S3035
Invited Speaker
ESTRO 2026
shown to prolong progression-free survival (PFS) compared with observation (11-13) or intermittent hormonal therapy (14). Recently, targeted radioligand therapy (TRT) with 177Lu-PSMA-617, which combines the beta-emitter Lutetium-177 (177Lu) with a ligand to prostate-specific membrane antigen (PSMA), has been shown to improve outcomes both before or after chemotherapy in metastatic CRPC and in orHSPC (8- 10, 15-17). Emerging preclinical and clinical evidence suggests that the combination of SBRT and TRT can produce synergistic effects, including increased DNA damage, inhibition of tumor repopulation, and improved radiosensitization of resistant tumor clones. Moreover, combined therapy may permit dose reduction in SBRT, thereby decreasing collateral damage to surrounding healthy tissues. The integration of TRT with SBRT represents a promising multimodal approach in oncology, aiming to enhance therapeutic efficacy while minimizing systemic toxicity (18). Radioligand therapy utilizes tumor-specific ligands labeled with radionuclides to selectively deliver cytotoxic radiation to malignant cells, whereas SBRT provides localized high-dose irradiation to tumor sites. This will prevent second-line treatments, such as long-term ADT and improve overall survival and quality of life (15). Current research focuses on optimizing treatment sequencing, radionuclide selection, and patient stratification to maximize therapeutic outcomes. This presentation highlights the mechanistic rationale, clinical potential, and challenges of integrating TRT with SBRT, underscoring the role of combined therapy, as a next-generation strategy in precision oncology. References: 1. Hamdy F (2023) N Engl J Med .389,92 2. Kerkmeijer LG (2021) J Clin Oncol .39,787-796 3. Murthy V (2021) J Clin Oncol .39,1234-1242 4. Zilli T (2022) Radiother Oncol .176,199-207 5. Cornford P (2024) Eur Urol .86,148-163 6. Moris L (2020) Eur Urol . 77, 614-627 7. Kamran SC, American Soc of Clinical Oncology 8. Tilki D (2024) Eur Urol .86,164-182 9. Ahmadi BJU Int .111,543-548 10. DaviesEur Urol Focus.5,147-154 11. Ost J Clin Oncol 36,446-453 12. Phillips R (2020), JAMA Oncol 6,650-659 13. Deek MP (2022) J Clin Oncol 40,3377-3382 14. Tang C (2023) JAMA Oncol 9,825-834 15. Alibhai SM (2015)Cancer.121,2350-2357 16. Sartor O (2021) N Engl J Med .385,1091-1103 17. Privé BM (2026)T he Lancet Oncology, 27,461-469 18. Kishan AU (2025) J Clin Onco l.43,3812-3821.
Advances in quantitative imaging, including AI-based partial-volume correction and improved SPECT/CT reconstruction, may enable the generation of quantitatively reliable, voxel-level TRT dose maps, a prerequisite for cross-modality integration into radiotherapy workflows. This would allow the calculation of biologically weighted composite dose distributions (e.g. EQD 2 ), enabling direct comparison with EBRT planning data. To illustrate these challenges and opportunities, meningioma represents a clinically relevant model for such combined approaches. These tumours frequently express somatostatin receptors and are treated with both EBRT and SSTR-targeted TRT. Here, EBRT provides homogeneous irradiation of the visible tumour, while TRT can complement this by targeting microscopic or infiltrative disease. Integrated dosimetry could enable adaptive treatment strategies, including cross-modality dose painting. In conclusion, combined EBRT–TRT strategies require a re-evaluation of dose comparability across modalities. Only by establishing biologically meaningful and comparable dose frameworks can these therapies be integrated into clinical treatment planning. 5423 Clinical rationale for combined therapies: The nuclear medicine physicians’ point of view Daniela E. Oprea-Lager Medical Imaging, Radboud University Medical Center, Nijmegen, Netherlands In patients with localized prostate cancer (PC), external beam radiation therapy (EBRT) offers excellent tumor control (1-3). In high-risk localized and oligometastatic PC, the initiation of a treatment with curative intent remains desirable. These patients can be treated with EBRT to the prostate, or oligometastatic lesions, with or without elective nodal radiotherapy (ENRT) and
androgen deprivation therapy (ADT) (4-6). Nevertheless, up to 50% of patients develop progressive disease within 5 years (7).
In patients with PC progression, the initiation of lifelong ADT is common practice. However, ADT is associated with side effects, including cardiovascular events, mood changes, weight gain, hot flashes, loss of libido, and erectile dysfunction (8-9). Furthermore, ADT is not a curative treatment; it merely puts active tumor cells into a resting phase rather than eliminating them, eventually leading to the development of castration- resistant PC (CRPC) (10). Therefore, it is essential to increase the curation chance for patients with high- risk localized and oligometastatic PC. In men with oligorecurrent (i.e., one to five lesions) hormone-sensitive prostate cancer (orHSPC), the use of stereotactic body radiotherapy (SBRT), has been
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