AUA & ASTRO & SUO: Clinically Localized Prostate Cancer (2022)

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Guidelines based on literature searches up to August-September 2021

Target population: patients with clinically localized prostate cancer, defined as up to clinical stage T3 (by digital rectal examination [DRE]) prostate cancer without nodal or distant metastasis (c≤T3N0M0) on conventional imaging.

Risk stratification[edit | edit source]

  • Based on (3):
    1. PSA
    2. Clinical stage
      • Digital rectal exam (DRE) should be performed and documented in the chart to evaluate the clinical T-stage.
      • Prostate imaging (ultrasound or MRI) is NOT at this time used to assign clinical T-stage for risk classification
        • The Panel acknowledges that imaging (e.g., MRI) findings may provide additional information regarding local tumor extent, and may be utilized in disease prognostication/treatment planning.
    3. Cancer grade on biopsy
      •  % biopsy cores positive is used to stratify intermediate-risk into favorable vs. unfavorable
      • World Health Organization/ International Society of Urologic Pathologists (WHO/ISUP) Grade Group system or the older Gleason score system is used to assign cancer grade
        • Higher Gleason score associated with increased risks of biochemical recurrence, metastatic disease, prostate cancer-specific mortality, and all-cause mortality.
        • Gleason score also a strong predictor of prostate cancer mortality in patients who did not undergo curative treatment.
  • Categories (3):
    • Presence of any feature from a higher-risk category determines classification
      • PSA <10 with clinical stage T1c and grade group 3 is intermediate-risk, unfavorable
    • Low risk
      1. PSA <10 ng/ml AND
      2. Grade Group 1 AND
      3. Clinical stage T1-T2a
    • Intermediate risk
      • PSA 10-<20 ng/ml OR
      • Grade Group 2-3 OR
      • Clinical stage T2b-c
        • Favorable:
          • <50%* biopsy cores positive AND
            • Grade Group 1 with 1 intermediate-risk factor OR
            • Grade Group 2 with 0 other intermediate-risk factors
        • Unfavorable:
          • Grade Group 1 with 2 intermediate-risk factors
          • Grade Group 2 with ≥ 1 other intermediate-risk factor OR ≥50%* biopsy cores positive
          • Grade Group 3
    • High risk
      • PSA ≥20 ng/ml OR
      • Grade Group 4-5 OR
      • Clinical stage T3
    • *Percent biopsy cores positive is the total number of cores containing cancer divided by total number of cores obtained x 100. This is not the percentage of cancer within a positive core.
      • Multiple cores from the same lesion should be considered as a single core (i.e., for the calculation of percentage cores positive in risk assessment).
        • If all cores are negative, that is considered a single negative core.
        • If one or more cores from the same lesion is positive, that is considered a single positive core, with the highest Gleason score used for risk stratification
    • Changes from 2017 guidelines: removal of very-low risk category and criteria for favorable vs. unfavorable intermediate-risk disease
    • Comparison with 2022 NCCN risk stratification (PROS-2)
      • Similarities:
        • Risk-stratification for low and high-risk identical
      • Differences
        • NCCN guidelines include very low and very high-risk categories
        • GG1 with 1 intermediate-risk factor and >50% cores positive classified as
          • NCCN: unfavorable-intermediate
          • AUA: undetermined
  • Other factors for risk assessment
    • Intraductal and cribiform patterns on prostate biopsy
      • Associated with worse prognosis
      • Should be considered when counseling.
    • PSA density
      • In active surveillance patients, PSA density ≥ 0.15 ng/mL/cc has been associated with the risk of upgrading on subsequent biopsy
        • The Panel recognizes the continuous nature of risk associated with the spectrum of PSA density values and cautions against use of threshold values in isolation for management decision-making.
    • Tissue-based genomic markers
      • Predict risks of adverse pathology, biochemical recurrence, metastasis, and prostate cancer death.
      • Examples: Polaris, Oncotype Dx, Decipher
      • Most of the studies to date evaluated surgical (i.e., prostatectomy) rather than biopsy specimens; performance of tissue-based genomic markers on biopsy specimens for risk stratification remains unknown. Few studies have used biopsy specimens.
      • Should not be routinely used for risk stratification or clinical decision-making; however, may be used selectively when added risk stratification may alter shared-decision making.
        • Examples of patients for whom tissue-based genomic markers may help clarify risk:
          • High-volume (multiple involved cores) Gleason score 6 cancer
          • Favorable intermediate-risk prostate cancer who are interested in active surveillance.

Germline testing[edit | edit source]

  • Potential goals of germline testing in clinically localized prostate cancer (3):
    1. Enhanced risk stratification
    2. Identification of genes that may guide treatment decisions
    3. Providing information to determine the need for personal and family member cancer screening.
  • Prostate cancer associated genes to date include: ATM, BRCA1, BRCA2, CHEK2, HOXB12, MLH1, MSH2, MSH6, NBN, PALB2, PMS2, and TP53.
    • BRCA2/BRCA1 genetic aberrations are more likely to have worse disease and a poorer prognosis.
  • Testing is typically performed via a saliva or blood sample.
  • Indications (5):
    1. Strong family history of prostate cancer
      • Examples: first-degree relative or multiple second-degree relatives diagnosed with Grade Group 2 or higher prostate cancer, particularly at early age (< 60 years), particularly if metastatic or lethal
    2. Strong personal or family history of related cancers
      • Examples: breast, colorectal, ovarian, pancreatic, upper tract urothelial carcinoma
    3. Known family history of familial cancer risk mutation
      • Examples: BRCA1, BRCA2, ATM, Lynch-syndrome associated genes
    4. Ashkenazi Jewish ancestry
      • Particularly in patients with Grade Group 2 or higher disease
    5. Adverse tumor characteristics
      • Examples: High-risk disease; intermediate-risk disease with intraductal or cribriform morphology

Staging[edit | edit source]

Indications[edit | edit source]

  • Asymptomatic low/intermediate-risk: staging should NOT be performed
    • May be considered for unfavorable, intermediate-risk.
  • High-risk: staging should be performed

Modality[edit | edit source]

  • Cross sectional imaging (CT or multi-parametric MRI) and bone scan should be used to stage patients with clinically localized prostate cancer, when indicated.
    • For both mpMRI scan and CT scan, the assessment of nodal metastasis is based on size criteria, and these modalities have moderate sensitivity and high specificity.
    • To evaluate for the presence of bone metastasis, conventional bone scan should be obtained as the initial staging study.
  • Molecular imaging may be obtained to evaluate for metastases in patients with prostate cancer at high risk for metastatic disease with negative conventional imaging
    • Molecular imaging is also referred to as next generation imaging (NGI)
    • Gallium 68 prostate-specific membrane antigen (PSMA)-11 (Ga 68 PSMA-11) and piflufolastat F-18 PSMA (18F-DCFPyL) PET scanning have been FDA approved for initial staging for patients at high risk of metastasis (as well as for evaluation of biochemical relapse after treatment).
      • proPSMA (2020) was a multicenter randomized trial that compared Ga-68 PSMA PET with conventional imaging using CT scan and bone scan in patients with high-risk prostate cancer before definitive therapy and found that Ga-68 PSMA PET scan was found to have a 27% greater accuracy than conventional imaging, with better sensitivity and specificity, in the detection of nodal or distant metastasis.
    • Limited data to date demonstrating a clinical benefit to novel imaging modalities for patients with negative conventional imaging
      • Identification of disease with molecular imaging may influence treatment (e.g., the addition of systemic therapy or metastases-directed therapy); uncertain incremental oncologic benefit of altering treatment based on the identification of metastases with molecular imaging among patients with negative conventional imaging.

Management[edit | edit source]

Shared-decision making[edit | edit source]

  • Estimate of life expectancy should factor into the shared-decision making discussion.
  • Baseline disease-specific function (e.g., urinary, sexual, and bowel function) and the value or utility they place on each (ideally using standardized instruments, with or without decision aids) should be assessed
    • Patients should be informed that all prostate cancer treatments carry risks, particularly effects on urinary, sexual, and bowel function
    • Standardized instruments minimize clinician bias and to facilitate longitudinal comparisons.
  • Key Components of Shared Decision-Making for Localized Prostate Cancer Treatment Selection (5):
    1. Informing patients about the severity of their cancer (risk level)
    2. Assessing patients’ relevant comorbidities and life expectancy
    3. Informing patients about the likelihood of cure, recurrence, and other oncologic endpoints of each management strategy/ treatment option (ideally using a risk calculator or nomogram)
    4. Assessing patients’ baseline disease-specific function (e.g., urinary, sexual, and bowel function) and the value or utility they place on each (ideally using standardized instruments, with or without decision aids)
    5. Informing patients about their likelihood of specific short- and long-term side effects of each management strategy/ treatment option

Treatment by risk stratum[edit | edit source]

Life expectancy ≤5 years[edit | edit source]

  • Watchful waiting should be recommended
    • Minimum estimated life expectancy of 8-10 years in order for treatment to result in a reduction in the risk of death.
    • Watchful waiting is appropriate for elderly patients or patients with significant comorbidities in whom competing risks of mortality are considerably greater than the risk of death from prostate cancer
  • Watchful waiting does not involve routine cancer surveillance, but rather aims to deliver palliative therapy for relief of symptoms should they develop.
    • The critical goal of watchful waiting is to maintain the patient’s QOL by avoiding treatment when prostate cancer is unlikely to cause mortality or significant morbidity. One of the principal aims of watchful waiting is avoidance of side effects from local treatment or ADT.

Low-risk[edit | edit source]

  • Active surveillance should be recommended as the preferred management option (Strong Recommendation; Evidence Level: Grade A).
    • Select patients with low-risk disease may elect definitive local therapy after an informed discussion between clinician and patient. In particular, clinicians may offer immediate treatment to select patients who are fully informed as to all options and risks with low-risk prostate cancer such as those who
      • Have a high probability of disease risk reclassification on active surveillance (e.g., high-volume cancer, higher PSA density) OR
      • Other risk factors for harboring higher-risk disease (e.g., family history of lethal prostate cancer, germline mutation associated with adverse pathology).
    • Patients electing to proceed with active surveillance should be informed of the importance of regular cancer surveillance to avoid missing the window of curability.

Favorable, intermediate-risk[edit | edit source]

  • Options (3):
    1. Active surveillance
    2. Radiation therapy (without ADT)
    3. Radical prostatectomy
  • Patients with favorable intermediate-risk disease who may be considered for active surveillance include those with (3):
    1. Low PSA density
    2. Low tumor volume
    3. Low percentage of Gleason pattern 4 disease on biopsy

Unfavorable, intermediate-risk or high-risk AND life expectancy >10 years[edit | edit source]

  • Options (2):
    1. Radiation therapy (with ADT)
      • For patients with sufficiently high-risk disease (clinically node positive, or with 2 of 3 of the following criteria: clinical stage T3 or T4, PSA ≥ 40 ng/mL, or ≥ Gleason 8), treatment with radiation and ADT can include two years of concurrent abiraterone acetate plus prednisone as well.
      • Duration of ADT:
        • Unfavorable, intermediate-risk: 4-6 months
        • High-risk: 18-36 months
    2. Radical prostatectomy

Modality[edit | edit source]

Active Surveillance[edit | edit source]

  • Patients should be monitored with (4):
    1. Serial PSA values
    2. Symptom assessments
    3. DRE
    4. Repeat prostate biopsy
      • mpMRI should be used to augment risk stratification in patients on active surveillance, but this should not replace periodic surveillance biopsy
        • The Panel believes that an mpMRI should be obtained if the initial (diagnostic) prostate biopsy was performed without mpMRI guidance.
          • If the mpMRI demonstrates findings suspicious for clinically-significant prostate cancer (PIRADS 4 or 5), then timely repeat (confirmatory) targeted biopsy is recommended, with disease risk re-established based on these biopsy results.
          • Conversely, if the mpMRI is assessed as PIRADS 1, 2, or 3, then repeat biopsy may be performed within approximately 12 months after diagnosis.
          • Thereafter, serial surveillance biopsies are recommended every one to four years depending on patient age, health, risk of progression, and preference
        • Evidence for the utility of serial prostate mpMRI to evaluate for changes in disease risk among patients on surveillance remains mixed; as such, mpMRI cannot be recommended as a stand-alone replacement for periodic repeat biopsy.
          • Meta-analysis found a pooled sensitivity and specificity for detecting Grade Group of 2 or more of 0.59 (95% CI 0.44 to 0.73) and 0.75 (95% CI 0.66 to 0.84), respectively.
  • Frequency of testing
    • Serial PSA values: should not be obtained more frequently than every 6 months
    • Symptom assessment and DRE: should be updated every 2 years
    • Serial surveillance biopsies: recommended every 1-4 years depending on patient age, health, risk of progression, and preference
      • The monitoring regimen for patients managed with active surveillance may be individualized.
        • Among patients at low risk of progression or with a more limited life expectancy, a less intense follow-up schedule may be implemented
    • Serial genomic testing among patients on active surveillance should be discouraged.
  • Increase in PSA while on active surveillance should initially prompt re-testing of PSA
    • Transient PSA elevations are common and PSA kinetics have variably been associated with pathology among patients on surveillance.
  • Serial PSA increases, new DRE abnormalities, or other concerns for clinical progression should prompt re-evaluation with MRI and possible prostate biopsy
    • Direct conversion to treatment may be considered less frequently,
    • Detection of significantly higher-volume or higher-grade disease on surveillance biopsy should then prompt discussion of definitive therapy.

Radical prostatectomy[edit | edit source]

Nerve-sparing[edit | edit source]
  • Preservation of the neurovascular bundles during radical prostatectomy (nerve-sparing), when oncologically appropriate, should be performed.
  • Decision to perform nerve-sparing is frequently multifactorial, and may include PSA, DRE, biopsy findings (grade, tumor volume, and location), MRI findings, as well as the patient’s baseline erectile function and stated prioritization of sexual function.
    • MRI (i.e. absence of extracapsular extension) should not be used in isolation to determine nerve-sparing, as the ability of MRI to predict extracapsular extension, particularly when microscopic, is suboptimal.
  • No RCTs comparing nerve-sparing versus non-nerve sparing radical prostatectomy
    • Observational studies have found that nerve-sparing is
      • Consistently associated with a lower likelihood of postoperative erectile dysfunction
      • Variously but favorably been associated with improved urinary continence after surgery
      • Not associated with significantly increased risks of positive surgical margins or biochemical recurrence
Pelvic lymphadenectomy[edit | edit source]
  • Advantages
    • Provides staging information which may guide future management
      • No consistent benefit in biochemical recurrence, metastasis-free, cancer-specific, and overall survival
        • Two recent trials randomized patients undergoing radical prostatectomy to limited versus extended PLND. In both trials, no statistically significant difference in subsequent biochemical recurrence-free survival was identified between the treatment arms.
          • One of the trials did note improved biochemical recurrence-free survival with extended lymph node dissection in an exploratory subgroup analysis of patients with Grade Group 3 to 5 tumors.
  • Disadvantages
    • Increased operating time
    • Increased risk of blood loss
    • Increased risk of lymphocele
  • Nomograms should be used to select patients for lymphadenectomy
    • Potential benefit of identifying lymph node positive disease should be balanced with the risk of complications
    • No threshold provided, should be based on shared-decision making
  • If performed, should be an extended dissection (obturator fossa, external iliac, and internal iliac), which improves staging accuracy compared to limited dissection
  • If suspicious regional nodes are encountered intraoperatively, radical prostatectomy should be completed
    • Retrospective studies have reported a benefit to completion of radical prostatectomy among patients found to have positive nodes compared to patients whose surgery was aborted and who were then treated with ADT alone.
  • Positive lymph nodes (pN1)
    • Heterogeneous natural history
      • Up to 30% of patients may remain free of disease long-term following surgery without further therapy.
    • Patients should be risk-stratified based on pathologic variables (particularly the number of positive nodes identified) and postoperative PSA to guide use of secondary therapy.
      • If undetectable post-operative PSA, consider surveillance with the option of early salvage should the patient experience biochemical recurrence. Adjuvant therapies (e.g. ADT or radiation) are alternatives.
      • If detectable post-operative PSA, salvage therapy with ADT is recommended.
        • The optimal timing (post-operative vs. at biochemical recurrence) of initiating ADT for patients with pN1 remains unknown.
Adjuvant radiotherapy[edit | edit source]
  • Should not be routinely recommended
    • Patients should be initially managed with PSA surveillance after radical prostatectomy
  • 3 recent randomized trials (GETUG-AFU 17, RAVES, RADICALS) evaluated adjuvant radiation therapy vs. surveillance with early salvage radiation therapy for PSA increase in patients with high-risk localized prostate cancer following radical prostatectomy.
    • Criteria for early salvage therapy was a PSA >0.1 ng/mL or >0.2 ng/mL depending on the trial
    • The proportion of patients in the early salvage therapy groups that received radiation therapy ranged from one third to one half.
    • Meta-analysis of these trials found no evidence of improvement in event-free survival (pooled HR 0.95, 95% CI 0.75 to 1.21) with receipt of adjuvant therapy and noted that adjuvant radiation was associated with increased risk of genitourinary toxicity.
  • There may be a role for adjuvant radiation in patients with high-risk features (e.g., Gleason 8 to 10 disease with extraprostatic extension, positive lymph nodes); there were few of these patients in the trials

Radiation[edit | edit source]

  • Approaches to optimize the therapeutic ratio in radiation oncology
    1. Simulation procedures: Bladder/rectum filling instructions, patient immobilization, placement of fiducial markers, and use of rectal spacers
    2. Imaging procedures: CT simulations, integrations of fusion imaging (e.g., MRI prostate), image-guided radiation therapy approaches (e.g., cone-beam CT)
    3. Planning procedures: Use of highly conformal radiation therapy such as intensity-modulated radiation therapy (IMRT), volumetric modulated arc therapy (VMAT), and stereotactic body radiation therapy (SBRT), combined with published target and normal tissue dose objectives to optimize planning
      • Most of these approaches have not been subject to prospective randomized phase III trial testing (except the use of rectal spacers)
  • Options by risk stratum
    • Low or favorable, intermediate-risk
      1. Dose-escalated hypofractionated external beam radiotherapy (EBRT) (moderate or ultra hypofractionation)
      2. Permanent low-dose rate (LDR) seed implant
      3. Temporary high-dose rate (HDR) prostate implant
    • Unfavorable, intermediate-risk or high-risk
      1. Dose-escalated hypofractionated EBRT (moderate only for high-risk; use of ultra not specified for unfavorable, intermediate-risk)
      2. Combined EBRT + brachytherapy (LDR, HDR)
  • EBRT
    • Current standard technique of external beam radiation therapy (EBRT) is IMRT
    • When EBRT is the primary treatment, dose escalation should be used
      • Multiple phase III randomized trials studies have consistently demonstrated improved biochemical PFS with dose-escalated EBRT (DE-EBRT) using both 3-D conformal radiation therapy (3DCRT) and IMRT with standard dose EBRT.
        • These trials (with the exception of one trial) did not demonstrate a significant improvement in metastatic-disease free survival, prostate cancer-specific survival, and overall survival
    • Hypofractionation (using fewer (but larger dose) radiation treatments) may be more convenient for patients with prostate cancer electing radiation therapy.
      • Clinicians should offer moderate hypofractionated EBRT for patients with low- or intermediate-risk prostate cancer who elect EBRT.
      • Clinicians may offer ultra hypofractionated EBRT for patients with low- or intermediate-risk prostate cancer who elect EBRT.
      • A systematic review compared hypofractionated (>2 Gy per fraction, range 2.35 to 3.4 Gy) versus conventionally fractionated (1.8 to 2 Gy) EBRT in patients with localized prostate cancer included 10 randomized trials. In pooled analyses, no differences were noted between hypofractionation versus conventional fractionation with regard to biochemical recurrence-free survival, metastasis-free survival, prostate cancer-specific survival or overall survival. There were also no differences identified with regard to acute genitourinary radiation therapy toxicity late genitourinary radiation therapy toxicity, or late gastrointestinal radiation therapy toxicity
  • Pelvic lymph nodes
    • Low or intermediate-risk: lymph nodes should not be radiated
      • Randomized trials have not shown a significant benefit for whole pelvic radiation therapy to prostate only radiation.
    • High-risk: lymph nodes may be radiated
      • POP-RT (2021)[1]
        • Population: 224 patients undergoing radical radiotherapy for node-negative prostate adenocarcinoma, with estimated nodal risk ≥ 20%
        • Randomized to prostate-only radiotherapy (PORT) vs. whole-pelvic radiotherapy (WPRT)
        • Outcomes
          • Primary: 5-year biochemical failure-free survival
          • Secondary: disease-free survival and overall survival
        • Results:
          • Significant improvement in biochemical failure-free survival and disease-free survival but no significant improvement in overall survival
        • Murthy, Vedang, et al. "Prostate-only versus whole-pelvic radiation therapy in high-risk and very high-risk prostate cancer (POP-RT): Outcomes from phase III randomized controlled trial." Journal of Clinical Oncology 39.11 (2021): 1234-1242.
        • AUA Guideline: Despite not showing an overall survival benefit, the Panel notes that elective nodal irradiation for high-risk patients may be offered given the reasonable morbidity (higher late grade II genitourinary toxicity with whole pelvis radiation but no difference in late gastrointestinal toxicity and no difference in grade III/IV genitourinary or gastrointestinal toxicity noted) as well as the reductions in biochemical failure and distant metastases.
    • When treating the pelvic lymph nodes with radiation, IMRT with doses between 45 Gy to 52 Gy should be used
  • ADT
    • Low or favorable, intermediate-risk: ADT should not be used routinely
    • Unfavorable intermediate-risk: short-course (4-6 months) ADT should be used
    • High-risk: longer-course (18-36 months) ADT should be used
    • When combined ADT and radiation are used, ADT may be initiated neoadjuvantly, concurrently, or adjuvantly.
      • The optimal sequencing of ADT and radiation has not been clearly defined.
    • When combining ADT with radiation therapy, combined androgen suppression (luteinizing hormone-releasing hormone [LHRH] agonist with an antiandrogen), an LHRH agonist alone, or an LHRH antagonist alone may be used.
  • Proton therapy
    • Proton beam delivers lower integral doses and mean doses to normal tissues than IMRT.
    • Has not been shown to be superior to other radiation modalities in terms of toxicity profile and cancer outcomes

Whole gland or focal ablation[edit | edit source]

  • May be considered in select, appropriately informed intermediate-risk prostate cancer patients (with clinical trial enrollment prioritized)
  • Should not be considered in high-risk (lack of data) or low-risk (should be managed with active surveillance) disease.
    • Lack of high-quality data comparing ablation outcomes to radiation therapy, surgery, and active surveillance in patients with intermediate-risk prostate cancer.
      • At the time of guideline publication, the only adequately powered randomized trial reported on prostate ablation was restricted to patients with low-risk prostate cancer and demonstrated that focal photodynamic therapy (PDT) lowered the likelihood of cancer progression and rates of surgery/radiation compared to active surveillance, at an expense of an increased likelihood of mild urinary or erectile dysfunction. PDT is not approved in the United States.
  • Patients considering ablation should be counseled regarding side effects and recurrence risk
  • Post-ablation follow-up includes PSA, DRE, MRI, and biopsy tailored to their specific health and cancer characteristics.

ADT monotherapy[edit | edit source]

  • Palliative ADT monotherapy may be recommended for patients with high-risk prostate cancer, local symptoms, and limited life expectancy.
    • Primary ADT should only be recommended for palliation of local disease-related symptoms in select patients with a limited life expectancy for whom definitive local therapy is not advised.
    • For such patients, the primary goals of care include symptom control/palliation and maintenance of QOL. As such, ADT may be used to manage urinary tract sequelae of local tumor growth through (albeit transient) cytoreduction.

Follow-up after Treatment[edit | edit source]

  • Individualized risk estimate of post-treatment prostate cancer recurrence should be provided to patients with prostate cancer
  • Specific intervals for PSA follow-up may be tailored to disease risk based on clinicopathologic features.
    • Initial monitoring should in general be performed more frequently and is recommended every 3-6 months for the first 2 years after treatment.
    • Subsequent monitoring between years 2 and 5 should occur every 6 months, with monitoring annually thereafter.
    • The duration and interval of follow-up beyond 10 years for patients with an undetectable PSA at that time should be a shared decision based on patient disease risk, age, comorbidity status, and preference.
  • Urinary, bowel, and sexual function should likewise be routinely evaluated, with the use of standardized/validated instruments recommended, in order to monitor the QOL impact from therapy.

Questions[edit | edit source]

  1. Describe the risk stratification of clinically localized prostate cancer?
  2. What are the goals of germline testing in patients with clinically localized prostate cancer?
  3. What are the indications for germline testing in patients with clinically localized prostate cancer?

Answers[edit | edit source]

  1. Describe the risk stratification of clinically localized prostate cancer?
  2. What are the goals of germline testing in patients with clinically localized prostate cancer?
  3. What are the indications for germline testing in patients with clinically localized prostate cancer?

References[edit | edit source]