How Surgery, Drug Therapy, and Immunotherapy Work Together – And Why Cancer Sometimes Comes Back
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In Part 1, we drew a broad map of cancer treatment and looked at why some cancers are easier to cure than others. In this Part 2, we go one step deeper into the treatment tools themselves.
For many patients and families, the questions sound like this:
- “If they can remove the tumor with surgery, why do I also need chemotherapy?”
- “If chemotherapy worked and the scans are clear, why does cancer sometimes come back?”
- “Immune therapy sounds powerful – does it replace chemotherapy?”
This article explains, in everyday language, how surgery, systemic therapy (drug treatment), and immunotherapy each work, how they are combined over time, and what is happening biologically when cancer recurs.
What you will learn in this article
- The different goals of cancer treatment (cure, control, symptom relief)
- How surgery works and where its limits are
- The main types of drug therapy and why they are needed even after “complete” surgery
- What immune checkpoint inhibitors are and how they differ from chemotherapy
- Why cancer sometimes comes back despite good initial response
- How follow-up and monitoring for recurrence are planned
Chapter 1 Goals and timing of treatment – not always “all or nothing”
Curative, disease-controlling, and symptom-relieving treatment
When doctors design a treatment plan, they are usually aiming at one of three broad goals:
- Curative treatment: the realistic aim is to eradicate all cancer cells so that the patient can live a normal lifespan without cancer-related problems.
- Disease control (chronic management): when complete eradication is unlikely, the goal is to keep the cancer in check for as long as possible, like a chronic disease.
- Symptom relief (palliation): when cancer is very advanced, treatment focuses on relieving pain, breathlessness, bleeding, or other distressing symptoms and preserving quality of life.
Importantly, these goals can change over time. A treatment that starts with curative intent may later shift toward long-term control if the cancer recurs. This is not a failure of effort, but a realistic adjustment to the biology of the disease.
Timing words that often confuse patients
Several technical terms describe when treatment is given:
- Neoadjuvant therapy: treatment (often chemotherapy or radiotherapy) given before surgery to shrink the tumor and make it easier or safer to remove.
- Adjuvant therapy: treatment given after surgery, to kill microscopic cancer cells that might still be hiding in the body.
- First-line, second-line, third-line therapy: the first, second, and later sets of drug regimens used as the disease evolves.
- Maintenance therapy: lower-intensity treatment given for a longer time to keep the disease stable after a good initial response.
Understanding these words helps clarify why surgery alone is often not enough, and why drug therapy may continue even when scans look “clean.”
Chapter 2 Surgery – powerful but not all-powerful
How surgery cures cancer when it works
For many solid tumors, surgery is still the most powerful curative tool. In an ideal situation:
- the tumor is confined to one area or organ
- it has not spread to distant organs
- the patient is fit enough for anesthesia and recovery
The surgeon removes the primary tumor and a surrounding “margin” of normal tissue, sometimes together with nearby lymph nodes. If all visible and microscopic disease in that region is removed, the patient can be essentially cancer-free.
Pathologists then examine the removed tissue under the microscope to confirm:
- whether the margins are clear (no cancer cells at the cut edge)
- how many lymph nodes contain cancer, if any
- grade and other biological features
These findings help estimate the risk of future recurrence and decide whether adjuvant treatment is recommended.
The limits of surgery – what it cannot do
Even when surgery appears “complete,” there are important limitations:
- Microscopic spread: very small numbers of cancer cells may have escaped through blood or lymph vessels long before diagnosis, too few to see on scans.
- Anatomical constraints: in organs like the pancreas or brain, it is impossible to remove wide margins without causing serious harm.
- Multifocal disease: in some cancers (such as some liver or breast cancers), multiple separate lumps may exist, not all visible at the time of surgery.
Because of these limits, surgery alone is often not enough, especially in higher-stage disease. This is where drug therapy comes in.
When surgery is not the main player
In some cancers, surgery is less central or not used at all:
- In many lymphomas and leukemias, the disease is spread throughout the blood and lymph system, so systemic therapy is the mainstay.
- In some advanced lung or gastrointestinal cancers, systemic therapy is started first to shrink tumors; surgery may be considered later if there is good response.
- In very frail patients or in tumors in inaccessible locations, radiotherapy or drug therapy may be chosen instead of surgery.
The decision is not “surgery good, no surgery bad,” but rather “which combination gives the best balance of benefit and risk for this particular patient and tumor.”
Chapter 3 Drug therapy – not just “chemotherapy” anymore
Classic cytotoxic chemotherapy
When people hear “chemotherapy,” they often imagine medicines that attack rapidly dividing cells in a broad way. These drugs:
- damage DNA or interfere with cell division
- affect both cancer cells and some normal cells (bone marrow, hair follicles, gut lining)
- can cause side-effects such as nausea, hair loss, and lowered immunity
Despite these drawbacks, classic chemotherapy remains very important. In some diseases (such as certain leukemias, lymphomas, and testicular cancers), it can achieve cure rates that were unthinkable decades ago.
Molecular targeted therapies
Targeted therapies aim at specific molecules or pathways that cancer cells depend on more than normal cells. Examples include:
- drugs that block growth factor receptors (e.g., EGFR inhibitors in some lung cancers)
- drugs that inhibit abnormal fusion proteins or mutant kinases
- drugs that cut off blood supply signals (anti-angiogenic agents)
These treatments can often be taken as tablets, and their side-effect patterns are different from classic chemotherapy. They do not work for everyone; they tend to be effective when the tumor carries a particular mutation or biomarker.
Hormone therapies
Some cancers, especially breast and prostate cancer, are driven by hormones. In these cases, treatments that block hormone production or hormone receptors can:
- reduce the growth signals that the tumor receives
- significantly lower the risk of recurrence after surgery or radiotherapy
- sometimes keep advanced disease under control for many years
Hormone therapies are often taken for long periods (for example, 5–10 years in some breast cancers), and adherence over time is crucial.
Antibody–drug conjugates (ADCs) and other “smart” drugs
Antibody–drug conjugates are a hybrid: an antibody that recognizes a specific marker on cancer cells is linked to a potent chemotherapy drug. The idea is:
- the antibody guides the drug to cancer cells that express the target
- the toxic payload is released inside or near the cancer cell
- normal cells may be relatively spared
These agents are increasingly used in breast, lung, and other cancers, often after other lines of therapy have failed.
Chapter 4 Immunotherapy – turning the immune system back on
Immune checkpoint inhibitors in simple terms
Our immune system constantly patrols for abnormal cells, including potential cancer cells. To prevent over-reactions, it has “brakes” – checkpoint molecules such as PD-1, PD-L1, and CTLA-4.
Cancer cells can exploit these brakes to hide from immune attack. Immune checkpoint inhibitors are antibodies that:
- block the interaction between PD-1 and PD-L1, or CTLA-4 and its ligands
- release the brakes on T-cells
- allow T-cells to recognize and attack cancer cells again
They are now widely used in cancers such as non-small-cell lung cancer, melanoma, kidney cancer, and some stomach and esophageal cancers.
How immunotherapy differs from chemotherapy
Key differences include:
- Mechanism: chemotherapy directly damages dividing cells; immunotherapy modulates the immune system.
- Side effects: chemotherapy affects rapidly dividing tissues; immunotherapy can cause “autoimmune-like” inflammation (e.g., colitis, thyroiditis, pneumonitis).
- Patterns of response: some patients have remarkable and long-lasting responses to immunotherapy, while others show little benefit.
Because immunotherapy unleashes the immune system, careful monitoring is needed to catch and manage immune-related side effects early.
Not a magic bullet
Immunotherapy is sometimes portrayed as a miracle cure, but in reality:
- only a subset of patients respond, even within approved cancer types
- predictive biomarkers (such as PD-L1 expression, tumor mutational burden, or MSI status) are helpful but not perfect
- in many cases, immunotherapy is combined with chemotherapy or targeted therapy rather than used alone
It is a powerful new tool, but not a universal replacement for other treatments.
Chapter 5 Combining treatments – why “one more therapy” can matter
Adding therapies to hit cancer from multiple angles
Modern cancer care often combines treatments to:
- reduce tumor burden with surgery or radiotherapy
- eliminate microscopic disease with drug therapy
- boost the immune response with immunotherapy
Examples:
- Breast cancer: surgery + radiotherapy + hormone therapy ± chemotherapy ± HER2-targeted therapy.
- Colorectal cancer: surgery + adjuvant chemotherapy; in rectal cancer, radiotherapy is often added before or after surgery.
- Lung cancer: surgery in early stages; combinations of chemotherapy, targeted therapy, and immunotherapy in more advanced stages.
Each added treatment brings extra side effects and burden, so doctors try to balance potential benefit against harm and the patient’s overall health and preferences.
Why treat after surgery if the scans are clear?
This is one of the most common questions.
After surgery, scans may show no visible tumor. However, imaging cannot detect a handful of cancer cells scattered in the body. If even one of those cells survives and begins to grow, recurrence can occur months or years later.
Adjuvant chemotherapy, hormone therapy, or targeted therapy aims to:
- kill these microscopic “leftover” cells
- reduce the chance of future recurrence
- improve long-term survival, even if the benefit is invisible in the short term
In many cancers, large clinical trials have shown that adjuvant therapy modestly but clearly improves the odds of cure, especially in higher-risk cases.
Chapter 6 Why does cancer come back? Biological reasons for recurrence
Micrometastases that were there from the start
One major reason for recurrence is that cancer cells had already spread in very small numbers before diagnosis.
These cells:
- may be hiding in lymph nodes or distant organs
- are too few to be seen on CT, MRI, or PET scans
- can remain dormant or slow-growing for months or years
Later, under certain conditions, they start to grow and form detectable metastases.
Resistant clones and tumor heterogeneity
Cancers are not made of identical cells. Within a single tumor, there can be many sub-clones with different genetic changes.
When we use chemotherapy, targeted therapy, or even immunotherapy:
- the treatment may kill most sensitive cells
- but some resistant sub-clones survive
- over time, these resistant clones grow and become dominant
This process is similar to antibiotic resistance in bacteria. It explains why a drug that worked well at first can stop working later.
Sanctuary sites and protective microenvironments
Some organs and tissues act as “sanctuaries” where drugs or immune cells have difficulty reaching therapeutic levels. Examples include:
- the brain (protected by the blood–brain barrier)
- some parts of the bone marrow
- areas with poor blood supply
Cancer cells that survive in these niches may later cause localized or distant recurrence.
New primary cancers, not just recurrence
In some organs (like the liver, head and neck region, or lung), the environment may be chronically damaged by viruses, alcohol, smoking, or other factors. Over time, completely new primary cancers can arise in the same organ, independent of the original tumor.
From the patient’s perspective, this still feels like “cancer came back,” but biologically it may be a new disease. This is one reason why long-term surveillance is important even for patients who were successfully treated once.
Chapter 7 Monitoring for recurrence – what follow-up tries to catch
Regular visits and imaging
After initial treatment, follow-up usually includes:
- regular physical examinations and symptom review
- periodic imaging (e.g., ultrasound, CT, MRI, or mammography)
- tests tailored to the cancer type (for example, colonoscopy after colorectal cancer)
The schedule and duration of follow-up vary by cancer type and stage. The aim is to detect recurrences or new primaries early, when additional treatment might still be effective.
Tumor markers and blood tests
In some cancers, blood tests can help monitor disease activity (for example, PSA in prostate cancer, CEA in some colorectal cancers, CA 19-9 in pancreatic or biliary cancers). However:
- markers are not perfect – they can be elevated for non-cancer reasons
- not all patients with cancer have elevated markers
- treatment decisions are rarely based on markers alone
They are one piece of information among many.
ctDNA and MRD – a look into the future
As we touched on in Part 1, researchers are studying circulating tumor DNA (ctDNA) to detect minimal residual disease (MRD): traces of cancer DNA in the blood even when scans are clear.
In the future, if these tests become reliable and widely available, they may allow:
- more precise prediction of recurrence risk
- earlier detection of relapse
- personalized decisions on who really needs intensive adjuvant therapy and who can safely avoid it
For now, ctDNA remains an evolving tool, used mainly in research and in limited clinical settings.
Chapter 8 Talking with your doctor about treatment goals
Questions that can clarify the plan
Because cancer treatments are complex and often combined, it is completely understandable for patients to feel overwhelmed. Questions such as the following can help:
- “Is the main goal of this treatment to cure the cancer, control it long-term, or relieve symptoms?”
- “How does this surgery (or chemotherapy, or immunotherapy) fit into the overall plan?”
- “What are the realistic benefits, and what side effects should I expect?”
- “If this line of treatment stops working, what are the next options?”
Understanding the intent behind each step can make it easier to cope with side effects and to make choices that fit one’s values and life plans.
When plans need to change
Sometimes, despite best efforts, cancer progresses. In those moments, shifting from “cure at all costs” to “living as well as possible for as long as possible” is not giving up; it is adapting to reality with courage and honesty.
Palliative care teams can play a vital role here, not only at the very end of life but much earlier, to manage symptoms and support patients and families emotionally.
Chapter 9 Summary and looking ahead
In this Part 2, we:
- reviewed how surgery, drug therapy, and immunotherapy each contribute to cancer treatment
- explained why adjuvant therapy may be recommended even after apparently complete surgery
- looked at biological reasons for recurrence: micrometastases, resistant clones, sanctuary sites, and new primary cancers
- outlined how follow-up aims to catch recurrence or new cancers as early as possible
The key message is that modern cancer treatment is rarely a single shot. It is a sequence and combination of tools, chosen and adjusted according to tumor biology and patient factors over time.
In Part 3, we will focus on radiotherapy in more detail:
- how conventional X-ray radiotherapy works
- what IMRT and stereotactic radiotherapy actually do
- when radiotherapy is used instead of surgery, and when it is combined with surgery or drug therapy
This article was edited by the Morningglorysciences team.
The content is for general informational purposes only and is not a substitute for individual medical advice. For decisions about diagnosis or treatment, please always consult your treating physician.
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