Principles of cancer care

Cancer is one of the greatest health care concerns for patients and their health care providers. An individual's lifetime risk of developing cancer is approximately 40% and cancer is the second leading cause of death in the United States. Once cancer is confirmed, further diagnostics to assess the tumor grade and tumor stage are required, and a comprehensive assessment of the patient (e.g., evaluation of nutritional status, social support, and mental health) should be performed. Treatment (curative or palliative) is based on the characteristics of the tumor and the ability of the patient to tolerate therapy. Anticancer therapy may include a combination of surgery, chemotherapy, immunotherapy, radiation therapy, and/or targeted therapy. Complications arise frequently as a result of cancer progression or as a consequence of cancer treatment; proactive management (e.g., prophylactic antiemetic regimens for chemotherapy) may greatly improve patients' quality of life. The majority of cancer treatment is managed by oncologists but all health care providers will see patients who have cancer as a comorbidity and should be familiar with common treatments, complications, and the need for multidisciplinary cancer care.

Characterizing the cancer ^[1]

• Confirmation of cancer
  • Typically confirmed if malignant cells are identified on histopathologic analysis of a tissue sample
  • If the location is challenging to biopsy or the patient is frail and has advanced disease, the diagnosis may be assumed based on characteristic imaging and/or tumor markers. ^[2]
• Once confirmed, additional disease characteristics are determined in order to plan management.
  • Tumor grading
    • Based on histopathologic findings
    • Usually classified from low-grade (well-differentiated) to high-grade (poorly differentiated or undifferentiated) tumors
  • Tumor staging: identifies the extent of spread with additional diagnostics (e.g., imaging, biopsies)
  • Molecular profile: characterizes mutations, specific proteins, and tumor cell markers ^[1][3][4]
  • See “General oncology” for additional information.

Anticancer treatment plans ^[5][6]

Treatment plans are typically developed and overseen by a multidisciplinary team (e.g., medical oncology, surgical oncology, radiation oncology, palliative care).

• Educate the patient about the nature of their disease and treatment options to facilitate shared decision-making.
• Perform a multidisciplinary pretreatment evaluation (see “Preparation for cancer treatment”).
• Establish treatment goals and clearly communicate them to the patient. ^[7]
  • Curative therapy: The aim is to cure the disease.
  • Palliative therapy: The aim is to prolong survival or relieve symptoms and improve the quality of life.
• Select therapy: typically a combination of different treatment modalities (e.g., surgery, chemotherapy, radiotherapy).
• Determine the timeline and estimated duration of treatment.
• Discuss possible enrollment in clinical trials with the patient.
• Discuss advance care planning for patients receiving palliative treatment.

Shared decision-making is vital in cancer care; patient and clinician priorities might be different. ^[8]

Anticancer therapies

Surgery ^[9]

• Complete resection (potentially curative): The entire tumor is removed along with a margin of surrounding healthy tissue.
• Partial resection (typically palliative): The tumor is debulked to facilitate systemic therapy and/or provide symptom relief.

Chemotherapy ^[10]

• Curative chemotherapy: an aggressive regimen of chemotherapeutic agent(s) administered with the intention of achieving complete remission
  • Induction chemotherapy: chemotherapy utilized to drastically reduce the tumor cell count
  • Consolidation chemotherapy: chemotherapy utilized to eradicate remaining tumor cells
  • Maintenance chemotherapy: low-dose chemotherapy utilized to maintain remission
  • Neoadjuvant therapy: chemotherapy and/or radiation before elective surgery
  • Adjuvant therapy: chemotherapy and/or radiation after surgery
• Palliative chemotherapy: a regimen of chemotherapeutic agents used to reduce local symptoms and/or prolong survival
• See also “Chemotherapeutic agents.”

Radiation therapy

• May be used with curative or palliative intent
• Options include external beam radiotherapy and brachytherapy.
• See also “Radiation therapy.”

Other therapies

• Cancer immunotherapy: e.g., checkpoint inhibitors, chimeric antigen receptor T-cell therapy ^[11]
• Targeted therapy: e.g., monoclonal antibodies, small molecule inhibitors, immunotoxins ^[12]
• Hormone therapy: the use of hormone modulators to manage malignancies whose growth is accelerated by circulating hormones ^[13]

Assessing response to anticancer therapy

• Hematopoietic tumors: usually determined by molecular analysis of a bone marrow aspirate or peripheral blood ^[14]
• Solid tumors: varies according to the type of cancer ; clinical scores (e.g., RECIST) may be useful ^[15]

Postcancer treatment care ^[16]

• Monitoring for recurrent and second cancers ^[1]
• Management of general health, comorbidities, and long-term complications arising from cancer or anticancer treatment
  • Physical complications include cardiotoxicity, neuropathy, premature menopause, lymphedema, and chronic pain. ^[17]
  • Psychosocial sequelae include anxiety, PTSD, and fear of recurrence. ^[18]
• Promotion of a healthy lifestyle including regular physical exercise ^[19]

Cancer patients are at risk of recurrence and of developing a new primary cancer after successful treatment; regular follow-up is vital.

Prechemotherapy screening

The following assessments should be performed to establish a baseline, identify potential complications, and determine fitness for treatment regimens.

Frailty assessment ^[20][21][22]

• Assess using a validated tool: Eastern Cooperative Oncology Group (ECOG) scale , Karnofsky performance status ^[23]
• Treatment may need to be adjusted for patients with limited physiologic reserve; consult geriatrics.

Assessment of organ function ^[24]

• CBC
• CMP
• Liver chemistries ^[25]
• ECG and echocardiogram ^[26]
• Baseline imaging (as indicated) ^[27]

Prevention of complications

• Infection screening: to identify current or latent infections prior to chemotherapy or immunotherapy
  • Common: HIV screening, viral hepatitis panel ^[28][29][30]
  • Consider: HSV, VZV, tuberculosis ^[31][32]
• Immunizations
  • Verify vaccination status and titers if necessary.
  • Provide missing and additional immunizations as indicated. ^[33][34][35]
• Dental evaluation ^[36][37]

Additional evaluations

• HLA typing: for transplant candidates
• LDH: prognostication in certain cancers, e.g., cancer of unknown primary site ^[38][39]

Unrecognized asymptomatic or latent infections may develop into life-threatening illnesses when patients become immunosuppressed. Screen patients for common infections and consult an infectious diseases specialist for management.

Managing fertility during anticancer therapy ^[40][41][42]

• Perform a pregnancy test on all patients of childbearing age. ^[40]
• Refer patients to a reproductive specialist to discuss options for fertility preservation. ^[43][44]
• Provide counseling on contraceptive options to both men and women. ^[40]

Obtaining permanent venous access ^[45][46]

Patients require a central venous catheter (CVC) if they will receive prolonged infusions of chemotherapeutic or vesicant agents or frequent blood sampling.

Multidisciplinary cancer care

Multidisciplinary care is associated with improvements in clinical outcomes and the patient's quality of life. ^[47]

Primary care involvement

• Inform the patient's primary care provider of the diagnosis and treatment plan. ^[48]
• The primary care provider's role may include: ^[49]
  • Provision of preventive care measures, e.g., immunizations
  • Diagnosis and management of common complications
  • Patient referrals, e.g., to psychiatry or hospice care

Nutritional assessment ^[50][51][52]

• Monitor weight, appetite, and nutritional intake.
• Consider dietitian consultation and provide specialized nutrition support as needed.

Psychosocial support ^[53][54]

• Identify and treat mental health comorbidities using validated screening tools, e.g., Patient Health Questionnaire-9 (PHQ-9).
• Refer to psychiatry/psychologist as appropriate.
• Offer a social work consultation. ^[55][56][57]
• Suggest local support groups for patients and families.

Specific referrals

• Older patients or patients with functional impairments: Refer to physical therapy and/or occupational therapy. ^[58]
• Patients with advanced cancer or overwhelming symptoms: Refer to palliative care (see “Overview of palliative medicine”).
• Suspected hereditary cancer syndrome: Refer for genetic counseling.

Depending on the diagnosis and stage, up to ∼ 80% of patients with cancer have major depression, but it is often underdiagnosed and undertreated. ^[53][54]

Treatment-related emergencies

• Cancer treatment can result in life-threatening complications, e.g., febrile neutropenia, tumor lysis syndrome.
• See “Oncologic emergencies” and “Neutropenic fever”; for details on the diagnosis and management of these conditions.

Infection in patients with neutropenia has a high risk of death and should be treated accordingly, with prompt aggressive treatment and close monitoring. ^[1]

Chemotherapy-induced nausea and vomiting (CINV) ^[59][60]

Definition ^[60][61]

• Any nausea and vomiting associated with chemotherapy
• Further subcategorized as:
  • Acute CINV: onset within 24 hours after chemotherapy
  • Delayed CINV: onset between 24 and 120 hours after chemotherapy
  • Anticipatory CINV: onset prior to chemotherapy as a conditioned response following nausea or vomiting with previous chemotherapy
  • Breakthrough CINV: occurs despite the use of standard antiemetic prophylaxis
  • Refractory CINV: occurs in patients with a history of CINV unresponsive to prophylactic and rescue antiemetic therapy during previous chemotherapy

Epidemiology

• 30–60% of patients who receive chemotherapy develop CINV. ^[62]
• Risk factors include female sex, younger age, anxiety, and a history of motion or morning sickness. ^[63]

Management ^[59][60]

• Base the antiemetic regimen on patient characteristics and the emetogenicity of the chemotherapeutic agents.
  • Initial regimen
    • Start CINV prophylaxis on the first day of chemotherapy and continue for up to 4 days depending on the regimen.
    • Commonly used agents: dexamethasone, 5-HT3 receptor antagonists, NK1 receptor antagonists
  • Breakthrough CINV or refractory CINV: Add antiemetics of a different class (e.g., olanzapine, benzodiazepines, dopamine receptor antagonists).
  • Anticipatory CINV: Optimize prophylaxis and consider benzodiazepines and/or behavioral therapy.
• Patients with active nausea/vomiting may require management of dehydration, including electrolyte correction.

Chemotherapy-induced diarrhea ^[64][65][66]

Definition ^[66]

• ≥ 3 loose or watery stools per day in patients receiving chemotherapy
• Subdivided into:
  • Uncomplicated diarrhea
  • Complicated diarrhea

Epidemiology

• Up to 80% of patients receiving chemotherapy ^[65][67]
• Irinotecan and 5-fluorouracil are most frequently associated with diarrhea. ^[64][66]

Management of uncomplicated diarrhea ^[64][66]

• Initiate oral rehydration therapy.
• Recommend dietary interventions.
• Take precautions against perianal skin irritation.
• Consider loperamide. ^[66]
• Advise patients to seek immediate medical attention if symptoms of complicated diarrhea develop.
• Further management
  • Improvement in symptoms: Continue loperamide until there is no diarrhea for > 12 hours, then slowly reintroduce a normal diet.
  • No improvement or worsening of symptoms: Manage as complicated diarrhea.

Management of complicated diarrhea ^[64][66]

• Request diagnostic studies to assess for complications and rule out other causes of diarrhea.
  • Routine laboratory studies include CBC, BMP, liver chemistries, CRP, stool cultures, and C. difficile toxin test.
  • Consider blood cultures and abdominal imaging based on clinical evaluation.
• Admit for inpatient management and consider gastroenterology consult.
  • Administer initial fluids for dehydration and hypovolemia.
  • Start antidiarrheal medications.
    • First-line: loperamide ^[66]
    • Persistent diarrhea: Consider octreotide. ^[66]
  • Consider additional pharmacotherapy (e.g., antibiotics, oral budesonide) as needed. ^[66]

Do not assume a diagnosis of chemotherapy-induced diarrhea before completing a thorough assessment; differential diagnoses include life-threatening infections, e.g., C. difficile infection and neutropenic enterocolitis. ^[66]

Anticancer therapy-induced myelosuppression ^[68]

• One of the most common side effects, particularly during induction chemotherapy ^[69]
• Actively monitor for myelosuppression in all patients receiving chemotherapy or systemic radiotherapy.
  • Perform regular CBCs, typically before each treatment cycle.
  • Advise patients to seek immediate attention if they develop a fever, symptoms of anemia, or symptoms of thrombocytopenia.
• If myelosuppression is identified, start early management, which can include:
  • Adjustments in the chemotherapy regimen
  • Transfusion of blood products (check for special transfusion requirements)
  • Agents that mobilize or stimulate cell production, e.g., granulocyte colony-stimulating factor

Patients with cancer often require blood products that have been irradiated, are leukoreduced, and/or come from CMV seronegative donors. ^[70]

Anticancer therapy-induced anemia ^[71][72]

• Screen for and treat vitamin B12, folate, and iron deficiency anemia. ^[72]
• Transfusion of packed RBCs: indicated for severe anemia or certain patients with moderate anemia ^[73]
• Erythropoiesis-stimulating agents (ESA): Consider in select patients after anemia workup. ^[71][72]

Anticancer therapy-induced thrombocytopenia ^[74][75][76]

• Initial management
  • Initiate emergency management of thrombocytopenia for patients with significant active bleeding.
  • Consider platelet transfusions; indications for platelet transfusion are similar to patients without cancer.^[74]
  • In consultation with oncology, consider delaying, or reducing the dose of, scheduled chemotherapy. ^[76]
• Discuss additional measures, such as pharmacological prophylaxis or treatment, with hematology.
  • Recombinant IL-11 (oprelvekin) is approved for treating chemotherapy-induced thrombocytopenia but has severe adverse effects. ^[77]
  • Antifibrinolytics and thrombopoietin-receptor agonists (TPO-RAs) have been used but efficacy and indications for use are still being studied. ^[77][78][79]

Anticancer therapy-induced neutropenia ^[80][81][82]

• Advise patients on infection prevention measures. ^[83]
  • Wash hands regularly.
  • Avoid eating unwashed fruits or vegetables and undercooked meat, seafood, or eggs.
  • Keep catheter sites clean and dry.
  • Remain up-to-date on recommended vaccinations.
  • Avoid contact with unwell individuals.
  • Follow local health authority guidance on mask-wearing and social distancing to reduce the risk of COVID-19 infection.
• Consider granulocyte colony-stimulating factor (e.g., filgrastim, pegfilgrastim) or granulocyte-macrophage colony-stimulating factor (e.g., sargramostim) for: ^[80][82]
  • Patients with febrile neutropenia who are at high risk for complications
  • Prophylaxis in certain patients receiving cancer treatment
• Antimicrobial prophylaxis (e.g., trimethoprim/sulfamethoxazole against Pneumocystis jirovecii pneumonia, fluconazole against invasive candidiasis) is limited to high-risk patients under specialist guidance. ^[81]
• Monitor frequently for signs of infection and maintain a low threshold for starting aggressive antimicrobial treatment (see “Neutropenic fever”).

Mucositis ^[84][85][86]

• Mucositis is the presence of inflammatory or ulcerative lesions in the mouth or GI tract following anticancer treatment.
• Symptoms include oral pain, dysphagia, and diarrhea.

Epidemiology ^[84][86]

• 20–40% of patients receiving chemotherapy
• 60–85% of patients undergoing hemopoietic stem cell transplantation (HSCT)
• Almost all patients receiving head and neck radiation ^[85]

Prevention ^[84][85]

• Educate the patient on good oral hygiene.
  • Use a soft toothbrush and brush twice daily.
  • Rinse the mouth 4–6 times a day with alcohol-free mouthwash.
  • Frequently inspect the oral mucosa.
• Advise:
  • Regular lubrication of the lips with vaseline or paraffin
  • Ample fluid intake
  • Avoidance of alcohol, smoking, and spicy, acidic, or sharply edged food
• Refer for dental evaluation and treatment (e.g., repair or replace any poorly fitting prosthesis) prior to and during cancer therapy.
• Depending on the treatment regimen, consider the following in consultation with a specialist:
  • Oral mucositis prophylaxis: oral cryotherapy, low-level laser therapy, benzydamine mouth wash, recombinant human keratinocyte growth factor-1
  • Gastrointestinal mucositis prophylaxis: probiotics, sulfasalazine, amifostine

Because of the high risk of mucositis, prophylaxis is recommended for patients receiving fluorouracil, high-dose regimens used for conditioning prior to HSCT, and radiotherapy. ^[84][85]

Management ^[84][85][86]

• Ensure nutritional support and hydration.
• Optimize systemic pain management (consider patient-controlled analgesia).
• Oral mucositis
  • Start topical interventions, e.g., 2% viscous lidocaine, 0.5% doxepin, or 0.2% morphine mouthwashes.
  • Consider, depending on treatment regimen, gabapentin, topical or systemic steroids, or low-level laser therapy. ^[84]
• Gastrointestinal mucositis
  • Consider hyperbaric oxygen therapy and sucralfate enemas depending on the specific regimen.
  • See “Radiation proctitis” for further information.

Provide adequate pain management to patients with mucositis. Consider initiating opioid analgesia early.

Extravasation of chemotherapeutic agents ^[87][88]

• Reported in up to 6% of patients with cancer ^[88]
• Clinical features include pain, pressure, and swelling at the IV site, leakage of infusion fluid, and alterations to IV flow. ^[88]

Prevention ^[87]

• Provide appropriate training to staff who will place intravenous catheters and administer chemotherapy.
• For peripheral IV catheterization:
  • Avoid:
    • Small veins
    • Veins overlying a joint, in the antecubital fossa, the lower limbs, or the dorsum of the hand
    • Areas affected by lymphedema
  • Select flexible IV catheters; avoid winged steel infusion devices.
• Following IV catheterization, and prior to each infusion:
  • Check for blood return.
  • Flush with 10–20 mL of saline.
  • Inspect for signs of extravasation.
• For prolonged infusions (≥ 12 hours), use central venous access.

Management ^[87][88]

• Immediately disconnect the infusion but leave the IV catheter in place.
• Aspirate as much medication as possible then remove the IV catheter.
• Mark the boundaries of infiltration with a nonwashable marker.
• Identify the extravasated medication and contact a specialist (e.g., oncology, plastic surgery) to start specific management.
  • Vesicants
    • Cause tissue damage, blister formation, and frank necrosis when extravasated
    • Examples include anthracyclines, taxanes, vinca alkaloids, and some alkylating agents (e.g., mechlorethamine).
  • Irritants
    • Cause local pain at the injection site when extravasation occurs; large amounts can result in inflammatory reactions and ulcers
    • Examples include topoisomerase I inhibitors, topoisomerase II inhibitors, and platinum-based agents.
  • Neutrals
    • Rarely result in acute reactions when extravasated
    • Examples include monoclonal antibodies, methotrexate, and gemcitabine.
• Elevate the limb and provide pain management as needed.
• Reassess regularly until fully healed. ^[87]
• Consult plastic surgery or orthopedic surgery if the affected area is extensive or the patient has symptoms of compartment syndrome.

Extravasation of vesicants may lead to severe complications such as soft tissue necrosis or compartment syndrome. ^[88]

Chemotherapy-induced alopecia ^[89][90]

• A form of temporary alopecia seen in patients receiving chemotherapy
• Hair regrowth typically occurs 2–6 months after stopping chemotherapy, but, in rare cases, hair loss is permanent. ^[89]

Epidemiology

• Occurs in ∼ 65% of patients receiving chemotherapy ^[89]
• Frequently causes considerable psychological distress ^[89][90]

Chemotherapeutic agents that frequently cause severe alopecia include doxorubicin, daunorubicin, paclitaxel, docetaxel, cyclophosphamide, irinotecan, and etoposide. ^[89]

Management during chemotherapy

• Preventive strategies
  • Patient education ^[90]
    • Wash hair only when necessary and use a soft brush and satin pillowcase.
    • Avoid damage to the hair, e.g., bleaching, coloring, use of curling irons or hot rollers.
  • Use of scalp-cooling devices during chemotherapy ^[91]
• Use of camouflage techniques, e.g., change of hairstyle, wigs, or headwraps ^[89]
• Refer for psychological support if emotionally distressed. ^[89]

Scalp cooling is contraindicated in patients with hematologic malignancies because of the risk of reduced chemotherapy delivery to malignant cells in the scalp circulation. ^[92]

Post-chemotherapy treatment

• Topical treatments may help promote regrowth.
• Examples:
  • Bimatoprost 0.03% solution applied to the eyelid margin for eyelash alopecia ^[93]
  • Minoxidil for scalp alopecia ^[91]

Other complications

• Additional complications may arise depending on the treatment modality and agents.
  • Dermatological: e.g., xerosis, hand-foot syndrome, Stevens-Johnson syndrome ^[94][95]
  • Cardiovascular: e.g., arrhythmia, restrictive cardiomyopathy, and accelerated coronary artery disease ^[96][97]
  • Neurological: e.g., encephalopathy and chemotherapy-induced peripheral neuropathy ^[98]
• Management typically includes optimization of fluids and electrolytes and symptomatic treatment.
• Severe treatment reactions might require terminating or modifying treatment.
• See “Chemotherapeutic agents” and “Radiation therapy” for a more comprehensive list of complications.

Cancer-related emergencies

• Patients with cancer can develop life-threatening complications as a result of the disease (e.g., superior vena cava syndrome, leukostasis).
• See “Oncologic emergencies” for details on the diagnosis and management of these conditions.

Cancer pain ^[99][100]

• Cancer pain, caused by either the primary cancer, metastatic disease, and/or associated treatment, can be difficult to control.
• For further information, including dosages, see “Pain management in palliative care.”

Pain is undertreated in as many as 80% of cancer patients; assess pain frequently, adjust pain management accordingly, and involve specialists early. ^[99]

Cancer-related fatigue ^[101][102]

• A chronic, distressing exhaustion that is severe, persistent, and not relieved with rest
• Occurs in approx. 80% of patients during chemotherapy or radiation therapy ^[101]
• Management ^[101][102]
  • Identify and treat reversible causes. ^[101]
    • Blood tests: CBC, inflammatory markers, liver chemistries, BMP, thyroid function tests
    • Urinalysis
    • Depression screening, e.g., PHQ-9
  • Encourage physical activity.
  • Consider:
    • Psychosocial interventions
    • A short-term course of corticosteroids in patients with metastatic disease

Cancer anorexia-cachexia syndrome ^[103][104]

• A syndrome characterized by progressive wasting of skeletal muscle mass with or without loss of body fat that occurs in patients with advanced cancer ^[103]
• Occurs in ∼ 50% of patients with advanced cancer; typically a sign of poor prognosis ^[103]
• Results from an excess of proinflammatory cytokines (IL-1, IL-6, IFN-γ, and TNF-α) as a result of tumor growth → ↑ basal metabolic rate and catabolism ^[105]
• Clinical features
  • Weight loss
    • > 5% of total body weight in 6 months
    • OR > 2% weight loss if ongoing and BMI is < 20 kg/m² or muscle mass is depleted
  • Muscle wasting; (temporal, deltoid, and quadricep regions) and loss of subcutaneous fat
  • Decreased appetite
  • Fatigue
  • Dependent edema and ascites
• Management ^[103]
  • Refer to a registered dietitian.
  • Encourage oral nutrition; do not routinely use parenteral or enteral tube feeding in patients with advanced cancer. ^[103]
  • Consider pharmacological therapy to increase appetite and weight gain. ^[103]
    • First line: short-term trial of progesterone analog or corticosteroid
    • Cannabinoid (e.g., dronabinol) use remains controversial. ^{[103][106][107]}
  • Provide psychosocial support to patients and their families. ^[104]

Cancer anorexia-cachexia syndrome is an indicator of a poor prognosis.

Deep vein thrombosis (DVT) ^[108][109]

• Patients with cancer are at an increased risk of DVT formation, DVT recurrence, and bleeding during DVT treatment.
• Tailor management to the patient, including the type of cancer and anticancer therapy.
• See “Deep vein thrombosis” and “DVT prophylaxis.”

Paraneoplastic syndromes

• Cancer can cause a wide range of paraneoplastic syndromes, with symptoms ranging from mild to severe.
• See “Paraneoplastic syndromes” for further information.