Long-term survival in a case report with metachronous quadruple primary malignancies involving multiple organ systems

Quadruple metachronous primary malignancies are extremely rare, and combinations involving digestive, hematologic, and genitourinary systems have scarcely been reported. This case contributes to the literature by illustrating the diagnostic complexity, therapeutic decision-making, and long-term survival achievable through comprehensive, sequential multimodal management. A 67-year-old man presented with throat discomfort and hoarseness, leading to a diagnosis of hypopharyngeal squamous cell carcinoma treated surgically followed by radiotherapy. Two years later, surveillance imaging revealed gastric wall thickening, and biopsy confirmed diffuse large B-cell lymphoma, achieving complete remission after R-CHOP and gastric radiotherapy. Persistent elevation of prostate-specific antigen prompted repeated biopsies, ultimately diagnosing high-risk prostate adenocarcinoma managed with external-beam radiotherapy and androgen-deprivation therapy, resulting in a complete biochemical response. Subsequently, new-onset sore throat led to identification of oropharyngeal squamous cell carcinoma, treated with chemo-immunotherapy and palliative radiotherapy, achieving a durable partial response. The patient has survived 11 years since the initial diagnosis. This case underscores the importance of vigilant long-term surveillance, accurate differentiation of recurrence from new primaries, and individualized multimodal treatment. Multidisciplinary coordination plays a key role in optimizing outcomes in patients at risk for multiple primary cancers.