Main Session
Sep
29
PQA 06 - Genitourinary Cancer, Gynecological Cancer, and Health Care Access and Engagement
3304 - TP53 Mutation Status and Pathologic Lymph Node Involvement in Prostate Cancer: Implications for Elective Nodal Irradiation
Presenter(s)
Victor Lee, MD, BS - Yale New Haven Hospital, Middletown, CT
V. Lee1, S. Aneja2, Y. An1, B. A. McGibbon1, A. A. Patel3, S. M. McBride4, and J. J. Kang5; 1Department of Therapeutic Radiology, Yale School of Medicine, New Haven, CT, 2Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, CT, 3Yale University School of Medicine, New Haven, CT, 4Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, 5Memorial Sloan Kettering Cancer Center, New Haven, CT
Purpose/Objective(s):
Practice patterns regarding the selection of patients for elective pelvic lymph node irradiation (ENI) in prostate cancer remain variable and treatment decisions often rely on clinicopathologic nomograms with limited accuracy. Mutations in the tumor suppressor gene TP53 have been associated with advanced or metastatic prostate cancer. We hypothesized that TP53 mutations may also help identify patients at increased risk of occult nodal disease and may refine selection for ENI.Materials/Methods:
We analyzed clinical and genomic data from 351 patients with prostate adenocarcinoma from The Cancer Genome Atlas (TCGA) who underwent radical prostatectomy with pathologic lymph node (pN) evaluation. Patients were stratified by pathologic negative (pN0) or positive (pN+) nodal status. Associations between clinicopathologic variables and pN status were assessed using chi-square and t-tests. Multivariable logistic regression was performed to identify independent predictors of pN+ status, including clinical T stage, Gleason grade and TP53 mutation status.Results:
Among 351 patients, 66 (18.8%) had pathologic lymph node involvement. TP53 mutations were present in 59 (16.8%) of patients overall, and were significantly enriched in pN+ cases (31.8% pN+ vs 13.3% pN0, p=0.001). Higher Gleason grade and advanced pathologic T stage were also associated with pN+ (p<0.001). On multivariable analysis, TP53 mutation remained independently associated with increased odds of pN+ (OR: 2.52, 95% CI 1.30-4.85, p=0.006).Conclusion:
TP53 mutation is independently associated with pathologic lymph node involvement in prostate cancer and may serve as a genomic marker of occult nodal disease. Incorporation of TP53 status from diagnostic biopsy into risk stratification models could improve selection of patients for ENI, beyond conventional clinical parameters. This approach has the potential to personalize radiation field design and reduce both undertreatment of subclinical nodal disease and overtreatment in low-risk patients. Prospective validation is warranted.