Clinical and Genomic Characterization of Secondary Rectal Cancer After Radiotherapy for Prostate Cancer.

Area of Science:

• Oncology
• Genetics
• Radiation Oncology

Background:

• Radiotherapy (RT) for prostate cancer (PC) increases the risk of secondary rectal cancer (SRC).
• SRC presents unique challenges in treatment and outcomes compared to primary rectal cancer (PRC).

Purpose of the Study:

• To compare the molecular profile, clinical characteristics, and oncologic outcomes of SRC after PC with those of PRC.
• To identify differences that could inform clinical management strategies for SRC.

Main Methods:

• A case-control study comparing SRC and PRC patients treated between 1994 and 2022.
• Analysis of clinical data and DNA sequencing (targeted and whole-exome) to assess tumor profiles.
• Statistical comparison of oncologic outcomes using log-rank tests and Cox regression models.

Main Results:

• SRC patients had more distal and anterior tumors, received less neoadjuvant treatment, and exhibited shorter overall and disease-free survival than PRC patients.
• SRC tumors showed lower mutational burden, fewer APC alterations, and higher SMAD4 inactivation rates.
• Whole-exome sequencing revealed a higher rate of frameshift deletions in SRC tumors.

Conclusions:

• Secondary rectal cancer following prostate cancer radiotherapy has distinct clinical and molecular characteristics.
• Patients with SRC demonstrate worse survival outcomes compared to patients with PRC.
• These findings underscore the need for tailored management approaches for SRC.