Our analysis of 68 NSCLC-derived ISCM cases with complete demographic and topographic data reveals key characteristics of this disease. ISCM exhibits a significant male predominance (male-to-female ratio of 4.2:1) with a mean age of 58.1 years (1, 9), consistent with our 72-year-old male patient; notably, males face double the mortality risk of females (10), potentially attributable to underdiagnosis in females due to more insidious presentations (9). Regarding risk factors, nicotine promotes brain metastasis in lung cancer (11), likely contributing to our heavy-smoking patient's primary and metastatic disease, although a direct nicotine-ISCM link remains unproven. Clinically, manifestations include pain, numbness/sensory deficits, weakness/paraplegia, sphincter dysfunction, incontinence, and gait disturbances, which may rapidly progress to complete paraplegia; while ISCM resembles epidural metastases clinically, it shows a higher frequency of Brown-Séquard syndrome (3).

In terms of affected segments, our analysis of these 68 cases solidifies cervical involvement (47.1%, 32/68) as the most common site, aligning with reports of cervical vulnerability (1, 9), challenging prior reports of thoracic predominance (12–15), followed by thoracic (25%, n = 17), lumbar (5%, n = 4), conus medullaris (7%, n = 5), and multisegmental involvement (>3 segments, 14%, n = 10). This distribution corroborates Kalayci's observation of infrequent multisegmental involvement (1) and is consistent with our patient, who had a cervical lesion spanning fewer than three segments. Regarding prognosis, among 60 patients with survival data, mean survival was 10.79 months for males vs. 6.69 months for females, with 47 deaths and 13 survivors; this apparent male survival advantage may reflect limited historical female sample size and improved outcomes from modern microsurgery/multimodal therapy, consistent with Wu et al.'s report of better overall survival in females experiencing post-treatment symptom improvement (10).

For imaging, MRI is the cornerstone diagnostic tool (16, 17), with gadolinium-enhanced MRI demonstrating high sensitivity (1, 3, 18, 19). When ISCM is clinically suspected, MRI of the entire spine should ideally be obtained within 24 h to localize the lesion and assess for multifocal disease. Immediate initiation of corticosteroid therapy is standard to mitigate cord edema, followed by definitive treatment (e.g., surgery or radiotherapy), which should also be pursued urgently, ideally within 24 h of confirmation, to preserve neurological function (20). Characteristically, ISCM exhibits peripheral rim or nodular enhancement (“rim sign” and “flame sign”)—key distinguishing features from primary tumors (21, 22)—alongside T2 hyperintensity, intense enhancement, small size relative to primary tumors, normal cord caliber, and disproportionate peritumoral edema (23), all features present in our case (Figures 1A,B). Finally, differential diagnosis requires distinction from: primary intramedullary tumors (e.g., ependymoma), which often cause symmetric fusiform expansion with slow growth and may show a “cap sign” [19]; and intradural extramedullary tumors (e.g., meningioma), which typically present with radicular pain, cause cord displacement with homogeneous enhancement, and may exhibit a “dural tail sign” (23).

Current therapeutic approaches include radiotherapy, chemotherapy, surgical resection, palliative care, and multimodal therapy. The optimal sequencing of therapies must be individualized and is heavily influenced by tumor histology and biology. For example, in highly chemosensitive, systemic diseases such as primary spinal Ewing sarcoma, upfront chemotherapy may be a viable and effective strategy to achieve neurological improvement, challenging a uniform surgical-first approach (24). In contrast, for metastatic ISCM from solid tumors like NSCLC, where rapid cytoreduction and decompression of a well-demarcated lesion are often the goals, surgical resection—as demonstrated in our case—provides immediate and frequently irreplaceable benefits. Among reviewed cases and our report: 16 received radiotherapy alone, 5 surgery alone. Combination therapies included: surgery + radiotherapy (9 cases), surgery + chemotherapy (3 cases), radiotherapy + chemotherapy (16 cases). Ten patients underwent multimodal therapy (surgery + radiotherapy + chemotherapy). Mean survival was: surgery alone 2.5 months, radiotherapy alone 5.8 months; combination therapy: surgery + radiotherapy 7 months, surgery + chemotherapy 15 months, radiotherapy + chemotherapy 11.8 months; Most compellingly, multimodal therapy (surgery + radiotherapy + chemotherapy) demonstrated superior survival over single/dual-modality approaches, with a mean survival of 24.6 months. Our patient's management trajectory—initial surgery followed by chemotherapy—reflects this combinatorial strategy. At 11-month follow-up, mild CEA elevation (5.23 ng/ml) prompted supplemental radiotherapy (40 Gy/20 fractions), yielding symptom stabilization and pain reduction. Radiotherapy typically halts tumor growth and stabilizes neurological decline (3, 6) but poses tolerance and myelotoxicity concerns in elderly patients. It remains a safe option for radiosensitive ISCM (e.g., small cell carcinoma, lymphoma). Surgery may benefit patients with favorable functional status, limited systemic disease, and good prognosis (6, 15, 25).

Systemic therapy, particularly modern systemic agents, plays a crucial and expanding role in the management of ISCM. In recent years, cancer pharmacotherapy has diversified significantly, with survival benefits now achievable not only through conventional cytotoxic chemotherapeutic agents but also via molecularly targeted agents and immune checkpoint inhibitors. For the management of ISCM secondary to advanced NSCLC, cisplatin combined with pemetrexed represents the well-tolerated and conveniently administered first-line treatment (26). Additionally, molecularly targeted drugs offer three main options: agents targeting the epidermal growth factor receptor (EGFR) mutation (osimertinib, afatinib, gefitinib), which have demonstrated efficacy against NSCLC-associated ISCM (27–29); ALK inhibitors (e.g., ceritinib, lorlatinib) that readily penetrate the blood-brain barrier (30, 31); and immune checkpoint inhibitors targeting PD-L1. Notably, approximately 25%–36% of NSCLC tumors express PD-L1 (32), and nivolumab, which inhibits PD-L1, has been established for NSCLC treatment, representing a potential option for patients with asymptomatic small solitary ISCM (33, 34). In our reported case, favorable maintenance was achieved using sustained pemetrexed combined with nedaplatin, which exhibits lower nephrotoxicity than cisplatin.

Our experience, consistent with the literature, positions surgical intervention as a cornerstone in the modern, multimodal management of select patients with ISCM. The rationale for surgery is threefold and often irreplaceable by other modalities. First, and most critically, maximal safe resection provides the most immediate and effective decompression of the spinal cord, rapidly halting neurological deterioration and creating the optimal environment for potential recovery. This is paramount in the cervical region, where the risk of catastrophic quadriparesis is high (6, 15, 35). Second, surgery offers a definitive histopathological diagnosis, which is crucial for guiding subsequent systemic therapy, especially in the era of targeted agents and immunotherapy (9). Finally, surgical cytoreduction can enhance the efficacy of adjuvant therapies by reducing tumor burden.

Evidence increasingly supports this aggressive approach. As demonstrated in our case and corroborated by literature, surgery can maintain or improve neurological function and is associated with superior survival outcomes compared to conservative management. For instance, Kalayci et al. (1) reported a mean survival of 9.4 months with surgery vs. 5 months without, while Dam et al. (6) found a median survival of 7.4 months with surgery compared to 2.6 months without. Notably, ISCM from NSCLC appears to be more frequently amenable to surgical resection than from SCLC (10), and satisfactory functional outcomes are achievable (15, 35, 36). In our patient, who underwent C6-T1 laminectomy and microsurgical resection, the advantages of neural tissue decompression, tumor burden reduction, and symptom alleviation were clearly demonstrated, with preserved ambulatory function at follow-up.

From a technical spine surgery perspective, the choice of procedure, such as the laminectomy for posterior access, must be tailored to the lesion. The universal imperative is the utilization of microsurgical techniques to achieve precise dissection at the tumor-spinal cord interface. The use of intraoperative neuromonitoring is strongly advocated to maximize the safety of resection within these eloquent neural tissues.

Patient selection is the keystone of success. The ideal candidate, as exemplified by our 72-year-old patient [who, contrary to some older recommendations (13), benefited significantly despite his age], typically presents with a well-demarcated, solitary metastasis, preserved preoperative neurological function (e.g., ASIA Grade D), and controlled systemic disease. Surgery is also a primary option for radio-resistant tumors or after radiotherapy failure (9, 35). Conversely, it is generally not advised for patients with multisegmental involvement (12), widespread systemic metastases, or a nonfunctional preoperative status (13).

It is important to acknowledge the ongoing debate and the limitations of surgery. Some studies indicate a minimal impact of surgery on postoperative survival (15, 25, 37), highlighting that the decision to operate must be made on a case-by-case basis within a multidisciplinary framework. Furthermore, for large, symptomatic ISCMs carrying a risk of subsequent hemorrhage, microsurgical resection can serve a preventive role, mitigating the risk of rebleeding and sudden neurological deterioration (36).

Lung cancer causes 56% of intramedullary metastases. The median interval from primary diagnosis to metastasis is 6 months. Rising ISCM incidence underscores the importance of early diagnosis/treatment for neurological preservation. Gross total resection may be considered for patients with rapid neurological decline, suitable characteristics, and a well-demarcated focal mass (37). Multimodal therapy improves survival over monotherapy (38). ISCM management depends on primary tumor histology, extracranial spread, treatment strategies, and patient condition. Treatment must be individualized, requiring comprehensive assessment of clinical, radiological, and pathological factors.