Approach to the Patient with Cancer¶
Oncology and Hematology | Part 4 | Section 1 Neoplastic Disorders · Part 4 – Oncology: Solid Tumors · Chapter 73
Key Clinical Points¶
- Biopsy is mandatory for cancer diagnosis; exception: Hepatocellular Carcinoma (HCC) can be diagnosed via CT/MRI perfusion patterns.
- Staging is essential: Clinical staging (physical exam, imaging) vs. Pathologic staging (surgical resection, lymph node biopsy).
- TNM System: T (Tumor size), N (Nodes), M (Metastasis); stages I–IV based on permutations of these factors.
- Physiologic reserve assessment (Karnofsky Performance Index or ECOG Performance Scale) is critical for predicting treatment tolerance and determining intent (Curative vs. Palliative).
- Depression screening is critical: Incidence ≈ 25%; treat with SSRIs (fluoxetine 10–20 mg/d, sertraline 50–150 mg/d) or TCAs (amitriptyline 50–100 mg/d, nortriptyline 25–150 mg/d).
- RECIST Criteria: Complete response (disappearance of disease), Partial response (>50% reduction), Stable disease, Progressive disease (>25% increase).
- Tumor Markers are used for monitoring response, not for primary diagnosis (e.g., CEA, CA-125, PSA).
- Multidisciplinary team approach: Medical oncologists, surgical oncologists, radiation oncologists, nurses, pharmacists, and social workers.
- Follow-up: Historically monthly for 6–12 months; current guidelines emphasize history/physical as primary investigations.
- Global Disparities: Lung cancer is the leading cause of death worldwide; other cancers (liver, cervical, esophageal) are more prevalent in less developed countries.
1. DEFINITION & OVERVIEW¶
• Core Pathology: Cancer represents a breakdown of cellular cooperation and programmed death mechanisms. • Key Features: ◦ Cancer cells evade normal regulatory controls → uncontrolled proliferation. ◦ Patients experience profound psychological impact due to perceived bodily invasion. ◦ Unlike organ-specific diseases, cancer disrupts self-image and social roles. ◦ The disease's evolutionary analogy mirrors natural selection favoring malignant traits. • Clinical Context: ◦ Mortality: Median survival for pancreatic cancer equals that of aortic stenosis with CHF (≈ 8 months). ◦ Prevalence: 2.001 million new cases diagnosed annually in the US; 611,720 cancer-related deaths annually. ◦ Success Rate: Two-thirds of patients achieve cure with current therapies.
1.1 Magnitude of the Problem¶
• Global Burden: 20 million new cases and 9.7 million deaths estimated globally in 2022. • Primary Cause: Lung cancer is most common (18.4% of all cancers) and leading cause of death (25.3% of cancer deaths).
2. EPIDEMIOLOGY: Incidence and Mortality Trends¶
• Global Trends: ◦ Lung cancer: 18.4% of all cancers; 25.3% of deaths. ◦ Regional Disparities: Asia accounts for 59.2% of population but 46% of cases. • Modifiable Risk Factors (>30% of global burden): ◦ Smoking (18.1%), Alcohol (5.7%), Obesity (5.6%), Physical inactivity (3.2%). • Age as Primary Driver: ◦ 58% of cases occur in >65 years. ◦ Lifetime cancer risk: 40.5% for men, 38.9% for women. ◦ Age-specific incidence: - <50: 1/29 men, 1/19 women - 50–59: 1/15 men, 1/17 women - 60–69: 1/6 men, 1/10 women - ≥70: 1/3 men, 1/4 women
2.1 Regional and Demographic Distribution¶
• Developed Countries: Higher incidence of lung (2 imes), breast (3 imes), prostate (2.5 imes), colorectal (3 imes). • Less Developed Countries: Higher rates of liver (2 imes), cervical (2 imes), esophageal (2–3 imes). • Africa: Cervical, breast, and liver cancers dominate. • Asia: Stomach cancer incidence is 2 imes higher than in North America. • Racial/Ethnic Disparities: Black patients have twice the mortality for prostate, stomach, and uterine corpus cancers. • Table 73-1 Summary: Highlights high incidence of Prostate (29%) and Breast (32%); Lung cancer is a leading cause of death for both sexes (20% men, 21% women).
3. ETIOLOGY & PATHOPHYSIOLOGY¶
• Drivers: Complex interactions between genetic and environmental factors. • Risk Factors: 9 modifiable risk factors account for >30% of global burden (Smoking, Alcohol, Obesity, Physical inactivity). • Molecular Features: ◦ Genetic heterogeneity: Tumors with identical morphology may have distinct molecular profiles. ◦ Proliferation markers: Ki-67 correlates with aggressive behavior. • Host Factors: Influence treatment response through drug metabolism genes.
4. CLINICAL MANIFESTATIONS¶
• Clinical Evaluation: ◦ History: Identify occupational exposures, family cancer syndromes, and paraneoplastic symptoms. ◦ Physical Exam: Identify local tumor effects (masses, lymphadenopathy) and systemic signs (weight loss, fatigue). • Staging Framework: ◦ Clinical staging: Imaging (CT, MRI), physical exam. ◦ Pathologic staging: Surgical findings, histology. • TNM System: ◦ T: Tumor size (T1–4) ◦ N: Node involvement (N0–N3) ◦ M: Metastasis (M0–M1)
4.1 Physiologic Reserve Assessment¶
• Purpose: Predicts treatment tolerance and determines intensity of therapy. • Karnofsky Performance Index (Table 73-4): ◦ 100: Normal; no complaints; no evidence of disease. ◦ 90: Able to carry on normal activity; minor signs/symptoms. ◦ 70: Cares for self; unable to carry on normal activity or do active work. • ECOG Performance Scale (Table 73-5): ◦ Grade 0: Fully active, no restrictions. ◦ Grade 1: Restricted in physically strenuous activity; ambulatory; light/sedentary work. ◦ Grade 2: Ambulatory; capable of all self-care; unable to carry out any work activities. Up and about >50% of waking hours. ◦ Grade 3: Limited self-care; confined to bed or chair >50% of waking hours. ◦ Grade 4: Completely disabled; cannot carry on any self-care; totally confined to bed/chair. ◦ Grade 5: Dead.
5. DIFFERENTIAL DIAGNOSIS¶
• Diagnostic Requirement: Tissue confirmation is mandatory for most cancers. • Exception: Hepatocellular carcinoma (HCC) can be diagnosed via CT/MRI perfusion patterns. • Tumor Markers (Table 73-6): Used for monitoring response, NOT primary diagnosis. ◦ α-Fetoprotein: Hepatocellular carcinoma, gonadal germ cell tumor. ◦ Catecholamines: Pheochromocytoma. ◦ Carcinoembryonic antigen: Adenocarcinomas of the colon, pancreas, lung, breast, ovary. ◦ Neuron-specific enolase: Small-cell cancer of the lung, neuroblastoma. ◦ Prostate-specific antigen (PSA): Prostate cancer. ◦ CA-125: Ovarian cancer, some lymphomas. ◦ CD30: Hodgkin’s disease, anaplastic large-cell lymphoma. ◦ CD25: Hairy cell leukemia, adult T-cell leukemia/lymphoma. • Clinical Utility of Specific Markers: ◦ CEA: Elevated in 70% of colon cancers; normal <2.5 ng/mL. ◦ CA-125: Elevated in 80% of ovarian cancers; normal <35 U/mL. ◦ PSA: Elevated in 90% of prostate cancers; normal <4 ng/mL. • Limitations: Non-specificity, false positives in benign conditions (e.g., CA-125 in peritonitis or pregnancy).
6. INVESTIGATIONS & DIAGNOSIS¶
• Staging Framework: ◦ Clinical staging: Physical exam and imaging (CT, MRI). ◦ Pathologic staging: Surgical findings and histology. • Neoadjuvant Therapy: Pre-surgery treatment indicated by 'y' in staging; applicable for breast, head/neck, and lung cancers. • TNM Classification: ◦ T: Tumor size (T1–4) ◦ N: Node involvement (N0–N3) ◦ M: Metastasis (M0–M1) • Staging Algorithm (Figure 73-5): 1. Clinical Staging → Physical exam & Imaging. 2. Pathologic Staging → Surgical findings & Histology. 3. TNM Integration → Determine T, N, and M status. 4. Treatment Intent Determination → Based on ECOG/Karnofsky scores. • Age-Specific Patterns (Table 73-2): ◦ <20: CNS, leukemia dominate. ◦ 20–39: Breast (females), testicular (males) common. ◦ 40–49: Colorectal (both sexes), lung (males). ◦ >80: Lung, prostate (males); breast, colorectal (females).
6.1 Response Assessment¶
• RECIST Criteria: ◦ Complete response: Disappearance of disease. ◦ Partial response: >50% reduction. ◦ Stable disease. ◦ Progressive disease: >25% increase.
7. TREATMENT STRATEGIES¶
- Multidisciplinary Team Assembly:
- Medical oncologist (chemotherapy, immunotherapy).
- Surgical oncologist (resection, biopsy).
- Radiation oncologist (external beam, brachytherapy).
- Palliative care specialist (symptom management).
- Social worker (support services).
- Treatment Intensity Determination:
- ECOg 0–1 → Curative intent possible.
- ECOG ≥ 2 → Palliative focus.
- Depression Management:
- Screening: Use PHQ-9; score ≥ 10 indicates depression.
- Treatment (SSRIs): Fluoxetine 10–20 mg/d, Sertraline 50–150 mg/d.
- Treatment (TCAs): Amitriptyline 50–100 mg/d, Nortriptyline 25–150 mg/d.
- Monitoring: Watch for serotonin syndrome.
- Follow-up Protocol:
- Historical: Monthly for 6–12 months → less frequent.
- Current: History and physical are primary investigations.
Treatment Complications¶
• Chemotherapy: Myelosuppression, neuropathy. - Radiation: Dermatitis, fibrosis. - Surgery: Infection, anastomotic leak. - Immunotherapy: Immune-related adverse events (pneumonitis, colitis).
8. PROGNOSIS & COMPLICATIONS¶
• Prognostic Factors: ◦ Stage: Strongest predictor of survival. ◦ Performance Status: ECOG ≥ 2 correlates with <6-month survival. • Late Complications: ◦ Radiation: Secondary malignancies, fibrosis. ◦ Chemotherapy: Cardiotoxicity, secondary leukemia. ◦ Surgery: Chronic pain, functional impairment.
9. SPECIAL CONSIDERATIONS¶
• Geriatric Assessment: Comprehensive evaluation of frailty, cognition, and comorbidities to tailor treatment. • Palliative Care: Early referral improves quality of life. • Global Disparities: Address socioeconomic barriers to treatment access.
10. KEY PEARLS & CLINICAL TRAPS¶
• Biopsy Rule: Never diagnose cancer without tissue biopsy (except HCC). • Monitoring vs. Diagnosis: Tumor markers are monitoring tools, not diagnostic tests. • Response Criteria: Use RECIST for objective response assessment. • Performance Status: The best predictor of treatment tolerance and survival. • Multidisciplinary Care: Standard of care involving medical, surgical, and radiation oncology.
Reference Tables¶
TABLE 73-1 Distribution of Cancer Incidence and Deaths for 2021 SITES Cancer Incidence Prostate Lung Colorectal Bladder…¶
Harrison's 22e, p.497
| MALE | FEMALE | ||||
|---|---|---|---|---|---|
| SITES | % | NUMBER | SITES | % | NUMBER |
| Cancer Incidence | |||||
| Prostate | 29 | 299,010 | Breast | 32 | 310,720 |
| 11 | 116,310 | Lung | 12 | ||
| Colorectal | 8 | 81,540 | Colorectal | 7 | 71,270 |
| 6 | 63,070 | Endometrial | 7 | ||
| Melanoma | 6 | 59,170 | Melanoma | 4 | 41,470 |
| 5 | 52,380 | Lymphoma | 4 | ||
| Lymphoma | 4 | 44,590 | Pancreas | 3 | 31,910 |
| 4 | 41,510 | Thyroid | 3 | ||
| Leukemia | 4 | 36,450 | Kidney | 3 | 29,230 |
| 3 | 34,530 | Leukemia | 3 | ||
| All others | 19 | 200,520 | All others | 21 | 207,440 |
| 100 | 1,029,080 | All sites | 100 | ||
| Cancer Deaths | |||||
| Lung | 20 | 65,790 | Lung | 21 | 59,280 |
| 11 | 35,250 | Breast | 15 | ||
| Colorectal | 9 | 28,700 | Pancreas | 8 | 24,480 |
| 8 | 25,270 | Colorectal | 8 | ||
| Liver | 6 | 19,120 | Endometrial | 5 | 13.250 |
| 4 | 13,640 | Ovary | 4 | ||
| Esophagus | 4 | 12,880 | Liver | 3 | 10,720 |
| 4 | 12,290 | Leukemia | 3 | ||
| Lymphoma | 4 | 11,780 | Lymphoma | 3 | 8,360 |
| 3 | 10,690 | CNS | 3 | ||
| All others | 27 | 87,390 | All others | 26 | 75,4330 |
| 100 | 322,800 | All sites | 100 |
TABLE 73-2 The Five Leading Primary Tumor Sites for Patients Dying of Cancer Based on Age and Sex in 2018 RANK 1 2 3 4 5¶
Harrison's 22e, p.500
| RANK | SEX | ALL AGES | AGE, YEARS | |||||
|---|---|---|---|---|---|---|---|---|
| UNDER 20 | 20–39 | 40–49 | 50-64 | 65–79 | >80 | |||
| 1 | M | Lung | CNS | Colorectal | Colorectal | Lung | Lung | Lung |
| F | Lung | CNS | Breast | Breast | Lung | Lung | Lung | |
| M F |
Prostate Breast |
Leukemia Leukemia |
CNS Cervix |
Lung Colorectal |
Colorectal Breast |
Prostate Breast |
||
| 3 | M | Colorectal | Bone sarcoma | Leukemia | CNS | Pancreas | Liver | Colorectal |
| F | Colorectal | Soft tissue sarcoma | Colorectal | Lung | Colorectal | Pancreas | Colorectal | |
| M F |
Pancreas Pancreas |
Soft tissue sarcoma Bone sarcoma |
Testis CNS |
Pancreas Cervix |
Liver Pancreas |
Colorectal Colorectal |
||
| 5 | M | Liver | Lymphoma | Lymphoma | Esophagus | Esophagus | Liver | Pancreas |
| F | Ovary | Kidney | Leukemia | Ovary | Ovary | Ovary | Leukemia |
TABLE 73-3 Cancer Incidence and Mortality in Racial and Ethnic Groups, United States, 2016–2020 SITE Incidence per…¶
Harrison's 22e, p.501
| SITE | SEX | WHITE | BLACK | ASIAN/PACIFIC ISLANDER |
AMERICAN INDIANa | HISPANIC |
|---|---|---|---|---|---|---|
| Incidence per 100,000 Population | ||||||
| All | M | 511.2 | 533.9 | 299.0 | 504.1 | 377.2 |
| F | 499.3 | 409.9 | 307.3 | 465.5 | 351.3 | |
| 134.9 | 129.6 | 104.6 | 115.5 | |||
| Colorectal | M | 40.4 | 48.8 | 33.4 | 57.8 | 38.2 |
| F | 30.5 | 35.0 | 23.7 | 43.7 | 27.2 | |
| M F |
24.3 12.1 |
26.4 13.7 |
11.6 5.5 |
43.9 23.9 |
||
| Liver | M | 11.2 | 17.0 | 18.4 | 27.3 | 20.4 |
| F | 4.2 | 5.5 | 6.7 | 12.3 | 8.4 | |
| M F |
765.7 54.8 |
72,4 45.8 |
40.8 28.1 |
67.2 58.6 |
||
| Prostate | 110.7 | 186.1 | 60.9 | 91.9 | 90.9 | |
| M F |
7.1 3.4 |
13.0 7.4 |
11.8 6.9 |
13.1 7.8 |
||
| Cervix | 7.2 | 8.6 | 6.0 | 11.4 | 9.7 | |
| 27.9 | 28.9 | 21.7 | 30.4 | |||
| Deaths per 100,000 Population | ||||||
| All | M | 183.3 | 217.4 | 111.6 | 221.6 | 130.2 |
| F | 133.6 | 150.2 | 83.7 | 157.9 | 93.5 | |
| 19.7 | 27.8 | 11.8 | 21.1 | |||
| Colorectal | M | 15.5 | 22.4 | 11.0 | 23.1 | 13.6 |
| F | 11.1 | 14.4 | 7.8 | 16.0 | 8.5 | |
| M F |
5.3 2.3 |
5.2 2.2 |
2.4 1.0 |
9.9 4.2 |
||
| Liver | M | 8.5 | 13.0 | 12.6 | 19.9 | 13.1 |
| F | 3.7 | 4.8 | 5.2 | 8.8 | 6.0 | |
| M F |
44.9 32.9 |
51.3 28.0 |
25.9 15.6 |
52.3 37.0 |
||
| Prostate | 17.9 | 37.9 | 8.7 | 22.5 | 15.4 | |
| M F |
2.9 1.5 |
7.2 3.5 |
6.0 3.7 |
7.7 4.1 |
||
| Cervix | 2.0 | 3.3 | 1.7 | 2.3 | 2.5 | |
| 4.6 | 9.1 | 3.5 | 4.9 |
TABLE 73-4 Karnofsky Performance Index¶
Harrison's 22e, p.503
| PERFORMANCE STATUS |
FUNCTIONAL CAPABILITY OF THE PATIENT |
|---|---|
| 100 | Normal; no complaints; no evidence of disease |
TABLE 73-5 The Eastern Cooperative Oncology Group (ECOG) Performance Scale ECOG grade 0: Fully active, able to carry on…¶
Harrison's 22e, p.503
| ECOG grade 0: Fully active, able to carry on all predisease performance without restriction |
|
|---|---|
| ECOG grade 1: Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light housework, office work |
|
| ECOG grade 2: Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about >50% of waking hours |
|
| ECOG grade 3: Capable of only limited self-care, confined to bed or chair >50% of waking hours |
|
| ECOG grade 4: Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair |
|
| ECOG grade 5: Dead | |
| 80 | Normal activity with effort; some signs or symptoms of disease |
| 60 | Requires occasional assistance but is able to care for most needs |
| 40 | Disabled; requires special care and assistance |
| 20 | Very sick; hospitalization is necessary; active supportive treatment is necessary |
| 0 | Dead |
TABLE 73-6 Tumor Markers¶
Harrison's 22e, p.504
| TUMOR MARKERS |
CANCER | NONNEOPLASTIC CONDITIONS |
|---|---|---|
| Hormones | ||
| Human chorionic gonadotropin |
Gestational trophoblastic disease, gonadal germ cell tumor |
Pregnancy |
| Medullary cancer of the thyroid | ||
| Catecholamines | Pheochromocytoma | |
| Oncofetal Antigens | ||
| Hepatocellular carcinoma, gonadal germ cell tumor |
||
| Carcinoembryonic antigen |
Adenocarcinomas of the colon, pancreas, lung, breast, ovary |
Pancreatitis, hepatitis, inflammatory bowel disease, smoking |
| Enzymes | ||
| Prostate cancer | ||
| Neuron-specific enolase |
Small-cell cancer of the lung, neuroblastoma |
|
| Lymphoma, Ewing’s sarcoma | ||
| Tumor-Associated Proteins | ||
| Prostate-specific antigen |
Prostate cancer | Prostatitis, prostatic hypertrophy |
| Myeloma | ||
| CA-125 | Ovarian cancer, some lymphomas | Menstruation, peritonitis, pregnancy |
| Colon, pancreatic, breast cancer | ||
| CD30 | Hodgkin’s disease, anaplastic large-cell lymphoma |
— |
| Hairy cell leukemia, adult T-cell leukemia/lymphoma |