Abstract

Simple SummaryPatients with high-risk prostate cancer are usually treated with combination of radiotherapy and androgen deprivation therapy. However, there has been long strides of advancements in the domain of radiotherapy and systemic therapy in the last decade. Similarly, there has been significant improvement in the surgical sphere. Additionally, significant improvements in the genomic classifiers and imaging modalities have widened the scope of improved risk stratification and personalization of treatment in this patient population. In this study we have reviewed the modern paradigm of management of patients with high-risk prostate cancer in light of the emerging evidence. High-risk prostate cancer is traditionally treated with a combination of radiotherapy (RT) and androgen deprivation therapy (ADT). However, recent advancements in systemic treatment and radiotherapy have widened the spectrum of treatment for this patient population. Use of image guidance and intensity modulation, as well as the incorporation of brachytherapy, has led to safe radiotherapy dose escalation with reduced risk of recurrence. Clinical trials have helped define the role of pelvic nodal radiotherapy, the role of stereotactic ablative radiotherapy, and the optimal duration and sequencing of ADT in combination with radiotherapy. Emerging evidence has redefined the role of surgery in this cohort. Contemporary clinical trials have identified new systemic therapy options in high-risk prostate cancer. Finally, new imaging modalities including multi-parametric MRI and molecular imaging and genomic classifiers have ushered a new era in patient selection, risk stratification, and treatment tailoring.

Highlights

  • Dose-escalated RT is standard of care in prostate cancer, either through external beam radiotherapy (EBRT) or brachytherapy boost [8,9,10,11,12]

  • Two phase III studies are investigating the addition of apalutamide (ATLAS, NCT02531516 with primary endpoint of metastasis-free survival) and enzalutamide (ENZARAD, NCT02446444 with primary endpoint of overall survival) combined with androgen deprivation therapy (ADT) for patients with high-risk prostate cancer undergoing primary radiation therapy

  • A study of 34 patients’ post-radical prostatectomy who received either adjuvant or salvage radiotherapy with subsequent biochemical failure and no evidence of recurrence on conventional imaging evaluated the role of multiparametric MRI (mpMRI) and 18 F-Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) in staging [72]

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Summary

A Review on the Current Treatment Paradigm in High-Risk

Radiation Medicine Program, The Ottawa Hospital Cancer Centre, Ottawa, ON K1H 8L6, Canada. Simple Summary: Patients with high-risk prostate cancer are usually treated with combination of radiotherapy and androgen deprivation therapy. There has been long strides of advancements in the domain of radiotherapy and systemic therapy in the last decade. There has been significant improvement in the surgical sphere. Significant improvements in the genomic classifiers and imaging modalities have widened the scope of improved risk stratification and personalization of treatment in this patient population. In this study we have reviewed the modern paradigm of management of patients with high-risk prostate cancer in light of the emerging evidence

Introduction
Materials and Methods
Advances in Radiotherapy
Systemic Therapy for High-Risk Prostate Cancer
Importance of New Imaging Modalities and Molecular Imaging
Optimizing Local Therapy
Personalization of Therapy
Findings
Conclusions
Full Text
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