C-reactive protein (CRP) is an acute phase reactant produced by the liver that is often elevated in inflammatory conditions like infection and cancer. CRP levels can be measured by a simple blood test and levels above 10 mg/L are considered abnormally high. Many types of cancer can raise CRP levels, however not all cancers will cause CRP to become elevated. Understanding when CRP is likely to be elevated in cancer patients can help clinicians use this marker appropriately to monitor disease activity and treatment response.
What is CRP and how is it measured?
C-reactive protein or CRP is a protein made by the liver that circulates in the bloodstream. CRP is part of the acute phase response, which means the body rapidly increases CRP production during inflammatory states like tissue injury, infection, trauma or cancer growth. The level of CRP in the blood corresponds with the severity of inflammation or tissue damage. CRP testing measures the concentration of CRP in the blood, reported in mg/L or mg/dL.
Normal CRP levels are usually less than 10 mg/L in healthy individuals. Levels between 10-40 mg/L are mildly elevated, 40-200 mg/L are moderately elevated, and above 200 mg/L are severely elevated. Conditions like infection, rheumatoid arthritis, inflammatory bowel disease, heart attack, stroke, trauma, surgery, flare-ups of autoimmune disorders and some cancers can all raise CRP above normal levels. CRP testing is a simple blood test ordered by physicians to help monitor inflammation and disease activity.
How does cancer raise CRP levels?
Cancer leads to CRP elevation through several mechanisms. One way is that growing cancer cells release cytokines and interleukin-6 (IL-6), which stimulates CRP production by the liver. Tumors also release other inflammatory mediators that promote systemic inflammation, contributing to increased CRP. The localized tissue injury and necrosis caused by expanding cancer deposits also triggers an inflammatory response that raises CRP.
Additionally, cancer patients often have reduced albumin production from the liver. Albumin is a protein that normally keeps CRP levels in check. Lower albumin allows CRP to climb higher. Other factors like concurrent infections, medications, treatments and poor nutrition in cancer patients can also drive up CRP. However, the main mechanism is the inflammatory state created by growing, invasive cancer cells that leads the liver to produce more CRP.
Which types of cancers typically raise CRP levels?
Many different types of solid tumor cancers as well as blood cancers (leukemias and lymphomas) can raise CRP levels when active and progressing. However, there are some general trends in which cancers are most likely to elevate CRP:
- Lung cancer – Studies show 60-77% of lung cancer patients have elevated CRP at diagnosis or progression.
- Gastrointestinal cancers – Esophageal, pancreatic, colorectal, stomach and liver cancers commonly raise CRP.
- Genitourinary cancers – CRP elevation is common with renal, bladder and prostate cancers.
- Gynecological cancers – Ovarian, endometrial and cervical cancers often raise CRP.
- Head and neck cancers – Oral, pharyngeal, laryngeal and nasal cancers increase CRP.
- Hematological cancers – Lymphomas and acute leukemias frequently elevate CRP.
Some examples of CRP elevation rates by cancer type:
- Pancreatic cancer – Up to 90% of patients have elevated CRP
- Esophageal cancer – Approximately 85% of patients have elevated CRP
- Hepatocellular carcinoma – CRP elevated in 60-70% of cases
- Colorectal cancer – Raised CRP levels in 50-60% of patients
- Ovarian cancer – 50% of patients have CRP elevation
So gastrointestinal, lung, GU, gynecologic and hematologic malignancies have the strongest association with CRP elevation. This reflects the inflammatory nature of these cancer types.
Are there cancers that don’t raise CRP levels?
There are some cancers that are less likely to show significantly elevated CRP levels:
- Breast cancer – Less than 30% of breast cancer patients have CRP elevation
- Melanoma – CRP generally not raised except with widespread metastases
- Central nervous system cancers – CRP typically normal with brain tumors and spinal cord tumors
- Thyroid cancer – CRP rarely elevated even with progressive disease
- Early stage prostate cancer – Elevated CRP more common in metastatic prostate cancer
So breast cancer, melanoma, CNS cancers and thyroid cancers only infrequently raise CRP. Even in metastatic cases of these cancers, CRP may remain in the normal range. This reflects the less inflammatory nature of these cancer types. However, there can be exceptions in individual patients.
How do oncologists use CRP testing in cancer patients?
There are several uses for CRP testing in the management of cancer patients:
- Screening and diagnosis – Markedly elevated CRP in patients with suspected cancer supports working up for occult malignancy.
- Prognostic information – Higher CRP at diagnosis predicts poorer outcomes in many cancers.
- Monitoring treatment response – Decrease in CRP reflects successful response to chemotherapy, radiation, immunotherapy or surgery.
- Detecting recurrence – Rising CRP may signal cancer recurrence before it is clinically apparent.
- Evaluating symptoms – Elevated CRP helps determine if non-specific symptoms are due to cancer progression versus other causes.
So the CRP blood test provides oncologists with an objective, quantitative marker to complement imaging and other clinical information when managing cancer patients.
What are limitations of using CRP testing in cancer?
While CRP is a useful biomarker in oncology, there are some limitations to consider:
- CRP is non-specific – inflammation from other causes like infection can raise CRP and confound interpreting levels.
- Some cancers don’t elevate CRP – Values may remain normal even with active disease.
- Not all patients with the same cancer type react the same – Individual variability exists in CRP response.
- Need serial measurements – Single CRP values must be interpreted in context of prior results.
- Thresholds defining “elevated” not standardized – No universal cutoffs established for all cancers.
So CRP testing has limitations like any individual biomarker test. It provides supporting information but results must be interpreted carefully by clinicians in light of the clinical scenario. Serial measurements over time are most useful to monitor trends.
Conclusion
While not all types of cancer uniformly raise CRP levels, many common solid tumor and hematological malignancies demonstrate CRP elevation with active, progressive disease. Particularly gastrointestinal, lung, GU, gynecologic and blood cancers tend to show increased CRP relative to other cancer types. Oncologists use CRP blood testing to aid diagnosis, determine prognosis, monitor treatment response, detect recurrence and evaluate symptoms in appropriate contexts. CRP is best used together with imaging, symptom assessment and other labs in making clinical decisions for cancer patients.