The addition of immunotherapy to platinum plus etoposide chemotherapy as a first-line treatment for ES-SCLC represents a major breakthrough for this exceptionally lethal disease, resulting in a ~10% increase in progression-free survival and OS compared with standard treatment [8]. This case illustrates the degree of benefit that can be achieved with this approach, where the patient received atezolizumab for ~12 months and PR was maintained for more than 6 years, with manageable toxicity.

Long-term survival rates have been reported with PD-L1 inhibitors in clinical trials; the 18-month OS rate in the atezolizumab arm of the IMpower133 study was 34.0% [9], and the 5-year exploratory OS rate from a merged analysis of IMpower133 and the single-arm IMbrella A extension study was 12% [10]. Further, the 36-month survival rate with durvalumab in the CASPIAN study was 17.6% [11]. Although in these studies patients continued PD-L1 inhibitor treatment until disease progression, the patient reported here, who was enrolled in IMpower133, discontinued atezolizumab due to toxicity but maintained his initial response without progression.

Ours is not the first case report of a patient with ES-SCLC achieving long-term survival gains after immune checkpoint inhibitor (ICI) therapy. Zhang and colleagues reported a patient with ES-SCLC who survived for 50 months after treatment with sequential ICIs, including toripalimab, tislelizumab and durvalumab [12]. However, unlike our patient, this patient was continuously treated during periods of disease stability until progression. Konishi and colleagues reported a patient who received atezolizumab (along with etoposide plus platinum) for 6 months and was still alive 35 months later [13]. However, that patient received radiotherapy for chylothorax, followed by chemotherapy with nogitecan and then amrubicin after progression [13], whereas our patient received no further treatment after discontinuation of atezolizumab. Although the optimal duration of maintenance therapy with atezolizumab is not known, it is possible that our patient belongs to a subgroup of individuals in whom several months of such treatment results in sustained disease control. Further research is needed to identify biomarkers (or other factors) that may help characterise and define the subgroup of patients who can safely discontinue atezolizumab, and to determine the optimal duration of atezolizumab maintenance therapy.

Of potential prognostic importance is the patient’s early tumour response, since early tumour shrinkage/response is associated with improved survival in patients with ES-SCLC [14,15,16], although our patient also had a number of characteristics that could have contributed to his long-term survival, including age < 65 years [17, 18] and good performance status [16, 19,20,21,22,23]. Further, his neutrophil-to-lymphocyte ratio (2.05) was consistent with that considered to be prognostic for better survival (a ratio of ≤ 3.43), as reported in a study that investigated the prognostic role of inflammatory markers in patients with ES-SCLC who were treated with atezolizumab plus chemotherapy [24]. However, our patient also had risk factors for reduced survival, including male gender [16] and bone metastasis [17, 18].

Another potential indicator of prolonged survival in our patient was the development of immune-related adverse events, specifically immune-mediated hypothyroidism and nephropathy. It is possible that these treatment-related toxicities were connected to the patient’s exceptionally durable response to treatment since the development of such adverse events during immunotherapy is associated with improved survival in a range of cancer types, including lung cancer [25,26,27]. A pooled analysis of three phase III trials (IMpower130, IMpower132 and IMpower150) showed significantly prolonged survival in patients with non-small-cell lung cancer (NSCLC) who did versus did not develop immune-related adverse events with atezolizumab [28]. Further, immune-mediated thyroid dysfunction, which our patient developed, was associated with improved long-term survival in an analysis of patients with NSCLC receiving immunotherapy [29]. However, the relationship between survival and immune-related adverse events is less clear-cut in patients with SCLC. D’Aiello and colleagues found no relationship between immune-mediated thyroid dysfunction and survival in a mixed cohort of SCLC and NSCLC patients who were receiving immunotherapy [30], and two multicentre retrospective studies in SCLC patients, one conducted in Germany [31] and the other in the USA [27], reported conflicting results. The USA study found that immune-mediated adverse events were associated with significantly longer survival [27], whereas no such association was found in the German study [31]. Further data in larger patient cohorts are needed to clarify the relationship between immune-mediated adverse events and survival in patients with SCLC.

The limitation of this report is that inherent to all case reports, i.e., it is difficult to make generalisations or draw firm conclusions from observations of a single patient. In addition, next-generation sequencing was not undertaken, so genomic information potentially relevant to his survival status was not collected. Further, there is a possibility that the persisting changes we observed on CT were indicative of inflammation rather than persisting tumour; however, we were not able to confirm this. The strengths of our report include the good availability of clinical, laboratory and imaging data for the patient because the patient had participated in a clinical trial where regular and thorough assessments were made during trial visits.