Last reviewed by Dr. Dharmender Malik on 14 May 2026 · this article reflects the published primary literature and current clinical practice at FMRI Gurugram.
Introduction
Lu-177 PSMA-617 (Pluvicto) has been integrated into the standard of care for PSMA-positive metastatic castration-resistant prostate cancer since the 2022 FDA approval based on the VISION trial. But like all systemic therapies, Lu-177 PSMA-617 eventually progresses in most patients — and a clinical question that has emerged is: what comes next? This article walks through the established and investigational options after Lu-177 PSMA-617 progression, with explicit framing of which pathways are FDA / EMA approved standard-of-care and which remain investigational. Tb-161 PSMA-617 is one of the principal investigational salvage options under research-protocol study (VIOLET trial); it is not yet approved and is not a substitute for FDA / EMA approved alternatives.
The clinical question — what does Lu-177 progression actually mean?
AI Overview · short answer
After Lu-177 PSMA-617 progression in metastatic castration-resistant prostate cancer, treatment options depend on prior therapy exposure and disease characteristics[1]. Established options include: cabazitaxel chemotherapy (TROPIC, CARD evidence), Ra-223 for symptomatic bone-metastatic disease (ALSYMPCA, FDA/EMA 2013), PARP inhibitors for HRR-mutated disease (PROfound, TRITON3, TALAPRO-2), repeat Lu-177 PSMA-617 cycles in selected patients with documented prior response, and best supportive care with specialist palliative integration[2]. Investigational pathways include Tb-161 PSMA-617 (VIOLET phase 1/2 trial) and Ac-225 PSMA-617 (Sathekge cohort experience and emerging international trials)[3]. All decisions require multidisciplinary tumour board review and full Helsinki-framework informed consent for investigational pathways.
Progression on Lu-177 PSMA-617 in mCRPC is defined using standard Prostate Cancer Working Group (PCWG3) criteria, which combine PSA, radiographic, and clinical-symptomatic endpoints[4]:
- PSA progression — rise above nadir by at least 2 ng/mL or 25%, confirmed on second measurement 3+ weeks later.
- Radiographic progression — RECIST 1.1 progression on soft-tissue disease, or two or more new bone lesions on bone scan (with confirmation in selected scenarios per the "2+2 rule"), or new visceral disease.
- Clinical / symptomatic progression — symptomatic deterioration documented by validated clinical assessment, with consideration of pain, performance status, and need for radiation or other palliation.
Progression patterns after Lu-177 PSMA-617 vary substantially: some patients show PSA progression with stable imaging (the so-called "PSA flare" can be distinguished from true progression by confirmation), some show radiographic progression at PSMA-positive sites (the original disease re-emerging), some show emergence of PSMA-negative disease (de-novo or treatment-induced PSMA-negative clones, often distinguished by FDG PET), and some show mixed patterns. The progression pattern affects the optimal next-line therapy selection[5].
Established (FDA / EMA approved) salvage options
Several FDA / EMA approved therapies are available after Lu-177 PSMA-617 progression. The optimal choice depends on prior treatment exposure, disease characteristics, biomarker status, and patient factors[6]:
| Option | Setting / evidence | Typical role post-Lu-177 |
|---|
| Cabazitaxel | Post-docetaxel mCRPC (TROPIC, CARD trials) | Standard cytotoxic option, particularly for patients without prior cabazitaxel |
| Docetaxel (if not previously used) | First-line cytotoxic chemotherapy in mCRPC (TAX 327) | Standard if chemotherapy-naive post-Lu-177 |
| Ra-223 dichloride | Symptomatic bone-metastatic CRPC (ALSYMPCA) | Bone-dominant disease without significant visceral metastases |
| Abiraterone or enzalutamide (if not previously used) | mCRPC (COU-AA-301/302, AFFIRM, PREVAIL) | If ARPI options remain available |
| PARP inhibitor (olaparib, rucaparib, talazoparib, niraparib) | HRR-mutated mCRPC (PROfound, TRITON3, TALAPRO-2, MAGNITUDE) | For BRCA1/2, ATM, and other HRR-pathway mutation carriers |
| Repeat Lu-177 PSMA-617 cycles | Emerging cohort evidence; not yet FDA-labelled for retreatment | Selected patients with documented prior response, adequate residual marrow / kidney reserve, continued PSMA expression |
| Best supportive care + specialist palliative | WHO palliative-care framework | Patients with limited life expectancy or poor performance status for whom further disease-modifying therapy is not appropriate |
Importantly, multiple of these options are often used sequentially. The order is individualised based on prior treatment, disease characteristics, and patient values. Multidisciplinary tumour board review is essential.
Tb-161 PSMA-617 — the principal investigational pathway
Tb-161 PSMA-617 is the principal investigational radioligand-therapy pathway under research-protocol study for patients with Lu-177 PSMA-617 progression. The rationale is the additional Auger and conversion electron emission of Tb-161 — theoretically delivering 2-3× greater dose to small tumour cell clusters and micrometastases that may limit Lu-177 efficacy[7]:
- VIOLET phase 1/2 trial (Sydney, Australia) — first-in-human trial of Tb-161 PSMA-617 in mCRPC patients with documented progression on prior Lu-177 PSMA-617 therapy. The protocol uses up to 6 cycles of Tb-161 PSMA-617 with PSMA PET-CT eligibility confirmation. Initial findings have been presented at international meetings; primary publication is anticipated. ClinicalTrials.gov registration NCT05521412.
- Paul Scherrer Institute (Switzerland) experience — preclinical and early-clinical investigation of Tb-161 PSMA-617; selected first-in-human experience under research-protocol oversight.
- Heidelberg (Germany) experience — selected research-protocol experience with Tb-161 PSMA-617 in heavily pretreated patients with Lu-177 progression.
- Indian research-protocol experience — emerging cohort experience at selected Indian tertiary centres under DCGI clinical-trial authorisation and institutional ethics committee oversight.
Tb-161 PSMA-617 remains investigational — not FDA, EMA, or DCGI approved for any indication. Patient access requires participation in an IRB-approved clinical trial or, in limited settings, compassionate-use or expanded-access pathway. Standard-of-care alternatives (cabazitaxel, Ra-223, PARP inhibitors if eligible) remain the default options for most patients[8]. For deeper coverage of Tb-161 see our companion Tb-161 clinical handbook.
Ac-225 PSMA-617 — the other investigational radioligand option
Ac-225 PSMA-617 is the other principal investigational radioligand pathway in this setting. Unlike Tb-161 (beta + Auger), Ac-225 is an alpha-emitter with substantially different physics — much shorter tissue range (40-100 micrometres) and substantially higher linear energy transfer per emission[9]:
- Sathekge cohort experience (Pretoria, South Africa) — the principal cohort data on Ac-225 PSMA-617 in mCRPC, including patients with prior Lu-177 PSMA-617 progression. Published in J Nucl Med 2020 and subsequent updates. Demonstrated PSA response in heavily pretreated patients, including some with documented Lu-177 progression.
- Heidelberg, Lyon, and selected European centres — additional cohort experience with Ac-225 PSMA-617 under research-protocol oversight.
- Indian cohort experience — emerging at AIIMS and other Indian centres under DCGI clinical-trial authorisation.
Ac-225 PSMA-617 also remains investigational and is delivered only under research-protocol oversight. The principal toxicity concern with Ac-225 is xerostomia (severe dry mouth) due to high salivary-gland dose deposition — substantially higher in incidence than with Lu-177. The relative merits of Tb-161 vs Ac-225 in the Lu-177-progression setting are not established by direct comparative trials. For coverage of Ac-225 specifically see our companion Ac-225 PSMA-617 article[10].
Framing the decision — a structured approach
For a patient and clinician working through the decision after Lu-177 PSMA-617 progression, a structured framework includes the following considerations[11]:
- What is the progression pattern? PSA-only progression vs radiographic progression at PSMA-positive sites vs PSMA-negative new disease vs mixed pattern. FDG PET-CT may help distinguish PSMA-discordant disease.
- What prior treatment has the patient received? Prior docetaxel exposure determines whether cabazitaxel or docetaxel is appropriate. Prior abiraterone / enzalutamide / apalutamide / darolutamide determines whether ARPI options remain available. Prior cycle response on Lu-177 PSMA-617 may inform retreatment-cycle suitability.
- What is the biomarker status? Germline and somatic testing — BRCA1, BRCA2, ATM, CHEK2, PALB2, HOXB13 status — supports PARP inhibitor consideration. MSI-H status supports immune checkpoint inhibitor consideration.
- What is the disease pattern? Bone-dominant symptomatic disease without visceral metastases supports Ra-223 consideration. Diffuse small-volume PSMA-positive disease theoretically supports Tb-161 investigational pathway consideration (micrometastasis-level disease).
- What is the patient's performance status and organ reserve? Adequate marrow, kidney, and liver function are required for most disease-modifying options. Limited reserve may make best supportive care the appropriate path.
- What are the patient's values? Trade-offs between potential life extension, treatment toxicity, time spent in clinical settings, and quality of life. Some patients value continued aggressive therapy; others prioritise symptom management.
- What investigational pathways are accessible? Trial availability varies geographically and over time. CTRI, ClinicalTrials.gov, and EU Clinical Trials Register are the principal registries for available trial pathways.
The decision is rarely a single binary choice and is often a sequence — for example, cabazitaxel first, then Ra-223 if bone-dominant disease emerges, then PARP inhibitor if HRR-mutated, with investigational pathways considered if standard options are exhausted.
Repeat Lu-177 PSMA-617 cycles — what's the evidence?
One specific option that has emerged is repeat Lu-177 PSMA-617 cycles after the initial 6-cycle course[12]:
- Rationale — patients with documented response to the initial Lu-177 course, continued PSMA expression on repeat Ga-68 PSMA PET-CT, and adequate residual marrow / kidney reserve may benefit from additional cycles.
- Evidence — single-institution cohort experience suggests meaningful response in selected retreatment patients, with response rates lower than initial-course Lu-177 but clinically meaningful in patients with otherwise limited options. Not yet captured in the FDA label as a retreatment indication.
- Selection criteria — typically documented initial response, PSMA expression on imaging, adequate residual marrow (typically platelets above 100, neutrophils above 1.5), preserved kidney function (eGFR above 50 mL/min), and absence of progressive PSMA-negative disease.
- Practical considerations — typically 2-4 additional cycles delivered at 8-week intervals; some centres use slightly reduced administered activity per cycle for retreatment courses.
Repeat Lu-177 cycles are not yet a guideline-endorsed standard but are reasonable in selected patients reviewed at multidisciplinary tumour board. They are typically considered alongside the established alternatives (cabazitaxel, Ra-223, PARP inhibitor if eligible).
Supportive care integration
Patients reaching the Lu-177 progression point are typically in the heavily-pretreated mCRPC population, where supportive care integration is particularly important[13]:
- Specialist palliative care — early integration alongside disease-modifying therapy is associated with improved quality of life and may improve survival in metastatic-disease cohorts; recommended in NCCN and ESMO guidelines.
- Bone-pain management — escalation through paracetamol, NSAIDs (with renal considerations), weak then strong opioids, neuropathic agents, palliative external-beam radiation to symptomatic sites, and Ra-223 for diffuse symptomatic bone disease.
- Bone-supportive therapy — zoledronic acid or denosumab for skeletal-related event reduction (does not extend OS in this setting but reduces fractures, spinal cord compression, and need for radiation).
- Anaemia and fatigue management — transfusion support, erythropoiesis-stimulating agents in selected patients, fatigue-focused supportive care.
- Psychological support and family-system care — cancer-care psychology, structured support groups, family counselling.
- Goals of care conversation — explicit discussion of patient values, prognosis, and decision-making frameworks for ongoing treatment vs hospice integration.
Supportive care is not a substitute for disease-modifying therapy where appropriate options remain; it is an integrated part of the comprehensive care plan throughout the disease course.
Accessing investigational pathways
For patients and referring oncologists evaluating investigational Tb-161 or Ac-225 PSMA-617 pathways, the access process has structured requirements[14]:
- Clinical-trial registries — CTRI (India), ClinicalTrials.gov (US-anchored international), and EU Clinical Trials Register are the principal sources of currently-available trials. Eligibility is trial-specific.
- Trial-specific eligibility — typically includes prior Lu-177 PSMA-617 progression, continued PSMA expression on imaging, adequate organ reserve, performance status, and absence of trial-specific exclusions (other concurrent therapies, prior alpha-emitter exposure, specific comorbidities).
- Multidisciplinary review — eligibility is established at multidisciplinary tumour board at the trial centre, not by single physician.
- Informed consent — explicit Helsinki-framework informed consent including discussion of investigational status, available standard-of-care alternatives, expected and unknown toxicities, and trial-specific procedures.
- Compassionate-use / expanded-access pathway — in limited settings, where a clinical trial is not currently open, regulators may authorise compassionate-use access. Pathway varies by jurisdiction; in India, DCGI permission is required.
- Cost considerations — clinical-trial-based access may be partially or fully covered by the trial sponsor; compassionate-use access is typically patient-funded. Cross-border travel logistics apply for international trial participation.
The honest framing of investigational-pathway access: it requires patient effort to identify available trials, structured multidisciplinary review, careful informed consent, and acceptance that efficacy and toxicity are not yet fully characterised. For most patients, working sequentially through the established FDA / EMA approved alternatives first is the appropriate sequence.
What this means for the patient and family
Practical guidance for a patient and family facing Lu-177 PSMA-617 progression[15]:
- Engage in multidisciplinary review. The decision is not one for nuclear medicine alone — it involves medical oncology, urology, genetics (for HRR testing), and specialist palliative care. Request a multidisciplinary tumour board discussion.
- Get biomarker testing if not already done. Germline and somatic testing (BRCA1, BRCA2, ATM, CHEK2, PALB2, HOXB13) may open PARP inhibitor pathways. MSI-H testing may open immunotherapy consideration.
- Get current imaging. Ga-68 PSMA PET-CT confirms continued PSMA expression; FDG PET may identify PSMA-discordant disease. Multiphasic imaging characterises bone and visceral disease distribution.
- Discuss standard-of-care alternatives first. Cabazitaxel, Ra-223 (if symptomatic bone-dominant), PARP inhibitor (if eligible), and repeat Lu-177 cycles (if selection criteria met) are FDA / EMA approved with substantial evidence bases.
- Consider investigational pathways with full informed consent. Tb-161 PSMA-617 (VIOLET trial) and Ac-225 PSMA-617 (Sathekge cohort experience and emerging trials) are research-protocol options if standard alternatives are exhausted or contraindicated.
- Integrate supportive care. Specialist palliative care, bone-supportive therapy, symptom management, and goals-of-care discussion are part of comprehensive care across the entire post-Lu-177 progression period.
- Be honest about prognosis and patient values. Heavily-pretreated mCRPC has limited life expectancy; quality-of-life trade-offs become increasingly important. Goals-of-care alignment between patient, family, and clinical team is part of comprehensive decision-making.
The bottom line
- Progression on Lu-177 PSMA-617 in mCRPC is defined by PCWG3 criteria combining PSA, radiographic, and clinical-symptomatic endpoints; progression patterns vary and affect optimal next-line therapy[4].
- Established FDA / EMA approved options include cabazitaxel, Ra-223 (for symptomatic bone-metastatic disease), PARP inhibitors (for HRR-mutated disease), abiraterone or enzalutamide if not previously used, and repeat Lu-177 PSMA-617 cycles in selected patients[6].
- Investigational pathways include Tb-161 PSMA-617 (VIOLET phase 1/2 trial, Sydney) and Ac-225 PSMA-617 (Sathekge cohort experience and emerging international trials); both require IRB-approved trial participation or compassionate-use authorisation[7][9].
- Tb-161 theoretical advantage over Lu-177 is the additional Auger and conversion electron emission delivering ~2-3× greater dose to small tumour cell clusters at equivalent activity; clinical translation is being evaluated in VIOLET[7].
- Repeat Lu-177 PSMA-617 cycles are reasonable in selected patients with documented initial response, continued PSMA expression, and adequate residual marrow / kidney reserve; not yet FDA-labelled for retreatment[12].
- Biomarker testing (HRR-pathway genes, MSI status) is recommended for all mCRPC patients including at progression points; opens PARP inhibitor and immunotherapy pathways[11].
- Specialist palliative care integration is recommended throughout, alongside disease-modifying therapy; goals-of-care alignment between patient, family, and clinical team is integral to comprehensive decision-making[13].
Important
This article is general clinical information about treatment options after Lu-177 PSMA-617 progression in metastatic castration-resistant prostate cancer. Individual treatment decisions depend on disease characteristics, prior therapy, biomarker status, organ reserve, performance status, and patient values, and should be made through multidisciplinary tumour board review with informed consent. Investigational therapies are not substitutes for FDA / EMA approved alternatives.
"The clinical question after Lu-177 PSMA-617 progression is rarely a single binary choice — it is a sequence of structured decisions across cabazitaxel, Ra-223, PARP inhibitors where eligible, repeat Lu-177 cycles in selected cases, and investigational Tb-161 or Ac-225 PSMA-617 pathways. Multidisciplinary review, biomarker testing, current imaging, and integrated supportive care frame the decision. Standard-of-care alternatives remain the default; investigational pathways require explicit informed consent."
Dr. Ishita B. Sen, MD · Director & Chief, Nuclear Medicine, FMRI
Post-Lu-177 progression review · FMRI
At FMRI Gurugram, multidisciplinary review for patients with Lu-177 PSMA-617 progression covers established FDA / EMA approved alternatives (cabazitaxel, Ra-223, PARP inhibitors), repeat Lu-177 PSMA-617 cycle consideration where appropriate, and investigational research-protocol pathways under DCGI authorisation and full Helsinki-framework informed consent. Standard-of-care alternatives remain the default.
Request review · WhatsApp +91 8800 988936
For patients & referring clinicians
Frequently asked questions
Q01
What happens if Lu-177 PSMA-617 stops working?
Several options remain after Lu-177 PSMA-617 progression in mCRPC. Established FDA / EMA approved options include cabazitaxel chemotherapy, Ra-223 for symptomatic bone-metastatic disease, PARP inhibitors for HRR-mutated disease (BRCA1/2, ATM, etc.), abiraterone or enzalutamide if not previously used, and repeat Lu-177 PSMA-617 cycles in selected patients with documented prior response. Investigational pathways include Tb-161 PSMA-617 (VIOLET trial) and Ac-225 PSMA-617 (Sathekge cohort experience). Best supportive care with specialist palliative integration is part of comprehensive care throughout. The decision is multidisciplinary and individualised [1][6].
Q02
What is Tb-161 PSMA-617 salvage therapy?
Tb-161 PSMA-617 is an investigational radioligand therapy under research-protocol study for mCRPC patients with documented progression on prior Lu-177 PSMA-617 therapy. The theoretical advantage is Tb-161's additional Auger and conversion electron emission, which delivers ~2-3× greater dose to small tumour cell clusters than Lu-177 at equivalent activity — potentially addressing the micrometastatic disease component that may limit Lu-177 efficacy. The principal current trial is VIOLET (Sydney, Australia, NCT05521412). Tb-161 PSMA-617 is NOT FDA, EMA, or DCGI approved [7][8].
Q03
What is the VIOLET trial?
VIOLET is the principal first-in-human phase 1/2 clinical trial of Tb-161 PSMA-617 for metastatic castration-resistant prostate cancer post-Lu-177 PSMA-617 progression, conducted in Sydney, Australia, under research-protocol oversight. The trial uses Tb-161 PSMA-617 with up to 6 cycles in selected patients with disease progression on prior Lu-177 therapy. Initial findings have been presented at international meetings; primary publication is anticipated. ClinicalTrials.gov registration NCT05521412 [7].
Q04
Can Lu-177 PSMA-617 cycles be repeated?
Yes — in selected patients. Single-institution cohort experience suggests meaningful response in retreatment patients with documented initial response, continued PSMA expression on Ga-68 PSMA PET-CT, adequate residual marrow (typically platelets above 100, neutrophils above 1.5), and preserved kidney function (eGFR above 50 mL/min). Typically 2-4 additional cycles delivered at 8-week intervals. Not yet captured in the FDA Pluvicto label as a formal retreatment indication, but reasonable in selected patients reviewed at multidisciplinary tumour board [12].
Q05
What is Ac-225 PSMA-617 and how does it differ from Tb-161?
Ac-225 is an alpha-emitter; Tb-161 is a beta-emitter with additional Auger contribution. Ac-225 has much shorter tissue range (40-100 micrometres) and substantially higher linear energy transfer per emission — theoretical advantage at single-cell kill. Tb-161 has similar range to Lu-177 (~0.7 mm) plus sub-cellular Auger contribution — theoretical advantage at micrometastasis level. Both are investigational; both have evidence from research-protocol cohorts including post-Lu-177 progression patients. Direct comparative trials of Tb-161 vs Ac-225 in this setting have not been conducted. Ac-225 PSMA-617 has notable xerostomia (severe dry mouth) toxicity concerns [9][10].
Q06
What biomarker testing should I get?
Germline and somatic genetic testing for homologous-recombination-repair (HRR) pathway genes — BRCA1, BRCA2, ATM, CHEK2, PALB2, HOXB13 — is recommended for all metastatic prostate cancer patients per NCCN and AUA guidelines, including at progression points. Findings open PARP inhibitor pathways (olaparib for BRCA1/2 and selected HRR mutations; rucaparib, talazoparib, niraparib in other approved settings). MSI-H testing supports immune checkpoint inhibitor consideration. Genetic counselling is part of the testing pathway because germline findings have family-screening implications [11].
Q07
What is the role of FDG PET in post-Lu-177 progression assessment?
FDG PET-CT can help characterise post-Lu-177 PSMA-617 progression. Some patients show progression at PSMA-positive sites (the original disease re-emerging — typical for selected next-line PSMA-targeted approaches). Some show emergence of PSMA-negative disease (de-novo or treatment-induced PSMA-negative clones) — FDG PET-CT can identify these as FDG-avid lesions discordant with PSMA imaging. PSMA-FDG discordant disease patterns affect the optimal next-line therapy decision: PSMA-positive patterns may support continued PSMA-targeted approaches; PSMA-negative patterns generally do not [5].
Q08
When is Ra-223 used after Lu-177 progression?
Ra-223 dichloride is FDA and EMA approved (2013) for symptomatic bone-metastatic castration-resistant prostate cancer. In the post-Lu-177 progression setting, Ra-223 is appropriate for patients with bone-dominant symptomatic disease, absence of significant visceral metastases (or minimal), and adequate marrow reserve. ALSYMPCA showed median overall survival 14.9 vs 11.3 months (HR 0.70) vs placebo. Standard regimen: six monthly intravenous infusions. Sequencing with Lu-177 PSMA-617 is individualised — both target bone-dominant disease; the optimal sequence is not established by direct comparative trials [6].
Q09
How do I access a Tb-161 trial?
Trial access requires identification of a currently-open Tb-161 trial through ClinicalTrials.gov, EU Clinical Trials Register, or CTRI (Clinical Trials Registry India). Eligibility is trial-specific and typically includes prior Lu-177 PSMA-617 progression, continued PSMA expression on imaging, adequate organ reserve, and acceptable performance status. Eligibility is established at multidisciplinary tumour board at the trial centre. Informed consent is comprehensive and includes discussion of investigational status, available alternatives, expected and unknown toxicities. International trial participation may require travel; cost considerations vary [14].
Q10
What is best supportive care in this setting?
Best supportive care integrates specialist palliative care alongside disease-modifying therapy throughout the treatment course. It includes bone-pain management (escalating analgesia plus palliative external-beam radiation to symptomatic sites), bone-supportive therapy (zoledronic acid or denosumab), anaemia and fatigue management, psychological and family-system support, and goals-of-care discussion. Early palliative care integration is associated with improved quality of life and may improve survival in metastatic-disease cohorts (Temel et al., NEJM 2010). It is recommended throughout, not only at end of life [13].
Q11
What is the prognosis after Lu-177 PSMA-617 progression?
Prognosis varies substantially with prior treatment, disease characteristics, performance status, and individual patient factors. Median survival data from heavily-pretreated mCRPC cohorts post-Lu-177 PSMA-617 progression are still being characterised in cohort studies. What is consistent across observation: continued multimodal therapy (cabazitaxel, Ra-223, PARP inhibitor where eligible, repeat Lu-177 cycles, investigational pathways) extends median survival compared with best supportive care alone in eligible patients. Individual prognosis is best discussed with the multidisciplinary team based on specific patient factors [15].
Q12
How do I arrange a post-Lu-177 progression review at FMRI?
At FMRI Gurugram, multidisciplinary review for patients with Lu-177 PSMA-617 progression covers established FDA / EMA approved alternatives (cabazitaxel, Ra-223, PARP inhibitors per biomarker status), repeat Lu-177 PSMA-617 cycle consideration where appropriate, and investigational research-protocol pathways under DCGI authorisation and full Helsinki-framework informed consent. Standard-of-care alternatives remain the default. WhatsApp +91 8800 988936 to begin a confidential review.
Citations & references
All clinical numbers above are sourced from the primary literature listed below. Every reference links to the open journal page or the regulatory archive — open in a new tab to verify.
[1] Sartor O, de Bono J, Chi KN, et al. Lutetium-177-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer (VISION).
N Engl J Med. 2021;385(12):1091-1103.
View source ↗[2] Cornford P, van den Bergh RCN, Briers E, et al. EAU-EANM-ESTRO-ESUR-SIOG Guidelines on Prostate Cancer. Part II — 2024 Update.
Eur Urol. 2024.
View source ↗[3] Müller C, Umbricht CA, Gracheva N, et al. Terbium-161 for PSMA-targeted radionuclide therapy of prostate cancer.
Eur J Nucl Med Mol Imaging. 2019;46(9):1919-1930.
View source ↗[4] Scher HI, Halabi S, Tannock I, et al. Design and end points of clinical trials for patients with progressive prostate cancer and castrate levels of testosterone: PCWG3.
J Clin Oncol. 2016;34(12):1402-1418.
View source ↗[5] Hofman MS, Emmett L, Sandhu S, et al. [
177Lu]Lu-PSMA-617 versus cabazitaxel in patients with metastatic castration-resistant prostate cancer (TheraP).
Lancet. 2021;397(10276):797-804.
View source ↗[6] NCCN Clinical Practice Guidelines in Oncology: Prostate Cancer. National Comprehensive Cancer Network.
View source ↗[7] Hofman MS, Buteau JP, Iravani A, et al. VIOLET phase 1/2 trial of
161Tb-PSMA-617 in mCRPC. ClinicalTrials.gov NCT05521412.
View source ↗[8] World Medical Association. WMA Declaration of Helsinki — Ethical principles for medical research involving human subjects.
View source ↗[9] Sathekge M, Bruchertseifer F, Vorster M, et al. Predictors of overall and disease-free survival in metastatic castration-resistant prostate cancer patients receiving
225Ac-PSMA-617 radioligand therapy.
J Nucl Med. 2020;61(1):62-69.
View source ↗[10] Kratochwil C, Bruchertseifer F, Giesel FL, et al.
225Ac-PSMA-617 for PSMA-targeted alpha-radiation therapy of metastatic castration-resistant prostate cancer.
J Nucl Med. 2016;57(12):1941-1944.
View source ↗[11] Pritchard CC, Mateo J, Walsh MF, et al. Inherited DNA-Repair Gene Mutations in Men with Metastatic Prostate Cancer.
N Engl J Med. 2016;375(5):443-453.
View source ↗[12] Yadav MP, Ballal S, Sahoo RK, et al. Efficacy and Safety of
177Lu-PSMA-617 Radioligand Therapy in mCRPC.
Indian J Nucl Med. 2020;35(3):220-228.
View source ↗[13] Temel JS, Greer JA, Muzikansky A, et al. Early palliative care for patients with metastatic non-small-cell lung cancer.
N Engl J Med. 2010;363(8):733-742.
View source ↗[14] Clinical Trials Registry India (CTRI), Indian Council of Medical Research.
View source ↗[15] Memorial Sloan Kettering Cancer Center prostate cancer nomograms.
View source ↗[16] de Bono JS, Oudard S, Ozguroglu M, et al. Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer (TROPIC).
Lancet. 2010;376(9747):1147-1154.
View source ↗[17] de Wit R, de Bono J, Sternberg CN, et al. Cabazitaxel versus Abiraterone or Enzalutamide in Metastatic Prostate Cancer (CARD).
N Engl J Med. 2019;381(26):2506-2518.
View source ↗[18] Parker C, Nilsson S, Heinrich D, et al. Alpha emitter radium-223 and survival in metastatic prostate cancer (ALSYMPCA).
N Engl J Med. 2013;369(3):213-223.
View source ↗[19] de Bono J, Mateo J, Fizazi K, et al. Olaparib for Metastatic Castration-Resistant Prostate Cancer (PROfound).
N Engl J Med. 2020;382(22):2091-2102.
View source ↗[20] Lehenberger S, Barkhausen C, Cohrs S, et al. The low-energy β
- and electron emitter
161Tb as an alternative to
177Lu for targeted radionuclide therapy.
Nucl Med Biol. 2011;38(6):917-924.
View source ↗[21] Müller C, Reber J, Haller S, et al. Direct in vitro and in vivo comparison of
161Tb and
177Lu using a tumour-targeting somatostatin analogue.
Eur J Nucl Med Mol Imaging. 2014;41(3):476-485.
View source ↗[22] Sgouros G, Bodei L, McDevitt MR, Nedrow JR. Radiopharmaceutical therapy in cancer: clinical advances and challenges.
Nat Rev Drug Discov. 2020;19(9):589-608.
View source ↗[23] Saad F, de Bono J, Chi KN, et al. PSMAfore trial of Lu-177 PSMA-617 in pre-chemotherapy mCRPC.
Lancet Oncol. 2024.
View source ↗[24] Atomic Energy Regulatory Board (Government of India). Safety Code for Nuclear Medicine Facilities. AERB/RF-MED/SC-2 (Rev. 2).
View source ↗[25] Drug Controller General of India / CDSCO. Drugs and Cosmetics Act and Rules.
View source ↗[26] Hofman MS, Lawrentschuk N, Francis RJ, et al. PSMA PET-CT in patients with high-risk prostate cancer before curative-intent surgery or radiotherapy (proPSMA).
Lancet. 2020;395(10231):1208-1216.
View source ↗[27] Kratochwil C, Fendler WP, Eiber M, et al. EANM procedure guidelines for radionuclide therapy with
177Lu-labelled PSMA-ligands.
Eur J Nucl Med Mol Imaging. 2019;46(12):2536-2544.
View source ↗[28] Pomykala KL, Hadaschik BA, Sartor O, et al. Next generation radiotheranostics promoting precision medicine.
Ann Oncol. 2023;34(6):507-519.
View source ↗[29] Eychenne R, Chérel M, Haddad F, et al. Overview of the Most Promising Radionuclides for Targeted Alpha Therapy.
Pharmaceutics. 2021;13(6):906.
View source ↗[30] ESMO Clinical Practice Guidelines: Prostate Cancer. European Society for Medical Oncology.
View source ↗
About the Author
Dr. Ishita B. Sen
MBBS · MD (Nuclear Medicine) · DNB · Post-doctoral Fellowship, Memorial Sloan Kettering Cancer Center, New York
Director and Chief of Nuclear Medicine at Fortis Memorial Research Institute. Co-founder of Theranostic Physicians Private Limited (TPPL). Two decades of clinical practice in PSMA imaging and PSMA-directed radioligand therapy, with one of the largest Indian institutional experiences in Lu-PSMA.