Guideline sources The following summarized guidelines for the evaluation and management of prostate cancer are prepared by our editorial team based on guidelines from the European Society of Medical Oncology (ESMO 2023; 2020), the American Urological Association (AUA/SUO 2023), the American Society of Clinical Oncology (ASCO 2023; 2022; 2021; 2020), the European Association of Urology (EAU 2023), the International Society of Urological Pathology (ISUP/EANM/SIOG/ESUR/EAU/ESTRO 2022), the Canadian Urological Oncology Group (CUOG/CUA 2022), the American Urological Association (AUA/ASTRO 2022; 2019), the American Urological Association (AUA/SUO/ASTRO 2021), the American Urological Association (AUA/ASTRO/ASCO 2018), the American Urological Association (AUA 2018), the U.S. Preventive Services Task Force (USPSTF 2018), and the American Urological Association (AUA/ASCO 2009). 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 24 25 26 27 28 Definition https://web.pathway.md/diseases/recXj11agry4hkwmf 1/24 6/29/23, 11:31 PM Prostate cancer Pathway Prostate cancer is a neoplastic disease arising from malignant transformation of cells within the prostate gland, of which adenocarcinoma is the most common subtype. 24 Epidemiology Risk factors include advanced age, race (African black men, Caucasians), family history, exposure to radiation, UTIs, smoking, obesity, physical inactivity, diet factors (red meat, dairy protein, dietary fat), and elevated endogenous hormones (insulin-like growth factors). 26 Pathophysiology The incidence of prostate cancer in the United States is estimated at123-183 cases per 100,000 person-years. 25 Disease course The progression of prostate cancer is impingent on activation of the androgen receptor nuclear receptor, and as such, treatment options for invasive disease rely on targeting this pathway. Progression to castrate-resistant prostate cancer is mediated by aberrant reactivation of the androgen receptor, as well as alterations in cell cycle pathways that result in uncontrolled proliferation. 27 Prognosis and risk of recurrence In men with localized prostate cancer, the 10-year disease-specific mortality ranges from 3% to 18%, depending on the risk category. In men with metastatic prostate cancer, the 5-year survival rate is estimated at 29.3%. 24 28 Calculator Calculator Calculat Eastern Cooperative Oncology G Karnofsky performance status s TNM cl Guidelines 1. Screening and diagnosis Indications for screening, general considerations: As per SUO/AUA 2023 guidelines, engage in shared decision-making with persons eligible for prostate cancer screening and proceed based on the person's values and preferences. B Show 4 more As per ISUP/SIOG/ESUR/ESTRO/EANM/EAU 2022 guidelines, do not subject males to PSA testing without counseling them on the potential risks and benefits. D Show 3 more https://web.pathway.md/diseases/recXj11agry4hkwmf 2/24 6/29/23, 11:31 PM Prostate cancer Pathway Landmark trials: ERSPC In men between the ages of 55 and 69 years, prostate cancer screening was superior to no screening with respect to death from prostate cancer. Schroder FH et al. N Engl J Med. 2009 Mar 26. Indications for screening, general population, age < 54 years: As per SUO/AUA 2023 guidelines: Consider beginning prostate cancer screening and obtaining a baseline PSA test in males aged 45-50 years. C Obtain regular prostate cancer screening every 2-4 years in males aged 50-69 years. A As per AUA 2018 guidelines: Do not obtain PSA screening in < 40 years old males. D Do not obtain routine screening in 40-54 years old males at average risk. D Indications for screening, general population, age 55-69 years: As per SUO/AUA 2023 guidelines, obtain regular prostate cancer screening every 2-4 years in males aged 50-69 years. A As per ESMO 2020 guidelines, do not obtain population-based PSA screening for prostate cancer in 55-69 years old males because of associated overdiagnosis and overtreatment. D As per AUA 2018 guidelines: Balance the benefits of reducing the rate of metastatic prostate cancer and prevention of prostate cancer death against the known potential harms associated with screening and treatment for the decision to obtain PSA screening in 55-69 years old males. Ensure shared decision-making and proceed based on a the individual's values and preferences. B Consider preferring a routine screening interval of 2 years over annual screening to preserve the majority of the benefits and to reduce the harms, overdiagnosis, and false positives of screening in males participated in shared decision-making and decided on screening. C As per USPSTF 2018 guidelines: Individualize the decision on obtaining screening for prostate cancer in 55-69 years old males with a discussion of potential benefits and harms of screening (based on family history, race/ethnicity, comorbid medical conditions, patient values about the benefits and harms of screening, and treatment-specific outcomes, and other health need). Recognize that screening offers a small potential benefit of reducing the chance of death from prostate cancer in some males of this age, while many males will experience potential harms of screening, including false-positive results requiring additional testing and possible prostate biopsy, overdiagnosis and overtreatment, and treatment complications, such as incontinence and erectile dysfunction. Do not obtain screening in individuals not expressing a preference for screening. B Do not obtain PSA-based screening for prostate cancer in 70 years old males. D Indications for screening, general population, age > 70 years: https://web.pathway.md/diseases/recXj11agry4hkwmf 3/24 6/29/23, 11:31 PM Prostate cancer Pathway As per ISUP/SIOG/ESUR/ESTRO/EANM/EAU 2022 guidelines, offer an individualized risk- adapted strategy for early detection in well-informed males with a life expectancy of at least 10-15 years. B As per ESMO 2020 guidelines, do not screen for prostate cancer in asymptomatic males with a life expectancy < 10 years. D As per AUA 2018 guidelines, do not obtain routine PSA screening in > 70 years old males or any male with a < 10-15 year life expectancy. D Indications for screening, high-risk population: As per SUO/AUA 2023 guidelines, obtain prostate cancer screening beginning at age 40-45 years in males at increased risk of developing prostate cancer based on the following factors: strong family history of prostate cancer black ancestry germline mutations. B As per EAU 2023 guidelines, obtain screening for prostate cancer in > 40 years old patients with persistent hemospermia. B As per ISUP/SIOG/ESUR/ESTRO/EANM/EAU 2022 guidelines: Obtain early PSA screening in well-informed males at elevated risk of prostate cancer from 50 years of age, or earlier in the following cases: Situation Guidance From 45 years of age Family history of prostate cancer From 45 years of age African descent From 40 years of age. A Carrying BRCA2 mutation Offer a risk-adapted strategy based on initial PSA level (> 1 ng/mL at 40 years of age and > 2 ng/mL at 60 years of age) with follow-up intervals of 2 years in patients initially at risk. Postpone follow-up to 8 years in patients not at risk. B As per ESMO 2020 guidelines, consider obtaining early PSA screening (baseline PSA followed by risk-adapted follow-up) in > 50 years old males, or earlier in individuals with any of the following: Situation Guidance > 45 years of age Family history of prostate cancer > 45 years of age African-Americans > 40 years of age. C BRCA1/2 mutation carriers Indications for screening, repeat screening: As per SUO/AUA 2023 guidelines: https://web.pathway.md/diseases/recXj11agry4hkwmf 4/24 6/29/23, 11:31 PM Prostate cancer Pathway Re-evaluate the patient within the normal screening interval (2-4 years) or sooner, depending on the risk of clinically significant prostate cancer and life expectancy, if the clinician and patient decide to continue screening after a negative biopsy. B Do not discontinue prostate cancer screening based solely on a negative prostate biopsy. D As per SUO/AUA 2023 guidelines, consider personalizing the re-screening interval or discontinuing screening based on patient preference, age, PSA, prostate cancer risk, life expectancy, and general health following shared decision-making. C 2. Classification and risk stratification Risk assessment, undiagnosed: As per SUO/AUA 2023 guidelines, consider using validated risk calculators to inform the shared decision-making process regarding prostate biopsy. C As per SUO/AUA 2023 guidelines, consider obtaining adjunctive urine or serum markers when further risk stratification would influence the decision regarding whether to proceed with a biopsy. C As per ISUP/SIOG/ESUR/ESTRO/EANM/EAU 2022 guidelines, use one of the following tools to decide on biopsy indication in asymptomatic males with a PSA level of 2-10 ng/mL and a normal DRE: risk-calculator A prostate MRI A additional serum, urine, or tissue-based biomarker tests. B Risk assessment, newly diagnosed, localized disease: As per ASTRO/AUA 2022 guidelines, use the clinical T stage, serum PSA level, Gleason score, and tumor volume on biopsy to risk stratify patients with newly diagnosed prostate cancer. B Show 2 more As per ASCO 2020 guidelines, obtain MRI and/or tissue-based molecular biomarker testing to identify clinically significant cancers in patients with newly diagnosed prostate cancer eligible for active surveillance, only in situations where assay results, in conjunction with routine clinical factors, will likely affect management. B As per ESMO 2020 guidelines, classify localized disease as low-, intermediate-, or high-risk to assess prognosis and guide therapy. B Risk assessment (newly diagnosed, advanced disease): assess for symptoms of metastatic disease at the time of presentation in patients with a newly diagnosed metastatic hormone- sensitive prostate cancer patient, to guide discussions of prognosis and further disease management. B Staging: use the TNM classification for staging and the 2014 ISUP system for grading prostate cancer. A 3. Diagnostic investigations https://web.pathway.md/diseases/recXj11agry4hkwmf 5/24 6/29/23, 11:31 PM Prostate cancer Pathway Prostate magnetic resonance imaging: As per AUA 2023 guidelines: Consider obtaining prostate MRI before the initial biopsy to increase the detection of grade group 2 prostate cancer. C Use the PI-RADS system in the reporting of multiparametric MRI. B As per ESMO 2020 guidelines, obtain a multiparametric MRI before prostate biopsy. B Adjunctive biomarkers: Consider obtaining adjunctive urine or serum markers when further risk stratification would influence the decision regarding whether to proceed with prostate biopsy. C Do not obtain biomarker testing reflexively after a negative initial biopsy in patients with a low probability of harboring grade group 2 prostate cancer. D Consider obtaining blood- or urine-based biomarkers selectively for further risk stratification after a negative biopsy if results are likely to influence the decision regarding repeat biopsy or otherwise substantively change the management. D Imaging for staging, clinically localized: As per ASTRO/AUA 2022 guidelines, do not obtain routine abdominopelvic CT or bone scan in asymptomatic patients with clinically localized, low- or intermediate-risk prostate cancer. D Show 2 more As per ISUP/SIOG/ESUR/ESTRO/EANM/EAU 2022 guidelines, obtain pre-biopsy MRI for local staging information in patients with localized disease. B Show 4 more As per ASCO 2020 guidelines: Consider obtaining next-generation imaging (positron emission tomography, positron emission tomography/CT, positron emission tomography/MRI, whole-body MRI) when conventional imaging (CT, bone scan, and/or prostate MRI) is negative in patients with a high risk of metastatic disease. C Consider obtaining next-generation imaging for clarification of equivocal findings or detection of additional sites of disease to potentially alter management if conventional imaging is suspicious or equivocal. C As per ESMO 2020 guidelines: Obtain abdominopelvic MRI or CT and bone scan for metastases in patients with intermediate-risk localized disease. B Obtain chest and abdominopelvic CT and bone scan for metastases in patients with high- risk localized disease. B Imaging for staging, metastatic: As per SUO/ASTRO/AUA 2021 guidelines: Obtain conventional imaging to assess the extent of metastatic disease (bone, lymph node, and visceral metastasis) in patients with newly diagnosed metastatic hormone-sensitive prostate cancer. B Assess the extent of metastatic disease (low- versus high-volume) in patients with newly diagnosed metastatic hormone-sensitive prostate cancer. Define high-volume as 4 bone https://web.pathway.md/diseases/recXj11agry4hkwmf 6/24 6/29/23, 11:31 PM Prostate cancer Pathway metastases with at least 1 metastasis outside of the spine/pelvis and/or the presence of visceral metastases. B As per ASCO 2020 guidelines, consider obtaining next-generation imaging in the initial evaluation of patients presenting with hormone-sensitive prostate cancer with demonstrable metastatic disease on conventional imaging to clarify the disease burden and potentially shift the treatment intent from multimodality management of oligometastatic disease to systemic anticancer therapy alone or in combination with targeted therapy for palliative purposes. C As per ESMO 2020 guidelines, obtain spinal MRI to detect subclinical cord compression in patients with castration-resistant prostate cancer with vertebral metastases. B Obtain urgent spinal MRI in patients with vertebral metastases and neurological symptoms. B Germline testing, positive family history: As per ISUP/SIOG/ESUR/ESTRO/EANM/EAU 2022 guidelines, consider obtaining germline testing in patients with high-risk prostate cancer with a family member diagnosed with prostate cancer at age < 60 years. C Show 2 more As per ESMO 2020 guidelines, obtain germline testing for BRCA2 and other DDR genes associated with cancer predisposition syndromes in patients with a family history of cancer. Consider obtaining these tests in all patients with metastatic prostate cancer. B Germline testing, metastatic disease: As per ISUP/SIOG/ESUR/ESTRO/EANM/EAU 2022 guidelines, consider germline testing in patients with metastatic prostate cancer. C As per SUO/ASTRO/AUA 2021 guidelines, offer genetic counseling and obtain germline testing in patients with metastatic hormone-sensitive prostate cancer, regardless of age and family history. E 4. Diagnostic procedures Prostate biopsy, indications: As per SUO/AUA 2023 guidelines, perform targeted biopsies of the suspicious lesion B and consider performing a systematic template biopsy in biopsy-na ve patients with a suspicious lesion on MRI. B Show 2 more As per SUO/AUA 2023 guidelines, consider performing near-term prostate biopsy when the risk of clinically significant prostate cancer is sufficiently low based on available clinical, laboratory, and imaging data. C As per ISUP/SIOG/ESUR/ESTRO/EANM/EAU 2022 guidelines, perform combined targeted and systematic biopsy in biopsy-na ve patients with positive multiparametric MRI (PI-RADS 3). A Show 3 more As per SUO/ASTRO/AUA 2021 guidelines, obtain tissue diagnosis from the primary tumor or site of metastases when clinically feasible in patients with suspected advanced prostate cancer with no prior histologic confirmation. B https://web.pathway.md/diseases/recXj11agry4hkwmf 7/24 6/29/23, 11:31 PM Prostate cancer Pathway Prostate biopsy, pre-biopsy evaluation: As per ESMO 2020 guidelines: Obtain a multiparametric MRI before prostate biopsy. B Use a prostate cancer risk calculator and/or obtain multiparametric MRI to confirm the indication for biopsy in patients with elevated PSA levels. B Prostate biopsy, approach: As per SUO/AUA 2023 guidelines, consider using a transrectal or transperineal route when performing a prostate biopsy. C As per ISUP/SIOG/ESUR/ESTRO/EANM/EAU 2022 guidelines, prefer the transperineal over transrectal route for prostate biopsies due to the lower risk of infectious complications. A As per ESMO 2020 guidelines, use the transperineal over transrectal US-guided approach for prostate biopsies. B Prostate biopsy (antibiotics prophylaxis): administer targeted agents based on the rectal swab or stool culture, augmented prophylaxis ( 2 different classes of antibiotics), or alternative antibiotics (such as fosfomycin trometamol, cephalosporin, aminoglycoside) for antibiotic prophylaxis for transrectal biopsy. B Show 2 more Prostate biopsy, technical considerations: As per SUO/AUA 2023 guidelines: Obtain at least 2 needle biopsy cores per target in patients with suspicious prostate lesions on MRI. B Consider using software registration of MRI and ultrasound images during fusion biopsy, when available. E As per ISUP/SIOG/ESUR/ESTRO/EANM/EAU 2022 guidelines, perform rectal cleansing with povidone-iodine before transrectal prostate biopsy. A Show 6 more Prostate biopsy, reporting: As per ISUP/SIOG/ESUR/ESTRO/EANM/EAU 2022 guidelines, use the following terminology for reporting prostate biopsies: benign/negative for malignancy (include a description if appropriate) active inflammation granulomatous inflammation high-grade prostatic intraepithelial neoplasia gigh-grade prostatic intraepithelial neoplasia with atypical glands, suspicious for adenocarcinoma focus of atypical glands/lesion suspicious for adenocarcinoma/atypical small acinar proliferation, suspicious for cancer adenocarcinoma (provide type and subtype, and presence or absence of cribriform pattern) intraductal carcinoma. A As per ESMO 2020 guidelines, report and evaluate each biopsy individually according to the ISUP recommendations. B https://web.pathway.md/diseases/recXj11agry4hkwmf 8/24 6/29/23, 11:31 PM Prostate cancer Pathway Prostate biopsy (counseling): Inform patients undergoing a prostate biopsy about the risk of identifying cancer with a sufficiently low risk of mortality that could safely be monitored with active surveillance rather than treated. B Communicate with patients following biopsy to review biopsy results, reassess the risk of undetected or future development of grade group 2 diseases, and mutually decide whether to discontinue screening, continue screening, or perform adjunctive testing for early risk reassessment. B Prostate biopsy (repeat biopsy): do not use PSA threshold solely to decide whether to repeat the biopsy after a negative biopsy. D Show 5 more Molecular testing: As per AUA 2023 guidelines, do not obtain biomarker testing reflexively after a negative initial biopsy in patients with a low probability of harboring grade group 2 prostate cancer. D Consider obtaining tissue-based biomarkers selectively for further risk stratification after a negative biopsy if results are likely to influence the decision regarding repeat biopsy or otherwise substantively change the management. D As per ASCO 2020 guidelines, consider obtaining tissue-based molecular biomarker testing in situations where assay results, in conjunction with routine clinical factors, will likely affect management. C Show 2 more As per ESMO 2020 guidelines, consider obtaining tissue-based molecular assays in conjunction with clinicopathological factors for treatment decision-making in patients with localized prostate cancer. C Show 2 more 5. Medical management Management of local/locoregional disease, initial treatment, low-risk localized disease: As per ASTRO/AUA 2022 guidelines, offer active surveillance as the preferred management option in patients with low-risk localized prostate cancer. A As per ESMO 2020 guidelines: Offer active surveillance in patients with localized low-risk disease. B Consider offering radical prostatectomy or radiotherapy (external beam or brachytherapy) as an option in patients with low-risk prostate cancer not suitable for active surveillance. C Management of local/locoregional disease, initial treatment, intermediate-risk localized disease: As per ASTRO/AUA 2022 guidelines, discuss active surveillance, radiotherapy, and radical prostatectomy in patients with favorable intermediate-risk prostate cancer. A Show 2 more As per ISUP/SIOG/ESUR/ESTRO/EANM/EAU 2022 guidelines, offer active surveillance in highly selected patients with ISUP grade group 2 disease (< 10% pattern 4, PSA < 10 ng/mL, < cT2a, low disease extent on imaging and low biopsy extent, defined as < 3 positive cores https://web.pathway.md/diseases/recXj11agry4hkwmf 9/24 6/29/23, 11:31 PM Prostate cancer Pathway and cancer involvement < 50% core involvement/per core), or another single element of intermediate-risk disease with low disease extent on imaging and low biopsy extent, accepting the potential increased risk of metastatic progression. B Show 9 more As per ESMO 2020 guidelines: Offer radical prostatectomy or radiotherapy (external beam or brachytherapy) in patients with intermediate-risk localized prostate cancer. B Offer short-course of androgen deprivation therapy for 4-6 months in patients with intermediate-risk disease receiving radical radiotherapy. A Management of local/locoregional disease, initial treatment, high-risk localized disease: As per ESMO 2023 guidelines: Offer EBRT plus androgen deprivation therapy-abiraterone-prednisone in patients with very high-risk M0 prostate cancer (defined by N1 disease or at least 2 risk factors among T3-T4, PSA > 40 ng/mL, Gleason score 8-10). B Offer long-course androgen deprivation therapy (24-36 months) plus abiraterone- prednisone (24 months) in patients receiving radical radiotherapy for very-high-risk disease. B As per ASTRO/AUA 2022 guidelines, offer a choice between radical prostatectomy or radiotherapy plus androgen deprivation therapy in patients with unfavorable intermediate- or high-risk prostate cancer and estimated life expectancy > 10 years. A Show 2 more As per ISUP/SIOG/ESUR/ESTRO/EANM/EAU 2022 guidelines, offer radical prostatectomy as part of potential multimodal therapy in selected patients with high-risk localized prostate cancer. A Show 5 more As per ESMO 2020 guidelines: Consider offering neoadjuvant docetaxel chemotherapy before radiotherapy in young, fit patients with very high-risk localized prostate cancer. B Consider offering radical prostatectomy plus pelvic lymphadenectomy in selected patients with high-risk disease. C Management of local/locoregional disease, initial treatment, locally advanced disease: As per ASCO 2021 guidelines, consider offering docetaxel plus abiraterone and prednisolone should in patients with non-castrate locally advanced prostate cancer patients. B Show 2 more As per ESMO 2020 guidelines, offer EBRT plus androgen deprivation therapy in patients with locally advanced prostate cancer. B Management of local/locoregional disease, initial treatment, non-curative/palliative intent: As per ASTRO/AUA 2022 guidelines: Offer watchful waiting in asymptomatic patients with prostate cancer and limited life expectancy (determined on a patient-specific basis). A Consider offering palliative androgen deprivation therapy alone in patients with high-risk prostate cancer, local symptoms, and limited life expectancy. E https://web.pathway.md/diseases/recXj11agry4hkwmf 10/24 6/29/23, 11:31 PM Prostate cancer Pathway As per ISUP/SIOG/ESUR/ESTRO/EANM/EAU 2022 guidelines: Offer watchful waiting in asymptomatic patients ineligible for local curative treatment and in patients with a life expectancy of < 10 years (based on comorbidities and age). A Offer a deferred treatment policy using androgen deprivation therapy monotherapy in M0 asymptomatic patients unwilling or unable to receive any form of local treatment in the presence of a PSA-doubling time > 12 months, a PSA < 50 ng/mL, and well-differentiated tumor. B As per ESMO 2020 guidelines, offer watchful waiting with delayed androgen deprivation therapy for symptomatic progression in patients not suitable for or unwilling to undergo radical treatment. A Management of local/locoregional disease, technical considerations for radical prostatectomy: As per ASTRO/AUA 2022 guidelines, perform nerve-sparing surgery, when oncologically appropriate, in patients electing radical prostatectomy. B Show 4 more As per ISUP/SIOG/ESUR/ESTRO/EANM/EAU 2022 guidelines, inform patients that no surgical approach (open-, laparoscopic-, or robotic radical prostatectomy) has clearly shown superiority in terms of functional or oncological results. B Show 3 more Management of local/locoregional disease, technical considerations for radiotherapy: As per ASTRO/AUA 2022 guidelines, ensure available target localization, normal tissue avoidance, simulation, advanced treatment planning/delivery, and use image guidance procedures to optimize the therapeutic ratio of EBRT delivered for prostate cancer. B Show 15 more As per AUA/ASCO/ASTRO 2018 guidelines, offer moderate hypofractionation in patients with low-risk prostate cancer declining active surveillance and receiving EBRT to the prostate, with or without radiation to the seminal vesicles. A Show 14 more Management of local/locoregional disease, adjuvant therapy after radical prostatectomy: As per ASTRO/AUA 2022 guidelines: Do not offer adjuvant radiotherapy after radical prostatectomy routinely in patients with localized disease. D Consider offering adjuvant therapy or observation in patients with positive lymph nodes identified at radical prostatectomy and an undetectable postoperative PSA. C As per ISUP/SIOG/ESUR/ESTRO/EANM/EAU 2022 guidelines, do not offer adjuvant androgen deprivation therapy in pN0 patients. D Show 3 more As per ESMO 2020 guidelines, do not offer routine adjuvant postoperative radiotherapy after radical prostatectomy. D As per AUA/ASTRO 2019 guidelines: Inform patients with localized prostate cancer eligible for radical prostatectomy about the potential for adverse pathologic findings that portend a higher risk of cancer recurrence and https://web.pathway.md/diseases/recXj11agry4hkwmf 11/24 6/29/23, 11:31 PM Prostate cancer Pathway that these findings may suggest a potential benefit of additional therapy after surgery. B Offer adjuvant radiotherapy in patients with adverse pathologic findings at prostatectomy including seminal vesicle invasion, positive surgical margins, or extraprostatic extension because of demonstrated reductions in biochemical recurrence, local recurrence, and clinical progression. A Management of local/locoregional disease, salvage therapy: As per ISUP/SIOG/ESUR/ESTRO/EANM/EAU 2022 guidelines, offer salvage radiotherapy and additional hormonal therapy in patients with persistent PSA levels after radical prostatectomy and no evidence of metastatic disease. B As per ESMO 2020 guidelines, monitor serum PSA levels following radical prostatectomy. Offer salvage radiotherapy in the event of PSA failure. B Show 2 more As per AUA/ASTRO 2019 guidelines, offer salvage radiotherapy in patients with PSA or local recurrence after radical prostatectomy in the absence of evidence of distant metastatic disease. B Show 2 more Management of advanced/metastatic disease (evaluation): assess the extent of metastatic disease (lymph node, bone, and visceral metastasis) in patients with newly diagnosed metastatic hormone-sensitive prostate cancer. B Management of advanced/metastatic disease (general principles of management): Discuss treatment options with advanced prostate cancer patients based on life expectancy, comorbidities, preferences, and tumor characteristics. Incorporate a multidisciplinary approach when available in patient care. B Optimize pain control or other symptom support in patients with advanced prostate cancer and encourage engagement with professional or community-based resources, including patient advocacy groups. B Management of advanced/metastatic disease, systemic therapy: As per ASCO 2023 guidelines, offer docetaxel, abiraterone, enzalutamide, apalutamide, or darolutamide, in combination with androgen deprivation therapy, as the standard of care in patients with non-castrate metastatic prostate cancer. A Show 7 more As per SUO/AUA 2023 guidelines: Offer androgen deprivation therapy in combination with either androgen pathway-directed therapy (abiraterone acetate plus prednisone, apalutamide, enzalutamide) or chemotherapy (docetaxel) in patients with metastatic hormone-sensitive prostate cancer. A Offer androgen deprivation therapy in combination with docetaxel and either abiraterone acetate plus prednisone A or darolutamide in selected patients with de novo metastatic hormone-sensitive prostate cancer. B As per ESMO 2023 guidelines, offer androgen deprivation therapy-docetaxel-abiraterone- prednisone as first-line therapy in fit patients with de novo metastatic hormone-sensitive prostate cancer, especially in patients with multiple bone metastases (> 3) or visceral metastases. Offer androgen deprivation therapy-docetaxel-darolutamide as first-line therapy https://web.pathway.md/diseases/recXj11agry4hkwmf 12/24 6/29/23, 11:31 PM Prostate cancer Pathway in patients with metastatic hormone-sensitive prostate cancer, including patients with de novo metastatic hormone-sensitive prostate cancer as well as cases progressed to metastatic disease. (I, B). B Show 2 more As per ISUP/SIOG/ESUR/ESTRO/EANM/EAU 2022 guidelines, offer immediate systemic treatment with androgen deprivation therapy to palliate symptoms and reduce the risk for potentially serious sequelae of advanced disease (spinal cord compression, pathological fractures, ureteral obstruction) in M1 symptomatic patients. A Show 9 more As per SUO/ASTRO/AUA 2021 guidelines, offer androgen deprivation therapy with either LHRH agonists or antagonists or surgical castration in patients with metastatic hormone- sensitive prostate cancer. B Show 4 more Management of advanced/metastatic disease, radiotherapy: As per ISUP/SIOG/ESUR/ESTRO/EANM/EAU 2022 guidelines, do not offer radiotherapy combined with androgen deprivation therapy in patients with high-volume (CHAARTED criteria) M1 disease outside of clinical trials (except for symptom control). D As per ESMO 2020 guidelines, offer radiotherapy to the primary tumor combined with the systemic treatment in patients with low-volume metastatic hormone-na ve prostate cancer. A Management of advanced/metastatic disease (surgery): do not offer surgery combined with androgen deprivation therapy in patients with high-volume (CHAARTED criteria) M1 disease outside of clinical trials (except for symptom control). D Management of advanced/metastatic disease, management of metastases: As per ISUP/SIOG/ESUR/ESTRO/EANM/EAU 2022 guidelines, offer metastasis-directed therapy in M1 patients only within a clinical trial setting or well-designed prospective cohort study. A As per ESMO 2020 guidelines: Offer a single fraction of EBRT for palliation of painful, uncomplicated bone metastasis. A Offer a bisphosphonate or denosumab in patients with bone metastases from castration- resistant prostate cancer at risk for clinically significant skeletal-related events. B Management of castration-resistant prostate cancer, non-metastatic, pretreatment evaluation: As per ISUP/SIOG/ESUR/ESTRO/EANM/EAU 2022 guidelines, confirm testosterone levels to be < 50 ng/dL before diagnosing castration-resistant prostate cancer. A As per ASCO 2020 guidelines, consider obtaining next-generation imaging in patients with non-metastatic castration-resistant prostate cancer only if a change in clinical care is contemplated. Consider obtaining next-generation imaging to clarify the presence or absence of metastatic disease, assuming patients have received or are ineligible for local salvage treatment options. C Management of castration-resistant prostate cancer, non-metastatic, surveillance: As per SUO/AUA 2023 guidelines, obtain conventional imaging or prostate-specific membrane antigen positron emission tomography at intervals of 6-12 months to assess for https://web.pathway.md/diseases/recXj11agry4hkwmf 13/24 6/29/23, 11:31 PM Prostate cancer Pathway the development of metastatic disease in patients with non-metastatic castration-resistant prostate cancer. E As per CUOG/CUA 2022 guidelines, obtain regular imaging every 6-12 months, depending on the PSA-doubling time values, in patients not treated for non-metastatic castration- resistant prostate cancer. B As per SUO/ASTRO/AUA 2021 guidelines, obtain serial PSA measurements at 3-6-month intervals and calculate a PSA-doubling time starting at the time of development of castration resistance in patients with non-metastatic castration-resistant prostate cancer. B Management of castration-resistant prostate cancer, non-metastatic, observation and androgen deprivation therapy: As per CUOG/CUA 2022 guidelines, maintain androgen deprivation therapy in the non- metastatic castration-resistant prostate cancer state. Discontinue first-generation androgen receptor antagonists (such as bicalutamide, flutamide). B Show 2 more As per SUO/ASTRO/AUA 2021 guidelines, consider offering observation with continued androgen deprivation therapy in patients with non-metastatic castration-resistant prostate cancer, particularly at lower risk (PSA-doubling time > 10 months) for developing metastatic disease. C Management of castration-resistant prostate cancer, non-metastatic, nonsteroidal antiandrogens: As per CUOG/CUA 2022 guidelines, offer apalutamide, enzalutamide, or darolutamide in patients with high-risk non-metastatic castration-resistant prostate cancer (defined as a PSA- doubling time < 10 months) with an estimated life expectancy of > 5 years. A As per ISUP/SIOG/ESUR/ESTRO/EANM/EAU 2022 guidelines, offer apalutamide, darolutamide, or enzalutamide to prolong the time to metastases and overall survival in patients with M0 castration-resistant prostate cancer at high risk of developing metastasis (PSA-doubling time < 10 months). A As per SUO/ASTRO/AUA 2021 guidelines, offer apalutamide, darolutamide, or enzalutamide with continued androgen deprivation therapy in patients with non-metastatic castration- resistant prostate cancer at high risk of developing the metastatic disease (PSA-doubling time 10 months). A As per ESMO 2020 guidelines, consider offering apalutamide, darolutamide, or enzalutamide in patients with M0 (on bone scan and CT) castration-resistant prostate cancer at high risk of disease progression. B Management of castration-resistant prostate cancer (non-metastatic, chemotherapy and immunotherapy): do not offer systemic chemotherapy or immunotherapy in patients with non- metastatic castration-resistant prostate cancer outside a clinical trial. D Management of castration-resistant prostate cancer, metastatic, pretreatment evaluation: As per SUO/AUA 2023 guidelines: Obtain prostate-specific membrane antigen positron emission tomography in patients with metastatic castration-resistant prostate cancer with disease progression (PSA or radiographic progression or new disease-related symptoms) previously received docetaxel https://web.pathway.md/diseases/recXj11agry4hkwmf 14/24 6/29/23, 11:31 PM Prostate cancer Pathway and androgen pathway inhibitor planned for lutetium-177-prostate-specific membrane antigen-617. E Obtain germline (if not already obtained) and somatic genetic testing to identify deoxyRNA repair deficiency, MSI status, tumor mutational burden, and other potential mutations to inform prognosis and familial cancer risk and to direct potential targeted therapies in patients with metastatic castration-resistant prostate cancer. B As per ISUP/SIOG/ESUR/ESTRO/EANM/EAU 2022 guidelines: Confirm testosterone levels to be < 50 ng/dL before diagnosing castration-resistant prostate cancer. A Obtain somatic and/or germline molecular testing as well as testing for mismatch repair deficiencies or MSI in patients with metastatic castration-resistant prostate cancer. A As per SUO/ASTRO/AUA 2021 guidelines, obtain baseline laboratory tests (PSA, testosterone, LDH, Hgb, ALP), review the location of metastatic disease (bone, lymph node, visceral), assess disease-related symptoms and performance status to inform discussions of prognosis and treatment decision-making in patients with metastatic castration-resistant prostate cancer. B Management of castration-resistant prostate cancer, metastatic, general principles of management: As per ISUP/SIOG/ESUR/ESTRO/EANM/EAU 2022 guidelines, counsel, manage, and treat patients with metastatic castration-resistant prostate cancer in a multidisciplinary team. A Show 3 more As per SUO/ASTRO/AUA 2021 guidelines, consider taking into account the prior treatment and offering therapy with an alternative mechanism of action in sequencing agents. C Management of castration-resistant prostate cancer, metastatic, hormonal therapy: As per SUO/AUA 2023 guidelines, offer continued androgen deprivation therapy with abiraterone acetate plus prednisone, docetaxel, or enzalutamide in patients with newly diagnosed metastatic castration-resistant prostate cancer not received prior androgen receptor pathway inhibitors. B As per CUOG/CUA 2022 guidelines, offer abiraterone acetate 1,000 mg/day plus prednisone 5 mg BID, or enzalutamide 160 mg/day as first-line therapy in asymptomatic or minimally symptomatic chemotherapy-na ve patients with metastatic castration-resistant prostate cancer. A Show 3 more As per ISUP/SIOG/ESUR/ESTRO/EANM/EAU 2022 guidelines, offer abiraterone or enzalutamide in patients previously treated with 1-2 lines of chemotherapy. A Avoid sequencing of androgen receptor-targeted agents. B As per ESMO 2020 guidelines, offer abiraterone or enzalutamide in asymptomatic/mildly symptomatic patients with chemotherapy-na ve metastatic castration-resistant prostate cancer. A Show 2 more Management of castration-resistant prostate cancer, metastatic, chemotherapy: As per ESMO 2023 guidelines, offer cabazitaxel in patients with metastatic castration- resistant prostate cancer received a novel androgen receptor axis inhibitor (abiraterone, https://web.pathway.md/diseases/recXj11agry4hkwmf 15/24 6/29/23, 11:31 PM Prostate cancer Pathway apalutamide, darolutamide, or enzalutamide) and docetaxel and considered fit enough to receive this treatment. A As per CUOG/CUA 2022 guidelines, offer docetaxel 75 mg/m IV every 3 weeks with 5 mg oral prednisone BID in patients with metastatic castration-resistant prostate cancer. A Show 5 more As per ISUP/SIOG/ESUR/ESTRO/EANM/EAU 2022 guidelines: Offer docetaxel 75 mg/m every 3 weeks in chemotherapy-na ve patients with metastatic castration-resistant prostate cancer eligible for cytotoxic therapy. A Offer chemotherapy in patients previously treated with abiraterone or enzalutamide. Offer cabazitaxel in patients previously treated with docetaxel. Offer cabazitaxel in patients previously treated with docetaxel and progressing within 12 months of treatment with abiraterone or enzalutamide. A As per SUO/ASTRO/AUA 2021 guidelines: