Treatment for cancer

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cancer treatment modalities overview 2025 surgery chemotherapy immunotherapy radiation

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Cancer Treatment: A Comprehensive Overview

Cancer treatment encompasses multiple modalities, broadly divided into local and systemic approaches. The primary goal is eradication (cure); when not achievable, treatment shifts to palliation - ameliorating symptoms, preserving quality of life, and extending survival. In practice, modalities are frequently combined.

Harrison's Principles of Internal Medicine, 22E (2025)

1. Surgery

Surgery remains the most effective single modality for treating solid tumors. At least 40% of cancer patients are cured by surgery alone.

Types of surgical intent:

Curative (R0 resection) - complete tumor excision with adequate normal tissue margins; the gold standard
R1 resection - microscopic residual tumor at margins (may require reoperation)
R2 resection - macroscopic residual tumor at margins
Palliative surgery - achieves local control, preserves organ function, or enables debulking to make subsequent systemic therapy more effective
Sentinel node biopsy - minimizes morbidity while obtaining critical staging information

Modern approaches:

Laparoscopic/minimally invasive surgery for abdominal and pelvic tumors
Resection of lymph node drainage basins provides both prognostic information and, in some locations, survival benefit

Limitations: Many patients with solid tumors present with disease that is not practically resectable, particularly with distant metastases.

2. Radiation Therapy

Radiation targets locally advanced or residual disease after surgery, or is used as the definitive local treatment when surgery is not feasible.

Mechanisms: High-energy beams cause DNA strand breaks, killing rapidly dividing cancer cells. Effects are largely confined to the treated field.

Modalities:

External beam radiation - X-rays, proton beams, or other particles directed at the tumor
Brachytherapy - radioactive implants placed within or near the tumor (e.g., prostate cancer)
Stereotactic radiosurgery (SRS/SBRT) - highly focused, high-dose radiation in few fractions (e.g., Gamma Knife for brain metastases)
Photodynamic therapy - light-activated photosensitizers producing localized cytotoxic reactive oxygen species

Common applications: Breast (post-lumpectomy), prostate, head and neck, lung, cervical cancers; brain metastases; bone metastases for pain control.

Side effects are largely limited to the treatment field (e.g., mucositis, skin changes, pneumonitis) but may affect adjacent normal tissues.

3. Chemotherapy

Chemotherapy uses cytotoxic drugs that interfere with DNA replication or cell division, exploiting the fact that cancer cells divide more rapidly than most normal cells.

Major drug classes:

Class	Mechanism	Examples
Alkylating agents	Cross-link DNA strands	Cyclophosphamide, cisplatin, carboplatin
Antimetabolites	Block nucleotide synthesis	5-fluorouracil, methotrexate, gemcitabine
Topoisomerase inhibitors	Disrupt DNA unwinding	Irinotecan, etoposide, doxorubicin
Taxanes / vinca alkaloids	Disrupt mitotic spindle	Paclitaxel, docetaxel, vincristine
Anthracyclines	DNA intercalation + free radicals	Doxorubicin, epirubicin

Treatment goals by setting:

Neoadjuvant - shrink tumor before surgery/radiation
Adjuvant - eliminate micrometastases after local treatment
Definitive - primary treatment (e.g., hematologic malignancies)
Palliative - control disease progression and symptoms in metastatic setting

High-dose chemotherapy with hematopoietic stem cell rescue (autologous or allogeneic transplant) can be curative in select settings (lymphomas, leukemias, multiple myeloma).

Key limitations: Affects rapidly dividing normal cells (bone marrow, GI epithelium, hair follicles) causing myelosuppression, nausea/vomiting, mucositis, and alopecia.

4. Targeted Therapy

Targeted therapy exploits specific molecular alterations present in cancer cells, offering greater selectivity than conventional chemotherapy.

Major pathways targeted:

HER2/EGFR - receptor tyrosine kinase inhibitors (trastuzumab, erlotinib, lapatinib, cetuximab)
RAS/RAF/MEK/MAPK pathway - BRAF inhibitors (vemurafenib for BRAF V600E-mutant melanoma), MEK inhibitors
PI3K/AKT/mTOR pathway - mTOR inhibitors (everolimus), PI3K inhibitors
BCR-ABL fusion kinase - imatinib, nilotinib, dasatinib (transformative in CML)
ALK/ROS1 rearrangements - crizotinib, alectinib (non-small cell lung cancer)
VEGF/angiogenesis - bevacizumab, sunitinib, sorafenib
CDK4/6 - palbociclib, ribociclib (hormone receptor-positive breast cancer)
PARP - olaparib, rucaparib (BRCA-mutated breast/ovarian cancer)
Antibody-drug conjugates (ADCs) - monoclonal antibodies linked to cytotoxic payloads delivered directly to cancer cells (e.g., trastuzumab deruxtecan, sacituzumab govitecan)

The critical prerequisite for most targeted therapies is molecular profiling (tumor biopsy or liquid biopsy) to identify the actionable driver mutation.

5. Immunotherapy

Immunotherapy harnesses the body's immune system to recognize and destroy cancer cells. It represents one of the most significant advances in oncology over the past decade.

Main categories:

a. Immune Checkpoint Inhibitors (ICIs)

Cancer cells exploit inhibitory checkpoint pathways (PD-1/PD-L1, CTLA-4) to evade immune destruction. ICIs block these brakes, allowing T cells to attack the tumor.

Anti-PD-1: pembrolizumab (Keytruda), nivolumab - approved for melanoma, NSCLC, head & neck, bladder, MSI-H tumors across histologies
Anti-PD-L1: atezolizumab, durvalumab, avelumab
Anti-CTLA-4: ipilimumab - often combined with anti-PD-1

Notable 2025 approvals: Pembrolizumab before and after surgery for locally advanced head and neck squamous cell carcinoma showed a 13.7% increase in major pathologic response and 34% reduction in recurrence (KEYNOTE-689 trial), per AACR 2025.

b. CAR-T Cell Therapy (Chimeric Antigen Receptor T-cell)

Patient T cells are extracted, genetically engineered to express a receptor targeting a tumor antigen (e.g., CD19, BCMA), expanded, and reinfused. Currently approved for:

Relapsed/refractory B-cell lymphomas (axicabtagene ciloleucel, tisagenlecleucel)
Multiple myeloma (idecabtagene vicleucel targeting BCMA)
B-cell acute lymphoblastic leukemia

c. Cancer Vaccines

Therapeutic vaccines - stimulate immune response against tumor antigens (e.g., sipuleucel-T for prostate cancer)
mRNA vaccines - personalized neoantigen vaccines in clinical trials (promising in melanoma, NSCLC)

d. Cytokines

IL-2 (aldesleukin) for metastatic melanoma and renal cell carcinoma
Interferons (IFN-alpha) in hematologic malignancies

Unique toxicities: Immune-related adverse events (irAEs) - can affect any organ: colitis, pneumonitis, hepatitis, endocrinopathies, skin reactions.

6. Hormonal / Endocrine Therapy

Applicable to hormone-sensitive tumors:

Breast cancer - tamoxifen (selective estrogen receptor modulator), aromatase inhibitors (anastrozole, letrozole, exemestane), fulvestrant (ER degrader)
Prostate cancer - androgen deprivation therapy (LHRH agonists/antagonists: leuprolide, degarelix), anti-androgens (enzalutamide, abiraterone)
Thyroid cancer - TSH suppression with levothyroxine

7. Hematopoietic Stem Cell Transplantation (HSCT)

Used as consolidation or rescue therapy, primarily for hematologic malignancies:

Autologous HSCT - patient's own cells reinfused after high-dose chemotherapy (lymphoma, myeloma)
Allogeneic HSCT - donor cells provide graft-vs-tumor (GVT) effect in addition to myeloablative conditioning (AML, ALL, MDS)

8. Ablative and Interventional Approaches

Radiofrequency ablation (RFA) - heat destroys tumors in liver, kidney, lung
Cryoablation - freezing destroys tumors; used in prostate, kidney, liver
Thermal ablation / microwave ablation - similar indications to RFA
Transarterial chemoembolization (TACE) - delivers chemotherapy directly into hepatic artery feeding liver tumors

Summary of Modality Selection Principles

Setting	Preferred Approach
Localized solid tumor	Surgery ± adjuvant radiation/chemotherapy
Locally advanced	Neoadjuvant chemoradiation → surgery
Hematologic malignancies	Chemotherapy ± targeted therapy ± HSCT
Driver mutation present	Targeted therapy as first-line
High tumor mutational burden / MSI-H	Immunotherapy (checkpoint inhibitors)
Metastatic (hormone-sensitive)	Hormonal therapy
Metastatic (general)	Systemic therapy (chemo/targeted/immuno)
Oligometastatic	Surgery/SBRT to metastases
Palliation	Least-toxic effective regimen; symptom control

Emerging and Future Directions (2025-2026)

Liquid biopsy / ctDNA - guiding treatment decisions (e.g., detecting MRD after surgery to determine who needs adjuvant immunotherapy)
Antibody-drug conjugates - rapidly expanding indications (Datroway for TNBC, sacituzumab govitecan)
PARP inhibitors in BRCA-mutated cancers - moving to chemotherapy-free regimens
Personalized mRNA neoantigen vaccines - phase 3 trials underway
Metabolic targeting - exploiting cancer cell metabolic dependencies (reviewed in Xiao et al., Cell Metab 2023, PMID 37557070)
Bispecific antibodies and NK cell therapies - expanding beyond CAR-T

Sources:

Harrison's Principles of Internal Medicine, 22nd Edition (2025, McGraw-Hill) - Chapter 78: Cancer Treatment
Cancer treatment and survivorship statistics, 2025 - NCDB national data
Kulkarni P et al. Cancer Immunotherapy - An Overview. Cancer Treat Res, 2025 (PMID 40847226)
Dabas P & Danda A. CAR-T cell therapy review. Med Oncol, 2023 (PMID 37608202)

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