Cancer of unknown primary site

Cancer of Unknown Primary Site (Cancer of Unknown Primary Site)

1) Disease Description (Causes and Symptoms)

• Definition: A group of malignant tumors in which cancer has been confirmed by biopsy, but the primary site (where it first developed) cannot be identified despite all examinations. It is known to account for approximately 2–6% of all malignant tumors.
• Causes/Pathophysiology:
  • In most cases, no clear cause is identified. General risk factors for cancer development (smoking, infection, diet, obesity, etc.) may be involved.
  • Pathophysiologically, this refers to cases in which metastasis has already progressed and the primary tumor is small or has disappeared, or the primary site cannot be identified even through imaging or tissue examination.
• Main symptoms:
  • Painless lymph node enlargement (cervical, axillary, or inguinal)
  • Pleural effusion or ascites (shortness of breath, chest pain, abdominal distension)
  • Bone pain (pain due to bone metastasis, pathological fractures)
  • Weight loss, generalized weakness, and local symptoms depending on the site of occurrence, etc.

2) Treatment Methods

• Diagnostic approach first: After obtaining sufficient tissue (biopsy), identify the histologic subtype and treatment targets through immunohistochemistry (IHC), molecular genomic testing (gene panel), and, if necessary, electron microscopy.
• Local treatment:
  • Surgery: Limited use (when there is a localized lesion and surgery can achieve a cure)
  • Radiation therapy: Pain relief and control of local lesions (such as bone metastasis and brain metastasis)
• Systemic treatment:
  • Chemotherapy (standard anticancer therapy): Selected according to the stage and histologic type
  • Targeted therapy/immunotherapy: If molecular markers (e.g., EGFR, ALK, HER2, MSI, etc.) are identified, targeted therapy or immune checkpoint inhibitors may be used
  • Hormone therapy: Considered when tissue characteristics indicate it (e.g., findings suggestive of breast cancer, positive hormone receptors, etc.)
• Supportive and symptomatic treatment:
  • Pleural effusion/ascites: Chest tube insertion, thoracentesis, paracentesis, and pleurodesis when necessary
  • Bone metastasis: Analgesics, radiation, and bone-modifying agents (bisphosphonates or denosumab)
• Clinical trials: Because of the limitations of standard treatment, considering a clinical trial is recommended for individual patients
• Lifestyle management and precautions:
  • Side effects such as infection, bone marrow suppression, and weight changes need to be monitored during treatment
  • Management of fluid retention (pleural effusion and ascites), pain control, rehabilitation, and nutritional management should be carried out concurrently

3) Checkpoints Before an Outpatient Visit (Including Items to Bring and Records, and Sample Questions)

• Items/materials to bring:
  • List of currently taken medications (including prescription drugs, over-the-counter medications, and supplements)
  • Past medical history (history of other cancers and previous surgery, radiation, or anticancer treatment)
  • Recent test results (blood tests, biopsy reports, CT/MRI/PET-CT images and radiology reports)
  • Records of when symptoms began and how they have changed (weight changes, pattern and intensity of pain, shortness of breath, etc.)
  • Allergy history (medications, contrast agents, etc.)
• Items that are useful to record during the outpatient visit:
  • Frequency and intensity of current symptoms (pain score, shortness of breath, etc.)
  • Whether daily activities are limited
• Sample questions (questions to prepare in advance before the appointment):
  • Can I receive the recent test results, particularly the biopsy findings and molecular test results?
  • Please provide information related to when the recent symptoms worsened.

4) Examples of General Questions to Ask the Doctor

• "What is the histologic subtype suspected based on the current biopsy results?"
• "What is the purpose and expected benefit of the additional tests you recommend (e.g., a gene panel or PET-CT)?"
• "Is the goal of treatment to cure the disease or to relieve symptoms (prolong survival)?"
• "What are the main side effects of each treatment, and how can they be managed?"
• "Is participation in a clinical trial possible, or are there any suitable studies?"

5) Examples of Disease-Specific Questions

• "Based on the immunohistochemical findings from the biopsy (e.g., CK7/CK20, TTF-1, ER/PR, etc.), which primary site is suspected?"
• "If a specific driver mutation is found on molecular panel testing, which targeted therapy options would you consider first?"

Additional Reference (Key Points Related to Testing and Prognosis)

• Imaging tests: The probability of identifying the primary site with PET-CT has been reported to be approximately 20–30%.
• Factors affecting prognosis: The patient's overall condition (PS), histopathologic subtype, extent of metastasis, response to treatment, etc. Some patients may achieve long-term survival through treatment, but in cases of multiple metastases, the effectiveness of treatment may be limited.

(This information is for general guidance only. Individual diagnosis and treatment decisions should be made in consultation with qualified medical professionals.)