Tests
Your Organizational Guidance
ebpracticenet urges you to prioritize the following organizational guidance:
Recommendations nationales de bonne pratique pour la prise en charge du cancer localisé de la prostate: première partiePublished by: KCELast published: 2014Nationale praktijkrichtlijn voor de aanpak van gelokaliseerde prostaatkanker: deel 1Published by: KCELast published: 20141st tests to order
serum prostate-specific antigen (PSA)
Test
Serum PSA levels may be increased in patients with prostate cancer; however, other nonmalignant conditions (e.g., prostatitis and benign prostatic hyperplasia) may increase PSA levels. PSA levels may also vary according to race.[53]
Routine PSA screening is controversial. In the US, shared decision-making prior to PSA screening is recommended for selected patients.[54][57][58][59] Guidelines differ on when to start screening discussions. The American Cancer Society recommends a screening discussion at age 50 years in men who are at average risk of prostate cancer and have a life expectancy of at least 10 years.[57] The US Preventive Services Task Force recommends considering screening for prostate cancer from ages 55 to 69 years.[58] The American Urological Association and Society of Urologic Oncology recommend offering a baseline screening test at ages 45 to 50 years in men at average risk of developing prostate cancer.[54]
Early PSA screening at ages 40 to 45 years may be considered for men at higher risk (e.g., black ancestry, germline mutations, strong family history of prostate cancer).[54][57]
Decisions about screening and rescreening intervals should be individualized following discussion of the risks and benefits. For men with a newly elevated PSA, a repeat test may be considered after a few weeks, and before further evaluation, because PSA levels may fluctuate and often normalize on retesting.[54][55]
PSA testing may be combined with digital rectal exam (DRE) as part of screening because approximately 25% of men diagnosed with prostate cancer have a normal PSA.[56] DRE is recommended in all patients with an abnormal PSA to aid decisions regarding biopsy.[26] However, DRE as a stand-alone screening test is not recommended.[26]
Total PSA is the initial test of choice (i.e., the sum of both the free and bound forms). Risk of prostate cancer typically increases with increasing PSA level. However, elevated PSA levels should be correlated with patient age as PSA typically increases with age, regardless of presence of prostate cancer.[60]
Men with PSA levels above the median for their age group are at higher risk for aggressive prostate cancer. Conversely, men 60 years or older with PSA <1 nanogram/mL, or men 75 years or older with a PSA <3 nanograms/mL, are at very low risk for aggressive prostate cancer.[26]
Age-specific PSA thresholds have not been universally adopted because there is a lack of strong evidence to differentiate between using an age-specific threshold or a fixed PSA threshold.[61][62] In the UK, PSA levels above the age-specific threshold can be used to inform the decision to refer patients with possible symptoms of prostate cancer for further evaluation.[62]
An increase in PSA of 0.75 nanograms/mL/year may be a sign of prostate cancer, even if this increase occurs within the standard age-specific reference range.[63]
In certain circumstances it may be helpful to measure the percentage of free PSA: for example, in men with previously negative prostate biopsies and whose PSA level is between 4 and 10 nanograms/mL.[64] A free PSA of <10% suggests the presence of aggressive prostate cancer.
PSA density (the ratio of serum PSA level to prostate volume) can be calculated to inform risk stratification and guide treatment planning. Risk of clinically significant prostate cancer is increased with increasing PSA density.[65][66] A PSA density <0.15 nanograms/mL/g is one of the criteria for very low-risk disease.[3][67] See Classification.
PSA doubling time (PSADT) and PSA velocity (PSAV) may be used in the pretreatment setting for risk stratification and to predict response to treatment, and during follow-up to monitor disease progression. Currently, PSAV is more often used in the pretreatment setting, while PSADT is usually reserved for monitoring PSA during follow-up.[68] There is disagreement as to the value of PSAV and PSADT as an adjunct to routine PSA evaluation; decisions about further evaluation should not be based solely on PSAV results.[54][70][71][72]
Result
elevated PSA (value should be correlated with patient age); elevated PSA density; decreased PSADT; elevated PSAV
prebiopsy multiparametric MRI
Test
Prebiopsy multiparametric MRI (if available) is recommended to help identify candidates for biopsy.[26][73][74] Results may inform MRI-targeted biopsy. Multiparametric MRI can accurately differentiate clinically significant tumors from clinically insignificant tumors (particularly if carried out in accordance with the Prostate Imaging Reporting and Data System [PI-RADS] protocol), which can help minimize unnecessary biopsies.[75][76][77][78] See Criteria.
Results of prebiopsy assessment should be discussed with patients as part of shared decision-making before proceeding to biopsy.
Patients must be carefully selected to minimize unnecessary biopsies and overdiagnosis, while ensuring those with clinically significant tumors are identified and managed appropriately.
Selecting patients for biopsy should be individualized based on patient-specific risk factors (e.g., age, PSA level, abnormal digital rectal exam [DRE] findings, comorbidities, family history) and prebiopsy assessment.[26]
National Comprehensive Cancer Network (NCCN) guidelines recommend evaluation for biopsy in average-risk patients (ages 45-75 years) and high-risk patients (ages 40-75 years) if they have a PSA >3 nanograms/mL and/or a very suspicious DRE.[26] Biopsy may be considered for selected patients ages >75 years who have a PSA ≥4 nanograms/mL or a very suspicious DRE.[26]
Result
may identify clinically significant lesions on the prostate
prostate biopsy
Test
A prostate biopsy is required to confirm diagnosis (i.e., presence of prostatic intraepithelial neoplasia or carcinoma), tumor grade (based on the Gleason score), and the presence of perineural invasion.
Patients must be carefully selected to minimize unnecessary biopsies and overdiagnosis, while ensuring those with clinically significant tumors are identified and managed appropriately.
Selecting patients for biopsy should be individualized based on patient-specific risk factors (e.g., age, PSA level, abnormal DRE findings, comorbidities, family history) and prebiopsy assessment.[26]
National Comprehensive Cancer Network (NCCN) guidelines recommend evaluation for biopsy in average-risk patients (ages 45-75 years) and high-risk patients (ages 40-75 years) if they have a PSA >3 nanograms/mL and/or a very suspicious DRE.[26] Biopsy may be considered for selected patients ages >75 years who have a PSA ≥4 nanograms/mL or a very suspicious DRE.[26]
Prostate biopsy samples are obtained by systematic core needle biopsy performed via a transrectal or transperineal approach. The transperineal approach is often preferred due to lower risk of infection. Transrectal ultrasound (TRUS) is used to guide the needle, regardless of the biopsy approach used.[80][81]
The addition of MRI-targeted biopsy to systematic biopsy is recommended when a suspicious lesion has been identified by prebiopsy multiparametric MRI.[26][82] Combined MRI-targeted and systematic biopsy improves detection of clinically significant prostate cancer and reduces regrading of tumors on final histopathologic analysis.[83][84][85][86] The optimal technique for MRI-targeted biopsy has not been determined; options include cognitive (visual) fusion biopsy, software-assisted TRUS-MRI fusion biopsy, and direct (in-bore) MRI-guided biopsy.[87][88]
A negative prostate biopsy does not exclude a diagnosis of prostate cancer, particularly if clinical suspicion is high and/or PSA is persistently elevated or rising.
In the presence of a negative biopsy, multiparametric MRI and/or biomarker testing should be considered if multiparametric MRI was not done previously.[26] If multiparametric MRI was previously done, follow-up with DRE and PSA should be performed at 12-24 month intervals, with consideration of biomarker testing. Repeat biopsy with MRI targeting is recommended if suspicion of cancer is high based on the results of these tests (e.g., positive MRI, persistently high PSA, abnormal DRE, high PSA density).[26][89][90][91]
Result
may detect malignant cells in one or more biopsy specimens (assigned to Grade Group 1-5)
Tests to consider
prebiopsy biomarker tests and risk calculators
Test
The following tools may be considered to further refine patient selection for biopsy, especially in patients with mildly elevated PSA levels or with negative multiparametric MRI results:[26][65][74][79]
biomarker assays (e.g., Prostate Health Index, SelectMDx, 4Kscore, ExoDx Prostate Test, MyProstateScore, IsoPSA)
risk calculators (e.g., Prostate Biopsy Collaborative Group, Sunnybrook, European Randomized Study of Screening for Prostate Cancer, Prostate Cancer Prevention Trial Risk calculators)
PSA density.
The optimal use of biomarker testss/risk calculators (e.g., in combination with prebiopsy MRI and/or with each other) for selecting patients for biopsy is unclear.
Results of prebiopsy assessment should be discussed with patients as part of shared decision-making before proceeding to biopsy.
Result
may be positive for serum or urine biomarkers (test results are presented as a risk score)
testosterone
Test
Routine test for patients in whom treatment (e.g., androgen deprivation therapy) is considered once a diagnosis has been confirmed.[114]
Result
normal
LFTs
Test
Routine test for patients in whom treatment (e.g., androgen deprivation therapy) is considered once a diagnosis has been confirmed.
Result
normal
CBC
Test
Routine test for patients in whom treatment (e.g., androgen deprivation therapy [ADT]) is considered once a diagnosis has been confirmed.
Anemia may occur due to advanced disease, ADT, nutritional decline, bone marrow infiltration, the chronic inflammatory state, and rarely gross hematuria.
Symptomatic anemia may warrant blood transfusion.
Result
normal, except for advanced disease
renal function
Test
Routine test for patients in whom treatment (e.g., androgen deprivation therapy) is considered once a diagnosis has been confirmed.
Abnormal renal function tests may indicate more locally advanced disease with tumor causing obstruction of ureters, resulting in renal failure.
Result
normal, except for locally advanced disease causing obstruction
bone scan (technetium-99)
Test
Bone imaging is recommended for detecting metastases in patients with high-risk or very high-risk disease.
For patients with unfavorable intermediate-risk disease, bone imaging may be considered.[3]
Bone imaging (or treatment) is not required for asymptomatic patients with very low-risk, low-risk, or favorable intermediate-risk prostate cancer who have a life expectancy of ≤5 years.[3][92] See Classification.
A technetium-99 bone scan is the standard technique for initial bone imaging. Other imaging studies (e.g., CT, MRI, PET/CT, or PET/MRI) can be used if findings on bone scan are equivocal.[3]
Result
may identify bone lesions
CT scan
Test
CT is a standard technique for initial bone imaging and soft-tissue imaging.
The primary role of CT scan in prostate cancer is to evaluate the prostate size and to assess for the presence of enlarged pelvic lymph nodes.
Also used in the detection and staging of metastases in patients with high-risk or very high-risk disease.
For patients with unfavorable intermediate-risk disease, soft-tissue imaging is recommended and bone imaging may be considered.[3]
Bone imaging and soft-tissue imaging (or treatment) are not required for asymptomatic patients with very low-risk, low-risk, or favorable intermediate-risk prostate cancer who have a life expectancy of ≤5 years.[3][92] See Classification.
Intraprostatic disease, extracapsular extension, or seminal vesicle involvement cannot be evaluated accurately by CT because it lacks the soft-tissue resolution.
Result
may identify enlarged prostate and/or metastatic disease (e.g., enlarged pelvic lymph nodes, and metastatic lesions in bone and soft tissue)
MRI
Test
MRI is a standard technique for initial soft-tissue imaging.
MRI is recommended for detecting and staging metastases in patients with high-risk or very high-risk disease.
For patients with unfavorable intermediate-risk disease, soft-tissue imaging is recommended.[3]
Soft-tissue imaging (or treatment) is not required for asymptomatic patients with very low-risk, low-risk, or favorable intermediate-risk prostate cancer who have a life expectancy of ≤5 years.[3][92] See Classification.
On axial T1-weighted images, the prostate appears homogeneous and zonal anatomy is not easily differentiated. However, nodal and bony disease is identifiable.
On axial T2-weighted images, the zonal anatomy of the prostate is clearly visualized. The peripheral zone is, typically, of high signal intensity. This is contrary to the tumor, which appears as low signal intensity.
Result
may identify suspicious intraprostatic lesions and/or metastatic disease (e.g., enlarged pelvic lymph nodes, and metastatic lesions in bone and soft tissue)
prostate-specific membrane antigen (PSMA)-PET/CT
Test
Prostate-specific membrane antigen (PSMA) targeted imaging with PET/CT is superior to conventional imaging (bone scan, CT, MRI) for staging and detecting metastases in patients with prostate cancer.[93][94][95][96][97][98]
PSMA-PET/CT (with gallium [Ga-68] PSMA-11, piflufolastat F-18, or flotufolastat F-18) may be considered as an alternative to conventional imaging for initial staging.[3]
Bone imaging and soft-tissue imaging (or treatment) are not required for asymptomatic patients with very low-risk, low-risk, or favorable intermediate-risk prostate cancer who have a life expectancy of ≤5 years.[3][92] See Classification.
Result
may identify suspicious intraprostatic lesions and/or metastatic disease (e.g., enlarged pelvic lymph nodes, and metastatic lesions in bone and soft tissue)
PSMA-PET/MRI
Test
Prostate-specific membrane antigen (PSMA) targeted imaging with PET/MRI is superior to conventional imaging (bone scan, CT, MRI) for staging and detecting metastases in patients with prostate cancer.[99][100]
PSMA-PET/MRI (with gallium [Ga-68] PSMA-11, piflufolastat F-18, or flotufolastat F-18) may be considered as an alternative to conventional imaging for initial staging.[3]
Bone imaging and soft-tissue imaging (or treatment) are not required for asymptomatic patients with very low-risk, low-risk, or favorable intermediate-risk prostate cancer who have a life expectancy of ≤5 years.[3][92] See Classification.
Result
may identify suspicious intraprostatic lesions and/or metastatic disease (e.g., enlarged pelvic lymph nodes, and metastatic lesions in bone and soft tissue)
tumor molecular and genetic testing
Test
Molecular biomarker testing of tumor tissue may provide additional prognostic information, refine risk stratification, and help inform decision-making for patients with localized prostate cancer. Several tissue-based molecular assays have been validated and are commercially available, including Prolaris, Decipher (22-gene genomic classifier), and the 17-gene Genomic Prostate Score (Oncotype Dx Prostate).[101][102][103]
Guidelines recommend the Decipher (22-gene genomic classifier) in situations where assay results are likely to change management, for example, to guide initial treatment for newly diagnosed intermediate- or high-risk disease or to inform therapy following radical prostatectomy.[3][104][105][106][107][108][109]
Tumor genetic testing for somatic mutations may inform prognosis and guide treatment decisions (including eligibility for clinical trials and suitability for novel targeted therapies) for patients with metastatic disease.[3][110]
Multigene tumor testing for mutations affecting homologous recombination repair genes (including BRCA1, BRCA2, ATM, PALB2, FANCA, RAD51D, CDK12, and CHEK2) is recommended for patients with metastatic prostate cancer (with consideration of multigene testing in patients with regional disease).
Microsatellite instability (MSI) or mismatch repair (MMR) status and tumor mutational burden is recommended for patients with castration-resistant metastatic disease (with consideration of MSI or MMR testing in patients with regional or castration-sensitive metastatic disease).
Results of genetic and molecular testing should be discussed with patients as part of shared decision-making to inform decisions regarding management and treatment.
Result
may identify somatic genetic mutations or molecular biomarkers with prognostic and therapeutic significance
genetic evaluation and germline testing
Test
Genetic risk assessment, including counseling and germline testing, should be considered at initial workup for men with a strong personal or family history of cancer (e.g., prostate, breast, ovarian, endometrial, colorectal, pancreatic cancer) or an inherited syndrome (e.g., Lynch syndrome), or a known or suspected pathogenic variant in a cancer susceptibility gene.[26][35]
If not carried out previously, genetic evaluation (with genetic counseling and germline testing) should be offered to patients with prostate cancer who have any of the following: a clinically relevant mutation identified on somatic testing; metastatic, regional, or high-risk or very-high-risk localized prostate cancer (regardless of family history or somatic testing); high risk of hereditary prostate cancer based on personal or family history.[3][35][111]
Germline testing for a specific pathogenic variant can be carried out, if known; tailored multigene panel testing is recommended if the variant is unknown, based on personal and family history.[35][111][112] Multigene germline panels for patients with prostate cancer may include BRCA1, BRCA2, ATM, CHEK2, PALB2, HOXB13, MLH1, MSH2, MSH6, PMS2, EPCAM.[3][35][112]
Presence of a germline mutation can inform management decisions and prognosis, and may also highlight potential risk for other cancers and risk among family members.[3]
Results of genetic testing should be discussed with patients as part of shared decision-making to inform decisions regarding management and treatment.
Result
may identify germline genetic mutations with prognostic and therapeutic significance
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