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Prostate → mCRPC

Last reviewed: 2026-09-22 · Next review: 2026-12-21

clinic-ready — numbers from retrieved primary abstracts; re-check current FDA PARP labels and NCCN (NCCN not retrieved)

Who this applies to

mCRPC: radiographic and/or biochemical progression on ADT with castrate testosterone¹⁹.
Document de novo vs recurrent HSPC, volume, visceral disease, and the full prior-therapy list (ARPI, docetaxel in HSPC vs CRPC, RLT, PARP). Prior HSPC Pluvicto (PSMAddition) changes marrow/eligibility counseling¹⁰¹¹.
Fitness for taxane, marrow reserve (for RLT or chemo), renal function, dental status, and whether visceral or bulky nodal disease excludes Ra-223⁹⁴.

Standard options

Clinical context	Option	Key inclusion	Typical course
All mCRPC	Continue ADT and sequence by prior therapy, disease burden, fitness, and biomarkers¹⁹.	Castrate testosterone with progression¹⁹.	Ongoing¹⁹.
ARPI-naive or biomarker-defined disease	ARPI or label-restricted PARP plus ARPI combination⁶⁷⁸¹⁵¹⁶¹⁷¹⁸	Match prior exposure and exact companion-diagnostic label³¹⁶.	Regimen-specific¹⁹.
Prior ARPI with PSMA-positive disease or taxane eligibility	Radioligand or taxane-based pathway¹¹⁰¹¹⁵	Assess PSMA imaging, marrow reserve, prior taxane, and organ function¹⁰¹¹.	Regimen-specific¹⁰¹¹.
Symptomatic bone-predominant disease without visceral metastases	Radium-223 pathway⁹⁴	Match disease distribution and bone-protecting strategy⁹⁴.	Six cycles in ALSYMPCA/PEACE-3 contexts⁹⁴.

Continue ADT in all patients¹⁹.
ARPI-naive: abiraterone/prednisone or enzalutamide. If BRCA (and selected HRR per current FDA label) and ARPI-naive: PARP + ARPI combination — US labels are biomarker-restricted; do not use all-comer PROpel/TALAPRO-2 analyses as the indication⁶⁷⁸¹⁵¹⁶¹⁸.
After prior ARPI: if PSMA+, Pluvicto (VISION post-taxane; PSMAfore taxane-naive vs ARPI switch). Fit chemo-naive: docetaxel (TAX327). After ARPI + docetaxel: Pluvicto (PSMA+) or cabazitaxel (CARD preferred over ARPI switch)¹¹¹⁵².
BRCA / selected HRR after ARPI: PARP monotherapy (PROfound olaparib; TRITON3 rucaparib — benefit concentrated in BRCA; ATM exploratory HR 0.95 in TRITON3)³¹³.
Symptomatic bone-predominant, no visceral disease: radium-223 (ALSYMPCA). PEACE-3: enzalutamide + Ra-223 improved rPFS and OS vs enza alone; co-administer a bone-protecting agent. Do not pair Ra-223 with abiraterone (that combination was not in the retrieved ALSYMPCA or PEACE-3 sources)⁹⁴.
MSI-H/dMMR: pembrolizumab (later-line, histology-agnostic) — prostate-specific RCT numbers not in this pack¹⁹.
CONTACT-02 (cabozantinib + atezolizumab vs ARPI switch) improved PFS not OS — not a default OS-proven SOC¹⁹.
Clinical trial and best supportive care at every decision point¹⁹.

Therapy sequencing

Prior therapy / disease branch	Next treatment order	Evidence boundary
All mCRPC	Continue ADT while selecting the next systemic treatment¹⁹.	Confirm castrate testosterone and document every prior ARPI, taxane, PARP, and radioligand exposure¹⁹.
ARPI-naive mCRPC	ARPI, or biomarker-restricted PARP plus ARPI when its FDA criteria are met⁶⁷⁸¹⁵¹⁶.	Do not use all-comer PARP-combination analyses as an indication¹⁶¹⁸.
After one ARPI, PSMA-positive and taxane-naive	Discuss 177Lu-PSMA-617 or docetaxel according to disease burden, marrow reserve, and fitness¹¹⁵.	PSMAfore compares radioligand therapy with an ARPI switch; it does not establish a sequence against docetaxel¹¹.
After ARPI plus docetaxel	177Lu-PSMA-617 if PSMA-positive, or cabazitaxel rather than another ARPI switch when CARD criteria resemble the patient¹².	CARD does not select cabazitaxel for every taxane-exposed patient; VISION required prior ARPI and taxane¹².
BRCA or label-eligible HRR alteration after ARPI	PARP monotherapy³¹³.	Benefit was concentrated in BRCA in TRITON3; ATM is not interchangeable with BRCA¹³.
Symptomatic bone-predominant disease without visceral metastases	Radium-223; consider enzalutamide plus radium-223 only with the PEACE-3 bone-protecting strategy⁹⁴.	Do not combine radium-223 with abiraterone on the basis of this page's source set⁹⁴.
MSI-H/dMMR disease or later progression after standard options	Pembrolizumab when tumor-agnostic criteria are met, clinical trial, or supportive care¹⁹.	Prostate-specific randomized efficacy data for pembrolizumab are not in this source pack¹⁹.

Surveillance and treatment de-escalation

Setting	PSA	Imaging	Stop/de-escalate	Re-escalate
On any mCRPC regimen¹⁹	Every 4–8 weeks early, then every 3 months; testosterone to confirm castration¹⁹²⁰.	Every 8–12 weeks during active treatment or at progression; PSMA PET when considering radioligand¹⁹²⁰.	Continue ADT indefinitely. Complete fixed-duration regimens per label (radium-223 ×6, 177Lu-PSMA-617 ×4–6). Hold or discontinue individual agents for toxicity; PARP or ARPI hold for cytopenia, rash, or immune events per label⁹¹¹¹¹⁹.	Progression after current line → next option per prior-exposure table (taxane, radioligand, cabazitaxel, PARP, trial)²¹³¹⁹.
After radioligand or radium-223¹⁹	Continue PSA cadence with CBC, renal function, and symptom review¹⁹¹¹.	Restage at progression; dental assessment before future marrow-toxic therapy¹⁹¹¹.	Marrow reserve and prior RLT dose limit re-treatment intensity¹¹¹.	PSMA-negative or mixed disease may exclude further radioligand; reassess taxane, PARP, or trial¹¹¹¹⁹.

Bone-protecting agent with radium-223 or extensive bone disease per PEACE-3/ALSYMPCA counseling⁴⁹.
Re-staging at progression documents visceral disease (excludes further radium-223) and PSMA avidity (selects radioligand)⁹¹¹¹.

Landmark evidence

Trial	Population	Intervention arm	Control arm	Key outcomes (both arms)	Key HR	Evidence status
TAX327	mHRPC; N=1006⁵	Docetaxel 75 mg/m² q3wk + pred 5 mg BID⁵	Mitoxantrone 12 mg/m² q3wk + pred⁵	Median OS 18.9 vs 16.5 mo; PSA50 45% vs 32%⁵	OS HR 0.76 (95% CI 0.62–0.94)⁵	Tannock 2004 NEJM PMID 15470213⁵
TROPIC NCT00417079	Post-docetaxel mCRPC; N=755¹⁴	Cabazitaxel 25 mg/m² q3wk + pred 10 mg¹⁴	Mitoxantrone 12 mg/m² + pred¹⁴	Median OS 15.1 vs 12.7 mo; PFS 2.8 vs 1.4 mo; FN 8% vs 1%¹⁴	OS HR 0.70 (0.59–0.83)¹⁴	de Bono 2010 Lancet PMID 20888992¹⁴
CARD	After docetaxel + ARPI, PD ≤12 mo on ARPI; N=255²	Cabazitaxel 25 mg/m² + pred + G-CSF²	Alternate ARPI (abi or enza)²	Imaging PFS 8.0 vs 3.7 mo; OS 13.6 vs 11.0 mo²	Imaging PFS HR 0.54 (0.40–0.73); OS HR 0.64 (0.46–0.89)²	de Wit 2019 NEJM PMID 31566937²
COU-AA-301	Post-docetaxel; N=1195 (2:1)⁶	Abi 1000 mg + pred 5 mg BID⁶	Placebo + pred⁶	OS 14.8 vs 10.9 mo⁶	OS HR 0.65 (0.54–0.77)⁶	de Bono 2011 NEJM PMID 21612468⁶
COU-AA-302	Chemo-naive; N=1088⁷	Abi 1000 mg + pred 5 mg BID⁷	Placebo + pred⁷	rPFS 16.5 vs 8.3 mo⁷	rPFS HR 0.53 (0.45–0.62); OS HR 0.75 (0.61–0.93)⁷	Ryan 2013 NEJM PMID 23228172⁷
AFFIRM	Post-chemo; N=1199 (2:1)⁸	Enzalutamide 160 mg daily⁸	Placebo⁸	OS 18.4 vs 13.6 mo⁸	OS HR 0.63 (0.53–0.75)⁸	Scher 2012 NEJM PMID 22894553⁸
PREVAIL	Chemo-naive; N=1717¹⁵	Enzalutamide 160 mg daily¹⁵	Placebo¹⁵	12-mo rPFS 65% vs 14%¹⁵	rPFS HR 0.19 (0.15–0.23); OS HR 0.71 (0.60–0.84)¹⁵	Beer 2014 NEJM PMID 24881730¹⁵
ALSYMPCA NCT00699751	Bone-metastatic CRPC; N=921 updated⁹	Ra-223 50 kBq/kg q4wk ×6 + best SOC⁹	Placebo + best SOC⁹	Median OS 14.9 vs 11.3 mo⁹	OS HR 0.70 (0.58–0.83)⁹	Parker 2013 NEJM PMID 23863050⁹
VISION	PSMA+ after ARPI + taxane; N=831 (2:1)¹	177Lu-PSMA-617 7.4 GBq q6wk ×4–6 + SOC¹	SOC (no chemo/IO/Ra-223/investigational)¹	Imaging PFS 8.7 vs 3.4 mo; OS 15.3 vs 11.3 mo¹	rPFS HR 0.40 (99.2% CI 0.29–0.57); OS HR 0.62 (0.52–0.74)¹	Sartor 2021 NEJM PMID 34161051¹
PSMAfore NCT04689828	Taxane-naive PSMA+ after 1 ARPI; N=468; 57% crossover¹¹	177Lu-PSMA-617 7.4 GBq q6wk ×6¹¹	ARPI change (abi or enza)¹¹	rPFS 9.30 vs 5.55 mo (primary); updated 11.60 vs 5.59 mo¹¹	rPFS HR 0.41 (0.29–0.56); updated HR 0.49 (0.39–0.61). OS not in abstract¹¹	Morris 2024 Lancet PMID 39293462¹¹
PROfound	HRR+ after NHA; cohort A BRCA/ATM n=245³	Olaparib³	Physician-choice abi or enza³	Imaging PFS 7.4 vs 3.6 mo; OS 19.1 vs 14.7 mo (cohort A)³	PFS HR 0.34 (0.25–0.47); OS HR 0.69 (0.50–0.97)³	de Bono 2020 NEJM PMID 32343890; Hussain 2020 PMID 32955174³
TRITON3	BRCA or ATM after ARPI; N=405 ITT¹³	Rucaparib 600 mg BID¹³	Docetaxel or second ARPI¹³	BRCA PFS 11.2 vs 6.4 mo; ATM 8.1 vs 6.8 mo¹³	BRCA HR 0.50 (0.36–0.69); ATM HR 0.95 (0.59–1.52)¹³	Fizazi 2023 NEJM PMID 36795891¹³
PROpel NCT03732820	1L mCRPC, HRR-unselected¹⁶	Olaparib 300 mg BID + abi + pred¹⁶	Placebo + abi + pred¹⁶	ibPFS 24.8 vs 16.6 mo¹⁶	ibPFS HR 0.66 (0.54–0.81); OS HR 0.86 (0.66–1.12) immature at primary¹⁶	Clarke 2022 NEJM Evid PMID 38319800. Check FDA BRCA restriction¹⁶
MAGNITUDE NCT03748641	1L mCRPC; HRR+ n=423; HRR− futility¹⁷	Niraparib + AAP¹⁷	Placebo + AAP¹⁷	BRCA rPFS 16.6 vs 10.9 mo; HRR+ 16.5 vs 13.7 mo¹⁷	BRCA HR 0.53 (0.36–0.79); HRR+ HR 0.73 (0.56–0.96)¹⁷	Chi 2023 JCO PMID 36952634¹⁷
TALAPRO-2 NCT03395197	1L mCRPC unselected; N=805¹⁸	Talazoparib 0.5 mg + enza 160 mg¹⁸	Placebo + enza¹⁸	rPFS NR vs 21.9 mo (primary); final OS 45.8 vs 37.0 mo; grade ≥3 anemia 195 vs 18 patients (49% vs 4%) at OS analysis¹⁸	rPFS HR 0.63 (0.51–0.78); OS HR 0.80 (0.66–0.96); HRR+ OS HR 0.55 (0.36–0.83)¹⁸	Agarwal 2023 Lancet PMID 37285865; OS 2025 PMID 40683290. Check FDA HRR list¹⁸
PEACE-3 / EORTC 1333	1L mCRPC bone mets; N=446; BPA mandatory from 2018⁴	Enzalutamide + Ra-223 ×6⁴	Enzalutamide⁴	rPFS 19.4 vs 16.4 mo; final OS 38.2 vs 32.6 mo; fractures 24.3% vs 13.4% (primary paper)⁴	rPFS HR 0.69 (0.54–0.87); OS HR 0.76 (0.60–0.96)⁴	Gillessen 2025 Ann Oncol PMID 40450503; OS 2026 PMID 41763609⁴

Biomarkers

Marker	Current clinic role	Emerging / investigational	How it changes decision now	Limits
BRCA / HRR	Selects biomarker-restricted PARP monotherapy or PARP + ARPI combinations per current FDA label³¹³¹⁶¹⁷¹⁸	Expanding companion-diagnostic lists¹⁶¹⁸	Germline + somatic NGS; use the companion diagnostic that matches the intended PARP. Benefit concentrated in BRCA (TRITON3 ATM exploratory HR 0.95)³¹³.	Do not use all-comer PROpel/TALAPRO-2 analyses as the indication; ATM ≠ BRCA¹⁶¹⁸¹³.
MSI-H / dMMR / TMB	Pembrolizumab when tumor-agnostic criteria are met¹⁹	Broader IO combinations under study¹⁹	Consider in later-line MSI-H/dMMR disease¹⁹.	Prostate-specific randomized efficacy data for pembrolizumab are not in this source pack¹⁹.
PSMA PET	Pluvicto eligibility with an approved tracer¹¹¹	Earlier radioligand use in HSPC changes prior-exposure counseling¹⁰	Mixed/PSMA-negative lesions argue against RLT; PSMA+ after ARPI ± taxane opens 177Lu-PSMA-617 pathways¹¹¹.	Prior HSPC Pluvicto (PSMAddition) changes marrow/eligibility counseling¹⁰¹¹.
Prior ARPI / taxane exposure	Treatment-selection context for sequencing¹⁹²¹	—	Documents whether ARPI-naive, post-ARPI taxane-naive, or post-ARPI+taxane pathways apply (ARPI, Pluvicto, docetaxel, cabazitaxel/CARD)⁶⁷¹¹⁵²¹.	Exposure history is clinical context, not a molecular biomarker¹⁹.
Testosterone	Confirms castration while ADT continues¹⁹	—	Required to define mCRPC and continue ADT through all lines¹⁹.	Does not select among ARPI, taxane, PARP, or radioligand options¹⁹.

Upcoming research

Field direction: radioligand therapy is moving earlier (PSMAddition in PSMA-positive HSPC), while mCRPC sequencing among Pluvicto, taxane, and PARP after ARPI remains unsettled; AR degraders and neuroendocrine/lineage-plasticity strategies are next-wave themes without a new SOC default here¹⁰¹⁹.

Program or theme	Why it may change care	Evidence status
Earlier 177Lu-PSMA-617 (PSMAddition)	Already moved radioligand into PSMA-positive HSPC; spillover changes mCRPC prior-exposure counseling¹⁰.	Peer-reviewed HSPC result; mCRPC sequencing implications ongoing¹⁰.
CONTACT-02	Cabozantinib plus atezolizumab showed PFS without an OS standard-changing result in this pack¹⁹.	Not a new default sequence on this page¹⁹.
AR degraders / novel AR ligands; NEPC / lineage plasticity	Potential options after ARPI failure when adenocarcinoma biology shifts¹⁹.	Pipeline / investigational; no practice-changing phase 3 SOC here¹⁹.
Pluvicto vs taxane vs PARP after ARPI	Optimal order among these classes¹⁹.	No head-to-head phase 3 preferred sequence in this pack¹⁹.

Toxicity

Regimen group	Trial-first safety signal	Counseling focus
Taxanes	TROPIC febrile neutropenia 8% vs 1%; CARD used routine G-CSF¹⁴².	Urgent contact for fever/infection, diarrhea, neuropathy, or dehydration¹⁴².
177Lu-PSMA-617	Use the labeled product and pivotal source; prior marrow-directed treatment matters¹¹¹.	Review xerostomia, cytopenias, fatigue, nausea, renal effects, and radiation precautions¹¹¹.
PARP-based therapy	TALAPRO-2 final analysis grade ≥3 anemia 49% vs 4%¹⁸.	Monitor blood counts; promptly report dyspnea, chest symptoms, bleeding, or marked fatigue¹⁸.
Radium-223	PEACE-3 fractures 24.3% vs 13.4%⁴.	Use bone-protecting treatment when indicated; review marrow, gastrointestinal, and fracture symptoms⁴⁹.

On-treatment monitoring

SOC/option regimen	Hallmark monitoring toxicity and available rate	Patient action / clinic response
Abiraterone/prednisone plus ADT	COU-AA-302: grade 3–4 ALT increase 6% vs 1%, hypertension 4% vs 3%, hypokalemia 3% vs 2%, and cardiac disorders 8% vs 4%⁷.	Monitor blood pressure, potassium, liver tests, fluid retention, and cardiovascular symptoms; swelling, shortness of breath, palpitations, weakness, or jaundice needs prompt contact⁷.
Enzalutamide plus ADT	PREVAIL: grade ≥3 AEs 46% vs 37% with placebo; grade ≥3 hypertension 7% (treatment-arm rate in this row)¹⁵.	Monitor fatigue, falls/cognition, blood pressure, and seizure-like symptoms; a fall, new confusion, loss of consciousness, or chest symptoms needs prompt contact¹⁵.
Docetaxel/prednisone	TAX327 treatment-arm rates (single-arm rates in this row; mitoxantrone comparator named-event % not retained here): neutropenia 41%, grade 3–4 32%; febrile neutropenia 3%; infection 32%, grade 3–4 6%; sensory neuropathy 30%, grade 3–4 2%⁵.	Check CBC and sensory symptoms; fever/infection, severe diarrhea, dehydration, or progressive numbness/weakness needs urgent assessment⁵.
Cabazitaxel/prednisone	TROPIC: grade 3–4 neutropenia 81.7% and febrile neutropenia 7.5% (trial-level febrile neutropenia 8% vs 1% with mitoxantrone); grade 3–4 diarrhea 6.2%¹⁴. CARD with routine G-CSF: grade ≥3 neutropenia 44.7% and febrile neutropenia 3.2% (CARD treatment-arm rates; comparator named-event % not retained in this row)².	Check CBC and sensory symptoms; fever/infection, severe diarrhea, dehydration, or progressive numbness/weakness needs urgent assessment¹⁴².
177Lu-PSMA-617	PSMAfore treatment-arm rates (single-arm label/trial rates in this row; no paired ARPI-switch % retained here): dry mouth 60.8%, grade ≥3 0.9%; hematologic AEs 39.2%, grade ≥3 13.2%; anemia 27.3%, grade ≥3 6.2%¹¹.	Check CBC and renal function and review xerostomia, nausea, fatigue, and radiation precautions; bleeding, fever, reduced urine output, or marked fatigue should prompt contact¹¹.
Olaparib or rucaparib monotherapy	PROfound olaparib treatment-arm rates: anemia 50%, grade ≥3 23% (single-arm rates in this row). TRITON3 rucaparib treatment-arm rates: anemia/decreased hemoglobin 47%, grade ≥3 24%; neutropenia/decreased neutrophils 14%, grade ≥3 7%³¹³.	Monitor CBC and thromboembolic symptoms; dyspnea, chest pain, leg swelling, fever/infection, bleeding, or marked fatigue needs urgent assessment³¹³.
Olaparib plus abiraterone/prednisone	PROpel: anemia 46.0% vs 16.4%, grade 3–4 16% vs 3%; pulmonary embolism 6.5% vs 1.8%¹⁶.	Monitor CBC and thromboembolic symptoms; chest pain, new breathlessness, unilateral leg swelling, bleeding, or profound fatigue needs prompt contact¹⁶.
Niraparib plus abiraterone/prednisone	MAGNITUDE: anemia 52.4%, grade 3 30.7%; hypertension 34.0%, grade 3 16.5%; thrombocytopenia 24.1%, grade 3 8.5%¹⁷.	Monitor CBC, blood pressure, potassium, and liver tests; bleeding, fever, breathlessness, severe fatigue, or high-pressure symptoms needs prompt contact¹⁷.
Talazoparib plus enzalutamide	TALAPRO-2: grade 3–4 anemia 46.7%, neutropenia 18.3%, and thrombocytopenia 7.3%¹⁸.	Monitor CBC; dyspnea, chest symptoms, fever, infection symptoms, or bleeding needs urgent assessment¹⁸.
Radium-223 with or without enzalutamide	ALSYMPCA: grade 3–4 anemia 13%, neutropenia 2%, and thrombocytopenia 7%. PEACE-3 fractures 24.3% vs 13.4%⁹⁴.	Check CBC and bone protection; new focal bone pain, a fall, fracture symptoms, bleeding, or persistent gastrointestinal symptoms should prompt contact⁹⁴.
Pembrolizumab for MSI-H/dMMR disease	Prostate-specific randomized safety rates were not retrieved in this page¹⁹.	Review bowel, lung, liver, skin, and endocrine symptoms before each dose; persistent diarrhea/abdominal pain, cough/dyspnea, jaundice, or marked fatigue needs prompt contact¹⁹.

Epic phrase

#mCRPC

Counseling: Reviewed next-line options with continued ADT. After prior ARPI and taxane, VISION showed median overall survival about 15 vs 11 months with standard care (OS HR 0.62 vs SOC for 177Lu-PSMA-617). Docetaxel-naive after ARPI: PREVAIL enzalutamide improved 12-month rPFS (about 65% vs 14% with placebo; rPFS HR 0.19 vs placebo). Post-docetaxel cabazitaxel improved median OS 15.1 vs 12.7 months with mitoxantrone (OS HR 0.70 vs mitoxantrone). BRCA-mutated after ARPI: TRITON3 rucaparib improved PFS 11.2 vs 6.4 months with docetaxel or second ARPI (HR 0.50 vs docetaxel/second ARPI). Symptomatic bone-predominant disease: ALSYMPCA radium-223 median OS 14.9 vs 11.3 months with placebo (OS HR 0.70 vs placebo).
Counseling: Reviewed surveillance and de-escalation: continue ADT; PSA every 4–8 weeks early then every 3 months; imaging every 8–12 weeks on active treatment; complete fixed-cycle radium-223 (×6) or Pluvicto (×4–6); progression after current line → next option by prior exposure.
Monitoring: Continue ADT and monitor blood pressure, potassium/liver testing with abiraterone, and falls/cognition/cardiovascular and bone effects with ARPIs. Check CBC for taxanes, PARP therapy, radium-223, and Pluvicto; check renal function with Pluvicto; use bone protection with radium-223; review bowel/lung/liver/endocrine symptoms with pembrolizumab. Contact oncology promptly for fever/infection, progressive neuropathy, severe diarrhea/dehydration, marked fatigue, dyspnea, bleeding, new fracture symptoms, or other concerning treatment effects. *** after-hours/urgent-assessment instructions reviewed.
Discussed progression to mCRPC in the setting of * (PSA / radiographic / symptomatic) on *, with castrate testosterone. Prior therapies: * (ADT ± ARPI ± docetaxel in HSPC; any CRPC lines; *prior Pluvicto in HSPC)
Discussed sequence: continue ADT; for ARPI-naive disease consider ARPI or label-restricted PARP + ARPI; after ARPI, select Pluvicto or docetaxel by PSMA status and fitness; after ARPI + docetaxel, consider Pluvicto (PSMA+) or cabazitaxel rather than serial ARPI; reserve PARP monotherapy for label-eligible HRR disease after ARPI and radium-223 for symptomatic bone-predominant disease without visceral metastases. ***
Discussed disease extent: * (bone / nodes / visceral). PSMA PET: *. HRR / BRCA (germline + somatic): *. MSI / TMB: *. Discussed prognosis and goal of therapy to control but not cure the cancer, with attention to symptoms and QoL. Discussed next-line options based on prior exposure and biomarkers, with continued ADT. If ARPI-naive: abiraterone/prednisone or enzalutamide; if BRCA/HRR and ARPI-naive, discussed PARP + ARPI per current FDA label (not all-comer trial analyses). After prior ARPI, switching to a second ARPI is generally not preferred. Taxane: docetaxel if chemo-naive and fit; cabazitaxel if prior docetaxel (preferred over another ARPI after docetaxel + ARPI). Pluvicto if PSMA+ after ARPI, including patients appropriate to delay taxane or after prior taxane. PARP monotherapy if BRCA / selected HRR after ARPI. Radium-223 if symptomatic bone-predominant without visceral disease; enzalutamide + Ra-223 (PEACE-3) if 1L mCRPC bone mets and bone-protecting agent is used. Pembrolizumab if MSI-H/dMMR. Clinical trial vs supportive care. Discussed potential side effects of planned therapy: * (taxane: neuropathy, cytopenias, infection, alopecia, fatigue; cabazitaxel: diarrhea; Pluvicto: dry mouth, myelosuppression, fatigue, nausea, radiation precautions; PARP: cytopenias, nausea, fatigue, rare MDS/AML; ARPI: fatigue, cardiac, hepatotoxicity, falls). He opts to proceed with *
Given patient education info on ***
CBC, CMP, PSA, testosterone
Germline (Invitae), blood NGS (Foundation), tissue NGS (Caris) if not already complete
***PSMA PET for Pluvicto eligibility
Continue ADT
***Will obtain DEXA
Continue calcium/vitamin D; *denosumab / zoledronic acid for SRE prevention given bone mets; *dental clearance
Rx sent for ***
referral to SW for the prostate cancer support group
***refer to NM / rad onc for Pluvicto or Ra-223
***refer to palliative care
follow up ***

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Changelog

2026-09-22: Explicit Setting×PSA×Imaging surveillance table (PSA every 4–8 weeks early then q3mo; imaging q8–12 weeks); expanded Biomarkers to five-column clinic/emerging format (BRCA/HRR, MSI/TMB, PSMA, prior ARPI/taxane context, testosterone).
2026-09-22: Renamed Upcoming trial results to Upcoming research; reframed for ongoing trials and field direction.
2026-09-22: Named comparators or labeled single-arm rates in key monitoring cells; mirrored comparator-named efficacy counseling in the paired dotphrase.
2026-09-22: Added line-level source superscripts ([^n]) linked to numbered Sources.
2026-09-22: Added Surveillance and treatment de-escalation section; strengthened quantified benefit counseling in dotphrase.
2026-09-21: Replaced grouped monitoring with pivotal rates for each listed ARPI, taxane, radioligand, PARP, and radium-223 regimen.
2026-09-21: Added a prior-exposure sequencing table and regimen-level on-treatment monitoring for ADT/ARPI, taxane, radioligand, PARP, radium-223, and pembrolizumab pathways.
2026-09-21: Renamed the prospective-evidence section to Upcoming trial results.
2026-09-21: Removed Bottom line; added a compact Guidelines table and disease → setting page framing. No treatment recommendations or trial statistics changed.
2026-09-21: Weekly skim — no practice-changing updates since last review.
2026-09-14: added landscape table with both-arm outcomes and HRs from named-trial PubMed abstracts; PEACE-3 OS and PSMAfore rPFS included; PARP labels flagged as biomarker-restricted
2026-09-14: expanded from stub to living clinic brief (qualitative SOC and trial names; numbers deferred to primary sources)

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