Key Points
Treatment
Design and created by Guideline Central in participation with the American Society of Clinical Oncology.
Metastatic Castration-Resistant Prostate Cancer
American Society of Clinical Oncology
Publication Date: January 20, 2026
Key Points
- Metastatic prostate cancer is a major cause of disease burden in patients, representing an estimated 313,780 new cases (the highest incidence in males, representing 30% of all new cases) and being responsible for 35,770 deaths (the second highest cause of mortality in males, representing 11% of all cancer-related deaths) in 2025.
- This guideline addresses questions on diagnostics, genomic testing, treatment, and specifically treatment options for small cell, neuroendocrine, and poorly differentiated prostate cancer.
Treatment
Principles of Practice
General Note: The following recommendations (strong or conditional/weak) and terminology represent reasonable options for patients depending on clinical circumstances and in the context of individual patient preferences. Recommended care should be accessible to patients whenever possible.
Principles of Practice Statement 1
Metastatic castration-resistant prostate cancer (mCRPC) is defined as castrate levels of testosterone (<50 ng/mL or 1.7 nmol/L) with evidence of either new or progressive metastatic disease on radiologic assessment or two consecutive rising prostate-specific antigen (PSA) levels (minimal start value is 2.0 ng/mL) in the setting of existing metastatic disease.
Principles of Practice Statement 2
The Panel recommends both germline and somatic testing for patients with metastatic prostate cancer at the earliest available opportunity. Additional recommendations and discussion regarding the same are available in the Germline and Somatic Genomic Testing for Metastatic Prostate Cancer: ASCO Guideline.
Principles of Practice Statement 3
The Panel recommends personalizing treatment based on prior therapies received during castration sensitive setting, while also accounting for each patient's clinical status, cancer related symptoms and signs, therapy-related toxicities, potential drug interactions, cost, and drug availability.
Principles of Practice Statement 4
The Panel recommends continuation of androgen deprivation therapy (ADT) (or surgical castration) to maintain castrate levels of testosterone for every patient with mCRPC.
Principles of Practice Statement 5
The Panel recommends early integration of palliative and supportive care teams for symptom management and to review goals of care for patients with mCRPC. Additional information on the same is available in the Palliative Care for Patients With Cancer: ASCO Guideline Update.
Principles of Practice Statement 6
The Panel recommends the use of bone protective agents like denosumab (receptor activator of nuclear factor-kappa B [RANK] ligand inhibitor) or zoledronic acid (bisphosphonate) for patients with bone metastases to lower the risk of skeletal related events (SREs). Additional recommendations on the same are available in the Bone Health and Bone-Targeted Therapies for Prostate Cancer: ASCO Endorsement of a Cancer Care Ontario Guideline.
Principles of Practice Statement 7
Limited randomized clinical trial data exist for optimal sequencing of therapies for patients with mCRPC, as certain therapies studied in the mCRPC setting are now being utilized earlier during castration sensitive disease.
Patients Previously Treated With ADT Alone in Castration Sensitive or Nonmetastatic Castration-Resistant Prostate Cancer (CRPC) Setting and Whose Disease Has Progressed to mCRPC
Recommendation 1.1.1
The Panel recommends homologous recombinant repair (HRR) testing before initiation of systemic therapy (see Germline and Somatic Genomic Testing for Metastatic Prostate Cancer: ASCO Guideline [Yu E et al, 2024]). If positive for BRCA1/2 alterations then preferred options include either of niraparib + abiraterone, olaparib + abiraterone, or talazoparib + enzalutamide. ( M, S )
Practical Information for Recommendation 1.1.1: The Panel recommends personalized treatment based on therapies received during castration sensitive setting, while also accounting for each patient's clinical status, therapy-related toxicities, potential drug interactions, cost, and drug availability as per Principles of Practice Statement 3.
Recommendation 1.1.2
The Panel suggests the combination of talazoparib and enzalutamide for patients with any of the other HRR alterations (PALB2, ATM, ATR, CHEK2, FANCA, RAD51C, NBN, MLH1, MRE11A, CDK12). ( L, C )
Practical Information for Recommendation 1.1.2: Responses vary according to individual genes, but the strongest responses are seen in patients with PALB2 and CDK12 alterations in post-hoc subgroup analyses.
Recommendation 1.1.3
(Updated) The Panel recommends either enzalutamide or chemotherapy using docetaxel for patients with visceral disease (lung and/or liver metastases) and regardless of HRR alterations (please refer to 1.1.1 and 1.1.2 for preferred recommendations in patients with HRR alterations). ( H, S )
The panel recommends abiraterone with prednisone, darolutamide, apalutamide, or cabazitaxel in selected patients (see Practical Information). ( L, C )
Practical Information for Recommendation 1.1.3: Although there are limited data for abiraterone with prednisone, darolutamide, or apalutamide for patients with visceral disease in the mCRPC setting, these agents can be used as alternatives if there are concerns about side effects or drug interactions. Cabazitaxel may be used if allergic reactions or toxicity like peripheral neuropathy which precludes the use of docetaxel. The choice between an androgen receptor pathway inhibitor (ARPI) and chemotherapy may depend on the patient’s health, their ability to tolerate chemotherapy, the presence of symptoms and/or visceral disease, accessibility, cost, and the patient’s preference, especially if they are averse to chemotherapy.
Recommendation 1.1.4
(Updated) The Panel recommends docetaxel, abiraterone plus prednisone, enzalutamide with radium 223, or sipuleucel-T for patients with mCRPC without visceral metastases. The panel recommends radium 223 monotherapy for patients with symptomatic bone-only disease (lymph node <3 cm). ( M, S )
Practical Information for Recommendation 1.1.4: Unless contraindicated, the use of bone-protecting agents is strongly recommended in all patients receiving radium 223 (See Principle of Practice Statement 6). Symptomatic disease is defined as consistent use of pain medications or undergoing external-beam radiation therapy for cancer-related bone pain. The Panel recommends educating patients and caregivers regarding the lack of benefit in objective intermediate measurable end points (PSA levels, radiographic changes) associated with the use of sipuleucel-T. Enzalutamide monotherapy instead of enzalutamide with radium is an option in the presence of visceral metastasis or contraindications to abiraterone or radium 223.
Recommendation 1.1.5
The Panel recommends pembrolizumab for patients with microsatellite instability high (MSI-high) or mismatch repair deficient (dMMR) after progression on other agents listed previously. ( M, S )
Practical Information for Recommendation 1.1.5: For patients with tumor mutational burden-high ([TMB-H] ≥10 mut/Mb), the Panel recommends considering other therapeutic options listed previously prior to utilization of pembrolizumab, given modest clinical benefit.
Recommendation 1.1.7
The panel suggests metastasis-directed therapy in the form of radiation or surgical resection after a multi-disciplinary evaluation in selected patients with oligometastatic progression. ( L, C )
Figure 1. (Updated) Patients Previously Treated With ADT Alone
a Options listed are preferred options.
Patients Previously Treated With ADT and an ARPI and Whose Disease Has Progressed to mCRPC
Recommendation 1.2.1
The Panel recommends using olaparib monotherapy for patients with BRCA1/2 alterations. ( M, S )
Practical Information for Recommendation 1.2.1: Rucaparib may be offered as an alternative to olaparib for selected patients based on clinical judgment and patient preferences, pending availability.
Recommendation 1.2.2
The Panel suggests olaparib monotherapy for patients with any of the other HRR alterations. ( VL, C )
Practical Information for Recommendation 1.2.2: Patients with BRCA1, BRCA2, CDK12, and PALB2 gene alterations experienced the greatest benefit with poly (ADP-ribose) polymerase (PARP) inhibitors. The data supporting continuation of ARPI with a PARP inhibitor are limited. A second ARPI can be considered based on clinical judgment, patient co-morbidities, and factors for slowly progressive disease determined by slowly rising PSA without any radiologic progression or cancer-related symptoms. The Panel suggests referring to Recommendation 1.2.2.1 for alternate options.
Recommendation 1.2.2.1
(Updated) The Panel recommends using docetaxel chemotherapy, radium 223, or lutetium-177-PSMA-617 (177Lu-PSMA-617) (for patients with a PSMA-positive PET scan) for patients regardless of HRR alterations. ( M, S )
Practical Information for Recommendation 1.2.2.1: Cabazitaxel may be offered to selected patients if they have an allergic reaction or toxicity like peripheral neuropathy which precludes the use of docetaxel.
Recommendation 1.2.3
(Updated) The Panel recommends sipuleucel-T or local therapies per Recommendations 1.1.4 or 1.1.7, respectively, for selected patients. ( M, C )
Figure 2. (Updated) Patients Previously Treated With ADT and an ARPI
a Options listed are preferred options.
Patients Previously Treated With ADT and Docetaxel, and Whose Disease Has Progressed to Metastatic CRPC
Recommendation 1.3.1
The Panel recommends following Recommendations 1.1.1 and 1.1.2 for patients with HRR alterations. ( S )
Recommendation 1.3.2
(Updated) The Panel recommends either
an ARPI such as abiraterone with prednisone or enzalutamide, ( M, S )
or enzalutamide with radium 223, ( M, C )
or chemotherapy with cabazitaxel ( M, S )
(for patients regardless of HRR alterations).
Practical Information for Recommendation 1.3.2: The Panel recommends either abiraterone with prednisone, enzalutamide, enzalutamide with radium 223, or cabazitaxel. Which treatment is offered depends on the patient’s clinical status, presence or absence of symptoms from metastatic disease, cost and drug availability, and ability to tolerate therapy. Docetaxel rechallenge may be offered to patients with a favorable response to docetaxel (patients who received initial docetaxel therapy and achieved a favorable PSA nadir and durable response prior to clinical or radiologic progression) in the castration-sensitive prostate cancer (CSPC) setting.
Figure 3. (Updated) Patients Previously Treated with ADT and Docetaxel
a Options listed are preferred options.
Patients Previously Treated With ADT, ARPI and Docetaxel, and Whose Disease Has Progressed to Have Progressive Metastatic CRPC
Recommendation 1.4.1
(Updated) The Panel recommends 177Lu-PSMA-617 for PSMA-positive disease or radium 223 for PSMA-negative disease or chemotherapy using cabazitaxel. ( M, S )
Recommendation 1.4.2
The Panel recommends olaparib monotherapy for patients with HRR alterations. ( M, S )
Practical Information for Recommendation 1.4.2: As it has demonstrated a progression-free survival (PFS) benefit, rucaparib may be offered as an alternative to olaparib for selected patients with BRCA1/2 alterations based on clinical judgment and patient preferences, pending availability.
Recommendation 1.4.3
The Panel also recommends radium 223 or pembrolizumab for specific situations outlined earlier (as per Recommendations 1.1.4 and 1.1.5). ( M, S )
Recommendation 1.4.4
The Panel suggests clinical trials,
cabazitaxel + carboplatin, ( L, C )
carboplatin monotherapy, ( L, C )
best supportive care and hospice care ( NR, C )
for patients with disease progression despite previously mentioned options.
Figure 4. (Updated) Patients Previously Treated with ADT, ARPI, and Docetaxel
a Options listed are preferred options.
b Independent of other biomarkers.
b Independent of other biomarkers.
Treatment Options For De Novo or Treatment-Emergent Small Cell Neuroendocrine Carcinoma of the Prostate
Recommendation 2.1
The Panel recommends utilizing cisplatin or carboplatin plus etoposide for first-line systemic therapy as per Systemic Therapy for Small-Cell Lung Cancer: ASCO-Ontario Health (Cancer Care Ontario) Guideline. ( L, S )
Recommendation 2.2
The Panel suggests carboplatin plus cabazitaxel for patients with small cell neuroendocrine prostate cancer or those with deleterious alterations in two or more of TP53, RB1, and PTEN genes. ( L, C )
Recommendation 2.3
The Panel recommends enrollment in clinical trials after progression on platinum-based chemotherapy for eligible patients. ( NR, S )
Practical Information for Recommendation 2.3: Broad next-generation sequencing (NGS) testing at the time of disease progression may aid assessment of clinical trial eligibility.
Recommendation 2.3.1
In selected patients, the Panel suggests upfront chemotherapy (carboplatin and/or cisplatin plus etoposide) with immunotherapy followed by maintenance immunotherapy, lurbinectedin, topotecan, and tarlatamab may be utilized based on extrapolation from studies for small cell lung cancer. Prospective clinical studies for these agents for small cell prostate cancer are lacking and use of these agents should be considered on a case-by-case basis only. ( VL, C )
Practical Information for Recommendation 2.3.1: Clinicians should consider the possibility of treatment-emergent small cell or neuroendocrine carcinoma or an aggressive variant prostate cancer in patients with exclusively predominant visceral metastases with low PSA, predominant lytic bone lesions, bulky (≥5 cm) lymphadenopathy, rapid disease progression within 6 months of initiation of hormonal therapy, and alterations in any two of the three tumor suppressor genes TP53, RB1, and PTEN.
Figure 5. Treatment Options for De Novo or Treatment-Emergent Small Cell Neuroendocrine Carcinoma of the Prostate
Assessing for Response While on Systemic Therapy for mCRPC
Recommendation 3.1
The Panel recommends using a combination of 1) Clinical assessments to evaluate the tolerability of cancer therapy and cancer-related symptoms, 2) Blood tests including PSA, complete blood count (CBC) with differential, and comprehensive metabolic panel (CMP), and 3) Radiologic assessments to determine if patients are benefiting from systemic therapy. ( NR, S )
Practical Information for Recommendation 3.1: The use of rising PSA alone to determine disease progression in mCRPC, without evidence of clinical or radiographic progression is not recommended.
Recommended Scans for Response Assessment
Recommendation 3.2.1
The Panel recommends use of Tc99 bone scan and computed tomography (CT) chest, abdomen, and pelvis (CAP) to define progression for patients with mCRPC. These radiologic assessments can be performed every 3–6 months or in patients with rising PSA levels and/or evidence of clinical progression. ( M, S )
Practical Information for Recommendation 3.2.1: The Panel suggests Prostate Cancer Working Group (PCWG) 3 criteria be referred to in the clinical decision-making process. Currently, the role of PSMA positron emission tomography (PET)-CT is limited to identify PSMA expressing tumors for patients who will benefit with 177Lu-PSMA-617. In selected patients, PSMA PET can be used to stage patients with a rising PSA and concern for progression not visualized on conventional imaging. Prospective data on using PSMA PET scans for response assessment are still emerging, and at this time the Panel does not recommend their routine use.
Table 1. 10 Most Common Co-occurring Chronic Conditions Among Male Medicare Beneficiaries with Prostate Cancer (N = 1,016,617), 2011
| Beneficiaries less than 65 years (n = 26,243) | Beneficiaries 65 years and older (n = 990,374) | ||||
|---|---|---|---|---|---|
| n | % | n | % | ||
| Prostate cancer prevalence | 0.9 | Prostate cancer prevalence | 8.8 | ||
| Top 10 co-morbidities | Top 10 co-morbidities | ||||
| Hypertension | 17,767 | 67.7 | Hypertension | 693,283 | 70 |
| Hyperlipidemia | 13,589 | 51.8 | Hyperlipidemia | 590,154 | 59.6 |
| Diabetes | 9,982 | 38 | Ischemic heart disease | 457,844 | 46.2 |
| Ischemic heart disease | 9,291 | 35.4 | Anemia | 337,957 | 34.1 |
| Anemia | 8,478 | 32.3 | Diabetes | 312,519 | 31.6 |
| Arthritis | 7,833 | 29.9 | Arthritis | 308,537 | 31.2 |
| Chronic kidney disease | 6,286 | 24 | Chronic kidney disease | 239,960 | 24.2 |
| Depression | 6,162 | 23.5 | Cataract | 235,241 | 23.8 |
| Chronic obstructive pulmonary disease (COPD) | 4,646 | 17.7 | Heart failure | 203,231 | 20.5 |
| Heart failure | 4,636 | 17.7 | COPD | 145,818 | 14.7 |
Notes:
Prepared by Information Products Group (IPG)/Office of Information Products and Data Analytics (OIPDA) on May 15, 2013.
Data Source: CMS administrative claims data, January 2011–December 2011, from the Chronic Condition Warehouse (CCW), ccwdata.org.
Population: Male Medicare beneficiaries enrolled in fee-for-service (FFS) coverage of both Parts A and B for the entire year. Beneficiaries who were enrolled at any point during the year in a Medicare Advantage (MA) plan were excluded as were beneficiaries who first became eligible for Medicare after January of the calendar year. Beneficiaries who died during the year were included up to their date of death if they meet the other inclusion criteria. Beneficiaries less than 65 years of age are primarily receiving Medicare due to a disability.
Chronic Condition Measures: For these tables, chronic conditions were identified through Medicare administrative claims. Medicare beneficiaries were considered to have a chronic condition if the CMS administrative data had a claim indicating that they were receiving a service or treatment for the specific condition. The data tables include information for beneficiaries with one of twenty-eight chronic conditions identified in the CCW. Detailed information on the identification of chronic conditions in the CCW is available at: http://www.ccwdata.org/chronic-conditions/index.htm.
The list of 28 conditions include:
Acquired hypothyroidism, Acute myocardial infarction, Alzheimer's Disease (including related Disorders or senile dementia), Anemia, Asthma, Atrial fibrillation, Autism, Benign prostatic hyperplasia, Breast cancer, Colon cancer, Endometrial cancer, Lung cancer, Prostate cancer, Cataract, Chronic kidney disease, COPD, Depression, Diabetes, Glaucoma, Heart failure, Hip/pelvic fracture, Hypertension, Hyperlipidemia, Ischemic heart disease, Osteoporosis, Arthritis (OA and RA), Schizophrenia (and other psychotic disorders) and Stroke.
Table 2. Costs
| Drug | Dosage | Form | Average Wholesale Price (AWP) | Price per |
| Abiraterone acetate* | 250 mg | Tablet | $1.60–97.21 | Each |
| Abiraterone acetate* | 500 mg | Tablet | $195.51–206.85 | Each |
| Abiraterone (micronized formulation) | 125 mg | Tablet | $104.57 | Each |
| Abiraterone acetate/niraparib | 50–500 mg, 100–500 mg | Tablet | $375.00 | Each |
| Apalutamide | 60 mg | Tablet | $149.13 | Each |
| Apalutamide | 240 mg | Tablet | $596.51 | Each |
| Darolutamide | 300 mg | Tablet | $135.74 | Each |
| Enzalutamide | 40 mg | Tablet, capsule | $143.32 | Each |
| Enzalutamide | 80 mg | Tablet | $286.65 | Each |
| Olaparib | 100 mg, 150 mg | Tablet | $168.54 | Each |
| Rucaparib | 200 mg, 250 mg, 300 mg | Tablet | $173.70 | Each |
| Talazoparib** | 0.1 mg, 0.25 mg, 0.35 mg, 0.5 mg | Capsule | $721.58 | Each |
| Sipuleucel-T | 50 million cells/250 mL | Suspension, intravenous | $300.49 | mL |
| 177Lu-PSMA (vipivotide tetraxetan) | 1000 MBq/mL (27 mCi/1 mL) | Solution, intravenous | $54,621.00 | mL |
| Radium 223 (223Ra-dichloride) | 1100 kBq/mL (30 microcurie/mL) | Solution, intravenous | $35,051.76 | mL |
| Docetaxel* | 10 mg/mL, 20 mg/mL | Solution, intravenous | $23.40–$365.15 | mL |
| Cabazitaxel | 60 mg/1.5 mL | Solution, intravenous | $11,317.23 | mL |
| Pembrolizumab | 100 mg/4 mL | Solution, intravenous | $1,700.61 | mL |
Source – Lexicomp – UpToDate (Lexidrug, 9/27/2024)
* Price range due to multiple manufacturers of generic.
** Would always have additional cost of enzalutamide.
* Price range due to multiple manufacturers of generic.
** Would always have additional cost of enzalutamide.
Recommendation Rating Definitions
| Quality of Evidence | ||
|---|---|---|
| Term | Definitions | |
| H | - High | We are very confident that the true effect lies close to that of the estimate of the effect |
| M | - Moderate | We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. |
| L | - Low | Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect. |
| VL | - Very Low | We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect. |
| Ins | - Insufficient | Evidence is insufficient to discern the true magnitude and direction of the net effect. Further research may better inform the topic. Reliance on consensus opinion of experts may be reasonable to provide guidance on the topic until better evidence is available. |
| Strength of Recommendation | ||
|---|---|---|
| Term | Definitions | |
| S | - Strong | In recommendations for an intervention, the desirable effects of an intervention outweigh its undesirable effects. In recommendations against an intervention, the undesirable effects of an intervention outweigh its desirable effects. All or almost all informed people would make the recommended choice for or against an intervention. |
| C W | - Conditional - Weak | In recommendations for an intervention, the desirable effects probably outweigh the undesirable effects, but appreciable uncertainty exists. In recommendations against an intervention, the undesirable effects probably outweigh the desirable effects, but appreciable uncertainty exists. Most informed people would choose the recommended course of action, but a substantial number would not. |
| GPS | Good Practice Statement | Good practice statements represent the consensus of the Expert Panel and are used when high quality indirect evidence is available, but it would not be a good use of the Expert Panel’s resources to conduct a formal systematic review |
| NR | - Not Rated | |
Brozek JL, Akl EA, Compalati E, et al: Grading quality of evidence and strength of recommendations in clinical practice guidelines part 3 of 3. The GRADE approach to developing recommendations. Allergy 66:588-95, 2011
Source Citation
Taplin M, Riaz IB, Rumble RB, et al. Systemic Therapy in Men with Metastatic Castration Resistant Prostate Cancer: ASCO Living Guideline Update, Version 2025.1. J Clin Oncol. 2026 Jan 20. doi: 10.1200/JCO-25-02693
Garje R, Riaz IB, Naqvi SA, et al. Systemic Therapy in Men with Metastatic Castration Resistant Prostate Cancer: ASCO Guideline Update. J Clin Oncol. 2025 May 2. doi: 10.1200/JCO-25-00007
Disclaimer
This pocket guide is derived from recommendations in the American Society of Clinical Oncology Guideline. This resource is a practice tool based on ASCO® practice guidelines and is not intended to substitute for the independent professional judgment of the treating physician. Practice guidelines do not account for individual variation among patients. This pocket guide does not purport to suggest any particular course of medical treatment. Use of the practice guidelines and this resource are voluntary. The practice guidelines and additional information are available at www.asco.org/ genitourinary-cancer-guidelines. Copyright © 2025 by American Society of Clinical Oncology. All rights reserved.
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