From the Guidelines
Elevated PRHrP is most significant as a marker of potential prostate cancer, and its significance should be evaluated in the context of other diagnostic tools, such as PSA levels, digital rectal examination (DRE), and multiparametric magnetic resonance imaging (mpMRI). When evaluating the significance of elevated PRHrP, it is essential to consider the patient's overall clinical presentation, including their age, family history, and other risk factors for prostate cancer. The most recent and highest quality study, 1, suggests that PSA is a continuous parameter, with higher levels indicating a greater likelihood of prostate cancer, and that risk calculators and PSA density (PSA-D) may help predict the presence of clinically significant prostate cancer. Additionally, mpMRI is increasingly important for biopsy optimization, with a Cochrane meta-analysis showing that MRI had pooled sensitivity and specificity of 0.91 and 0.37 for ISUP grade 2 cancers, and 0.95 and 0.35 for ISUP grade 3 cancers, respectively. Key points to consider when evaluating elevated PRHrP include:
- PSA levels and velocity
- DRE results
- mpMRI findings
- Risk calculators and PSA-D
- Patient age, family history, and other risk factors for prostate cancer
- The need for biopsy and further testing. It is crucial to use the most recent and highest quality evidence, such as the 2024 update of the EAU-ESUR-ESTRO-SIOP guidelines on prostate cancer, 1, to guide clinical decision-making and ensure the best possible outcomes for patients with elevated PRHrP.
From the Research
Elevated PRHrP Significance
- Elevated PRHrP levels are associated with hypercalcemia of malignancy, which is often distinguishable from primary hyperparathyroidism by the presence of an obvious tumor 2.
- PRHrP is an important mediator of malignancy-related tumor progression and hypercalcemia, sharing considerable homology and functionality with parathyroid hormone 3.
- Serum PRHrP levels are elevated in patients with hypercalcemia of malignancy, and the prevalence of elevated PRHrP levels is substantial in patients with lung and upper respiratory tract malignancies 4.
- Assays for PRHrP can be used to investigate hypercalcemia in routine clinical practice, and measurement of both PTH and PRHrP can lead to a change in diagnosis in some patients 5.
- PRHrP is an emerging target in cancer progression and metastasis, with evidence supporting its role in skeletal metastasis, breast cancer initiation, growth, and metastasis, and brain metastasis in triple-negative breast cancer patients 6.
Clinical Implications
- Elevated PRHrP levels can be used as a diagnostic tool to distinguish between primary hyperparathyroidism and hypercalcemia of malignancy 2, 5.
- The measurement of PRHrP levels can be used to monitor the response to bisphosphonate treatment in patients with hypercalcemia of malignancy 4.
- The role of PRHrP in cancer progression and metastasis suggests that it may be a potential target for therapeutic intervention 3, 6.
Research Findings
- Studies have shown that PRHrP is ubiquitously expressed in normal tissues and is involved in various physiological processes, apart from its pathologic role in hypercalcemia of malignancy 2, 6.
- The discovery of PRHrP's role in malignancies has led to a greater understanding of the mechanisms underlying hypercalcemia of malignancy and has provided new avenues for research into the treatment of this condition 3, 4, 5, 6.