EPSCC is a rare, aggressive malignancy that originates outside of the lungs, yet shares histopathological features with small cell lung carcinoma (SCLC). This tumor typically demonstrates a high propensity for early metastasis, often to the liver, bones, and brain. The exact molecular mechanisms driving EPSCC are not fully understood, but like its pulmonary counterpart, it is associated with mutations in tumor suppressor genes such as p53 or RB1, leading to uncontrolled cellular proliferation and resistance to apoptosis. This cancer type commonly presents at advanced stages with a high potential for metastasis, particularly to distant organs such as the liver, bone, and brain. Among the various sites of metastasis, bone involvement is a significant factor that adversely impacts prognosis, contributing to both morbidity and mortality. The presence of bone metastases in EPSCC patients is associated with a poor overall survival rate, as these lesions often cause severe complications such as pain, fractures, and spinal cord compression. Recent studies indicate that survival rates are drastically reduced for patients with extrapulmonary small cell cancer that has spread to bone, with a 1-year survival rate often falling below 50% due to the rapid disease progression [5].

The treatment of EPSCC with bone metastasis is challenging, as the disease's aggressive nature makes it less responsive to conventional therapies. A combination of systemic chemotherapy, localized radiotherapy, and supportive care forms the cornerstone of the treatment plan. Chemotherapy regimens that include agents like etoposide and cisplatin or carboplatin are standard and typically offer modest benefits in terms of disease control. However, these therapies are often palliative rather than curative, and long-term survival remains rare. The use of radiotherapy, particularly for bone lesions causing pain or neurological complications, can provide some symptomatic relief and improve the quality of life, but it does not significantly alter the course of the disease [6]. In some cases, the addition of targeted therapies, such as immune checkpoint inhibitors, is being investigated, although results have been mixed, and further studies are necessary to establish their role.

The prognosis for patients with extrapulmonary small cell cancer and bone metastasis remains poor, with median survival times generally ranging from 6 to 12 months. Early diagnosis and aggressive treatment can improve survival slightly, but the prognosis is heavily influenced by the extent of metastasis, the patient's overall health, and the response to initial therapy. Some studies have suggested that patients who respond well to chemotherapy can live longer, but these individuals still face high recurrence rates and rapid progression upon relapse. For example, a study by Tokito found that while chemotherapy could extend survival in a subset of patients, the median survival for those with metastatic EPSCC involving bone was still under a year, with many patients experiencing deterioration within the first few months following treatment [7].

In light of the poor prognosis, treatment strategies for EPSCC with bone metastasis increasingly focus on improving quality of life and providing palliative care. For instance, bisphosphonates or denosumab, which inhibit bone resorption, are sometimes used to manage bone complications and reduce the risk of skeletal-related events (SREs) like fractures. These interventions may alleviate some of the symptoms associated with bone metastases, such as pain and hypercalcemia, thereby improving the patient’s quality of life. Despite the lack of curative treatments, ongoing research into molecular targets and novel therapies, including immunotherapy and combination approaches, offers hope for better outcomes in the future [8]. However, until more effective therapies are identified, the treatment course for patients with EPSCC and bone metastasis will largely be supportive and focused on symptom management, with survival remaining limited.