Metastatic cancer refers to malignancies that originate in one organ and spread to adjacent or distant organs via the blood or lymphatic systems. tumour cells continuously shed into the circulation, and while many are cleared by the immune system, some manage to evade immune defences and travel to distant sites in the body. Interestingly, different cancers tend to metasta- sise preferentially to specific organs. For example, breast cancer commonly spreads to the bones, brain, liver, and lungs, while lung cancer often metastasises to the adrenal glands, bones, brain, and liver. Prostate cancer tends to spread to bones, liver, lungs, and adrenal glands, and colorectal cancer typically in- volves the liver, lungs, and peritoneum.Clinically, metastatic cancer is cate- gorised based on its relation- ship to the primary tumour site:
◆ Locally advanced cancer involves nearby tissues or lymph nodes.
◆ Regional metastasis refers to spread to adjacent organs or areas.
◆ Distant metastasis is cancer that has travelled to far-off or- gans, often through the bloodstream or lymphatics.
Historically, the management of metastatic cancer has relied on four primary therapeutic modalities: surgery, radiation therapy, chemotherapy, and, more recently, immunotherapy, The 2018 Nobel Prize in Physiology or Medicine was awarded to Tasuku Honjo and James Allison for their discoveries in cancer immunology. Professor Honjo was awarded due to his discovery of the programmed death molecule-1 (PD-1) on T cells.
Localised treatments like surgery and radiation are directed at specific tumour sites, while systemic treatments such as chemotherapy and immunotherapy target cancer cells throughout the body.
For decades, chemotherapy using cytotoxic drugs to kill rapidly dividing cells remained the cornerstone for treating metastatic disease. However, recent advances have introduced targeted therapies and immunotherapy into treatment algorithms for several metastatic cancers with reasonable benefit. Targeted therapies or magic bullets focus on specific genetic mutations or molecular pathways essential for tumour growth, while immunotherapy harness the body’s immune system to recognise and attack cancer cells.
Assessing value: The clinical benefit vs. cost debateAs novel cancer therapies emerge, discussions around their value — the clinical benefits they offer in relation to their often-high costs — have aggrandised. This debate is especially relevant in lower- middle income countries (LMICs), where the cancer burden is increasing, but access to these new therapies remains limited due to financial constraints and out of pocket expenditure to the tune of 50 per cent.Physician opinions about the approval of new cancer drugs, particularly those based on surrogate endpoints (such as progres- sion-free survival or response rates rather than overall survival), vary widely. In LMICs, where healthcare resources are limited, prioritising the use of expensive therapies becomes a difficult decision- making process. It is crucial to understand how oncologists in these settings perceive the value of new drugs and the financial implications for their patients.The patient perspective: Small benefits, significant impactWhile clinicians and drug manufacturers may debate the magnitude of clinical benefit required to justify a drug’s cost, for many patients living with metastatic cancer, even modest gains are meaningful. A small extension in progression-free survival (PFS) or improvement in quality OF LIFE (QOL) can translate into re- newed hope, and precious time with loved ones. However, in some, the pricing is beyond their reach. Importantly, patient preferences in metastatic cancer care are deeply personal and varied. Some patients prioritise quality of life and opt for treatments with milder side effects, even if survival gains are modest.
Others may be willing to endure aggressive treatments for the chance of extending life by even a few months.In LMICs, social and financial considerations play a significant role in these de- cisions. The cost of novel targeted therapies and immunotherapies, travel expenses, and loss of income often add to the burden. In many families, treatment decisions are influenced not only by the patient but also by caregivers and relatives. Some patients continue treatment for the mental reassurance it provides, while others experience treatment fatigue or feel societal pressure to keep fighting, despite uncertain benefits.
With novel therapies like immunotherapy, the average time to response is four to six months which is a major test to their patience and financial resources. Moreover, even if systemic chemotherapy or novel targeted therapies offer limited survival benefits, they often alleviate symptoms, reduce tumour burden, and improve overall well-being. For many patients and families, this symptomatic relief alone justifies the continuation of therapy.Bridging the gap between evidence and experienceIn the context of metastatic cancer management in lower- middle income countries, understanding both the clinical and personal value of novel therapies is essential. While oncologists must navigate the complexities of clinical evidence, surrogate endpoints, and cost-effectiveness, they must also remain aligned to the perspectives of their patients — for whom small benefits can hold profound meaning or also a financial turmoil.
As the cancer burden grows and drug prices continue to rise, healthcare systems in re- source-limited settings must engage in evidence-based prioritisation of therapies. At the same time, having an open conversations between oncologists, patients, and families about realistic goals of care, potential benefits, and the financial implications of treatment can help ensure that decisions align with both medical evidence and patient values. Shared decision making is the key.