Prostate Cancer Guidelines 

Updated: Jul 31, 2017
  • Author: Bagi RP Jana, MD; more...
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Prostate Cancer Screening

Guidelines on prostate cancer screening have been issued by the following organizations:

  • American Cancer Society (ACS)
  • National Comprehensive Cancer Network (NCCN)
  • American Urological Association (AUA)
  • U.S. Preventive Services Task Force (USPSTF)
  • European Society for Medical Oncology (ESMO)
  • European Association of Urology/European Society for Radiotherapy and Oncology/International Society of Geriatric Oncology (EAU/ESTRO/SIOG)

The guidelines differ in their recommendations regarding whether or not to provide routine prostate-specific antigen (PSA)–based prostate cancer screening, in what age groups and life expectancies, and at what intervals. The guidelines agree that PSA-based prostate cancer screening requires an informed, shared decision-making process, and that the decision should reflect the patient’s understanding of the possible benefits and risks and should respect the patient’s preferences and values.

ACS Screening Guidelines

The ACS guidelines for early detection of prostate cancer were last updated in 2010. [1] The ACS does not recommend routine screening in any age group. Instead, asymptomatic men with at least a 10-year life expectancy should be given an opportunity to make an informed decision with their health care provider after receiving information on the uncertainties, risks and benefits of screening

Men should receive the information starting at the following ages:

  • Age 50 for those at average risk of developing prostate cancer
  • Age 45 for those at high risk, including African Americans and men with a first-degree relative (father, brother, son) diagnosed with prostate cancer before age 65
  • Age 40 for those at higher risk (more than one first-degree relative diagnosed with prostate cancer at an early age)

For men who are unable to decide whether they wish to be screened, the ACS advises that the patient’s health care provider can make the screening decision, taking into account the patient’s general health preferences and values.

Men who decide to be screened should be tested with a PSA test. A digital rectal exam (DRE) may also be done as a part of screening.

If screening does not detect cancer, the time between subsequent screenings depends on the results of the blood test, as follows:

  • PSA < 2.5 ng/ml – Retesting may be done every 2 years
  • PSA ≥ 2.5 ng/ml – Retesting should be done annually

Even after the decision to screen has been made, the discussion about the risks and benefits of testing should be repeated as new information becomes available.

NCCN Screening guidelines

The NCCN recommends performing a baseline evaluation, with a history and physical examination that includes the following:

  • Family history
  • Medications
  • History of prostate disease and screening, including prior PSA and/or isoforms, exams, and biopsies
  • Race
  • Family or personal history of BRC1/2 mutations

The clinician should then discuss of the risks and benefits of a baseline PSA test with the patient, and consider a baseline DRE to identify high-risk cancers associated with a seemingly normal PSA. In patients 45-75 years of age, subsequent evaluation is based on the results of those tests, as follows [10] .

  • PSA <1 ng/mL, DRE normal (if done): Repeat testing at 2–4 year intervals
  • PSA 1-3 ng/mL, DRE normal (if done): Repeat testing at 1–2 year intervals
  • PSA >3 ng/mL or very suspicous DRE result: Evaluate for biopsy

For men above the age of 75, screening may be cautiously considered in selected cases of very healthy men with little or no comorbidity. If PSA is measured and is <4 ng/mL, the DRE is normal (if done), and no other indications for biopsy are present, the NCCN recommends repeat testing in selected patients at 1–4 year intervals. If the PSA is >4 ng/mL or DRE results are very suspicious, the patient should be evaluated for biopsy.

The NCCN notes that men ≥60 years of age with serum PSA <1.0 ng/mL have a very low risk of metastasis or death from prostate cancer and may not benefit from further testing. The same is true of men age 75 years with a PSA of <3.0 ng/mL.

Evaluation for biopsy includes the following:

  • Repeat PSA
  • Perform DRE, if not done performed during initial risk assessment
  • Workup for benign disease

AUA screening guidelines

The current recommendations of the AUA date from 2013 and update the Association’s 2009 Best Practice Statement on Prostate-Specific Antigen (PSA). [2] The guidelines do not recommend routine screening for the following groups:

  • Any man with a life expectancy less than 10-15 years
  • Men under 40 years
  • Men between ages 40 to 54 years at average risk
  • Men over age 70

For men 55 to 69 years of age, the decision to undergo PSA screening involves weighing the benefits and risks. The guidelines strongly recommend:

  • Shared decision-making for men age 55-69 years who are considering PSA screening, and proceeding based on patients’ values and preferences
  • A routine screening interval of two years or more in those men who have participated in shared decision-making and decided on screening.

USPSTF screening guidelines

The USPSTF guidelines, which were updated in 2012, recommend against PSA-based screening for prostate cancer, while recognizing that some men will continue to request screening. [3] In such cases, screening should not be ordered prior to shared decision making that weighs the benefits and risks and takes into account the patient’s preferences and values.

ESMO screening guidelines

Likie USPSTF, ESMO guidelines recommend against population-based PSA screening for prostate cancer, as well as screening of asymptomatic men over 70 years old. [4]

EAU/ESTR/SIOG screening guidelines

In 2016, revised joint guidelines were issued by EAU/ESTRO/SIOG with the recommendation that men who are informed and request an early diagnosis should be given a PSA test and undergo a digital rectal examination (DRE). PSA testing should be offered to the following groups at elevated risk for developing prostate cancer [5] :

  • Men > age 50 
  • Men > age 45 and a family history of prostate cancer
  • African-American men > age 45 
  • Men with a PSA level of > 1 ng/mL at age 40
  • Men with a PSA level of > 2 ng/mL at age 60 

Follow-up testing at intervals of 2 years for the following at risk groups:

  • Men with a PSA level of > 1 ng/mL at age 40 
  • Men with a PSA level of > 2 ng/mL at age 60 

Postpone follow-up to 8 years in those not at risk.

Discontinue testing based on life expectancy and performance status; men who have a life expectancy of < 15-years are unlikely to benefit.

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Multiparametric Magnetic Resonance Imaging

The National Comprehensive Cancer Network (NCCN) advises that although standard MRI techniques can be considered for initial evaluation of high-risk patients, multiparametric magnetic resonance imaging (mpMRI) can be used in the staging and characterization of prostate cancer. mpMRI images are defined as those acquired with at least one more sequence in addition to the anatomic T2-weighted images, such as diffusion-weighted imaging and dynamic contrast images. In addition, the NCCN guidelines recommend considering mpMRI in patients undergoing active surveillance if anterior and/or aggressive cancer is suspected when PSA increases and systematic prostate biopsies are negative. [6]

The 2016 EAU/ESTR/SIOG guidelines recommend mpMRI prior to performing a repeat biopsy when clinical suspicion of prostate cancer persists in spite of negative biopsies. During repeat biopsy, target any mpMRI lesions seen. Additionally, the guidelines recommend performing mpMRI for local staging and metastatic screening in predominantly Gleason pattern 4 intermediate risk patients and for local staging in high-risk localised prostate cancer. [5]

 

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Management of Clinically Localized Prostate Cancer

American Urological Association

Guidelines from the American Urological Association, the American Society for Radiation Oncology (ASTRO) and the Society of Urologic Oncology (SUO) for management of clinically localized prostate cancer include the following recommendations for very-low-risk and low-risk disease [7] :

  • Abdominal-pelvic CT or routine bone scans hsould not be performed as part of the staging of asymptomatic patients with very-low-risk or low-risk prostate cancer. (Strong Recommendation; Evidence Level: Grade C)
  • Clinicians should recommend active surveillance as the best available care option for patients with very-low-risk localized prostate cancer. (Strong Recommendation; Evidence Level: Grade A)
  • Clinicians should recommend active surveillance as the preferable care option for most patients with low-risk localized prostate cancer. (Moderate Recommendation; Evidence Level: Grade B)
  • Clinicians may offer definitive treatment (ie, radical prostatectomy or radiotherapy) to select low-risk localized prostate cancer patients who may have a high probability of progression on active surveillance. (Conditional Recommendation; Evidence Level: Grade B)
  • Clinicians should not add androgen deprivation therapy (ADT) to radiotherapy for low-risk localized prostate cancer, except to reduce the size of the prostate for brachytherapy. (Strong Recommendation; Evidence Level: Grade B)
  • Clinicians should inform low-risk prostate cancer patients considering whole gland cryosurgery that consequent side effects are considerable and survival benefit has not been shown in comparison with active surveillance. (Conditional Recommendation; Evidence Level: Grade C)
  • Clinicians should inform low-risk prostate cancer patients who are considering focal therapy or high-intensity focused ultrasound (HIFU) that these interventions are not standard care options because comparative outcome evidence is lacking. (Expert Opinion)
  • Clinicians should recommend observation or watchful waiting for men with a life expectancy ≤5 years with low-risk localized prostate cancer. (Strong Recommendation; Evidence Level: Grade B)
  • In most cases of low-risk localized prostate cancer, tissue-based genomic biomarkers have not shown a clear role in the selection of candidates for active surveillance. (Expert Opinion)

For patients with intermediate-risk disease, care recommendations are as follows:

  • Clinicians should consider staging unfavorable intermediate-risk localized prostate cancer with cross-sectional imaging (CT or MRI) and bone scan. (Expert Opinion)
  • Clinicians should recommend radical prostatectomy or radiotherapy plus ADT as standard treatment options for patients with intermediate-risk localized prostate cancer. (Strong Recommendation; Evidence Level: Grade A)
  • Clinicians should inform patients that favorable intermediate-risk prostate cancer can be treated with radiation alone, but that the evidence basis is less robust than for combining radiotherapy with ADT. (Moderate Recommendation; Evidence Level: Grade B)
  • In select patients with intermediate-risk localized prostate cancer, clinicians may consider other treatment options such as cryosurgery. (Conditional Recommendation; Evidence Level: Grade C)
  • Active surveillance may be offered to select patients with favorable intermediate-risk localized prostate cancer; however, patients should be informed that this comes with a higher risk of developing metastases compared with definitive treatment. (Conditional Recommendation; Evidence Level: Grade C)
  • Clinicians should recommend observation or watchful waiting for men with a life expectancy ≤5 years with intermediate-risk localized prostate cancer. (Strong Recommendation; Evidence Level: Grade A)
  • Clinicians should inform patients with intermediate-risk prostate cancer who are considering focal therapy or HIFU that these interventions are not standard care options because comparative outcome evidence is lacking. (Expert Opinion)

For high-risk patients the guideline recommendations include the following:

  • Clinicians should stage high-risk localized prostate cancer patients with cross-sectional imaging (CT or MRI) and bone scan. (Clinical Principle)
  • Clinicians should recommend radical prostatectomy or radiotherapy plus ADT as standard treatment options for patients with high-risk localized prostate cancer. (Strong Recommendation; Evidence Level: Grade A)
  • Clinicians should not recommend active surveillance for patients with high-risk localized prostate cancer. Watchful waiting should be considered only in asymptomatic men with limited life expectancy (≤5 years). (Moderate Recommendation; Evidence Level: Grade C)
  • Cryosurgery, focal therapy, and HIFU treatments are not recommended for men with high-risk localized prostate cancer outside of a clinical trial. (Expert Opinion)
  • Clinicians should not recommend primary ADT for patients with high-risk localized prostate cancer unless the patient has both limited life expectancy and local symptoms. (Strong Recommendation; Evidence Level: Grade
  • Clinicians may consider referral for genetic counseling for patients (and their families) with high-risk localized prostate cancer and a strong family history of specific cancers (eg, breast, ovarian, pancreatic, other gastrointestinal tumors, lymphoma). (Expert Opinion)

European Society of Medical Oncology

The 2015 ESMO guidelines recommend watchful waiting with delayed hormone therapy as an option for localized disease or as an alternative for men with localized or locally advanced disease who are unwilling or unsuited for radical therapy. [4]

Other recommended treatment options include [4] :

  • Active surveillance for men with low-risk disease 
  • Radical prostatectomy (RP) or radiotherapy (external beam or brachytherapy) for men with low- or intermediate-risk disease 
  • Primary androgen deprivation therapy (ADT)  alone is not recommended for treatment of non-metastatic disease 
  • For patients with high-risk or locally advanced prostate cancer, external beam RT plus hormone treatment or RP plus pelvic lymphadenectomy 
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Bone Scan for Diagnosis of Metastatic Disease

The NCCN guidelines include scanning technology utilizing fluorine-18 sodium fluoride (18 F-NaF) as the tracer for the subsequent positron-emission tomography (PET) scan as an option for men with prostate cancer who undergo a bone scan to search for metastatic disease. PET and hybrid imaging bone scans appear more sensitive than conventional 99-technetium bone scans. [6]

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Castration-Resistant Prostate Cancer

The following organizations have published guidelines for the treatment of castration-resistant prostate cancer (CRPC):

  • American Society of Clinical Oncology (ASCO)/Cancer Care Ontario (CCO)
  • American Urology Association (AUA)
  • National Comprehensive Cancer Network (NCCN)
  • European Association of Urology/European Society for Radiotherapy and Oncology/International Society of Geriatric Oncology (EAU/ESTRO/SIOG)

American Society of Clinical Oncology/Cancer Care Ontario recommendations

ASCO and CCO released a joint clinical practice guideline for treatment of men with mCRPC in 2014. [8] The guideline recommendations include the following:

  • Pharmacologic androgen deprivation therapy (ADT) should be continued indefinitely
  • Offer patients one of three treatment options—abiraterone/prednisone, enzalutamide, or radium-223 (if cancer has spread to bone)—in addition to hormone deprivation
  • When considering chemotherapy, docetaxel/prednisone should be an option but side effects must be discussed
  • Offer cabazitaxel to men whose disease worsens even if docetaxel has been tried, but again, discuss side effects
  • Offer sipuleucel-T to men with no symptoms or minimal symptoms of cancer
  • Offer mitoxantrone, but include a discussion of the drug's limited clinical benefit and side effect risk
  • Offer ketoconazole or the anti-androgen therapies bicalutamide, flutamide or nilutamide but discuss the limited clinical benefit for these three medications
  • Do not offer the drugs bevacizumab (Avastin), estramustine, or sunitinib
  • Begin discussion of palliative care early on while discussing treatment options

American Urological Association recommendations

American Urological Association guidelines for the management of CRPC describe six index-patient scenarios for which recommendations could be formulated. [9]

Index patient no. 1: Asymptomatic non-metastatic CRPC

Recommendations are as follows:

  • Observation with continued ADT
  • First-generation antiandrogens (flutamide, bicalutamide, and nilutamide) or first-generation androgen-synthesis inhibitors (ketoconazole plus steroid) to patients unwilling to accept observation.
  • Systemic chemotherapy or immunotherapy should not be offered to patients with non-metastatic CRPC outside the context of a clinical trial

Index patient no. 2: Asymptomatic or minimally-symptomatic, metastatic CRPC with good performance status and without prior docetaxel chemotherapy

Recommendations are as follows:

  • Abiraterone plus prednisone, enzalutamide, docetaxel, or sipuleucel-T
  • First-generation antiandrogen therapy or ketoconazole plus steroid or observation to patients who do not want or cannot have one of the standard therapies

Index patient no. 3: Symptomatic, metastatic CRPC with good performance status and no prior docetaxel chemotherapy

Recommendations are as follows:

  • Docetaxel
  • Abiraterone plus prednisone, enzalutamide, or docetaxel
  • Ketoconazole plus steroid, mitoxantrone, or radionuclide therapy for patients who do not want or cannot have one of the standard therapies
  • Radium-223 to patients with symptoms from bony metastases and without known visceral disease
  • Treatment with either estramustine or sipuleucel-T should not be offered

Index patient no. 4: Symptomatic, metastatic CRPC with poor performance status and no prior docetaxel chemotherapy

Recommendations are as follows:

  • Abiraterone plus prednisone or enzalutamide
  • Ketoconazole plus steroid or radionuclide therapy to patients who are unable or unwilling to receive abiraterone plus prednisone
  • Docetaxel or mitoxantrone chemotherapy in select cases, specifically when performance status is directly related to the cancer
  • Radium-223 to patients with symptoms from bony metastases and without known visceral disease in select cases, specifically when the performance status is directly related to symptoms related to bone metastases.
  • Treatment with sipuleucel-T should not be offered

Index patient no. 5: Symptomatic, metastatic CRPC with good performance status and prior docetaxel chemotherapy

Recommendations are as follows:

  • Abiraterone plus prednisone, cabazitaxel, or enzalutamide
  • If the patient received abiraterone plus prednisone prior to docetaxel chemotherapy, offer cabazitaxel or enzalutamide
  • Ketoconazole plus steroid if abiraterone plus prednisone, cabazitaxel, or enzalutamide is unavailable
  • Re-treatment with docetaxel for patients who were benefiting from but discontinued treatment with docetaxel because of reversible adverse effects
  • Radium-223 to patients with symptoms from bony metastases and without known visceral disease

Index patient no. 6: Symptomatic, metastatic CRPC with poor performance status and prior docetaxel chemotherapy

Recommendations are as follows:

  • Palliative care
  • For selected patients, offer treatment with abiraterone plus prednisone, enzalutamide, ketoconazole plus steroid, or radionuclide therapy
  • Systemic chemotherapy or immunotherapy should not be offered

Bone health recommendations

Because the skeletal system is the most common site for prostate cancer metastasis, the guideline also makes recommendations regarding bone health not specific to any index patient group:

  • Offer preventive treatment (eg, supplemental calcium, vitamin D) for fractures
  • Choose either denosumab or zoledronic acid as preventative treatment for skeletal-related events

National Comprehensive Cancer Network recommendations

The NCCN guidelines for prostate cancer offer treatment recommendations for CRPC based on the presence or absence of visceral metastases. For the most part, these recommendations are based on high-level evidence and are supported by uniform NCCN consensus (category 1 recommendations). [6]

CRPC without distant metastasis

  • Enrollment in clinical trial is preferred
  • Observation is acceptable
  • Secondary hormone therapy can be considered for patients with prostate-specific antigen (PSA) doubling < 10 months; anti-androgen therapy is acceptable for patients who previously received medical or surgical castration, ketoconazole, corticosteroids, diethylstilbestrol or other estrogens

CRPC with bone metastases

Measures to promote bone health include the following:

  • Zoledronic acid or denosumab
  • Avoidance of invasive dental surgery during treatment
  • Calcium and vitamin D supplements to prevent hypocalcemia during treatment

Radium-233 can be used to treat symptomatic bone metastases without visceral metastases.

Metastatic CRPC with no visceral metastases

  • Sipuleucel-T for asymptomatic or minimally symptomatic patients
  • Abiraterone plus prednisone or enzalutamide for asymptomatic patients
  • Docetaxel with prednisone for symptomatic patients; may also be considered in a symptomatic patients with signs of rapid progression
  • Radium-233 for symptomatic patients
  • Secondary hormone therapy or enrollment in clinical trial may be considered

Second-line treatment for patients with no visceral metastases who experience progression of disease after treatment with enzalutamide or abiraterone is as follows:

  • Docetaxel with prednisone
  • Abiraterone, if the patient had previously taken enzalutamide
  • Enzalutamide, if the patient had previously taken abiraterone
  • Radium-233 for bone-predominant disease
  • Sipuleucel-T for asymptomatic or minimally symptomatic patients with no liver metastases, life expectancy > 6 mo, and ECOG performance status 0-1
  • Clinical trial
  • Other secondary hormone therapy (eg, antiandrogen, antiandrogen withdrawal, ketoconazole, corticosteroids, diethylstilbestrol or other estrogen)
  • Best supportive care

Second-line treatment for patients with no visceral metastases who experience progression of disease after treatment with docetaxel is as follows:

  • Enzalutamide
  • Abiraterone with prednisone
  • Radium-233 for bone-predominant disease
  • Cabazitaxel with prednisone
  • Sipuleucel-T for asymptomatic or minimally symptomatic patients with no liver metastases, life expectancy > 6 mo, and ECOG performance status 0-1
  • Clinical trial
  • Docetaxel rechallenge
  • Alternative chemotherapy (mitoxantrone)
  • Other secondary hormone therapy (eg, antiandrogen, antiandrogen withdrawal, ketoconazole, corticosteroids, diethylstilbestrol or other estrogen)
  • Best supportive care

Metastatic CRPC with visceral metastases

  • Docetaxel with prednisone (preferred treatment)
  • Addition of estramustine to docetaxel not recommended
  • Enzalutamide (category 1)
  • Abiraterone for men who decline chemotherapy

Second-line treatment for patients with visceral metastases who experience progression of disease after treatment with enzalutamide or abiraterone is as follows:

  • Docetaxel with prednisone
  • Clinical trial
  • Abiraterone, if the patient had previously taken enzalutamide
  • Enzalutamide, if the patient had previously taken abiraterone
  • Other secondary hormone therapy (eg, antiandrogen, antiandrogen withdrawal, ketoconazole, corticosteroids, diethylstilbestrol or other estrogen)
  • Best supportive care

Second-line treatment for patients with visceral metastases who experience progression of disease after treatment with docetaxel is as follows:

  • Enzalutamide
  • Abiraterone with prednisone
  • Cabazitaxel with prednisone
  • Clinical trial
  • Docetaxel rechallenge
  • Alternative chemotherapy (mitoxantrone)
  • Other secondary hormone therapy (eg, antiandrogen, antiandrogen withdrawal, ketoconazole, corticosteroids, diethylstilbestrol or other estrogen)
  • Best supportive care

European Association of Urology/European Society for Radiotherapy and Oncology/International Society of Geriatric Oncology recommendations

EAU, ESTRO and SIOG released a joint clinical practice guideline for prostate cancer in 2016. The guideline recommendations for patients with mCRPC  include the following [5] :

  • Treat with life prolonging agents (alphabetical order: abiraterone, docetaxel, enzalutamide, radium-223, sipuleucel-T). Base the choice of first line treatment on the performance status, symptoms, comorbidities and extent of disease.
  • Candidates for cytotoxic therapy should be offered docetaxel with 75 mg/m2 every 3 weeks.
  • In patients with progression following docetaxel chemotherapy, offer further life-prolonging treatment options, which include cabazitaxel, abiraterone, enzalutamide and radium-223.
  • Offer bone protective agents to patients with skeletal metastases to prevent osseous complications. However, the benefits must be balanced against the toxicity of these agents, and jaw necrosis, in particular, must be avoided.
  • Offer calcium and vitamin D supplementation when prescribing either denosumab or bisphosphonates.
  • Treat painful bone metastases early on with palliative measures such as EBRT, radionuclides, and adequate use of analgesics.
  • In patients with spinal cord compression, start immediate high-dose corticosteroids and assess for spinal surgery followed by irradiation. Offer radiation therapy alone if surgery is not appropriate.
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Castration Naive Prostate Cancer

National Comprehensive Cancer Network Recommendations:

 

M0 Castration Naive Diease can be treated with Orchiectomy or LHRH agonist +/- antiandrogen or LHRH antagonist or in selected patients observation

M1 Castration Naive Disease can be treated with ADT similar to M0 disease expect a atleast 7 day pretreatment with antiandrogen is recommended to prevent testosterone flare.  Patietns can be considered for Docetaxel 75 mg/m2 with or without prednisone for 6 cycles in addition to ADT.  Patients with low volume disease ( less than 4 metastatic sites) have less certain benefit from early treatment with docetaxel. 

Patients suspected to small cell should undergo biopsy and if confirmed should be considered for clinical trial or alternatively treated with cisplatin/etoposide or carboplatin/etoposide or docetaxel/carboplatin [6]

 

 

 

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