Is There an Opportunity to De-Escalate Treatments in Selected Patients with Metastatic Hormone-Sensitive Prostate Cancer?
Abstract
:Simple Summary
Abstract
1. Introduction
2. Why Intensify Treatment in mHSPC?
3. Current Management of mHSPC
3.1. ADT+ARPI
3.2. ADT+Docetaxel+ARPI
3.3. Radiotherapy to the Primary Tumour
3.4. Metastasis-Directed Therapy
4. De-Intensification of Treatment: Is There a Reason to Consider It?
5. The Role of Clinical and Molecular Biomarkers in Decision Making
5.1. Clinical Biomarkers
5.2. Molecular Biomarkers
6. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Trial | Phase | Experimental Arm | Disease Group | Primary Outcome |
---|---|---|---|---|
NCT04343885 | II | LuPSMA+docetaxel | De novo, high-volume mHSPC | Undetectable PSA at 12 months |
NCT04443062 | II | LuPSMA | Oligometastatic mHSPC | Disease progression after 6 months |
NCT04748042 | II | Olaparib+abiraterone+ADT+SABR | Oligometastatic mHSPC | Percentage of patients without failure after 24 months |
NCT04262154 | II | Atezolizumab+abiraterone+ADT+SABR | De novo mHSPC | Two-year failure rate |
NCT03795207 | II | Durvalumab+SABR | Relapsed low-volume mHSPC (visible on PET scan only) | Two-year progression-free survival |
NCT06312670 | II | Combining EPI-7386+enzalutamide+ADT | De novo, low volume | Biochemical response rate |
NCT03951831 | II | Combined hormonal chemoimmunotherapy (REGN2810)+docetaxel | De novo mHSPC | Undetectable PSA at 6 months |
NCT04126070 | II/III | Nivolumab+ADT+docetaxel in DNA damage repair defects | mHSPC | PSA decline to <0.2 ng/mL at 7 months |
NCT03879122 | II/III | Immunotherapy+docetaxel+ADT | De novo, high volume | OS |
NCT06392841 | II/III | Niraparib, abiraterone acetate and prednisone with HRR alterations | De novo mHSPC | PSA decline to <0.2 ng/mL at 24 weeks |
NCT05956639 | III | 6-month vs. Long-term Course of Rezvilutamide with ADT+Chemotherapy | De novo, high volume | Radiological progression free survival (rPFS) at 36 months |
NCT04821622 | III | Talazoparib With enzalutamide in men with DDR gene-mutated mCSPC | De novo mHSPC | rPFS |
NCT04720157 | III | 177Lu-PSMA-617+ARPI+ADT | De novo mHSPC | rPFS |
Trial | Phase | Experimental Arm | Disease Group | Primary Outcome |
---|---|---|---|---|
NCT05209243 | III | SBRT plus standard of care in castration sensitive oligometastatic prostate | Oligometastatic prostate carcinoma | rPFS |
NCT04115007 | III | Standard of care + SBRT | Oligometastatic prostate cancer | Castration-resistant prostate-cancer-free survival |
NCT05352178 | III | Addition of short-term androgen deprivation therapy (ADT) for 1 month or short-term ADT for 6 months together with an androgen-receptor-targeted therapy (ARTA) to metastasis-directed therapy (MDT) | Oligorecurrent hormone sensitive prostate cancer. | Poly-metastatic-free survival |
NCT04787744 | III | Standard systemic therapy with or without PET-directed local | Oligometastatic prostate cancer | Castration-resistant prostate cancer-free survival |
NCT04983095 | III | MD–SBRT in addition to standard treatment | Oligometastatic prostate cancer | Failure-free survival |
Disease Type | ADT | AR Pathway Inhibitor | Docetaxel+ARPI | Prostate RT | MDT |
---|---|---|---|---|---|
De novo, high volume | Suboptimal treatment | YES | YES | +/− (Symptom control) | NO |
De novo, low volume | Suboptimal treatment | YES | +/− Individualize | YES | +/− (no OS data) |
Metachronic disease, high volume | Suboptimal treatment | YES | YES | NO | NO |
Metachronic disease, low volume | Suboptimal treatment | YES | +/− Individualize | NO | +/− (no OS data) |
Treatment Strategies | Quality of Life Benefit | Fewer Adverse Effects | Fewer Economic Cost |
---|---|---|---|
Maintain ADT+ARPI continuous | SOC | ||
De-escalate by removing ADT | ¿? | + | + |
De-escalate by removing ARPI | ¿? | ++ | +++ |
De-escalate by removing all | ¿? | +++ | ++++ |
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© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
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Gómez-Aparicio, M.A.; López-Campos, F.; Buchser, D.; Lazo, A.; Willisch, P.; Ocanto, A.; Sargos, P.; Shelan, M.; Couñago, F. Is There an Opportunity to De-Escalate Treatments in Selected Patients with Metastatic Hormone-Sensitive Prostate Cancer? Cancers 2024, 16, 2331. https://doi.org/10.3390/cancers16132331
Gómez-Aparicio MA, López-Campos F, Buchser D, Lazo A, Willisch P, Ocanto A, Sargos P, Shelan M, Couñago F. Is There an Opportunity to De-Escalate Treatments in Selected Patients with Metastatic Hormone-Sensitive Prostate Cancer? Cancers. 2024; 16(13):2331. https://doi.org/10.3390/cancers16132331
Chicago/Turabian StyleGómez-Aparicio, María Antonia, Fernando López-Campos, David Buchser, Antonio Lazo, Patricia Willisch, Abrahams Ocanto, Paul Sargos, Mohamed Shelan, and Felipe Couñago. 2024. "Is There an Opportunity to De-Escalate Treatments in Selected Patients with Metastatic Hormone-Sensitive Prostate Cancer?" Cancers 16, no. 13: 2331. https://doi.org/10.3390/cancers16132331