Unexpected Long-Term Survival and Downstaging in Oligometastatic Non-Small Cell Lung Cancer Treated with Multimodal Therapy

Abstract

Background: Advances in the treatment of non-small cell lung cancer in the last 5 years (new techniques in radiotherapy, including stereotactic ablative radiotherapy, new targeted therapies and advances in immunotherapy) have increased the survival rates of patients diagnosed with this disease. Methods: Our study refers to a patient diagnosed in July 2017 with stage IV A lung cancer, cT3 N3 M1b (poorly differentiated adenocarcinoma, EGFR, ALK and PDL 1 negative), who underwent five lines of treatment and who has, at the time of writing this article (March 2025), a very good performance status, currently undergoing maintenance chemotherapy. Results: The results obtained confirm the revolutionary role of immunotherapy, but also the importance of chemotherapy and external radiotherapy, suggesting the synergistic effect between these three therapies. We also performed a literature review, highlighting the resistance to immunotherapy, rechallenge with immunotherapy, progression of metastatic NSCLC after first-line chemo-immunotherapy and the role of chemotherapy in line II and III after progression of NSCLC to immunotherapy. Conclusions: Results of studies evaluating new agents and their combinations, along with analysis of the mechanisms of evolution of primary and acquired resistance to immunotherapy are awaited, with the aim of selective and personalized treatment options to improve the survival and the quality of life for this category of patients.

Keywords: chemo-immunotherapy; long-term survival; metastatic non-small cell lung cancer; multiple therapeutic lines; radiotherapy.

Figure 1

PET CT. (a) T—spiculiform LSD tumor formation of 44 × 57 × 63 mm with SUV = 12.59, with central necrosis; (b) the tumor invades the superior apical and mediastinal pleura; (c) N—metabolically active mediastinal ADP with SUV max = 7.43 located in the Ao-pulmonary window (14 × 9 mm), (d) infracarinal (12.8 mm) and bilateral hilar (right maximum 21 × 16 mm and left maximum 11 × 7 mm); (e) M—metabolically active focus with SUV = 5.6 right humeral head, which corresponds to a small interruption of the bone cortex.

Figure 2

(a–e) PET CT reevaluation.

Figure 3

(a,b) Stable disease after 6 months of Nivolumab.

Figure 4

Progression after 23 months of Nivolumab.

Figure 5

Progression of the disease: (a) Thoracic CT hilar nodes; (b) mediastinal nodes.

Figure 6

(a,b) Reevaluation CT from 02/11/2020 vs. CT from 04/2020.

Figure 7

(a–c) Reevaluation of PET CT from 11/17/2021 vs. PET CT from 03/2018.

Figure 8

(a,b) CT reevaluation from 23/09/2022 vs. 06/2022.

Figure 9

(a,b) CT from 30/03/23 vs. CT from 09/2022: DISEASE PROGRESSION (primary tumor growth by 22.32%: 33 × 51 × 53 vs. 24 × 46 × 40 mm).

Figure 10

(a–d) PET CT from 06/14/2023 vs. PET CT from 11/2021: disease progression (primary tumor growth by 31.83%: 42 × 40 vs. 28 × 34.2 mm) and metabolic progression at SUV = 15.13 vs. 5.7; dimensional and metabolic regression on bilateral hilar lymph nodes (14 vs. 15.1 mm; SUV = 5.52 vs. 10.88), dimensional and metabolic progression of infracarinal lymph node (29 vs. 12 mm; SUV = 8.48 vs. 5.95 at PET CT from 03/2018, because they are not described at PET CT from 11/2021), without pathological uptake at the level of the scanned bone segments.

Figure 10

(a–d) PET CT from 06/14/2023 vs. PET CT from 11/2021: disease progression (primary tumor growth by 31.83%: 42 × 40 vs. 28 × 34.2 mm) and metabolic progression at SUV = 15.13 vs. 5.7; dimensional and metabolic regression on bilateral hilar lymph nodes (14 vs. 15.1 mm; SUV = 5.52 vs. 10.88), dimensional and metabolic progression of infracarinal lymph node (29 vs. 12 mm; SUV = 8.48 vs. 5.95 at PET CT from 03/2018, because they are not described at PET CT from 11/2021), without pathological uptake at the level of the scanned bone segments.