Abstract
Simple SummaryA significant number of prostate cancer patients will progress to metastatic castrate resistant prostate cancer despite optimal therapies. There is a growing need for alternative therapeutic strategies for this category of patients. Theragnostic refers to the ability to use an organ specific ligand and label it to both a diagnostic/imaging and therapeutic agent. Several prostate specific membrane antigen radioligands have been developed for imaging and treating PCa. Beta and alpha emitting radionuclides have been used with great success. Xerostomia is the greatest adverse event associated with radioligand therapy. More trials are necessary to determine the timing of introducing these novel therapies and to assess the efficacy as monotherapy as well as in combination with other novel agents to improve efficacy and reduce side effects to other organs.Prostate cancer (PCa) causes significant morbidity and mortality in men globally. While localized PCa may be managed with curative intent by surgery and/or radiation therapy, the management of advanced hormone resistant metastatic disease (mCRPC) is more challenging. Theranostics is a principle based on the ability to use an organ specific ligand and label it to both a diagnostic and a therapeutic agent. The overexpression of prostate specific membrane antigen (PSMA) on prostate cancer cells creates a unique opportunity for development of targeted radionuclide therapy. The use of both beta and alpha emitting particles has shown great success. Several clinical trials have been initiated assessing the efficacy and safety profile of these radionuclide agents. The results are encouraging with PSMA directed radioligand therapy performing well in patients who have exhausted all other standard treatment options. Future studies need to assess the timing of introduction of these radionuclide therapies in the management schema of mCRPC. Drugs or therapies are not without side effects and targeted radionuclide therapies presents a new set of toxicities including xerostomia and myelosuppression. New therapeutic strategies are being explored to improve outcomes while keeping toxicities to a minimum. This review aims to look at the various PSMA labelled tracers that form part of the theragnostic approach and subsequently delve into the progress made in the area of radionuclide therapy.
Highlights
Prostate cancer (PCa) is the second most frequent cause of cancer-related mortality in men globally
The median overall survival (OS) for the 177 Lu-Prostate Specific Membrane Antigen (PSMA)-617 + best standard of care (bSOC) arm was 15.3 months compared to 11.3 months in the bSOC only arm, with a 38% reduction in risk of death
The 177 Lu-PSMA-617 cohort had higher rate of treatment related adverse events compared to the bSOC only cohort, 85.3% vs. 28.8%, respectively [76]
Summary
Prostate cancer (PCa) is the second most frequent cause of cancer-related mortality in men globally. Therapy of PCa is a collaborative effort based on a multidisciplinary tumour board approach together with the patient and it is guided by the available resources. The widespread availability of screening tests has improved the early diagnosis of organconfined PCa, making definitive therapy feasible [1]. Brachytherapy).InInlocalized localized surgery high-risk or locally advanced disease, combination therapy with radical radiation therapy high-risk or locally advanced disease, combination therapy with radical radiation therapy and long-term androgen deprivation therapy (ADT). Long-term androgen deprivation therapy (ADT) with or without docetaxel is advised. Hormone sensitive sensitive metastatic metastatic disease thethe combination of ADT and Hormone diseaseisisbest bestmanaged managedwith with combination of ADT second generation anti-androgens (abiraterone acetate, enzalutamide, apalutamide and and second generation anti-androgens (abiraterone acetate, enzalutamide, apalutamide darolutamide) or ADT and docetaxel [2,3]. Hormone sensitive sensitive metastatic metastatic disease thethe combination of ADT and Hormone diseaseisisbest bestmanaged managedwith with combination of ADT second generation anti-androgens (abiraterone acetate, enzalutamide, apalutamide and and second generation anti-androgens (abiraterone acetate, enzalutamide, apalutamide darolutamide) or ADT and docetaxel [2,3]. [2,3].
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