After a Suspected Cancer Referral: Biopsy and Treatment

After a suspected cancer referral, the treating oncologist decides whether, how and where to take a biopsy, confirms the type of cancer and plans treatment. Dr. Shubham Jain, Senior Director Surgical Oncology, Fortis Cancer Institute, Defence Colony, New Delhi, India, stresses that a biopsy planned and performed correctly does not spread cancer, and that many patients referred in time can now be offered curative treatment.

This article follows the patient past the point of referral: how the diagnosis is confirmed, what to do when biopsy reports are slow, how doctors search for an unknown primary cancer, and the treatment options Dr. Jain describes at a high-volume centre. Which symptoms should prompt referral in the first place is covered in the complete guide to when to refer suspected cancer.

Does a biopsy spread cancer?

No. Many patients hesitate to have a biopsy because they believe it will cause the cancer to spread, and Dr. Jain hears this fear across countries, India included. His answer is unequivocal: if the biopsy is planned correctly and performed correctly, it will not lead to any spread of cancer. He calls the biopsy one of the most crucial tests a cancer patient needs to have, and the fear that it spreads cancer, in his view, the most important myth to dispel. A biopsy is how the type of cancer, and therefore the treatment, is established; a patient who refuses it delays the test that, in most cases, confirms what is wrong. Dr. Mohit Agarwal addresses the same myth, alongside staging, in his article on biopsy and staging myths.

Why the oncologist, not the referring doctor, should plan the biopsy

A biopsy sits between two extremes. At one end, some cancers do not always need tissue confirmation before treatment: Dr. Jain gives liver and kidney cancers as examples. A liver cancer arising in a cirrhotic liver, for instance, can often be diagnosed on the characteristic pattern of contrast-enhanced imaging. At the other end, a biopsy that is not planned or performed properly can do the patient more harm than good. A needle or incision track placed without regard to the operation that will follow can complicate the eventual surgery.

For that reason Dr. Jain does not ask primary care doctors to obtain a biopsy before referral. One imaging test of the area of concern is the essential first step; the decision on whether, how and where to take tissue is best left to the treating oncologist.

When biopsy results take too long: FNAC and frozen section

Slow pathology is a real constraint, and not only in Africa. Dr. Jain has worked across India and notes that in parts of its north-east, biopsy processing times are also long. Clinicians facing those delays have found two workarounds:

• Relying more on fine needle aspiration cytology (FNAC). FNAC draws cells, rather than a core of tissue, through a thin needle. It is not the recommended approach and not the best strategy, but in select situations, where a patient cannot stay in one place for a prolonged period while waiting for a diagnosis, treatment decisions can be based on an FNAC.
• Using a frozen section facility. Frozen section is a rapid technique in which tissue is frozen, cut and examined within minutes, typically during an operation. It gives some confirmation very quickly, but it is resource-intensive and is usually available at high-volume centres that treat cancer patients routinely.

Short of these, his advice is to refer a patient with suspected cancer to an oncologist, who can guide whether a biopsy is needed and where it should be taken from for the best result.

When the biopsy overturns the clinical diagnosis

Dr. Jain illustrates why clinical findings alone are not enough with a recent case: a severely emaciated patient from Tanzania with a very large abdominal mass. The doctors at home suspected lymphoma but had not performed a biopsy because the patient was so wasted. On examination in New Delhi, the patient had generalised lymphadenopathy (enlarged lymph nodes throughout the body), which also pointed towards lymphoma. A biopsy of one of the lymph nodes then showed a neuroendocrine carcinoma, a different cancer altogether. The result turned the clinical diagnosis on its head and opened a range of treatment options for the patient.

The lesson he draws is that even specialists find it difficult to predict a diagnosis or outcome from the history and examination alone. The basic workup for most patients stays the same: one imaging test that addresses the area of concern, and a biopsy where it is feasible.

How doctors approach cancer of unknown primary

Cancer of unknown primary is the situation in which metastatic deposits are found in an organ, such as the liver, but the cancer they came from cannot be identified. Dr. Jain calls it a very tricky situation and described his approach to a patient with liver metastases only:

1. PET imaging first, to be sure there is no other site of disease elsewhere in the body.
2. Immunohistochemistry on the biopsy. These stains, applied by the pathologists, can give clues to where the cancer is arising.
3. Directed, targeted investigation based on those clues: endoscopy if the pathology suggests an upper gastrointestinal origin, and detailed imaging and the relevant endoscopic examinations if it suggests the genitourinary tract.

Often the primary is never found. With metastases confined to the liver, treatment starts with chemotherapy, with palliative intent. If the patient benefits very well and his or her general condition improves, the team may then attempt a curative approach, which may involve surgery. That step depends on the patient's performance status, how the disease responds, and the patient's understanding that it can be attempted but nothing can be guaranteed.

How to manage a malignant wound

A wound suspected of being malignant should not be expected to heal on its own. Dr. Jain's sequence is:

1. Biopsy, to confirm the nature of the malignancy and the treatment options.
2. Imaging, to understand the underlying structures involved.
3. Surgery, if the ulcer is resectable, depending on the patient's condition.

The second myth: cancer is the patient's fault

Many patients believe their cancer was caused by their diet or habits. Until not long ago, Dr. Jain notes, clinicians themselves attributed most cancers to indulgences such as tobacco and alcohol. Tobacco, alcohol, diet and other modifiable factors do account for an estimated 30 to 50% of cancers, but many cancers arise from ageing, genetics or environmental exposure without anything the patient did. Blame helps no one, and destigmatising them matters clinically: stigma is what keeps people from seeking treatment in time.

After a suspected cancer referral: treatment options at a high-volume centre

Dr. Jain described the advances in surgery and supportive care that now make curative treatment possible for many patients who are referred in time.

Breast cancer surgery: conservation, oncoplasty and the axilla

Breast conservation surgery, which removes the cancer while preserving the breast, is routinely discussed with patients who have early breast cancer, including small ductal carcinomas, and should be offered wherever it is feasible. It brings a definite cosmetic advantage, but two conditions apply: it must be followed by radiotherapy, and strict criteria, based on imaging and the patient's family history, must be met before it is offered. Combined with oncoplasty, the surgical techniques that reshape the breast and position the scars, the cosmetic result is better than conservation surgery alone. Whole breast reconstruction is another option. Costs are listed on the breast cancer surgery cost page and the breast reconstruction cost page.

For the armpit, Dr. Jain's team offers:

• Sentinel lymph node biopsy: removing only the first lymph node or nodes that drain the tumour. A tracer injected beforehand makes the node detectable, and in the operating theatre a handheld probe registers a high count over the node, confirming that the sentinel node is in the specimen.
• Lymphovenous anastomosis: joining lymphatic channels to small veins, a technique used to reduce the risk of arm swelling (lymphoedema).
• Axillary reverse mapping: identifying the lymphatics that drain the arm so they can be preserved.

For women having a prophylactic (preventive) mastectomy, or a mastectomy for a very early cancer, robotic mastectomy with immediate breast reconstruction is also available.

Checking response to chemotherapy before surgery

Locally advanced breast cancer is often treated first with neoadjuvant chemotherapy (chemotherapy given before surgery). Patients usually notice the response themselves, as the lump shrinks or the skin changes improve. To confirm the response objectively, the imaging done before chemotherapy, whether ultrasound or CT, is repeated. Surgery remains an integral part of treatment: without it, in Dr. Jain's words, the treatment is simply palliative, so such a patient should be assessed by a surgeon who can offer the operation.

Protecting the heart during left-sided radiotherapy

The complication of greatest concern in radiotherapy for left-sided breast cancers and chest wall tumours is cardiotoxicity, damage to the heart. Radiation oncologists reduce it with deep inspiration breath-hold and gating: the patient is trained to hold the breath during the active phase of treatment, which moves the heart away from the beam, reduces chest wall motion and lets the radiation reach the planned target accurately. More precise machines and techniques, such as image-guided radiotherapy (IGRT), are adding further precision. Costs are on the radiotherapy cost page.

Robotic lobectomy for lung cancer

Lung cancer detected in time can be treated with surgery. Dr. Jain showed a robotic lobectomy, in which the affected part of the lung is removed through minimal access using robotic technology. It is indicated for various lung cancers he sees commonly, and patients recover from it very quickly and resume their normal activities.

Cytoreductive surgery and HIPEC for pseudomyxoma peritonei

Some patients with abdominal bloating have pseudomyxoma peritonei, known as "jelly belly", in which a jelly-like material fills the abdomen. It responds very well to cytoreductive surgery, which removes all visible disease, combined with hyperthermic intraperitoneal chemotherapy (HIPEC), chemotherapy delivered into the abdomen during the operation. Because the chemotherapy is heated, it penetrates better, and cure rates are much better. Many of these patients were once considered inoperable and untreatable; with these advances, many can now be offered a cure. See the CRS and HIPEC cost page.

Restoring the voice after laryngectomy

Laryngectomy, removal of the voice box, ends normal speech, but it no longer ends communication. Dr. Jain described a patient who had already received radiotherapy for laryngeal cancer, had residual disease, and needed salvage surgery to remove the larynx. A voice prosthesis enabled the patient to speak after the operation. For patients who do not want any further invasive procedure, an electrolarynx is an option: an external device held against the skin of the neck that creates vibrations at high speed, so the patient can vocalise. The voice it produces is slightly more mechanical.

Targeted therapy, immunotherapy and patient assistance programmes

Targeted therapy and immunotherapy are showing real results across various cancers. In Dr. Jain's experience, survival has improved, recurrences have fallen significantly and side effects are fewer. Price has been the sore point, because these are costly medicines, but generic versions and patient assistance programmes are bringing costs down. Under these programmes, manufacturers help patients procure the drugs for as little as a half or a third of the usual price. Until recently, regulations confined the programmes to patients in India; those rules are now relaxing, and international patients are increasingly able to benefit. Indicative costs are on the immunotherapy cost page.

Asked about mebendazole and ivermectin as adjunct tablets for cancer, Dr. Jain was clear that they are still being evaluated and that there is not yet sufficient scientific data to rely on them. Standard chemotherapy, and now targeted therapy and immunotherapy, remain the treatments with evidence behind them.

These answers, with the questions doctors asked, are on the masterclass Live Discussion. For the screening tests and red flags that bring patients to referral, see cancer screening guidelines, from mammography to colonoscopy. Other oncology series take different angles: Dr. Nithin S.G. explains how cancer is diagnosed, from tumour markers to biopsy, and Dr. Rajesh Kumar Jain reviews recent trends in surgical oncology.