HC15: Framework oncology and staging

Tumor grading

A tumor grade reflects intrinsic biological behavior of tumors. In general, a low grade is less aggressive. It is necessary to grade a tumor for treatment and prognosis:

• Lower grade → better prognosis
• Higher grade → worse prognosis

Tumors are graded based on the microscopic appearance of cancer cells. Dependent on the tumor, there are 2-4 degrees of severity. An example is:

• GX: grade cannot be assessed
  • Undetermined grade
• G1: Well-differentiated
  • Low grade
• G2: moderately differentiated
  • Intermediate grade
• G3: poorly differentiated
  • High grade
• G4: undifferentiated
  • High grade

Breast cancer grades:

The amount of grades differs per tumor type. In case of breast cancer, there are only 3 grades. These grades can be linked to the expected 5 year survival rates:

• Total: 91-95%
• Grade I: 75%
• Grade II: 53%
• Grade III: 31%

Staging systems

Tumor staging is used to determine the extent of disease spread in patients:

• Solid tumors
  • Local spread
  • Through lymphatics (lymphogenic)
  • Distant (hematogenic)
• Haemotological malignancies
  • Tells something about the disease extent and influence on normal bone marrow function

Cancer staging is useful for:

• Planning treatment
• Estimating prognosis
• Identifying clinical trials/studies
• Making a comparison between institutes
• Communication
  • Staging is a universal language

There is no unique staging system. However, most staging systems do consist of several common elements:

• Location of the primary tumor
• Tumor size and number of tumors
• Lymph node involvement
  • Spread of cancer into the lymph nodes
• Cell type and tumor grade
  • How closely the cancer cells resemble normal tissue
• Presence or absence of distant metastasis

In general, the higher the stage, the worse the prognosis.

TNM staging principles:

The TNM staging principles is the most used staging system for solid tumors:

• T-status: extent of the tumor
  • T1-T4
    • The larger the tumor, the higher the T
  • Size of the tumor and locally organ involvement
• N-status: regional lymph node involvement → absence or presence of metastasis
  • N0: no lymph nodes are involved
  • N1: 1 or 2 lymph nodes are involved
  • N2: infra- or subclavicular lymph nodes are involved
• M-status: distant metastasis
  • M0: absent
  • M1: present

The rules per tumor differ → prefix modifiers can be useful:

• cTNM → c = clinical
  • Before treatment
  • Mostly based on imaging or physical examination
• pTNM → p = histopathological
  • After surgery
• ypTNM → yp = pathological after pretreatment
  • After chemotherapy, but before surgery
  • There is a large difference between the c and p stage
• TNMx → x = not classified
  • Nothing is known about the tumor

For instance, a PA report states the following:

• Ductal adenocarcinoma
• Grade 3
• Diameter: 1,2 cm
• Free excision marks
• ER+/PR+
• Her2-
• Senital node: 0/2 lymph nodes contain metastasis

The TNM classification is pT1N0Mx.

Stages of breast cancer:

Breast cancer has 5 different stages:

• Stage 0: in situ cancer
• Stage 1: localized cancer
• Stage 2: further local spread, also usually includes spread to the nearest lymph nodes
• Stage 3: usually indicates more extensive lymph node involvement
• Stage 4: always indicates distant spread

Stages of lung cancer:

Lung cancer has 4 stages:

• Stage I: primary tumor
  • A small tumor in the lung
• Stage II: primary tumor + small lymph node involvement
• Stage III: primary tumor + lymph node metastasis
  • Lymph nodes are present in the mediastinum
• Stage IV: primary tumor + lymph node metastasis + metastatic tumor in the other lung/pleural involvement

A 67-year-old man has a primary lung tumor in the left upper lobe without signs of invasion in the pleura. The diameter is 6,5 cm. A PET scan shows the following:

• Elevated uptake in the primary process and in the mediastinum left
• A few tumor cells in a PET positive lymph node in the mediastinum
• No other abnormalities

The patient has an adenocarcinoma of stage cT3N2M0.

Other staging systems:

Several other staging systems are:

• Ann arbor staging: for lymphomas
  • Stage I: single lymph node region
  • Stage II: one side of the diaphragm
  • Stage III: both sides of the diaphragm
  • Stage IV: disseminated
• Duke’s classification: for colon cancer
• Breslow scale and Clark’s level: for melanomas
  • Breslow scale: looks at the thickness of the melanoma
  • Clark’s level: looks at the invasion in the epidermis and hypodermis
• FIGO: for gynaecological tumors, purely based on clinical investigation
  • Cervic
  • Vulva
  • Endometrium

How to stage and when to stage:

Staging is done as follows:

• How: where the disease is expected to spread
  • Knowledge of natural course of disease
  • Knowledge of imaging modalities
    • X-ray
    • Ultrasound
    • Endoscopies
    • MRI
    • CT-scan
    • PET-scan
• When: the chance of spread determines the extensiveness of search

These moments differ per cancer type → treatment modalities are used to look for sites where the metastasis is most likely to occur:

• Sarcomas
  • Usually no lymphogenic spread
  • High risk for lung metastasis
• Pancreatic cancer
  • High risk of liver metastasis early on
• Small cell lung cancer
  • High chance of brain metastasis

Treatment of cancer

Treatment of cancer is based on:

• Characteristics of the tumor (grade)
• Stage of the tumor
• Intention of treatment

Terminology:

Important terminology used in treatment is:

• Curative/palliative/best supportive care
  • Curative treatment: treatment aimed at cure
  • Palliative treatment: treatment to alleviate symptoms → cure isn’t intended
    • The palliative phase of a disease is not the same as the terminal phase
  • Best supportive care: treatment in the terminal phase
• Adjuvant/neoadjuvant/primary/systemic
  • Adjuvant: treatment given after primary treatment
    • To treat micro-metastases
  • Neoadjuvant: treatment given before primary treatment
    • Sometimes called induction therapy
    • Sometimes used to shrink the tumor so it can be removed easier
  • Primary treatment: the main treatment modality
  • Systemic treatment: affects a number of organs and tissues, or affects the body as a whole
    • Chemotherapy, targeted therapy or immunotherapy
• Concomitant/sequential/elective
  • Concomitant: 2 modalities in the same time period
  • Sequential: 2 modalities after each other
• Elective treatment/elective surgery
  • Elective: local treatment of an area clinically negative but with high risk of involvement
  • Elective surgery: prophylactive surgery of this area
• Pre-/per-/postoperative
  • Preoperative: before the operation
  • Peroperative: during the operation
  • Postoperative: after the operation

Examples

Examples are:

• A patient with 2 tumorous lymph nodes in the axilla from left sided breast cancer
  • Stage II cancer
  • Treatment is curative
• A patient with liver metastases from colon cancer
  • Stage IV cancer
  • Treatment is palliative
• A patient with lung, liver and brain metastases from lung cancer
  • Stage IV cancer
  • Treatment is supportive care