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Background <p>Prostate cancer (PCa) has been considered an immunologically “cold tumor.” Indeed, in advanced PCa, immune checkpoint inhibitors (ICIs) and anti-tumor vaccines have shown poor results in phase II and III trials, with the exception of sipuleucel-T, which demonstrated a modest survival benefit. Radiotherapy and targeted radioisotopes—such as <sup>223</sup>Radium and <sup>177</sup>Lu-PSMA-617 monotherapy—have contributed to prolonging progression-free survival in PCa patients in second- or third-line settings. However, the potential benefits of combining these treatments with immunotherapies have been inconsistently investigated, and outcomes have often been conflicting.</p> Objective <p>The aim of this systematic review was to collect and analyze clinical evidence regarding the benefits and risks of combining ionizing radiation-based treatments with the main immunotherapies used in clinical and experimental oncology for metastatic PCa.</p> Methods <p>We conducted a systematic review according to PRISMA-ScR criteria, searching the PubMed, Web of Science, Embase, and Medline databases from February 2000 to April 2024. We included phase I to phase III clinical trials that combined radiotherapy with immunotherapy (RT/IT) in patients with metastatic PCa.</p> Conclusion <p>We found that the combination of ipilimumab with stereotactic body radiotherapy (SBRT) at a dose of 8 Gy, administered approximately 12 days (range: 2–21) before immunotherapy, was associated with trials showing a significant improvement in progression-free survival. Additionally, we observed better objective responses when immunotherapies were combined with SBRT compared to radionuclides. An exception was <sup>177</sup>Lu-PSMA-617, which demonstrated promising synergistic effects after a few cycles at standard doses, suggesting a potential enhancement of the immune response, particularly when combined with anti-PD1 therapy (pembrolizumab). However, due to the limited data available in the literature for both radiotherapy and radionuclides, future randomized trials are needed to confirm these findings.</p>

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Combinations of treatments based on radiotherapy or radionuclides to enhance immunotherapy efficacy in advanced prostate cancer: a systematic review

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年6月23日

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  • Roberto Rosenfeld,
  • Stefano Sganga,
  • Marco Badalamenti,
  • Sveva Mortellaro,
  • Marta Scorsetti,
  • Ornella Garrone,
  • Giovanni Maria Iannantuono,
  • Elias Chandran,
  • Michele Ghidini,
  • Ciro Franzese

摘要

Background

Prostate cancer (PCa) has been considered an immunologically “cold tumor.” Indeed, in advanced PCa, immune checkpoint inhibitors (ICIs) and anti-tumor vaccines have shown poor results in phase II and III trials, with the exception of sipuleucel-T, which demonstrated a modest survival benefit. Radiotherapy and targeted radioisotopes—such as 223Radium and 177Lu-PSMA-617 monotherapy—have contributed to prolonging progression-free survival in PCa patients in second- or third-line settings. However, the potential benefits of combining these treatments with immunotherapies have been inconsistently investigated, and outcomes have often been conflicting.

Objective

The aim of this systematic review was to collect and analyze clinical evidence regarding the benefits and risks of combining ionizing radiation-based treatments with the main immunotherapies used in clinical and experimental oncology for metastatic PCa.

Methods

We conducted a systematic review according to PRISMA-ScR criteria, searching the PubMed, Web of Science, Embase, and Medline databases from February 2000 to April 2024. We included phase I to phase III clinical trials that combined radiotherapy with immunotherapy (RT/IT) in patients with metastatic PCa.

Conclusion

We found that the combination of ipilimumab with stereotactic body radiotherapy (SBRT) at a dose of 8 Gy, administered approximately 12 days (range: 2–21) before immunotherapy, was associated with trials showing a significant improvement in progression-free survival. Additionally, we observed better objective responses when immunotherapies were combined with SBRT compared to radionuclides. An exception was 177Lu-PSMA-617, which demonstrated promising synergistic effects after a few cycles at standard doses, suggesting a potential enhancement of the immune response, particularly when combined with anti-PD1 therapy (pembrolizumab). However, due to the limited data available in the literature for both radiotherapy and radionuclides, future randomized trials are needed to confirm these findings.