scholarly journals Recent Advances in the Management of Metastatic Prostate Cancer

2021 ◽  
pp. OP.21.00206
Author(s):  
Nicolas Sayegh ◽  
Umang Swami ◽  
Neeraj Agarwal
Keyword(s):  
Prostate Cancer ◽  
Metastatic Prostate Cancer ◽  
Standard Of Care ◽  
Serum Testosterone ◽  
Gonadotropin Releasing Hormone ◽  
Novel Agents ◽  
Prostate Specific Membrane Antigen ◽  
Castration Resistant Prostate Cancer ◽  
Releasing Hormone ◽  
Specific Membrane

Management of metastatic prostate cancer has undergone a revolution over the past decade with the introduction of several novel agents and repurposing of others. Several clinical trials reported improved outcomes with the intensification of androgen deprivation therapy by the addition of docetaxel chemotherapy or novel hormonal agents (abiraterone, enzalutamide, or apalutamide) in the metastatic castration-sensitive state. Relugolix has been recently approved as the first oral gonadotropin-releasing hormone receptor antagonist agent with a superior cardiovascular side-effect profile, and serum testosterone suppression compared with a gonadotropin-releasing hormone agonist, leuprolide. Poly-ADP ribose polymerase inhibitors (olaparib and rucaparib) have demonstrated significant clinical benefit for patients harboring deleterious mutations in genes belonging to the homologous recombination repair pathway and have received Food and Drug Administration approval. Recently, lutetium-177-prostate-specific membrane antigen-617 with standard of care treatment has shown to improve overall survival in men with advanced-stage prostate-specific membrane antigen–positive metastatic castration-resistant prostate cancer. These recent approvals, successes, and the ongoing investigation of multiple novel agents are expected to continue to dramatically improve survival outcomes of men with metastatic prostate cancer in the coming years.

The association of polymorphism in gonadotropin releasing hormone with serum testosterone level during androgen-deprivation therapy and prognosis in metastatic prostate cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e16570-e16570
Author(s):  
Masaki Shiota ◽  
Naohiro Fujimoto ◽  
Ario Takeuchi ◽  
Eiji Kashiwagi ◽  
Takashi Dejima ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Gene Polymorphism ◽  
Androgen Deprivation Therapy ◽  
Metastatic Prostate Cancer ◽  
Serum Testosterone ◽  
Gonadotropin Releasing Hormone ◽  
Androgen Deprivation ◽  
Serum Testosterone Level ◽  
Releasing Hormone ◽  
Testosterone Levels

e16570 Background: Serum testosterone suppression during androgen-deprivation therapy (ADT) have been reported to affect ADT efficacy. However, the factor affecting hormonal variations during ADT was less explored. Therefore, in this study, we investigated the missense polymorphisms in gonadotropin releasing hormone (GNRH) and hormonal variations during ADT as well as the prognosis among men treated with primary ADT for metastatic prostate cancer. Methods: This study included 80 Japanese patients with metastatic prostate cancer, whose serum testosterone levels during ADT were available. The association of the GNRH1 gene polymorphism (rs6185, S20W) and the GNRH2 gene polymorphism (rs6051545, A16V) with clinicopathological parameters including serum testosterone levels during ADT as well as the prognosis including progression-free survival and overall survival was examined. Results: The CT allele and the CT/TT alleles in the GNRH2 gene (rs6051545) were associated with higher serum testosterone levels during ADT compared with the CC allele. Consequently, the CT alleles was associated with higher progression risk after adjustment with age and serum testosterone levels during ADT [hazard ratio (95% confidence interval), 1.73 (1.00-3.00), P = 0.049]. Conclusions: Taken together, these findings suggested that genetic variation in rs6051545 ( GNRH2) may result in the inadequate suppression of on serum testosterone during ADT, which may lead to detrimental effect of ADT on prognosis among men with metastatic prostate cancer.

scholarly journals 225Actinium-labeled prostate-specific membrane antigen targeting peptide induces complete response in a metastatic prostate cancer patient

2021 ◽  
Vol 10 (5) ◽  
pp. 205846012110225
Author(s):  
Omer Aras ◽  
Stefan Harmsen ◽  
Richard Ting ◽  
Haluk B Sayman
Keyword(s):  
Prostate Cancer ◽  
Standard Of Care ◽  
Complete Response ◽  
Prostate Specific Membrane Antigen ◽  
Limited Data ◽  
Castrate Resistant Prostate Cancer ◽  
Targeting Peptide ◽  
Castrate Resistant ◽  
Specific Membrane

Targeted radionuclide therapy has emerged as a promising and potentially curative strategy for high-grade prostate cancer. However, limited data are available on efficacy, quality of life, and pretherapeutic biomarkers. Here, we highlight the case of a patient with prostate-specific membrane antigen (PSMA)-positive metastatic castrate-resistant prostate cancer who displayed complete response to 225Ac-PSMA-617 after having been resistant to standard-of-care therapy, then initially partially responsive but later resistant to subsequent immunotherapy, and resistant to successive 177Lu-PSMA-617. In addition, the patient’s baseline germline mutation likely predisposed him to more aggressive disease.

scholarly journals PSMA targeting in metastatic castration-resistant prostate cancer: where are we and where are we going?

2021 ◽  
Vol 13 ◽  
pp. 175883592110538
Author(s):  
Anne-Laure Giraudet ◽  
David Kryza ◽  
Michael Hofman ◽  
Aurélie Moreau ◽  
Karim Fizazi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Prostate Specific Membrane Antigen ◽  
Castration Resistant Prostate Cancer ◽  
Prostate Cancer Treatment ◽  
Normal Tissues ◽  
Drug Conjugates ◽  
Castration Resistant ◽  
Current State ◽  
Important Addition ◽  
Specific Membrane

Prostate-specific membrane antigen (PSMA) is highly expressed on the membrane of most prostate cancer cells and to a lesser extent in normal tissues. Many vectors targeting this protein have been created over the past decade and numerous clinical studies have positively demonstrated the tolerance and efficacy of radiolabeled prostate-specific membrane antigen ligands for PSMA radioligand therapy (PRLT). Preliminary results are encouraging that PRLT will become an important addition to the current therapeutic options in a number of settings. Improvement in radiopharmaceutical targeting and combination with other oncological agents are under investigation to further improve its therapeutic efficacy. These encouraging results have led to the development of other therapies using PSMA as a target, such as PSMA–targeted chimeric antigen receptor T-cells, PSMA–targeted antibody drug conjugates, and PSMA–targeted bi-specific T-cell-directed therapy. This narrative review details the current state and advancements in prostate-specific membrane antigen targeting in prostate cancer treatment.

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