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Chapter 73: Approach to the Patient with Cancer

Chapter 73 | Part 4: Oncology and Hematology

KEY CLINICAL POINTS

  • Cancer is a multifactorial disease characterized by uncontrolled cell growth and evasion of normal regulatory mechanisms.
  • Age is the most significant risk factor, with 58% of cancer cases occurring in individuals aged >65 years.
  • The TNM staging system (Tumor, Node, Metastasis) is the most widely used for cancer staging.
  • Supportive care and palliative management are critical components of cancer treatment, improving quality of life.
  • Cancer mortality rates have declined globally, but disparities persist among racial/ethnic groups.

1. DEFINITION & OVERVIEW

Cancer arises from cellular dysfunction and uncontrolled proliferation, diverging from normal cellular collaboration. It is characterized by malignant transformation, invasion, and metastasis. The disease profoundly impacts patient identity and self-image, often leading to psychological distress.

Table 73-1 Distribution of Cancer Incidence and Deaths for 2021

MALE FEMALE
SITES % NUMBER SITES % NUMBER
Prostate 29 299,010 Breast 32 310,720
Lung 11 116,310 Lung 12 118,270
Colorectal 8 81,540 Colorectal 7 71,270
Bladder 6 63,070 Endometrial 7 67,880
Melanoma 6 59,170 Melan,oma 4 41,470
Kidney 5 52,380 Lymphoma 4 36,030
Lymphoma 4 44,590 Pancreas 3 31,910
Oral cavity 4 41,510 Thyroid 3 31,520
Leukemia 4 36,450 Kidney 3 29,230
Pancreas 3 34,530 Leukemia 3 26,320
All others 19 200,520 All others 21 207,440
All sites 100 1,029,080 All sites 100 972,060

Table 73-2 The Five Leading Primary Tumor Sites for Patients Dying of Cancer

AGE, YEARS RANK SEX ALL AGES UNDER 20 20–39 40–49 50-64 65–79 >80
1 M Lung CNS Colorect al Colorect al Lung Lung Lung
1 F Lung CNS Breast Breast Lung Lung Lung
2 M Prostate Leukemi a CNS Lung Colorect al Prostate Prostate
2 F Breast Leukemi a Cervix Colorect al Breast Breast Breast
3 M Colorect al Bone sarcoma Leukemi a CNS Pancrea s Liver Colorect al
3 F Colorect al Soft tissue sarcoma Colorect al Lung Colorect al Pancrea s Colorect al
4 M Pancrea s Soft tissue sarcoma Testis Pancrea s Liver Bladder Pancrea s
4 F Pancrea s Bone sarcoma CNS Cervix Pancrea s Colorect al Pancrea s
5 M Liver Lympho ma Lympho ma Esophag us Esophag us Liver Pancrea s
5 F Ovary Kidney Leukemi a Ovary Ovary Ovary Leukemi a

1.1 Cellular and Molecular Basis

Cancer cells exhibit genetic mutations, altered signaling pathways, and resistance to apoptosis. They exploit evolutionary mechanisms of natural selection to outcompete normal cells. Molecular markers (e.g., Ki67, t(8;14) translocation) aid in diagnosis and prognosis.

1.2 Clinical Impact

Cancer diagnosis disrupts patient identity and social roles. Patients often experience existential distress, with the disease perceived as a betrayal of the body. Psychological and social consequences are significant, requiring holistic management.

2. EPIDEMIOLOGY

Cancer is the second leading cause of death globally, with age being the most significant risk factor. Incidence increases exponentially with age, with 58% of cases occurring in individuals >65 years. Disparities exist among racial/ethnic groups, with higher mortality rates in Black populations for certain cancers.

Table 73-3 Cancer Incidence and Mortality in Racial and Ethnic Groups

SITE SEX WHITE BLACK ASIAN/PA CIFIC ISLANDER AMERICA N INDIAN HISPANIC
Incidence per 100,000 Population All M 511.2 533.9 299.0 504.1 377.2
SITE SEX WHITE BLACK ASIAN/PA CIFIC ISLANDER AMERICA N INDIAN HISPANIC
Incidence per 100,000 Population All F 499.3 409.9 307.3 465.5 351.3
Incidence per 100,000 Population Breast M 134.9 129.6 104.6 115.5 100.7
Incidence per 100,000 Population Colorectal M 40.4 48.8 33.4 57.8 38.2
Incidence per 100,000 Population Colorectal F 30.5 35.0 23.7 43.7 27.2
Incidence per 100,000 Population Kidney M 24.3 26.4 11.6 43.9 23.5
Incidence per 100,000 Population Kidney F 12.1 13.7 5.5 23.9 13.3
Incidence per 100,000 Population Liver M 11.2 17.0 18.4 27.3 20.4
Incidence per 100,000 Population Liver F 4.2 5.5 6.7 12.3 8.4
Incidence per 100,000 Population Lung M 765.7 72,4 40.8 67.2 34.3
Incidence per 100,000 Population Lung F 54.8 45.8 28.1 58.6 24.0
Incidence per 100,000 Population Prostate M 110.7 186.1 60.9 91.9 90.9
Incidence per 100,000 Population Stomach M 7.1 13.0 11.8 13.1 11.4
Incidence per 100,000 Population Stomach F 3.4 7.4 6.9 7.8 7.7
Incidence per 100,000 Population Cervix M 7.2 8.6 6.0 11.4 9.7
Incidence per 100,000 Population Endometrial M 27.9 28.9 21.7 30.4 25.8

In 2024, 2.001 million new cancer cases were diagnosed, with lung cancer being the most common. Breast cancer is the second most common globally but ranks fourth in mortality. Disparities persist, with higher incidence in Asia and lower-income regions.

2.2 Racial/Ethnic Disparities

Table 73-3 shows incidence and mortality rates by race/ethnicity. Black populations have higher mortality rates for prostate, stomach, and uterine cancers. Asian populations have lower incidence but higher mortality for certain cancers.

3. ETIOLOGY & PATHOPHYSIOLOGY

Cancer arises from genetic mutations, epigenetic changes, and environmental exposures. Key drivers include oncogene activation, tumor suppressor inactivation, and genomic instability. Environmental factors like smoking, radiation, and infections (e.g., HPV, HBV) contribute to carcinogenesis.

Table 73-6 Tumor Markers

TUMOR MARKERS CANCER NONNEOPLASTIC CONDITIONS
Hormones Human chorionic gonadotropin Gestational trophoblastic disease, gonadal germ cell tumor, Pregnancy
Hormones Calcitonin Medullary cancer of the thyroid
Hormones Catecholamines Pheochromocytoma
Oncofetal Antigens a Fetoprotein Hepatocellular carcinoma, Cirrhosis, hepatitis, gonadal germ cell tumor
Oncofetal Antigens Carcinoembryonic antigen Adenocarcinomas of the colon, pancreas, lung, breast, ovary, Pancreatitis, hepatitis, inflammatory bowel disease, smoking
Enzymes Prostatic acid phosphatase Prostate cancer, Prostatitis, prostatic hypertrophy
Enzymes Neuron-specific enolase Small-cell cancer of the lung, neuroblastoma
Enzymes Lactate dehydrogenase Lymphoma, Ewing’s sarcoma, Hepatitis, hemolytic anemia, many others
Tumor-Associated Proteins Prostate-specific antigen Prostate cancer, Prostatitis, prostatic hypertrophy
Tumor-Associated Proteins CA-125 Ovarian cancer, some lymphomas, Menstruation, peritonitis, pregnancy
Tumor-Associated Proteins CA 19-9 Colon, pancreatic, breast cancer, Pancreatitis, ulcerative colitis
Tumor-Associated Proteins CD30 Hodgkin’s disease, anaplastic large-cell lymphoma
Tumor-Associated Proteins CD25 Hairy cell leukemia, adult T-cell leukemia/lymphoma

3.1 Genetic and Molecular Mechanisms

Mutations in oncogenes (e.g., RAS, MYC) and tumor suppressors (e.g., TP53, BRCA) drive malignant transformation. Epigenetic alterations (e.g., DNA methylation, histone modification) also contribute to cancer progression.

3.2 Environmental and Lifestyle Factors

Smoking, alcohol consumption, obesity, and exposure to carcinogens (e.g., asbestos, UV radiation) increase cancer risk. Infections like HPV, HBV, and H. pylori are linked to specific cancers (e.g., cervical, liver, gastric).

4. CLINICAL FEATURES

Symptoms vary by cancer type but include weight loss, fatigue, pain, and organ-specific manifestations. Psychological and social impacts are profound, with patients often experiencing anxiety, depression, and altered self-image.

4.1 Common Symptoms

Weight loss, fatigue, pain, and systemic symptoms (e.g., cachexia, paraneoplastic syndromes) are prevalent. Localized symptoms depend on tumor location (e.g., jaundice for liver cancer, hematuria for bladder cancer).

4.2 Psychological Impact

Patients often experience existential distress, fear of recurrence, and altered self-perception. Depression affects ~25% of cancer patients, with higher rates in those with greater functional impairment.

5. DIFFERENTIAL DIAGNOSIS

Differential diagnosis includes infectious diseases, benign tumors, and other malignancies. Conditions like infections (e.g., cholecystitis), metabolic disorders, and non-malignant tumors must be considered.

6. INVESTIGATIONS & DIAGNOSIS

Diagnosis relies on imaging (CT, MRI), biopsy, and tumor markers. Staging systems (e.g., TNM) guide treatment decisions. Pathologic staging involves surgical evaluation of tissue and lymph nodes.

Table 73-4 Karnofsky Performance Index

PERFORMANCE STATUS FUNCTIONAL CAPABILITY OF THE PATIENT
100 Normal; no complaints; no evidence of disease
90 Able to carry on normal activity; minor signs or symptoms of disease
80 Normal activity with effort; some signs or symptoms of disease
70 Cares for self; unable to carry on normal activity or do active work
60 Requires occasional assistance but is able to care for most needs
50 Requires considerable assistance and frequent medical care
40 Disabled; requires special care and assistance
30 Severely disabled; hospitalization is indicated, although death is not imminent
20 Very sick; hospitalization is necessary; active supportive treatment is necessary
PERFORMANCE STATUS FUNCTIONAL CAPABILITY OF THE PATIENT
10 Moribund, fatal processes progressing rapidly
0 Dead

Table 73-5 Eastern Cooperative Oncology Group (ECOG) Performance Scale

ECOG grade Description
0 Fully active, able to carry on all predisease performance without restriction
1 Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature
2 Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about >50% of waking hours
3 Capable of only limited self-care, confined to bed or chair >50% of waking hours
4 Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair
5 Dead

6.1 Diagnostic Tests

Imaging (CT, MRI, PET), biopsy, and tumor markers (e.g., PSA, CA-125) are critical. Molecular testing (e.g., FISH, NGS) identifies genetic abnormalities for targeted therapies.

6.2 Staging Systems

TNM staging (Tumor, Node, Metastasis) is the gold standard. Other systems include Dukes for colorectal cancer and Ann Arbor for lymphoma.

7. MANAGEMENT & TREATMENT

Treatment is multidisciplinary, combining surgery, chemotherapy, radiation, and supportive care. Palliative care is essential for advanced disease. Personalized approaches based on staging and biomarkers are critical.

7.1 Curative vs. Palliative Therapy

Curative approaches (surgery, chemo, radiation) are used for early-stage disease. Palliative care focuses on symptom management and quality of life for advanced or metastatic cancer.

7.2 Treatment Modalities

Surgery, chemotherapy, radiation, immunotherapy, and targeted therapies are used based on tumor type and stage. Neoadjuvant therapy may precede definitive treatment.

8. PROGNOSIS & COMPLICATIONS

Prognosis depends on stage, biomarkers, and patient comorbidities. Complications include treatment toxicity, infections, and late effects (e.g., secondary cancers, organ failure). Long-term follow-up is essential for recurrence detection.

8.1 Survival and Recurrence

5-year survival rates vary by cancer type. Early-stage cancers have higher cure rates, while advanced disease is associated with poor prognosis. Recurrence risk is highest within the first 2 years post-treatment.

Chemotherapy toxicity (e.g., myelosuppression), radiation side effects, and surgical complications (e.g., infections, organ dysfunction) are common. Late effects include secondary malignancies and endocrine disorders.

9. SPECIAL CONSIDERATIONS

Special populations require tailored approaches. Pregnancy, pediatric cancers, and geriatric patients face unique challenges. Racial disparities in cancer outcomes persist, necessitating equitable care strategies.

9.1 Pregnancy and Cancer

Cancer during pregnancy requires balancing maternal and fetal risks. Chemotherapy and radiation may be delayed until postpartum. Certain cancers (e.g., breast, cervical) have higher incidence in pregnant women.

9.2 Pediatric and Geriatric Patients

Pediatric cancers often present with atypical symptoms and require dose-adjusted therapies. Elderly patients face higher risks of treatment toxicity and comorbidities, requiring careful risk-benefit analysis.

10. KEY POINTS & CLINICAL PEARLS

  1. Age is the most significant cancer risk factor, with incidence increasing exponentially with age.
  2. TNM staging is critical for treatment planning and prognosis.
  3. Palliative care improves quality of life and should be integrated early in advanced disease.
  4. Tumor markers (e.g., PSA, CA-125) aid in diagnosis and monitoring.
  5. Multidisciplinary care and patient-centered communication are essential for optimal outcomes.