact of RT evolution on both local and systemic outcomes to identify the future direction for further improvement of the survival in ASCC.

Materials/Methods: Prospective or retrospective clinical studies in ASCC cohorts treated with definite chemoradiotherapy were retrieved from PubMed, Embase, MEDLINE, and Cochrane Library databases, and stratified by RT technique (2D/3D vs. IMRT). Data of locoregional control (LRC), distant metastasis (DM), progression-free survival (PFS) and overall survival (OS) were extracted and reconstructed by using sample-size-weighted trajectory models. The correlation between survival index were evaluated using weighted linear and non-parametric LOESS regressions. Sobel mediation analysis was utilized to assessed the causal pathway of the effect of LRC and DM on OS.

Results:

A total of 48 studies with 67 arms and 8,319 patients were analyzed. Trajectory analysis demonstrated an apparent improvement in LRC, a slight increasement in long-term survival, but an unchanged DM rate with modern RT. The 1, 2, 3-year LRC was 80.9%, 75.6% and 73.4% in the 2D/3D era compared to 89.7%, 85.2% and 84.3% in the IMRT era, maintaining a ~10% absolute gain. The 1, 2-year DM rates were 5.0% and 10.1% for 2D/3D vs. 6.0% and 9.6% for IMRT. And the 3-year DM rates were both 10.5%. The absolute increasement of 3-years OS was 4.9% (2D/3D: 79.5% vs. IMRT: 84.4%), and the gap narrowed to 2.3% at 5 years (2D/3D: 73.9% vs. IMRT: 76.2%). Regression analysis revealed a significant correlation between LRC an OS, the improved 2-year LRC correlated positively with 5-year OS (P = 0.002). However, LOESS regression unveiled a plateau trend: survival gains decelerated once 2-year LRC exceeded 85%. Mediation analysis confirmed that LRC’s impact on OS is primarily direct, it fails to improve OS through the reduction of DM. LRC and DM represent two parallel, independent risk factors.

Conclusion:

Modern IMRT has successfully maximized local control, yet the ~10% distant metastasis rate remains a non-negligible challenge. Given that LRC-driven survival gains reach a plateau at ~85% without reducing systemic risk, further local RT optimization may unlikely to yield proportional survival breakthroughs. Future research should shift from local intensification to systemic innovation—such as integrating immune checkpoint inhibitors—to achieve the next breakthrough in ASCC survival.