Androgen Deprivation Therapy (ADT) triggers thymic revitalization and increases thymic output, enhancing baseline anti-tumor immunity and responses to immunotherapies. Anti-tumor synergism has been identified by combining ADT with anti-PD-1 immunotherapy for androgen-independent tumors. This study is to investigate the combination of Leuprorelin ADT and Sintilimab (anti-PD-1) therapy in patients with advanced lung cancer.

Immune checkpoint blockades (ICBs) are widely used in the clinical treatment of lung cancer. Studies have shown that the quantity and function of tumor-infiltrating lymphocytes (TILs) are associated with the effectiveness of PD-1 inhibitors in treating advanced NSCLC. The thymus is crucial for the differentiation, development, and maturation of T cells. With age, thymic atrophy leads to immunosenescence, significantly affecting baseline anti-tumor immunity and responses to immunotherapies. Preliminary findings have indicated that androgen deprivation therapy (ADT) not only directly induces apoptosis in prostate cancer cells but also may exert anti-tumor effects by promoting thymic regeneration. Furthermore, anti-tumor synergism has been identified by combining ADT with anti-PD-1 immunotherapy for androgen-independent tumors. Therefore, this study aims to investigate the combination of Leuprorelin ADT and Sintilimab (anti-PD-1) therapy in patients with advanced lung cancer.

3.Inclusion Criteria:

1. Male patients aged ≥60 years.

2. ECOG performance status score of 0 ~1.

3. Expected survival time of more than 3 months.

4. Histologically or cytologically diagnosed advanced lung cancer according to the TNM staging system established by AJCC.

5. Patients who have not previously received any anti-PD-1 treatment.

6. Patients with adequate bone marrow function, no significant hepatic, renal, or coagulation dysfunction as per laboratory test criteria.

7. At least one tumor lesion meeting the following criteria:

   • No prior local treatments such as radiotherapy
   • Not biopsied during the screening period (if biopsy needed, baseline tumor assessment at least 14 days after the screening biopsy).
   • Measurable at baseline (longest diameter of the lesion ≥10 mm; For a lymph node, short diameter ≥15 mm).
   • If only one measurable lesion, no prior local treatments such as radiotherapy.

8. Ability to understand and voluntarily sign a written informed consent form.

9. Willingness to follow the study protocol and follow-up examinations.

Exclusion Criteria:

• Exclusion of cases that do not meet the inclusion criteria

We currently do not plan to share individual patient data (IPD) with other researchers due to confidentiality concerns and ethical restrictions. Additionally, the data collected in this study are considered proprietary and are crucial for ongoing and future research projects.