Senior Director, Surgical Oncology, Fortis Hospital, Vasant Kunj, New Delhi
Part 10 of 10 in When to Suspect Cancer and How to Refer
Cancer of Unknown Primary: How Doctors Find the Source
January 25, 2026
Sometimes a patient presents with metastatic cancer in an organ, but the original site of the disease is not obvious. Dr. Shubham Jain describes how a cancer of unknown primary is worked up, including when only liver metastases or oligometastases are present.
A structured workup, even without an obvious primary
The first step is a PET scan, to confirm there is no other site of disease elsewhere in the body. Pathology colleagues then perform immunohistochemistry on the biopsy sample, which can give clues to where the cancer is likely arising from. Based on these results, doctors move to directed and targeted imaging, for example endoscopy for a suspected upper gastrointestinal origin, or detailed imaging and cystoscopy for a suspected genitourinary origin.
Treatment even when the primary is never found
Dr. Jain notes that many times, despite this workup, the primary site is never identified. Where only liver metastases are present, treatment begins with palliative intent using chemotherapy. Depending on how the patient responds, and their performance status, a curative approach involving surgery may later be attempted, though this cannot be assured to the patient in advance.
A related diagnostic pitfall: biopsy can overturn the clinical picture
Dr. Jain illustrated this with a patient from Tanzania who arrived with widespread lymphadenopathy that looked clinically like lymphoma. A biopsy from one of the lymph nodes instead came back as neuroendocrine carcinoma, completely changing the diagnosis and opening different treatment options, a reminder that clinical impression alone is not sufficient before a biopsy is done.
This article is based on a Jivo Masterclass session conducted by Dr. Shubham Jain, Senior Director, Surgical Oncology, Fortis Hospital, Vasant Kunj, New Delhi. The article has been summarised with the assistance of an AI tool from the original masterclass recording. Watch the full Masterclass recording
Looking for a diagnosis or a second opinion for a complex cancer case? Get in touch with the Jivo team
This guide is based on a live Jivo Masterclass — Dr. Shubham Jain taught doctors across Africa on January 25, 2026.
FROM THE LIVE Q&A
Dr. Ali (Ethiopia)
How do you see complications from radiotherapy on the left side of the chest?
Dr. Shubham Jain
The most common complication with radiotherapy for left-sided breast cancers is cardiotoxicity. Radiation oncologists manage this with deep inspiratory breath-hold and gating techniques, training the patient to hold their breath during the active phase of radiotherapy so toxicity to the heart is reduced, chest wall motion is reduced, and radiation is delivered accurately to the target volume. More precise machines such as IGRT and 4D-CRT are also improving precision for left-sided breast and chest wall tumours.
Frequently Asked Questions
Which cancers have patient assistance programmes, and how do they work, and who is eligible?▼
Until very recently, patient assistance programmes for targeted therapy and immunotherapy were only available to Indian patients. Because these drugs are costly, companies assist with procuring them at up to a half or a third of the usual cost, which is out of reach for many domestic Indian patients too because of regulations. These regulations are now relaxing, and more international patients are able to receive the benefit of these programmes.
On the slide about smokers, it said 20 packs. Does that mean 20 packs smoked per day?▼
Not 20 packs per day, that would be 400 cigarettes a day, which is not possible. Pack-years is the number of packs smoked per day multiplied by the number of years smoked. Two packs a day for ten years makes 20 pack-years, as does one pack a day for twenty years, or half a pack a day for forty years.
How should a doctor practising in a resource-constrained setting, without enough diagnostic facilities to screen large populations, know which symptoms genuinely warrant referral and which could be a false alarm?▼
Any suspected cancer requires resources for investigation and treatment, so it should be evaluated at a good high-volume centre that gives the best chance of cure. It is difficult to assess the outcome or treatment at an initial stage, so the primary reliance has to be on the clinical signs and symptoms already discussed, which are the basis for suggesting a patient be evaluated at a high-volume centre.
Can you tell us something about malignant wounds?▼
A malignant wound anywhere needs to be confirmed on biopsy to establish the exact reason for it, and it should not be expected to heal on its own. It should be subjected to a biopsy to confirm the nature of the malignancy and the treatment options, with appropriate imaging to understand the underlying structures involved, and surgery offered if the wound is resectable.
A patient had laryngeal cancer and surgery affected his voice box. He wants an aid to help him use his voice but does not want an invasive procedure. Are there any options available for him?▼
Yes, definitely. An electrolarynx is an external prosthesis: once the device is attached to the skin it creates vibrations at high speed and the patient can vocalise using it.
How do doctors find the primary source when only liver metastases are found?▼
A PET scan first confirms there is no other site of disease in the body. Immunohistochemistry on a biopsy sample then gives clues to the likely origin, guiding directed and targeted imaging such as endoscopy or cystoscopy depending on the suspected site.
What happens if the primary cancer site is never identified?▼
Treatment can still proceed. Where only liver metastases are present, it typically begins with palliative chemotherapy, and depending on the patient’s response and performance status, a later curative approach involving surgery may be attempted.
In This Series: When to Suspect Cancer and How to Refer
- 1.When to Suspect Cancer and How to Refer
- 2.Breast Lump Assessment: Why Triple Assessment Comes Before a Diagnosis
- 3.Breast Cancer Screening: Mammography Guidelines and How to Prepare Patients
- 4.Persistent Hoarseness and Laryngeal Cancer: Warning Signs and Voice Rehabilitation
- 5.Persistent Cough and Lung Cancer: Warning Signs and Low-Dose CT Screening
- 6.Abdominal Bloating and Ovarian Cancer: Warning Signs and the Role of CA-125
- 7.Abnormal Vaginal Bleeding: Endometrial Cancer, Cervical Cancer and HPV Vaccination
- 8.Bowel Habit Changes and Colorectal Cancer: Colonoscopy Screening Guidelines
- 9.Common Myths About Cancer Diagnosis and Treatment
- 10.Cancer of Unknown Primary: How Doctors Find the Source