A tumor is a neoplasm formed through cellular proliferation and abnormal differentiation of the body's cells under various initiating and promoting factors. Once formed, neoplastic growth does not cease even if the causative factors are removed. Its growth is not regulated by normal physiological mechanisms and often disrupts normal tissues and organs.

Most tumors present as masses and are referred to as solid tumors. The etiology, pathogenesis, classification, and nomenclature of tumors are described in relevant pathology textbooks and will not be repeated in this chapter. This chapter focuses on clinical issues related to solid tumors and discusses the diagnosis and management of common superficial masses.

Diagnosis of Tumors

Accurate diagnosis is a prerequisite for effective tumor treatment. It should include not only the location and nature of the tumor but also, in the case of malignant tumors, the degree of malignancy and staging, to aid in formulating an appropriate treatment plan.

Clinical Diagnosis

Clinical manifestations depend on the tumor’s nature, tissue of origin, location, and stage of development. Malignant tumors are often asymptomatic in the early stages; when symptoms do appear, they are usually nonspecific. By the time characteristic symptoms develop, the disease is often advanced.

Local Manifestations

Mass

A mass is often the first manifestation of superficial or shallow tumors, sometimes accompanied by dilated or engorged veins. The consistency, mobility, and margins of the tumor may vary depending on its nature. Deep or visceral tumors are more difficult to palpate. Malignant tumors may present with metastases, such as enlarged lymph nodes, nodules, or masses in bones and visceral organs.

Pain

Expansion, ulceration, or infection of the tumor may stimulate or compress peripheral nerves or nerve trunks, causing local stabbing, throbbing, burning, dull, or radiating pain. This pain is often severe and more noticeable at night.

Ulceration

Rapidly growing tumors may outstrip their blood supply, leading to necrosis or secondary infection and ulceration. Malignant ulcers may produce foul-smelling or bloody secretions.

Bleeding

Tumors on the body surface or those communicating with external environments may bleed due to ulceration or vascular rupture. Upper gastrointestinal tumors may cause hematemesis or melena; lower gastrointestinal tumors may result in bloody or mucus-laden stools; urinary tract tumors may lead to hematuria; lung cancer may present with hemoptysis or blood-streaked sputum; cervical cancer may cause bloody vaginal discharge or bleeding.

Obstruction

Tumors may obstruct hollow organs, resulting in varied symptoms depending on the site. For example, pancreatic head cancer or bile duct cancer may cause obstructive jaundice; gastric cancer with pyloric obstruction may lead to vomiting; intestinal tumors may cause bowel obstruction; bronchogenic lung cancer may result in pulmonary atelectasis.

Symptoms from Tumor Metastasis

These may include regional lymphadenopathy; venous outflow obstruction in the affected region, leading to limb edema or varicosities; bone metastases, causing pain or palpable nodules and possibly pathological fractures; malignant pleural or peritoneal effusion associated with lung, liver, or gastric cancers.

Systemic Symptoms

Benign and early-stage malignant tumors generally cause no significant systemic symptoms. Common nonspecific systemic symptoms of malignant tumors include anemia, low-grade fever, weight loss, and fatigue. Cachexia often reflects late-stage systemic failure in malignancies, especially digestive tract tumors. Some tumors cause systemic changes due to endocrine hyperfunction or hypofunction. For example, pheochromocytoma may induce hypertension; parathyroid adenoma may cause bone alterations; intracranial tumors may lead to increased intracranial pressure and disorientation.

History and Physical Examination

Several aspects warrant attention:

Age

Embryonal tumors and leukemia are more common in children. Sarcomas, including those of bone, soft tissue, and lymphohematopoietic systems, are more frequent in adolescents. Carcinomas generally occur in middle-aged and older adults; when present in younger patients, they tend to progress rapidly, with metastases or secondary symptoms often dominating the clinical picture.

Disease Course

Benign tumors typically have a prolonged course, while malignant tumors progress more rapidly. Benign tumors may suddenly enlarge due to hemorrhage or infection; malignant transformation also leads to rapid growth. Low-grade malignancies progress slowly, such as basal cell carcinoma of the skin or papillary thyroid carcinoma. In elderly patients, malignant tumors tend to progress more slowly.

Other Medical History

Some tumors show familial clustering or hereditary tendencies. A family history should be considered when gastric, colorectal, esophageal, breast, or nasopharyngeal cancer is suspected.

Certain cancers are associated with precancerous conditions or related diseases. For example, gastric cancer is linked to atrophic gastritis, chronic gastric ulcers, and gastric polyps; papillomas or mucosal leukoplakia are associated with certain carcinomas; colorectal cancer is linked to adenomatous polyposis; liver cancer is associated with hepatitis B; nasopharyngeal carcinoma is linked to Epstein-Barr virus infection.

Personal behaviors and environmental factors, such as smoking, chronic alcohol consumption, dietary habits, occupational exposures, and environmental risks, should also be considered.

Physical Examination

General Physical Examination

A complete systemic examination is required, with particular attention to palpation of superficial lymph nodes.

Local Examination

Location of the Mass: The anatomical site of the mass helps in determining its tissue origin and nature. For large masses, the history may provide clues about the primary site.

Tumor Characteristics: Size, shape, consistency, surface temperature, vascularity, presence or absence of a capsule, and mobility are diagnostic clues. Benign tumors usually have a capsule and a consistency similar to the surrounding tissue. Malignant tumors generally lack a capsule, feel hard, exhibit prominent vascularity or increased surface temperature, and grow rapidly with poorly defined margins and fixed masses. Secondary changes such as necrosis, liquefaction, ulceration, or bleeding may occur.

Regional Lymph Node or Metastasis Assessment: For example, in breast cancer, axillary and supraclavicular lymph nodes should be examined; in pharyngeal tumors, cervical lymph nodes should be checked; for anal or vaginal cancer, inguinal lymph nodes should be assessed; in abdominal tumors, hepatic palpation and rectal examination may be required.

Laboratory Diagnosis

Routine Tests

Routine tests include blood, urine, and stool examinations. Patients with gastrointestinal tumors may present with anemia and occult blood in the stool; leukemia is often associated with marked changes in blood counts; urinary tract tumors may cause hematuria; in multiple myeloma, Bence-Jones proteins may be detected in the urine. Malignant tumors are often accompanied by an increased erythrocyte sedimentation rate (ESR). Although abnormal findings from routine tests are not specific indicators of malignancy, such positive results can provide valuable diagnostic clues.

Serological Tests

Biochemical methods can be used to detect tumor markers produced by tumor cells and distributed in blood, secretions, or excretions. Tumor markers may include enzymes, glycoproteins, hormones, embryonic antigens, or tumor metabolites. Most tumor markers differ in quantity rather than quality between malignant tumors and normal tissues, resulting in limited specificity. However, they are valuable as adjuncts in diagnosis, assessment of treatment efficacy, and follow-up.

Enzymatic Tests

Hepatocytes and osteoblasts can secrete alkaline phosphatase (ALP), so serum ALP levels are often elevated in liver cancer and osteosarcoma. ALP levels may also rise in cases of obstructive jaundice due to impaired bile excretion. Serum acid phosphatase levels are elevated in prostate cancer. Both acid and alkaline phosphatase levels may increase in prostate cancer with bone metastases accompanied by reactive bone formation. Elevated levels of lactate dehydrogenase (LDH) can occur in liver cancer and malignant lymphomas.

Glycoproteins

Serum α₁-acid glycoprotein is elevated in lung cancer. Markers such as CA19-9 and CA50 are elevated in cancers of the digestive system.

Hormones

Tumors of endocrine organs may result in increased hormone secretion, leading to paraneoplastic endocrine syndromes. Examples include pituitary tumors causing elevated growth hormone; insulinomas causing hyperinsulinemia and hypoglycemia; parathyroid tumors causing hypercalcemia. Human chorionic gonadotropin (HCG) is widely used in the diagnosis and management of choriocarcinoma.

Embryonic Antigens

Carcinoembryonic antigen (CEA), a group of glycoproteins produced by the fetal gastrointestinal tract, can be elevated in colorectal, gastric, lung, and breast cancers. Postoperative monitoring of CEA in colorectal cancer can help predict recurrence. Alpha-fetoprotein (AFP), a globulin produced by the yolk sac, liver, and gastrointestinal tract during fetal development, is elevated in hepatocellular carcinoma and malignant germ cell tumors, and is used in liver cancer screening in China with good results.

Others

Serum IgA antibodies against Epstein-Barr virus viral capsid antigen (VCA-IgA) are highly specific for nasopharyngeal carcinoma, with a positive rate of about 90% in patients and 6%–35% in healthy individuals, making it useful for screening. Various tumor-specific antigens and corresponding antibodies or monoclonal antibodies are also being developed for diagnostic purposes, such as monoclonal antibodies for gastric and colorectal cancers. In recent years, mass spectrometry (MS) technology in proteomics has provided new approaches for identifying novel tumor markers.

Flow Cytometry (FCM)

Flow cytometry is used to classify large numbers of cells based on different properties, describe characteristics of various cell populations, and isolate specific subpopulations for further analysis. It can be used to analyze chromosomal DNA ploidy, DNA index, and other parameters. Combined with pathological tumor types, it provides insights into the degree of malignancy and prognosis.

Imaging and Endoscopic Diagnosis

Imaging techniques include X-rays, ultrasound, radionuclide imaging, computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET). Contrast agents may be used to enhance imaging contrast and visualize blood vessels. Various endoscopic techniques enable direct visualization of the examination area for detecting masses and assessing their morphology and size, thus aiding diagnosis.

X-ray Examination

Fluoroscopy and Plain Films

Characteristic opacities may be seen in pulmonary and bone tumors.

Common Contrast Studies

Standard Contrast Studies: Barium is used for barium meals and enemas, and iodine-based agents (such as meglumine diatrizoate or iopamidol) are used for contrast imaging. Imaging may reveal filling defects, tissue destruction, or stenosis. For better visualization, gas-barium double contrast or smooth muscle relaxants (e.g., hyoscine) may be employed.

Catheter-based Contrast Studies: Specialized instruments are used to perform catheter-based imaging, such as retrograde pyelography and endoscopic retrograde cholangiopancreatography (ERCP).

Excretory Imaging: Imaging techniques are based on organ excretion, such as intravenous urography.

Angiography: Selective arterial catheterization enables visualization of tumor vasculature, e.g., hepatic, carotid, celiac, or mesenteric arteries. Digital subtraction angiography provides clearer vascular images.

Special X-ray Imaging

Selenium-based dry plate X-ray imaging and molybdenum target mammography are used for imaging soft tissues and breast tissue.

Ultrasound

Ultrasound is safe, simple, and non-invasive, and is widely used in diagnosing tumors of the liver, gallbladder, pancreas, spleen, thyroid, breast, brain, uterus, and ovaries. It is valuable for distinguishing cystic from solid masses. Ultrasound-guided biopsy yields a success rate of 80%–90%. Computer-assisted ultrasound and color Doppler imaging further aid diagnosis.

CT

CT offers high tissue density resolution and produces cross-sectional images that directly visualize tumors within solid organs. Contrast enhancement improves differentiation based on the pattern and degree of enhancement. CT is commonly used for the differential diagnosis of intracranial tumors, solid organ tumors, solid masses, and lymph nodes.

Radionuclide Imaging

Common radionuclides include technetium-99m, iodine-131, gold-198, phosphorus-32, xenon-133, gallium-67, ytterbium-169, and indium-113. Bone tumor detection has a high positive rate and can identify bone metastases earlier than X-rays, although false positives are possible. The positive rate is lower for gastrointestinal tumors.

MRI

MRI offers excellent soft tissue contrast and is non-invasive and safe. It provides particularly clear imaging of the nervous system and soft tissues. In addition to showing morphological changes, it can perform functional imaging and biochemical analysis, reflecting pathology at the molecular level and enabling objective tumor evaluation.

PET

PET uses tracers composed of basic tissue elements. The most widely used tracer in oncology is ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG), which visualizes differences in glucose metabolism between tumors and normal tissues. It is a non-invasive, dynamic, quantitative, molecular-level 3D imaging technique. Diagnostic accuracy approaches 90% for brain tumors, colorectal cancer, lung cancer, melanoma, breast cancer, and ovarian cancer. Combined PET/CT imaging is most commonly used.

Endoscopy

Endoscopy can be performed via natural orifices (e.g., gastroscopy, bronchoscopy, cystoscopy, colposcopy) or via artificial openings (e.g., laparoscopy, thoracoscopy, mediastinoscopy). It enables direct visualization of tumors or lesions and allows for tissue or cell sampling for pathological examination. Small lesions can be treated endoscopically (e.g., polyp removal), and catheters can be inserted into the ureters, bile ducts, or pancreatic ducts for contrast imaging. Advanced techniques such as endoscopic ultrasound, confocal endoscopy, electronic magnification endoscopy, and infrared endoscopy have been developed to visualize microstructures not visible with conventional endoscopy, playing an important role in early cancer diagnosis.

Pathological Diagnosis

This remains the most reliable method for confirming a tumor diagnosis and is often a prerequisite for initiating tumor treatment.

Biopsy

Biopsy involves obtaining tissue samples from the living body through methods such as excision, forceps biopsy, fine needle aspiration, curettage, or excisional procedures. Pathological examination of these tissues helps determine the nature of the disease, tumor origin, type, grade, and stage. It plays a critical role in distinguishing between benign and malignant tumors and is widely employed in clinical diagnosis.

Needle Biopsy

Specially designed needles are used under local anesthesia to obtain small tissue samples. This method is commonly applied to solid subcutaneous or visceral masses, such as those in the breast, thyroid, lung, and liver. During the procedure, large blood vessels and hollow organs should be avoided.

Forceps Biopsy

Frequently performed on tumors of the skin surface or mucosal linings of body cavities, this method is used during procedures such as gastrointestinal endoscopy or bronchoscopy.

Incisional Biopsy

This involves removing a small portion of the lesion, typically when the lesion is too large, complete excision is not feasible, or surgery would result in significant functional impairment or disfigurement. This approach provides essential information for further treatment planning.

Excisional Biopsy

This involves removing the tumor along with a portion of the surrounding normal tissue. In cases where the tumor is benign, this procedure may also serve a therapeutic purpose.

Each type of biopsy carries a potential risk of facilitating malignant tumor dissemination; thus, strict adherence to indications is required.

Cytological Examination

This method diagnoses diseases by observing changes in cell structure and morphology. Depending on specimen source, cytology is categorized into exfoliative cytology and fine needle aspiration cytology.

Exfoliative Cytology

This involves examining cells that are naturally shed under physiological or pathological conditions, such as those in sputum, pleural or peritoneal effusion, gastric fluid, urine, or cervical smears.

Fine Needle Aspiration Cytology

This involves using a fine needle to aspirate cells from a lesion for examination. Common applications include aspiration of lymph nodes, thyroid or breast masses, and percutaneous lung aspiration.

The advantages of cytology include simplicity, low cost, repeatability, minimal or no impact on subsequent treatment, rapid results, and non-invasiveness or minimal invasiveness. Its limitation lies in the inability to observe tissue architecture, which may affect diagnostic accuracy and make subtyping more challenging.

Molecular Pathological Diagnosis

With the advancement of molecular biology and precision medicine, molecular diagnostics has become the fifth level of tumor diagnosis. Both tumor tissue and body fluids can serve as specimens for analysis.

Immunohistochemistry (IHC)

This technique employs specific antibodies to bind to target protein antigens within tissue sections. The antibody-antigen complexes are visualized using chromogenic agents such as fluorophores, peroxidase, or metal ions. IHC offers strong specificity, high sensitivity, precise localization, and integration of morphological and functional information. It significantly enhances diagnostic accuracy, identifies tissue origin, detects microscopic cancer foci, aids in accurate staging, and assesses tumor malignancy. The method is technically accessible, cost-effective, and suitable for clinical practice.

Genetic Testing

Molecular biology techniques are used to detect relevant tumor-related genes in tissue samples. Methods include polymerase chain reaction (PCR), in situ hybridization, fluorescence in situ hybridization (FISH), and gene sequencing. Genetic testing plays an important role in tumor characterization, classification, prognosis assessment, and targeted therapy.

Liquid Biopsy

Liquid biopsy is a technique that analyzes tumors by examining blood or other body fluids. Circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) are the primary targets of liquid biopsy. This method offers minimal invasiveness and enables repeated testing, providing a unique advantage for tracking and monitoring tumor recurrence, progression, and drug resistance. It also offers improved representation of tumor heterogeneity.

Tumor Staging Diagnosis

Staging of malignant tumors facilitates the development of appropriate treatment plans, accurate evaluation of therapeutic outcomes, and prognosis assessment. The TNM staging system, proposed by the Union for International Cancer Control (UICC), is currently the most widely used system. T refers to the primary tumor, N to lymph nodes, and M to distant metastasis. Numbers from 0 to 4 following these letters indicate the extent of tumor progression, with 1 representing a low degree, 4 representing a high degree, and 0 indicating absence. The combination of these three components determines the stage of the tumor, with different TNM combinations corresponding to different stages. When tumor size cannot be assessed clinically, it is indicated as Tx. Tumor staging includes clinical staging (cTNM) and pathological staging after surgery (pTNM). Specific criteria for TNM staging of various tumors are established by professional consensus meetings. For example, the staging of breast cancer is as follows:

Stage 0: T_isN₀M₀
Stage I: T₁N₀M₀
Stage IIA: T_0–1N₁M₀, T₂N₀M₀
Stage IIB: T₂N₁M₀, T₃N₀M₀
Stage IIIA: T_0–2N₂M₀, T₃N_1–2M₀
Stage IIIB: T₄N_0–2M₀
Stage IIIC: T_0–4N₃M₀
Stage IV: Any combination of T and N that includes M₁

Common Treatment Methods for Solid Tumors

Benign tumors and borderline tumors are primarily treated with surgical resection. Borderline tumors require complete excision; otherwise, there is a high risk of recurrence or malignant transformation. Malignant tumors are treated with a combination of surgery, medical therapy, radiation therapy, and traditional Chinese medicine. The specific treatment plan should be determined through discussion within a multidisciplinary team (MDT) that considers the tumor characteristics, staging, and the patient’s overall condition. Generally, stage I malignant solid tumors are primarily managed with surgery. Stage II treatment focuses on local control, including resection or radiotherapy of the primary tumor and any potential metastases, supplemented by effective systemic chemotherapy. Stage III tumors require a comprehensive approach, incorporating preoperative, intraoperative, and postoperative radiotherapy or chemotherapy. Stage IV treatment emphasizes systemic therapy, combined with local symptomatic management where appropriate.

Surgical Treatment

Surgical oncology refers to the use of surgical methods to remove tumors. For most early-stage and relatively early-stage solid tumors, surgery remains the preferred treatment. Complete resection of benign tumors generally results in a cure. Even for malignant solid tumors, surgery offers a significant chance of cure, provided cancer cells have not yet spread.

Principles of Surgical Oncology

In addition to general surgical principles, surgical oncology follows specific foundational principles aimed at preventing intraoperative tumor cell shedding, implantation, and hematogenous metastasis.

Non-Cutting Principle

The tumor itself is not directly incised during surgery. Dissection proceeds from the periphery toward the center, with all procedures performed within surrounding normal tissue.

En Bloc Resection Principle

The primary lesion and regional lymph nodes are resected as one continuous block rather than separately.

No-Touch Technique Principle

The goal of the no-touch technique is to prevent intraoperative implantation and metastasis of tumor cells. All surgical maneuvers avoid direct contact with the tumor and any local metastatic lesions.

Classification of Surgical Procedures in Oncology

Surgical procedures can be classified by their purpose into preventive, diagnostic, curative, and palliative surgeries.

Preventive Surgery

This aims to treat precancerous conditions and prevent malignant transformation. For example, cryptorchidism is a risk factor for testicular cancer; early orchiopexy during childhood reduces the likelihood of cancer development. Patients with familial adenomatous polyposis may benefit from prophylactic colectomy; without it, approximately 50% of these patients will develop colorectal cancer by age 40, and nearly 100% by age 70.

Diagnostic Surgery

The main objective is to determine the nature of the tumor while minimizing trauma and risk. In recent years, endoscopic techniques have been increasingly used for diagnostic purposes. Common procedures include incisional biopsy and excisional biopsy.

Curative Surgery

This involves removing the entire tumor, surrounding potentially involved tissue, and regional lymph nodes to achieve complete tumor excision. Broadly, curative surgery includes tumor excision, wide excision, radical surgery, and extended radical surgery.

Tumor excision is applied to benign tumors, which often have an intact capsule that allows complete removal outside the capsule. It is also suitable for certain tumor-like lesions such as pigmented nevi or hemangiomas.

Wide excision is suitable for soft tissue sarcomas and some well-differentiated surface carcinomas. Surrounding normal tissue is excised along with the tumor, with the extent depending on tumor differentiation and location. For malignant skin tumors, 3–5 cm margins with excision down to the fascia are recommended. If tumors arise from muscle, the involved muscle group is removed entirely; high-grade malignancies may require amputation or joint disarticulation.

Radical surgery involves en bloc removal of all or part of the involved organ and regional lymph nodes. Extended radical surgery removes tissue beyond the standard dissection range. Radical surgery refers to the extent of resection; it does not guarantee complete eradication of disease, as recurrence rates vary. Conversely, other surgical methods may also achieve a cure. The choice of surgical approach for a given tumor should be based on evidence from clinical research. When lymph node dissection is not performed, an R0 resection (complete resection with no residual tumor) may still be indicated. Advances in surgical techniques and comprehensive oncology care have led to greater emphasis on function-preserving radical surgeries, which aim to maintain organ function and quality of life without compromising oncologic outcomes. Minimally invasive approaches, including thoracoscopic/laparoscopic and robot-assisted surgery, are also becoming more advanced. The field is evolving toward combining surgical thoroughness with controlled trauma.

Palliative surgery is performed when curative surgery is no longer feasible, to alleviate symptoms, reduce suffering, improve quality of life, prolong survival, and prevent or manage complications. For instance, palliative partial gastrectomy may control bleeding in advanced gastric cancer; sigmoid colostomy may relieve obstruction caused by rectal cancer. For tumors that are large and invasive, partial resection of the primary or metastatic lesions followed by adjunctive therapies may help control residual disease. This is known as debulking surgery and is used in cases such as ovarian cancer, Burkitt lymphoma, and testicular cancer. R1 surgery refers to gross tumor resection with microscopic residual disease (positive margins), whereas R2 surgery indicates gross residual tumor remains visible.

Treatment of recurrent and metastatic tumors is generally more difficult and less effective than treatment of primary tumors. However, surgical resection combined with other treatments can achieve meaningful results. When feasible, surgery should be considered for recurrent tumors. For example, recurrent soft tissue sarcomas may be managed with wide resection or even joint disarticulation or amputation. Local recurrence of breast cancer may be treated with further local excision. Surgical removal of metastatic tumors is more suitable for patients in whom the primary lesion is well controlled and who have only a single metastatic site.

Reconstructive and rehabilitative surgery aims to restore organ form and function as much as possible by surgically repairing anatomical defects resulting from curative oncologic surgery. Procedures such as breast reconstruction with rectus abdominis muscle flap after modified radical mastectomy and repair of head and neck defects after tumor resection help improve post-treatment quality of life.

Medical Treatment

Clinical oncology treatment forms a vital component of comprehensive tumor therapy. Since the 1950s, chemotherapy has been widely applied in tumor treatment. Over the past 40 years, advances in the understanding of tumor development and rapid progress in drug research have established chemotherapy, targeted therapy, and immunotherapy as key pillars of medical oncology.

Chemotherapy

Chemotherapy, or chemo for short, refers to the use of cytotoxic drugs to inhibit the proliferation of actively dividing tumor cells, aiming to suppress tumor growth and kill some tumor cells. Most chemotherapy drugs are administered intravenously in clinical practice, though some are available for oral, topical, or embolization routes.

Classification of Chemotherapeutic Drugs

Chemotherapeutic agents can be classified based on their chemical structure and origin or their mechanisms of action:

By structure and origin: Includes alkylating agents, antimetabolites, antitumor antibiotics, plant-derived drugs, hormones, and miscellaneous agents.
By mechanism of action: Includes drugs that interfere with nucleic acid biosynthesis, affect DNA structure and function, disrupt transcription and RNA synthesis, interfere with protein synthesis and function, or influence hormonal balance.

Chemotherapy Strategies

Chemotherapy can be stratified according to therapeutic goals and routes of administration.

Based on therapeutic goals, chemotherapy is divided into the following types:

Curative chemotherapy: Aimed at treating chemotherapy-sensitive tumors, such as acute lymphoblastic leukemia, malignant lymphoma, testicular cancer, and choriocarcinoma. Systemic chemotherapy is employed to achieve complete remission and potential cure.
Adjuvant chemotherapy: Administered post-surgery or radiotherapy as part of curative treatment to target potential micrometastases and reduce recurrence or metastasis risk. Early initiation after local treatment can improve cure rates.
Neoadjuvant chemotherapy: Administered before surgery or radiotherapy for localized tumors to shrink the tumor, increase resectability, or reduce surgical or radiation-induced damage, thereby preserving organ function. It additionally addresses micrometastases and lowers the risk of distant metastases, improving prognosis.
Palliative chemotherapy: Used for advanced-stage cancers where surgical treatment is no longer feasible, aiming to prolong survival, relieve symptoms, and improve quality of life.

Based on administration routes, chemotherapy can be divided into systemic and local chemotherapy. Local chemotherapy involves delivering the drug directly to the tumor site to increase localized exposure while minimizing systemic side effects. Techniques include intracavitary chemotherapy, intrathecal chemotherapy, and localized arterial perfusion chemotherapy.

Adverse Effects of Chemotherapy

All chemotherapeutic agents can cause varying degrees of damage to normal cells, leading to a range of adverse effects. These reactions can be categorized as early-onset and delayed toxicity:

Early-onset toxicity: Adverse effects occurring within 4 weeks of administration, including hematologic toxicity, gastrointestinal disturbances, temporary or permanent alopecia, central and peripheral neurotoxicity, liver and kidney damage, and urinary system effects.
Delayed toxicity: Observed in long-term survivors and includes reproductive toxicity (teratogenicity and infertility) and secondary primary tumors.

Targeted Therapy

Targeted therapy primarily includes small-molecule targeted drugs and antibody-based agents (such as monoclonal antibodies, bispecific antibodies, and antibody-drug conjugates or ADCs). Antibodies typically offer high selectivity, although their targets are often limited to cell surface molecules. Due to their large molecular size, antibody-based drugs are administered either intravenously or subcutaneously. In contrast, small-molecule drugs, owing to their smaller size, can target both intracellular and extracellular molecules and are generally administered orally.

Small-Molecule Targeted Drugs

These drugs can be further divided into multi-kinase inhibitors and selective inhibitors:

Multi-kinase inhibitors exhibit antitumor activity by simultaneously targeting multiple cellular kinases.
Selective inhibitors target fewer pathways, antagonizing specific tumor cell targets while minimizing off-target and dose-dependent effects.
Most small-molecule agents are tyrosine kinase inhibitors targeting BCR-ABL, EGFR, mTOR, ROS1, c-MET, RET, VEGFR, PDGFR, BTK, c-KIT, and others. Other commonly used drugs target the MAPK signaling pathway (RAS-RAF-MEK-ERK), such as Raf kinase inhibitors and MEK inhibitors. These agents are widely applied in lung cancer, melanoma, gastrointestinal stromal tumors, renal cancer, and others. Additional small-molecule drugs include cell cycle inhibitors and PARP inhibitors.

Antibody-Based Drugs

Commonly used clinical antibody-based drugs include:

Anti-C-erbB2 antibodies: Such as trastuzumab, pertuzumab, and ADCs, which are widely used for HER2-positive breast cancer, gastric cancer, and urothelial carcinoma.
Anti-EGFR antibodies: Such as cetuximab and panitumumab, used for the treatment of RAS wild-type metastatic colorectal cancer.
Anti-CD20 and CD30 antibodies: For example, rituximab is effective against CD20-positive B-cell lymphomas.
Anti-VEGF receptor or ligand antibodies: Such as bevacizumab and ramucirumab, which normalize tumor vasculature, alleviate hypoxia, and enhance sensitivity to chemotherapy, radiotherapy, and immunotherapy.

Immunotherapy

Tumor immunotherapy is an anti-tumor treatment strategy that has seen rapid development in recent years. Both immune checkpoint inhibitor therapy and chimeric antigen receptor T-cell (CAR-T) therapy were recognized as the most significant scientific breakthroughs of 2013 by the journal Science. The fundamental principle of immunotherapy is to restart and sustain the anti-tumor immune response cycle within the body, restoring the normal immune response against tumors to control or eliminate them. Major approaches include monoclonal antibody-based immune checkpoint inhibitors, therapeutic antibodies, tumor vaccines, cellular immunotherapy, and small molecule inhibitors.

Immune Checkpoints and Therapies

Immune checkpoints are immunosuppressive molecules that regulate immune responses to prevent damage to normal tissues. However, during tumorigenesis and progression, immune checkpoints are a major mechanism of immune tolerance. Immune checkpoint therapy enhances the anti-tumor immune response by modulating T-cell activity through targeting co-inhibitory or co-stimulatory signals. Therapies targeting CTLA-4 and PD-1/PD-L1 are considered milestones in the field of tumor immunotherapy.

Immune Checkpoint Blockade Therapy

Immune checkpoint blockade therapies, such as monoclonal antibodies (mAbs) or bispecific antibodies, can block immune checkpoint pathways to stimulate anti-tumor immune responses. Currently, commonly used immune checkpoint inhibitors (ICIs) include CTLA-4 inhibitors, PD-1 inhibitors, PD-L1 inhibitors, and LAG-3 inhibitors. Several ICIs have been approved by the U.S. Food and Drug Administration (FDA) for the treatment of melanoma, lung cancer, head and neck cancers, lymphoma, urothelial carcinoma, breast cancer, and renal cell carcinoma.

Clinical research has shown that combining CTLA-4 inhibitors with PD-1 inhibitors can produce stronger anti-tumor effects than monotherapies. In addition, inhibitors targeting other immune co-inhibitory molecules, such as TIGIT and TIM-3, have entered clinical trials and are expected to be approved in various countries.

Immune Checkpoint Agonist Therapy

Immune checkpoint agonists selectively activate tumor-specific T-cells that are only partially suppressed or remain partially active. These T-cells release tumor-destroying cytokines and trigger a cascade-like amplification of immune responses via autocrine or paracrine mechanisms, altering or even reversing the immunosuppressive tumor microenvironment. This approach ultimately contributes to tumor elimination. Stimulatory immune checkpoints in this category often belong to the tumor necrosis factor superfamily. Antibodies targeting stimulatory immune checkpoints, such as ICOS, OX40, and 4-1BB, are being actively developed and have entered clinical trials.

Tumor Immune Cell Therapy

Also referred to as adoptive cell therapy, tumor immune cell therapy involves collecting immune cells from the patient's blood or tumor tissue, modifying them ex vivo, and reinfusing them into the patient’s body to kill tumor cells. Commonly utilized immune cells in such therapies include TILs (tumor-infiltrating lymphocytes), LAKs (lymphokine-activated killer cells), CIKs (cytokine-induced killer cells), DCs (dendritic cells), NKs (natural killer cells), TCR-T cells, and CAR-T cells.

Tumor Vaccines

Tumor vaccines are designed to stimulate the body’s immune system to generate a specific anti-tumor immune response against tumor antigens, thus treating tumors or preventing recurrence. These vaccines are characterized by high specificity and minimal adverse effects. Tumor vaccines are categorized into several types, including cell-based vaccines, viral vaccines, protein/peptide vaccines, nucleic acid vaccines, anti-idiotype vaccines, and carbohydrate vaccines.

Other Immunotherapy Approaches

Cytokine Therapy

Cytokines exert their biological effects in a highly efficient manner, often acting locally through autocrine or paracrine mechanisms to modulate immune responses. Cytokine therapy enhances anti-tumor immune responses by altering cytokine concentrations in the tumor microenvironment. Additionally, cytokines serve as adjuvants in tumor vaccines to strengthen specific immune responses.

Oncolytic Virus Therapy

Oncolytic viruses are naturally occurring or genetically engineered viruses that selectively infect and kill tumor cells without harming normal cells. Compared to traditional immunotherapy, oncolytic virus therapy offers advantages such as high specificity, fewer adverse effects, multiple mechanisms for tumor destruction, and reduced risk of resistance. When combined with chemotherapy, radiotherapy, or immunotherapy, oncolytic virus therapy exhibits synergistic effects.

Emerging Strategies

Numerous drugs targeting the immune microenvironment have entered preclinical or early-phase clinical studies. These drugs have the potential for complementary or synergistic effects when used alongside existing immunotherapies, promising to become key components of future combination immunotherapy regimens.

Radiotherapy

Radiotherapy, often abbreviated as RT, is one of the primary treatment modalities for tumors. Approximately 70% of tumor patients require radiotherapy at some stage of their disease.

Types of Radiation

Clinically used radiation can be divided into two major categories:

Electromagnetic Radiation:

X-rays, generated when accelerated electrons strike a metal target.

Gamma (γ) rays, derived from natural or artificial radioactive isotopes.

Particle Radiation:

Alpha (α) rays, positively charged particles consisting of moving helium nuclei.

Beta (β) rays, negatively charged particles, namely electrons.

Others include proton rays, neutron rays, and negative pi-meson (π⁻) rays.

Radiotherapy Techniques

Commonly used clinical radiotherapy techniques include external beam therapy, brachytherapy, and stereotactic radiotherapy such as X-knife and Gamma-knife treatments.

External Beam Therapy

Also called external irradiation, this involves positioning the radiation source at a certain distance outside the body to deliver focused radiation to a targeted anatomical site. It remains the most widely used radiotherapy technique. Protons and heavy ions are emerging areas of interest, as their depth-dose curves exhibit a Bragg peak at the end, followed by a rapid drop to nearly zero. This property allows high-dose delivery to tumors while sparing surrounding healthy tissue, offering particular advantages in pediatric tumors and re-irradiation settings. Preliminary results have been promising.

Brachytherapy

Involves placing the radiation source directly within the diseased tissue or natural body cavities, such as the tongue, nasopharynx, esophagus, and cervix. It is also known as interstitial or intracavitary radiotherapy. Yttrium-90 (Y-90) microsphere selective internal radiation therapy is a specialized form of brachytherapy. It takes advantage of tumor-specific blood supply to selectively retain radioactive material within tumor tissues, delivering short-range radiation to kill tumor cells while minimizing damage to normal tissues. Its safety and efficacy have been clinically validated, particularly in the treatment of primary and metastatic liver cancer.

Stereotactic radiosurgery (SRS)

This technique uses stereotactic, isocentric methods to deliver high-dose, single-fraction radiation (X-rays or γ-rays) precisely to the tumor in three-dimensional space. The targeted lesion undergoes radiation-induced necrosis, while the surrounding normal tissue remains protected due to the steep dose fall-off at the margins, resulting in a sharp knife-like boundary akin to surgical resection. When the radiation source is X-rays, it is called an X-knife; with γ-rays, it is called a Gamma-knife. This approach suits tumors with fixed positions and small volumes—typically, X-knife is used for tumors less than 5 cm in diameter, while Gamma-knife is used for lesions under 3 cm. For larger body tumors or those near sensitive organs, fractionated high-dose stereotactic body radiotherapy (SBRT) is often used, achieving good tumor control with acceptable toxicity.

Intensity-modulated radiotherapy (IMRT)

Uses three-dimensional localization and computer-based inverse planning to shape the high-dose region to match the tumor's shape. This maximizes dose delivery to the lesion while sparing adjacent normal tissues and organs from unnecessary radiation. IMRT helps reduce radiation-related side effects, allows for dose escalation to the tumor, improves treatment outcomes, and enhances patients’ quality of life.

Clinical Applications of Radiotherapy

Curative Radiotherapy

Aims to eradicate tumors completely through radiation to achieve long-term survival. The radiation dose typically approaches the maximum tolerance of surrounding normal tissues.

Palliative Radiotherapy

Focuses on symptom relief and improving quality of life. Radiotherapy is effective in reducing tumor size, relieving compression and obstruction, controlling infections, promoting ulcer healing, achieving hemostasis, alleviating pain, and preventing pathological fractures.

Combined Modality Treatment

In many cases, radiotherapy alone does not provide satisfactory results. Therefore, it is commonly combined with surgery, chemotherapy, targeted therapy, and immunotherapy in clinical oncology to further enhance efficacy.

Indications for Radiotherapy

Tumors suitable for radiotherapy:

Highly radiosensitive tumors such as hematologic malignancies, germ cell tumors, and nephroblastomas (Wilms tumors).
Moderately sensitive superficial tumors and those located in natural body cavities, such as nasopharyngeal carcinoma, esophageal cancer, oral cancer, skin cancer, maxillary sinus cancer, external ear cancer, endolaryngeal cancer, cervical cancer, anal cancer, and liver cancer. Some of these tumors can also be surgically treated, but radiotherapy offers the advantage of preserving function. Nasopharyngeal carcinoma is primarily treated with radiotherapy, while anal cancer is optimally treated with concurrent radiotherapy and chemotherapy.
Malignant tumors located in anatomically challenging positions where surgery cannot achieve radical resection, such as cervical esophageal cancer and middle ear cancer.

Tumors suitable for combined surgery and radiotherapy:

These include breast cancer, esophageal cancer, bronchogenic lung cancer, rectal cancer, brain tumors (including pituitary tumors), cervical cancer, vulvar cancer, penile cancer, skin cancers of the limbs and trunk, and soft tissue sarcomas. Preoperative or postoperative radiotherapy is often used to reduce the risk of local recurrence. Intraoperative radiotherapy is also being explored, whereby a single high-dose of radiation is delivered to the tumor bed and surrounding lymphatic drainage area immediately after tumor excision. Since both radiotherapy and surgery are local treatments, their combination tends to improve local tumor control but has limited impact on reducing distant metastases.

Side Effects and Complications of Radiotherapy

Side effects mainly arise from irradiation of normal tissues and organs. Common adverse effects include radiation-induced skin and mucosal injury, radiation pneumonitis, bone marrow suppression, and gastrointestinal reactions. Additionally, for a small number of long-term survivors, there is a risk of radiation-induced secondary malignancies.

Comprehensive Treatment and Personalized Treatment

In most cases, using a single modality to treat malignant tumors presents significant limitations. A rational combination of multiple treatment approaches tends to achieve better outcomes. As understanding of tumor heterogeneity continues to deepen, along with advances in diagnostic technologies and drug development, increasing attention is being given to personalized precision treatment based on tumor biology.

Comprehensive Treatment of Tumors

Comprehensive treatment involves the planned and rational application of existing multidisciplinary treatment strategies, based on the patient's specific condition—such as physical status, psychological needs, tumor location, pathological type, extent of invasion, molecular characteristics, and disease progression. The goal is to achieve the best possible therapeutic effect, prolong survival, and improve quality of life. Common comprehensive treatment models include:

Conventional model (postoperative radiotherapy and chemotherapy), used in breast cancer and colorectal cancer.
Neoadjuvant chemotherapy/radiotherapy followed by surgery, applied in rectal cancer, osteosarcoma, and stage III breast cancer.
Chemotherapy or radiotherapy prior to surgery for patients who are initially inoperable, such as those with ovarian cancer or testicular cancer.
Concurrent chemoradiotherapy, used for Ewing sarcoma and non-small cell lung cancer.
Chemoradiotherapy combined with biological therapy, applied in non-Hodgkin lymphoma and gastric cancer.
Chemotherapy combined with targeted therapy, used in B-cell lymphoma and breast cancer.

Personalized Treatment of Tumors

Even among patients with similar physical conditions, tumor types, and stages, treatment outcomes may vary considerably. This is largely due to the high degree of tumor heterogeneity. Advances in diagnostic technologies have deepened understanding of this phenomenon. Detailed analysis of the biological characteristics of a patient’s tumor specimen can aid in diagnosis and the formulation of personalized treatment strategies, thereby improving outcomes.

Tumor Prevention and Follow-Up

Prevention

Malignant tumors result from the interaction of various factors, including environment, nutrition, diet, genetics, and viral infections. No single preventive measure is currently available. The Union for International Cancer Control (UICC) states that one-third of cancers can be prevented, one-third can be cured if diagnosed early, and one-third can have symptoms relieved and survival prolonged. Based on this, the concept of three-level prevention of malignant tumors has been proposed.

Primary Prevention

This focuses on preventing the causes of cancer by targeting risk factors. Over 80% of cancers are related to environmental factors, including lifestyle. It is important to modify harmful lifestyle habits, such as quitting smoking and reducing occupational exposure to carcinogens like asbestos, benzene, and certain heavy metals. A balanced diet with reduced fat and cholesterol intake, along with regular exercise, also contributes to cancer prevention.

In recent years, immunoprevention and chemoprevention have emerged as promising areas of primary prevention. Immunoprevention strategies include the large-scale use of the hepatitis B vaccine to prevent liver cancer. Chemoprevention approaches include the use of selective COX-2 inhibitors to prevent colorectal adenomas. However, the long-term efficacy and potential side effects of these preventive measures require further observation and validation.

Secondary Prevention

This involves the early detection, diagnosis, and treatment of malignant tumors. Regular screening of high-risk populations and areas of high incidence is a practical and effective approach. This allows for the detection and treatment of precancerous lesions—such as removing gastrointestinal adenomas or polyps, treating cervical chronic inflammation with atypical hyperplasia, managing chronic gastric ulcers, or treating non-healing leg ulcers. Additionally, identifying and treating early-stage malignant tumors can yield favorable outcomes.

Tertiary Prevention

This level of prevention focuses on clinical treatment, rehabilitation, and palliative care to alleviate patient suffering, improve quality of life, and prolong survival. Comprehensive and personalized treatment approaches are encouraged.

Follow-Up

Tumor treatment should not be considered complete once short-term recovery is achieved after therapy. Active treatment remains necessary in cases of recurrence or metastasis. Regular follow-up and re-examination are therefore essential after tumor treatment.

Follow-up should follow a structured protocol. Typically, during the first two years after treatment for malignant tumors, follow-up should occur at least once every three months. From years three to five, follow-up every six months is advised. After five years, annual follow-up should continue for life. The content of follow-up varies depending on the type of tumor but generally includes the following aspects:

Assessment of Local and Regional Lymph Node Recurrence

For example, after breast cancer surgery, examination of the chest wall, axillary lymph nodes, and supraclavicular lymph nodes is required.

Evaluation of Distant Metastases

Chest CT scans help assess lung metastases. Ultrasound or CT/MRI scans are used to detect liver metastases. In patients with abdominal malignancies, a digital rectal examination should not be omitted postoperatively, as it can detect pelvic implantation metastases. Suspected bone metastases can be evaluated with whole-body bone scans using emission computed tomography (ECT).

Monitoring of Tumor Markers, Hormones, and Biochemical Indicators

For example, complete blood counts should be monitored in leukemia patients; alpha-fetoprotein in liver cancer; carcinoembryonic antigen in colorectal cancer; human chorionic gonadotropin in choriocarcinoma and testicular cancer; and prolactin in postoperative monitoring of pituitary prolactinomas. An increase in these markers during follow-up—especially after initial normalization—often signals tumor recurrence.

Assessment of Immune Function

Evaluating the patient's immune status provides additional information. The outcomes of tumor treatment generally fall into three categories:

Clinical cure: All cancer cells have been eradicated by treatment, or a small number of micrometastatic foci remain that the immune system can eliminate, enabling long-term survival.
Progression: The tumor remains uncontrolled and continues to progress, leading to death.
Recurrence: After a period of remission, new lesions appear because the immune system cannot clear residual or metastatic cancer cells left after treatment.