Introduction:

The optimal management of high-risk, non-metastatic prostate cancer in men over 70 remains a clinical challenge. While observational studies often suggest a survival benefit for radical prostatectomy (RP) over primary radiotherapy with androgen deprivation therapy (XRT+ADT), these findings are susceptible to significant selection bias, often based on XRT patients’ older age. This study aimed to compare the effectiveness of these two primary treatment modalities on overall survival (OS) in a large, propensity score-matched cohort of elderly men with high-risk disease, and to evaluate the outcomes of different post-surgical pathways.

Methods:

Using the National Cancer Database (NCDB), we identified men aged ≥70 years with high-risk, non-metastatic (cN0/cM0) prostate cancer. High-risk disease was defined per NCCN criteria as clinical stage ≥cT3a, Gleason Grade Group 4–5, or PSA >20 ng/mL. Patients received either primary radical prostatectomy (RP) or definitive external beam radiotherapy with androgen deprivation therapy (XRT+ADT). Propensity score matching was performed to balance baseline patient and tumor characteristics. The primary endpoint was overall survival (OS), analyzed using the Kaplan-Meier method and multivariable Cox proportional hazards models to adjust for residual confounders. A secondary analysis compared OS across five distinct treatment pathways: RP alone, primary XRT+ADT, RP with salvage radiotherapy (sRT), RP with salvage ADT (sADT), and RP with both salvage modalities.

Results:

After matching, 32,753 patients were included (16,376 RP; 16,377 XRT+ADT). In the multivariable Cox model, treatment with XRT+ADT was associated with a significantly higher risk of all-cause mortality compared to RP (HR 1.13; 95% CI 1.08–1.18; p < 0.001). Compared to RP alone, primary XRT+ADT conferred a higher mortality risk (Adjusted HR 1.18), but this was superior to all salvage pathways. RP followed by sADT was associated with the worst survival (Adjusted HR 1.68; 95% CI 1.43–1.99; p < 0.001).

Conclusion:

In this large NCDB-based study of elderly men with high-risk prostate cancer, RP was associated with improved OS compared to primary XRT+ADT. However, the need for salvage therapy after surgery is a marker of aggressive disease and portends a worse prognosis than definitive primary radiotherapy. While likely influenced by selection bias, these findings suggest a potential survival benefit for well-selected elderly patients undergoing surgery and can help inform nuanced, shared decision-making conversations.

Funding: N/A