PCa Commentary | Volume 194 – October 2024

The EMBARK TRIAL: Enzalutamide (Xtandi) Monotherapy for Non-metastatic Hormone Sensitive Prostate Cancer.

The commentary discusses the EMBARK trial, which offers a useful model of options as to how to treat stage M0 prostate cancer patients who are at high risk for recurrence because of rapidly rising PSA values. Additional analysis of EMBARK found that 80+ % of men were already positive for metastases by PET/CT. The issue of when to initiate treatment for the remaining ~20% in EMBARK and other men with rising PSAs negative on scanning is complex and awaits clarification.

PCa Commentary | Volume 193 – September 2024

Tumor-Derived Exosomes – a Prostate Cancer Cell-to-Cell Communication System – a Primer

The commentary discusses the effects of androgen suppression (via agents like Lupron) and estrogen on bone density and fracture risk in men with prostate cancer. It highlights the PATCH trial, comparing the cardiovascular and bone health outcomes of using transdermal estrogen patches (tE2) versus LHRH agonists like Lupron. The findings suggest that tE2 may improve bone density and overall quality of life, potentially offering a new approach to managing metastatic prostate cancer.

PCa Commentary | Volume 192 – August 2024

Androgen Suppression, Estrogen, Bone Density and Fracture Risk

The commentary discusses the effects of androgen suppression (via agents like Lupron) and estrogen on bone density and fracture risk in men with prostate cancer. It highlights the PATCH trial, comparing the cardiovascular and bone health outcomes of using transdermal estrogen patches (tE2) versus LHRH agonists like Lupron. The findings suggest that tE2 may improve bone density and overall quality of life, potentially offering a new approach to managing metastatic prostate cancer.

PCa Commentary | Volume 191 – July 2024

Radioligand Therapy (RLT): 177Lu-PSMA-617: Pluvicto Update and Introducing 225-Actinium-617 RLT

This Commentary discusses a comprehensive discussion of RLT presented by Viscuse et al., J Nucl Med 2024: “Clinical Management of Advanced Prostate Cancer: Where Does Radiopharmaceutical Therapy Fit in the Treatment Algorithm?

PCa Commentary | Volume 190 – June 2024

PARADIGM SHIFT — Changes in the Management of De Novo Metastatic
Hormone-Sensitive Prostate Cancer (mHSPC)

This Commentary discusses current literature on the identification of optimal oligometastatic prostate cancer candidates for metastasis directed therapy.

PCa Commentary | Volume 189 – May 2024

Non-Metastatic Castration-Resistant Prostate Cancer:
Management Options, Associated Adverse Effects, and Treatment Outcomes.

This Commentary discusses non-metastatic castration-resistant PCa management options, associated adverse effects, and treatment outcomes.

PCa Commentary | Volume 188 – April 2024

Prostate Cancer Heterogeneity — Clinical Consequences and Therapeutic Relevance.

This Commentary discusses patient selection for acitve surveillance for PCa, outcomes, and monitoring for Gleason Grade progression.

PCa Commentary | Volume 186 – February 2024

ACTIVE SURVEILLANCE: Patient Selection, Outcomes, and Monitoring for Gleason Grade Progression.

This Commentary discusses patient selection for acitve surveillance for PCa, outcomes, and monitoring for Gleason Grade progression.

PCa Commentary | Volume 185 – January 2024

Identifying Optimal Oligometastatic PCa
Candidates for Metastasis Directed Therapy

This Commentary discusses current literature on the identification of optimal oligometastatic prostate cancer candidates for metastasis directed therapy.

PCa Commentary | Volume 184 – December 2023

Focal Therapy for Localized Prostate Cancer

This Commentary discusses current literature on focal brachytherapy and focal cryotherapy for the treatment of localized prostate cancer.

PCa Commentary | Volume 183 – November 2023

Artificial Intelligence in Prostate Cancer

This Commentary discusses current literature on artificial intelligence in prostate cancer diagnosis, risk stratification, and prediction of outcomes.

PCa Commentary | Volume 182 – October 2023

Oligometastatic Prostate Cancer: Metastasis Directed Therapy (MDT) – Treatment Options

This Commentary discusses current literature on oligometastatic prostate cancer and the use of metastasis-directed therapy (MDT) as a treatment option.

PCa Commentary | Volume 181 – September 2023

PSMA PET/CT Staging of Advanced PCa and AI-Guided Androgen Deprivation Therapy

This Commentary discusses current literature on PSMA PET/CT staging and AI-guided ADT for advanced prostate cancer diagnosis and treatment.

PCa Commentary | Volume 180 – August 2023

Digital Pathology and Artificial Intelligence

This Commentary discusses current literature on digital pathology and artificial intelligence in prostate cancer diagnosis and treatment.

PCa Commentary | Volume 179 – July 2023

Neuroendocrine Prostate Cancer: A Challenging Transformation in Late Disease

This Commentary discusses current literature on treatment-induced neuroendocrine prostate cancer (t-NEPC.)

PCa Commentary | Volume 178 – June 2023

Radioligand Therapy (RLT): A View Into the Future

This Commentary reviews and discusses current literature on the use of Radioligand Therapy (RLT ) in treating prostate cancer.

PCa Commentary | Volume 177 – May 2023

Decipher: Predicting Prognosis and Assisting Treatment Decisions

This Commentary discusses Decipher, a genomic risk-stratifier that estimates prognosis on the basis of the unique molecular characteristics of a man’s prostate cancer, and can offer guidance in treatment decisions.

PCa Commentary | Volume 176 – April 2023

PARP Inhibition with Olaparib: A Potential New Indication for First-line Therapy for Metastatic Castration-Resistant Prostate Cancer

This Commentary reviews the underlying biology of PARP inhibitors and data supporting olaparib plus abiraterone as first-line therapy for mCRPC.

PCa Commentary | Volume 175 – March 2023

METASTATIC HORMONE SENSITIVE PROSTATE CANCER (mHSPC):
Many Treatment Options

This Commentary discusses the results of the ARASENS and PEACE-1 trials and their ramifications for treatment regimens for mHSPC.

PCa Commentary | Volume 174 – February 2023

MANAGING BIOCHEMICAL FAILURE AFTER RADIATION THERAPY — The Importance of Considering Both PSA and PSA Doubling Time.

This Commentary discusses the importance of considering both PSA and PSA doubling time for determining biochemical recurrence.

PCa Commentary | Volume 173 – January 2023

SEQUENCING BAT WITH XTANDI: An Effective Option

This Commentary discusses Bipolar Androgen Therapy: an effective, but likely underused, option in the sequence of treatments for mCRPC.

PCa Commentary | Volume 172 – December 2022

METASTASES DIRECTED THERAPY (MDT):
Can Concomitant Hormone Suppression Be Avoided?

This Commentary discusses selecting men for MDT+ADT versus MDT alone in the oligometastatic prostate cancer space.

PCa Commentary | Volume 171 – November 2022

Nonmetastatic Castration-Resistant Prostate Cancer: The “Ides” of Androgen Receptor Inhibition — Enzalutamide, Apalutamide and Darolutamide.

This Commentary explores treatment regimens combining enzalutamide, apalutamide, or darolutamide with androgen deprivation for nmCRPC.

PCa Commentary | Volume 169 – September 2022

ANDROGEN DEPRIVATION THERAPY (ADT) AND RADIOTHERAPY: Basic Mechanisms and New Developments.

This Commentary looks at ADT and radiotherapy, as well as evolution of cellular resistance to ADT therapy and potential treatment.

PCa Commentary | Volume 166 – June 2022

CAR-T CELL IMMUNOTHERAPY OF PROSTATE CANCER: PROMISING, BUT CURRENTLY ONLY A “WORK-IN-PROGRESS”

This Commentary looks at developing research on how to use CAR-T cell immunotherapy to treat prostate cancer.

PCa Commentary | Volume 165 – May 2022

Lutetium-177—PSMA-617 Therapy: Now FDA-Approved and to Be Available Shortly: The Treatment in Context

This Commentary looks at Lutetium-177 PSMA-617 therapy radioligand therapy for metastatic castration-resistant prostate cancer.

PCa Commentary | Volume 164 – April 2022

Recurrent Prostate Cancer – An Emerging Management Trifecta: PSMA PET/CT; Oligometastatic Cancer; Focal CyberKnife Treatment.

This Commentary looks at an emerging management trifecta for recurrent prostate cancer: PSMA PET, oligometastatic cancer & focal therapy.

PCa Commentary | Volume 163 – March 2022

DECIPHER GENOMIC CLASSIFIER: Its Risk Predictions Assist in Decision-Making.

This Commentary looks at how the Decipher assay assists in decision-making for how to treat patients with prostate cancer.

PCa Commentary | Volume 162 – February 2022

ACTIVE SURVEILLANCE: Patient Selection and Monitoring – An Update

This Commentary gives an update on patient selection and monitoring for prostate cancer active surveillance.

PCa Commentary | Volume 161 – January 2022

BIPOLAR ANDROGEN THERAPY (BAT): A Treatment Option for Metastatic Castration-Resistant Prostate Cancer (mCRPC)

This Commentary looks at bipolar androgen therapy (BAT) for metastatic castration-resistant prostate cancer (mCRPC).

PCa Commentary | Volume 160 – December 2021

Gene Mutations in the BRCA Family and PARP Inhibition Therapy

This Commentary looks at gene mutations in the BRCA family and PARP inhibition therapy for advanced prostate cancer.

PCa Commentary | Volume 159 – November 2021

GENE EXPRESSION PROFILING: Application of Genomics to Therapy Selection for Patients with Metastatic Hormone-Sensitive Prostate Cancer (mHSPC).

This Commentary looks at the application of genomics to therapy selection for patients metastatic hormone-sensitive prostate cancer (mHSPC).

PCa Commentary | Volume 158 – October 2021

Therapy of the Primary Tumor in Newly Diagnosed Metastatic Hormone-Sensitive Prostate Cancer (mHSPC): To Treat or Not to Treat. That is the Question.

This Commentary considers the benefits of therapy of the primary tumor in de novo mHSPC, especially as this patient population grows.

PCa Commentary | Volume 157 – September 2021

Metastatic Hormone Sensitive Prostate Cancer (mHSPC): Increasing in Incidence; Treatment Options Evolving

This Commentary considers the increased incidence of and evolving treatment options for metastatic hormone-sensitive prostate cancer.

PCa Commentary | Volume 156 – August 2021

PYLARIFY — A New PET Imaging Agent for Staging Primary Prostate Cancer and Recurrence

This Commentary looks at Pylarify, a new PET/CT imaging agent for staging primary prostate cancer and recurrence.

PCa Commentary | Volume 155 – July 2021

HOT FLASHES: Physiology and Treatment — A Basic Primer

This Commentary looks at causes and management options for hot flashes, a common side effect of ADT treatment for prostate cancer.

PCa Commentary | Volume 154 – June 2021

Treatment-Induced Neuroendocrine Prostate Cancer – Tough to Diagnose and Tough to Treat: A Primer but Concluding with a Review of a New Study Offering Hope.

This Commentary looks at the current state of causes, diagnosis, and treatment for neuroendocrine prostate cancer.

PCa Commentary | Volume 153 – May 2021

PSMA Targeted RadioIigand Therapy for Metastatic Prostate Cancer: Where We Currently Stand and Where Research is Heading

This Commentary provides an overview of PSMA-targeted radioligand therapy with Lutetium-177 or Actinium-225 and positive impact on progression-free survival.

PCa Commentary | Volume 152 – April 2021

GENOMIC SEQUENCING and GENOMIC CLASSIFIERS: Aids to Decision Making.

This Commentary provides a primer on using genomic classifiers and genomic sequencing to guide management decisions for prostate cancer.

PCa Commentary | Volume 151 – March 2021

OLIGOMETASTATIC PROSTATE CANCER: Metastases Directed Therapy – Patient Selection, Imaging and Outcomes

This Commentary will addresses the guidance from four clinical trials regarding patient selection and imaging choices to best select patients most likely to benefit from MDT.

PCa Commentary | Volume 148 – December 2020

ACTIVE SURVEILLANCE – What’s New

This Commentary discusses Active surveillance (AS) as an increasingly recommended strategy for carefully selected men with a biopsy diagnosis of low grade, localized prostate cancer. 

PCa Commentary | Volume 147 – November 2020

OLAPARIB and RUCAPARIB (PARP inhibitors)

This Commentary discusses how olaparib and rucaparib offer a needed additional treatment option for men with mCRPC.

PCa Commentary | Volume 146 – October 2020

Radium-223 (Xofigo); A Radioisotope Treatment for Prostate Cancer Metastatic to Bone. The radiobiology of Radium-223 suggests greater effectiveness when used early in metastatic castration-resistant prostate cancer (mCRPC).

The August issue of PCa Commentary This Commentary discusses how radium-223 therapy for mCRPC prolongs survival, improving with earlier use and when combined with other agents.​

PCa Commentary | Volume 145 – September 2020

PSA, PSA Dynamics, and Advances in Imaging: PSA and the PSADT (PSA doubling time) Guide the Management of Prostate Cancer.

The August issue of PCa Commentary discusses how advances in imaging are detecting metastatic prostate cancer at increasingly lower PSA levels in men who have undergone radical prostatectomy and radiation therapy. Dr. Weber details how imaging techniques such as the Ga68- PSMA PET/CT-11 and subsequent refinements are finding metastatic disease at lower than previously expected PSA levels (below 0.2 ng/mL), and how PSA doubling time (PSADT) is now being used to guide the application of hormone or chemotherapy in these men.

PCa Commentary | Volume 144 – August 2020

THE CHECKPOINT INHIBITORS – In Search of a Role in the Treatment of Prostate cancer: The Current Status

The August issue of PCa Commentary discusses the current status of using checkpoint inhibitors for treating prostate cancer, including results from the Keynote-028 and Keynote-199 looking at the efficacy of pembrolizumab in heavily penetrated patients. He further discusses results related to the BRCA family of gene mutations, links between the gut microbiome and checkpoint inhibitors, as well as detailing two current clinical trials (Keynote 365 and Checkmate 9KD) examining combination therapy in mCRPC patients.

PCa Commentary | Volume 143 – February / March 2020

ANTI-PSMA 177-LUTETIUM RADIOLIGAND THERAPY:
An Update on Outcomes; the Vision Trial; and Future Directions

The February / March issue of PCa Commentary discusses using anti-PSMA 177-lutetium radioligand therapy for treating advanced metastatic prostate cancer. Dr. Weber examines the background of this therapy, early trials, and details the results of the VISION Trial. He further examines future implications and possibilities for this therapy in treating advanced metastatic prostate cancer.

PCa Commentary | Volume 142 – January 2020

ANTI-TUMOR IMMUNE RESPONSE POTENTIATED by RADIOTHERAPY:
A concept arising from pre-clinical studies is now clinically supported by the results of the ORIOLE trial.

January’s issue of PCa Commentary discusses the implications of the ORIOLE Trial, which examined the effects of patients of primary radiotherapy or surgery on patients with mHSPC, as well as looking at pre-treatment imaging and genomic data to look at mechanisms explaining progression-free survival in both groups. The study found that the use of SART improved progression-free survival and found no additional bone lesions in the group.

PCa Commentary | Volume 141 – December 2019

PARP INHIBITION THERAPY — Clinical Importance of Genetic Variants of BRCA 1/2 and ATM in Men with Metastatic Castration-Resistant Prostate Cancer.

December’s issue of PCa Commentary discusses PARP inhibitor therapy as a potential new entry into the regimens of standard-of-care treatment for metastatic castration-resistant prostate cancer patients with BRCA 1/2 and ATM mutations. This Commentary highlights findings from the late-breaking PROfound trial, which evaluated olaparib for the treatment of heavily pretreated men with DNA damage repair (DDR) alterations and reported impressive results.

PCa Commentary | Volume 140 – November 2019

Role of Androgen Suppression Added to Salvage Radiotherapy Following Prostatectomy for High-Risk Prostate Cancer: In Selected Cases, No Benefit and Associated Harm

The findings from this randomized Phase III trial supported the current standard of care for this situation. It compared two treatments initiated after a PSA rise to levels between 0.2 – 4.0 ng/mL after a prostatectomy and lymphadenectomy. The study involved 761 men with localized cancer having a high risk for recurrence, i.e., extracapsular extension or seminal vesicle involvement, or nodular disease with positive surgical margins. Salvage radiation to the prostate region was given to all. 

PCa Commentary | Volume 139 – October 2019

OLIGOMETASTATIC PROSTATE CANCER: Is It an Intermediate Stage of Cancer, and If So, How Should It Be treated?

It has been suggested that a few (usually 3-5, i.e., ‘oligometastatic’) lesions at the time of biochemical failure after primary treatment might represent an indolent disease state with limited potential for additional spread. This hypothesis was first made in 1995 by Hellman and Weichselbaum (J Clin Oncol). Those authors’ thoughts were paraphrased by Tran and Antonarakis (J Oncol Pract. 2016) in “Altering the Natural History of Oligometastatic Prostate Cancer with Local Therapies: Reality Versus Illusion.”

PCa Commentary | Volume 138 – September 2019

Active Surveillance: Update and New Developments

This issue reviews the current state of active surveillance with an article from Laurence Klotz, MD, entitled “Active Surveillance for Prostate Cancer: How to Do It Right.” This Commentary covers the role of multiparametric MRI and genomic testing panels in carefully selecting and following prostate cancer patients who choose active surveillance in order to safely delay primary treatment and achieve excellent outcomes.

PCa Commentary | Volume 137 – August 2019

Radium-223 (‘Xofigo’): A Radioisotope Treatment for Bone Metastases – Where Does It Fit in the Management of Prostate Cancer?

This issue reviews the clinical significance of bone metastases in castrate-resistant prostate cancer (CRPC) patients, the mechanism of action of radium-223, and the isotope’s utility in managing these patients. This Commentary also features take-away points from a lecture titled “Real World Treatment Experience with Radium-223” by Daniel George, MD, on the role of radium-223 in the schema of metastatic CRPC treatment.

PCa Commentary | Volume 136 – July 2019

The Natural History of Prostate Cancer and the Prognostic Utility of PSA Doubling Time.

This issue reviews a report Catherine H. Marshall, MD, MPH, presented at the 2019 ASCO Annual Meeting, entitled “Outcomes of Men with Recurrent M0 Prostate Cancer Who Defer Androgen Deprivation Therapy Until Metastasis – Medical Oncologist Perspective.” The discussion will analyze outcome data from three retrospective related observation trials included in Dr. Marshall’s report, and how PSA doubling time can guide appropriate timing of hormone suppression initiation so as to balance the dual goals of delaying metastases and avoiding the toxicity of therapy.

PCa Commentary | Volume 135 – June 2019

Managing PSA Recurrence Following Primary Radiation Therapy: Evolving Regimens for Focal Treatment.

Biochemical recurrence following primary irradiation is relatively common. “A recent series of 2694 patients treated with doses above 78 Gy revealed 10-year biochemical recurrence risks of approximately 10%, 23%, and 44% in low-, intermediate-, and high-risk patients, respectively. […] After primary whole-gland radiotherapy several series showed that nearly all recurrences (89-100%) regrow at the site of the primary largest and/or highest-grade index lesion,” as quoted in “Focal Salvage Treatment of Radiorecurrent Prostate Cancer”, Marieke et al., Cancers (Basel). 2018 Dec. [An excellent review] This biology offers carefully selected patients the opportunity of treatment focused on the control of the local disease recurrence.

PCa Commentary | Volume 134 – May 2019

RADIOLIGAND THERAPY – The “VISION” Protocol: A treatment opportunity for men with late-stage metastatic castration-resistant prostate cancer.

Radioligand therapy (RLT), or in other words, PSMA directed endoradiation with Lutetium-177, has been developed to the extent that it is a realistic option for men with late-stage, heavily pretreated, metastatic castration-resistant prostate cancer. This therapy has been extensively studied in many trials with the general consensus that the treatment is safe with minimal adverse effects and consistently has led to a >50% decline in PSA in a range of ~40 to 60% of the men. This Commentary will highlight examples of these studies.

PCa Commentary | Volume 133 – April 2019

GENOMIC SEQUENCING FOR PROSTATE CANCER – Which Men Gain a Clinical Benefit from Genomic Testing?

The commonly cited goal of ‘personalized medicine’ in regards to treatment selection based on genomic testing is in the early ‘work in progress’ stage. Breathtaking advances in next generation sequencing (NGS) are very promising, but currently only limited options exist for therapeutic guidance. Dr. Oliver Sartor acknowledges this in the recent NEJM review, Metastatic Prostate Cancer, Feb 2018: “The use of advanced genomic analysis is now feasible to a greater extent than ever before. Whether its use improves treatment decisions is not yet clear.”

PCa Commentary | Volume 132 – March 2019

Resistance to Therapeutic Agents Targeting the Androgen Receptor and Insights into Sequencing Treatments for Optimal Outcomes

Ever since the first orchiectomy for metastatic prostate cancer in 1941, researchers and clinicians have been determinedly trying to restrain the androgen receptor (AR) by manipulating its hormone environment. But like Houdini, after initial suppression this wily adversary wriggles a bit and then escapes — transitioning prostate cancer into a castration-resistant state. Alterations in the AR eventually frustrate the beneficial gains from  LHRH inhibitors and anti-androgens like Zytiga, Xtandi, Erleada, etc. This escape is accomplished by a variety of different mechanisms, presenting the challenge of anticipating and circumventing the persistence of AR signaling.

PCa Commentary | Volume 131 – February 2019

ENZALUTAMIDE (‘XTANDI’): AN UPDATE: The Many Faces of Enzalutamide

Many important developments have taken place since Enzalutamide (ENZ) was reviewed in the March/April 2014 issue. This Commentary will discuss these developments and the current indications for ENZ and new studies of ENZ as monotherapy. A subsequent Commentary will address sequencing, resistance, and possible potentiation of immunotherapy.

PCa Commentary | Volume 130 – January 2019

Ga68-PSMA-11 PET/CT Scanning at Initial Diagnosis for High-Risk Prostate Cancer: What is missed by conventional staging and does it matter?

For this Commentary, eleven research papers reporting the results for the Ga68-PSMA PET/CT applied to high-risk prostate cancer were reviewed. For interest, here is the list of research locations: Australia (3, where the scan is readily available), India, Turkey, Germany (2), Jordan, and the USA (3, UCSF, UCLA, and Johns Hopkins).

PCa Commentary | Volume 129 – December 2018

THE AXUMIN PET/CT SCAN:  ITS CLINICAL UTILITY — AN UPDATE

It has been one year since the Commentary featured the Axumin PET/CT in the November 2017 issue.  A great deal of new research about this scan performance has been published since then. The material in this issue is based on this research. Overall, these studies focus on the Axumin scan, which provides clinically relevant information at PSA levels that lead to significant changes in treatment plans for a majority of men. 

PCa Commentary | Volume 128 – November 2018

IMMUNOTHERAPY FOR PROSTATE CANCER:
Immune Checkpoint Inhibitors — The Search for Clues for Which Men Will Benefit and How Best to Treat Them.

Harnessing our immune system to treat cancer has been an elusive goal for decades. Research in immunotherapy is intense with active study of the newest advances, i.e. checkpoint inhibitors and CAR T-cell technology. Checkpoint inhibitors have yielded encouraging results in selected patients (10% – 40% responding) with melanoma, bladder and kidney, non-small cell lung cancer, and cancer of the head and neck. However, the results of prostate cancer immunotherapy have been disappointing in unselected patients. Why is this?

PCa Commentary | Volume 127 –October 2018

DECIPHER AND A HYBRID CLINICAL – GENOMIC CLASSIFIER:
Improving the Prognostic Accuracy of NCCN Risk Categories

The article will discuss how Decipher is constructed, its benefits as a supplement to the standard risk assessments tools, and offer examples of its use in clinical practice. Additionally, the Commentary will highlight the work of Dr. Dan Spratt and colleagues that integrates the NCCN system with Decipher to achieve further prognostic accuracy (“Spratt, et al., Journal of Clinical Oncology, Feb. 2018”).

PCa Commentary | Volume 126 – September 2018

ESTROGEN — OUR SISTER HORMONE:
Addressing the Dark Side of Androgen Deprivation Therapy (ADT)

Many of the important adverse effects associated with androgen suppression with Lupron, Firmagon, or orchiectomy result from estrogen deficiency. Estimates vary, but 50%, 75%, or as much as 80% of a man’s serum estrogen arises from enzymatic conversion of serum testosterone. And when ADT drops serum testosterone into the low range of 20 – 30 ng/dL, a profound estrogen deficiency results.

PCa Commentary | Volume 125 – August 2018

NEUROENDOCRINE PROSTATE CANCER: An Adverse Development in Advanced Disease — Which Largely Has Flown Under the Radar.

Neuroendocrine prostate cancer (NEPC) is a form of the disease which, as best currently understood, arises from standard adenocarcinoma in a process termed “transdifferentiation.” This transformation develops in advanced stages of prostate cancer—usually in metastatic CRPC, and is thought to result as an adaptation to the selective pressure of androgen deprivation. It’s usually seen after prior therapy with, for example, abiraterone and/or enzalutamide and is one source of resistance to these agents.

PCa Commentary | Volume 124 – July 2018

ACTIVE SURVEILLANCE: EFFORTS TO IMPROVE ITS PERFORMANCE

The goal of active surveillance (AS) is to delay treatment, avoiding its associated adverse effects for as long as appropriate, while ensuring that selective delayed intervention will still result in a good outcome. This management strategy has been under development for more than 20 years. It has been increasingly accepted as an appropriate option for men with low-risk disease, but further refinement is required in patient selection and monitoring strategy.

PCa Commentary | Volume 123 – June 2018

RADIOLIGAND THERAPY (RLT) with 177-LUTETIUM

PSMA is a transmembrane protein of 750 amino acids expressed on the surface of ~90-95% of prostate cancer cells, increasingly expressed as aggressiveness increases. The expression of PSMA is negatively related to androgen receptor abundance so that ADT promotes increased PSMA expression. Its normal function is to ferry nutrients such as folate and glutamate into the cell to support growth and metabolism. Short sections of this convoluted protein molecule can be targeted and linked by small molecules (e.g., “617”) or antibodies (e.g., “J591”). These molecules can be fused to radiation emitting nuclides such as Lutetium-177, Actinium-225, or several others under investigation.

PCa Commentary | Volume 122 – June 2018

New Guidance on the Management of PSA Rise in the Setting of Nonmetastatic Castration-Resistant Prostate Cancer (nmCRPC)

At the 2018 Genitourinary Session of the American Association of Clinical Oncology, two presentations reported similar findings which offer management guidance for men whose PSAs are rising despite androgen suppression but have no objective evidence of metastatic spread. For men with metastases, Zytiga and Xtandi are commonly prescribed, but to date there have been no approved treatments for therapy at the nonmetastatic CRPC stage.

PCa Commentary | Volume 121 – April 2018

AR-V7: The Clinical Utility of Knowing Your Status … And When the Information Is Most Useful.

A test for the splice-variant AR-V7, Oncotype Dx AR-V7 Nucleus Detect (Genomic Health, Inc.), has become commercially available. This Commentary will focus on the clinical significance of test results — their predictive and prognostic value.

PCa Commentary | Volume 120 – March 2018

METASTASIS DIRECTED THERAPY:
What Can Be Learned From The First Reported Prospective, Randomized, Multicenter Phase II Clinical Trial?

In December 2017, the JCO published the trial results of Ost and colleagues: “Surveillance or metastasis-directed therapy for oligometastatic prostate cancer recurrence.”1 Up to this time, there have been numerous retrospective and observational studies of varying design which, taken together, strongly suggest that progression-free survival can be prolonged by the focal treatment of three or fewer lesions at the time of PSA recurrence after primary therapy. This regimen is now termed “metastasis-directed therapy” (MDT) and was discussed in detail in an earlier Commentary.

PCa Commentary | Volume 119 – Jan/Feb 2018

KNOW YOUR BRCA STATUS:
The Clinical Importance of Mutations in Genes that Repair Injury to DNA

The message is clear. At diagnosis, 6% of men carry mutations in the BRCA1 or BRCA2 gene. At the stage of metastatic castration-resistant prostate cancer, nearly 12% of men exhibit these germline (inherited) mutations. Finally, as the course of the disease progresses through various therapies, the number of BRCA and BRCA-like mutations further increases and can be found in up to 23% of men.