Topic: Advanced Disease

The Role of Radiotherapy in Oligometastatic Prostate Cancer and How to Treat the Primary in De Novo Oligometastatic Disease

by Daniel A. Hamstra, MD, PhD | Dec 2023

Daniel A. Hamstra, MD, PhD, FASTRO, FASCO, discusses the use of radiotherapy in oligometastatic prostate cancer treatment and how to approach treating the primary in de novo oligometastatic disease. In this presentation, Dr. Hamstra covers:

The history and definition of oligometastatic disease.
The history of radiation therapy in localized and metastatic prostate cancer.
Results from the STAMPEDE, PEACE-1, and STOMP and ORIOLE trials.
The Pros and Cons of including radiation therapy in systemic therapy.
Progression to Survival and Overall Survival rates in radiation therapy patients.

Dr. Hamstra concludes by highlighting the need for more data on low-volume versus high-volume patients, and he recommends enrolling eligible patients in the ongoing SWOG S1802 trial.

PCa Commentary | Volume 182 – October 2023

by Edward Weber, MD | Oct 2023

Background

With the increased use of PSMA PET/CT scanning both at initial diagnosis of advanced prostate cancer and at disease recurrence, a substantial number of men will be found to have some extent of metastatic disease — either metastatic hormone-sensitive prostate cancer (mHSPC) or castration-resistant prostate cancer (CRPC). The second of these states will have arisen in what is termed ‘non-metastatic’ castration-resistant cancer (rising PSA despite castrate level of testosterone), in which, upon PET scanning, metastases are frequently identified. There is no current consensus regarding the appropriate treatment regimens for these disease states. Three options have been studied:

Metastases-directed radiation therapy only, i.e., no androgen deprivation therapy (ADT)
until progression
MDT combined with ADT
The newest option, MDT combined with intermittent hormone therapy (IHT)
Studies to date report that all three options prolong overall survival compared to ADT only.

Dividing mHSPC into High Tumor Burden vs Low Tumor Burden

Two major clinical trials (STAMPEDE and CHAARTED) have defined ‘high burden’ as: the presence of visceral metastases or four or more bone lesions one or more beyond the vertebral bodies and pelvis. These studies were based on standard CT and bone scans. This distinction between high and low burden disease has been developed to guide therapeutic regimens such as systemic treatment with Docetaxel with ADT +/- newer anti-androgen receptor agents i.e., Zytiga or Xtandi) for high-burden disease. For low burden disease, MDT+/- ADT are options, including ablation of the prostate.

An early trial reported by Palma et al, Lancet 2019, established that MDT alone for men with 1-5
metastases had a superior overall survival than ADT only (SABR-COMET trial). Currently recruiting is NCT03721341 using MDT for treatment of 4-10 oligometastatic lesions combined with a variety of standard of care options as selected by the treating physician vs any chosen treatment option but without MDT.

Currently recent and ongoing studies in low burden disease focus on avoiding ADT until disease progression thus avoiding ADT toxicity.

New Techniques Under Development for Estimating Prognosis

Patient selection for MDT is currently best made with PSMA PET/CT scanning, which offers greater sensitivity than conventional imaging. Research is developing techniques to predict prognosis with greater sensitivity. One promising option is assessing the metabolic aggressiveness of the metastatic lesions under consideration for MDT by measuring the PET SUV (specific uptake value) of individual lesions. SUV is a measure of cancer aggressiveness. In this assessment the SUVmax is calculated, which totals the combined metabolic activity of all the lesions. This requires special technology.

However, the mHSPC disease state is a heterogeneous collection of members each with different
biological behavior and a different risk of progression. An estimate of prognoses for a man with
mHSPC can be assessed by applying the genomic classifier Decipher on tissue from the primary.
A more technologically advanced assessment of biological behavior would be evaluating
microRNA or circulating tumor DNA in blood.

Initial Studies: The ORIOLE and STOMP trials of MDT

The above-named studies were two early randomized trials of mHSPC employed MDT (with stereotactic radiation therapy) versus observation only in men with 3 or fewer metastatic sites.

The outcome of both trials (as reviewed by Deek et al., JCO 2022), was a prolongation of progression-free survival (PFS) in both studies. MDT targeted three or fewer lesions based on CT and bone scans in each man in the MDT arm. Progression-free survival was superior in both trials compared to observation only with a pooled median PFS of 11.9 months in the MDT arms and 5.9 months with observation only. Men in the study with high-risk mutations in the genes BRCA 1/2, ATM. RB1 and TP53 who received MDT also benefited, but to a lesser extent with a median PFS of 7.5 months.

In the ORIOLE trial at onset, in addition to CT and bone scans, men also had PSMA PET scans. The PET scans detected a total of 36 lesions of which 16 had not been seen on the CT and bone scans, emphasizing the importance of basing MDT on imaging with PSMA PET/CT.

The EXTEND Trial (NCT03599765)

The question addressed in “Addition of Metastases-Directed Therapy to Intermittent
Hormone Therapy for Oligometastatic Prostate Cancer,” Tang et al., JAMA Oncol. 2023, was “Does the addition of metastasis-directed therapy to intermittent hormone therapy improve progression-free survival for men with oligometastatic prostate cancer?” The study anticipated that the known “synergy” between hormone therapy and radiation therapy, would benefit the MDT treated group. MDT was delivered with the CyberKnife to 5 or fewer lesions. The study was randomized 1:1 between those receiving MDT therapy plus IHT and those receiving IHT only. The participants were stratified by the number of metastatic lesions (1-2 vs 3-5). All men received radiation to the prostate. Although some had received varying periods of HT pre-study, at trial onset androgen suppression was delivered for 6 months, after which hormone therapy was withheld until progression. Progression was defined as clinical or a PSA rise of greater than 25% or greater than 2 ng/mL above the nadir.

Both the ORIOLE and EXTEND trials found evidence that the immune system was sensitized to
attack metastatic sites that were too small to be imaged. The presumed explanation: In
destroying the targeted lesions intracellular proteins were released that sensitized T-cells to
attack additional metastatic site too small to be imaged.

Results

At the time of the report’s analysis the median PFS had not been reached in the MDT /IHT arm but was 15.8 months in the IHT-only group.

A secondary goal of the trial was to prolong the duration during which the testosterone level was near normal. After stopping ADT at 6 months the men in IHT group experienced testosterone levels greater than 150 ng/dL (low normal) for only 6 months before disease progression. In the MDT/IHT arm the median duration of having a testosterone level about 150 ng/dL had not been determined at the time of data analysis.

The trial reached its goal: By adding MDT to intermittent androgen suppression PFS was prolonged and the duration of normal testosterone level before progression was extended compared to intermittent hormone therapy only.

BOTTOM LINE

The increased use of PSMA scanning at the time of diagnosis is associated with an increased prevalence of metastatic hormone sensitive prostate cancer. A variety of treatment regimens using metastasis directed therapy (MDT) are under active study.

PCa Commentary | Volume 181 – September 2023

by Edward Weber, MD | Sep 2023

Background

The function of initial staging of prostate cancer is to accurately estimate the risk of progression in order to guide optimal therapy. The influential National Comprehensive Cancer Network (NCCN)
recommends a PSMA PET/CT as part of initial staging for men in the risk categories of intermediate- and high-risk cancer as defined by clinicopathologic features: PSA, Gleason score, clinical tumor stage and number of positive biopsy cores. For men with a life expectancy of >10 years molecular analysis (i.e., Decipher, Prolaris or OncotypeDx Prostate) is suggested by the NCCN.

PSMA PET/CT in advanced cancer identifies lesions that are missed on conventional CT and bone scans. Yaxley et al., BJU Int 2019 reported the results of primary staging by PSMA PET/CT in 1253 men, half and half with intermediate and high-risk disease in the largest published study on this subject. Metastases were identified in 12.1%; 8.2% in men with PSA values <10 ng/ml and 47% with PSA values > 20 ng/mL. Segregated by Gleason Grade, metastases were found in 6.4% with GG 2-3 (Gleason 3+3 and 3+4). Extra-pelvic lymph nodes occurred in 47%. Bone metastases were found in 5.2% in men with intermediate-risk and in 20% high-risk cancer.

Enter the Immune System — Its Influence on Cancer Behavior

The influence of immune cell infiltration within the tumor and from the surrounding microenvironment is not taken into account in assigning a Gleason score and therefore is not considered in the NCCN classifications of risk. The variety of promoter and suppressive lymphocytes and macrophages that comprise these infiltrations are not fully identified under the microscope and play no role in standard risk assessments.

The immune microenvironment of the primary tumor influences both the initiation and early progression (i.e., toward a higher Gleason score) of the developing cancer. Immune elements compete (i.e., pro-tumor and anti-tumor) to suppress malignant clones from progressing — while others promote disorganization and aggressiveness. Protective cells include immune enhancing CD8+T-cells, Killer T-cells, protective macrophages; immune suppressive cells include T-regulation cells and immune suppressive macrophages. In fact, recent studies reveal that the ratio of one particular gene in anti-tumor macrophages to a different gene in pro-tumor macrophages can by itself determine the outcome in a man’s cancer — and possibly all cancers. (Bill et al., SCIENCE, Aug 2023).

These immune cellular elements are not only found within and surrounding tumors but also can be identified in the blood to various amounts. Based on their presence in the blood, Chinese researchers have “developed and validated a machine-learning nomogram for the prediction of risk stratification of prostate cancer based on subsets of these lymphocytes in the blood.” This nomogram functioned better than the standard NCCN prognostic risk groups. (Yang et al., Journal of Translational Medicine 2023.)

The Predictive Power of Artificial Intelligence

The genomic classifier Decipher has been multiply validated to estimate prognosis based on its risk scale of 0 to 1.0. However, AI has the capability to derive a prediction — for example of an individual man’s response to a given treatment. When whole mount pathology slides, multiply stained, are digitized into a scanner, the AI process identifies standard histology but also detects the subtypes of immune cells infiltrating the tumor and the surrounding microenvironment. This comprehensive analysis presents a complete picture of a man’s cancer, its predicted behavior and supports individualized management.

Two Examples of Clinically Useful Applications of AI for Intensifying or De-intensifying
Therapy

Commentary #180 discusses a study assessing the relative benefits of adding ADT to
radiation therapy in men with advanced cancer based on a derived biomarker.
At the 2023 annual meeting of the American Society of Clinical Oncology, Armstrong and
colleagues from Duke University presented their abstract, “Development and validation of an
AI-derived digital pathology-based biomarker to predict benefit of long-term androgen deprivation therapy with radiotherapy in men with localized high-risk prostate cancer across
multiple phase III NRG/RTOG trials,” i.e., a goal “to guide ADT duration to maximize benefits
and minimize risks.”
“Pre-treatment prostate biopsy slides were digitized from six randomized trials evaluating the
benefit of radiation therapy +/- ADT” in men with localized high-risk prostate cancer with end
points of distant metastases (DM) and prostate cancer-specific mortality. The data from this
training set was then validated in a major trial comparing radiation plus 4 vs. 28 months of ADT and determined a distinguishing biomarker. Their study found that 28 months of ADT was 13% better than 4 months in the biomarker-positive group as compared to only 2% better in the biomarker-negative group, a finding that could influence clinical decision-making.
[A spokesman for Artera AI.com said the company is working on developing a test based on this
study for commercial availability.]

BOTTOM LINE

PSMA PET/CT scans and applications of AI in prostate cancer management are aiding individualized patient management.

PCa Commentary | Volume 180 – August 2023

by Edward Weber, MD | Aug 2023

Background

Ever since 1675 when the Dutch lens maker, Leeuwenhoek, looked down the newly invented microscope at rainwater and reported seeing ‘animalcules – tiny dancing creatures” (bacteria), pathologists have been similarly looking down their scopes and guiding prostate management by applying their expertise in pattern recognition.

In the 1960s, Dr. Donald Gleason organized those patterns into doublets of 3, 4 (i.e., 3+4) and 5 to create the prognostic Gleason Score — now further refined. Anthony D’Amico, professor of Radiation Oncology at Harvard Medical School is credited for establishing prognostic categories segregating “risk of recurrence” into low-, intermediate- and high-risk prostate cancer (with intermediate-risk now subdivided into favorable” and “unfavorable.”)

[Google reminds us that “A prognostic biomarker provides information about the patient’s overall cancer outcome, regardless of therapy, whilst a predictive biomarker gives information about the effect of a therapeutic intervention.”]

Feng, Spratt et al., have now advanced the art by generating a personalized precision predictive model by utilizing large data sets, machine learning and the less human-dependent “deep learning” — both components of artificial intelligence. Their analysis was directed toward discovering a biomarker that can predict which men with intermediate-risk prostate cancer benefit from the addition of ADT to radiotherapy.

Their study found that some men gained much, but others only minimally. Previous data has found that only 60% of men with intermediate-risk cancer benefit from the addition of ADT to radiotherapy — although those with “unfavorable” intermediate-risk benefit more so. The challenge was identifying who benefits and who does not.

The Spratt AI Study

“Artificial Intelligence Predictive Model for Hormone Therapy Use in Prostate Cancer,” NEJM Evidence, June 29, 2023., by Dr. Daniel Spratt with many collaborators on behalf of NRG Prostate Cancer AI Consortium.

Dr. Spratt: “With the first-ever predictive biomarker of ADT benefit in prostate cancer, created with AI, we are able to further realize the ability to create a personalized approach for the treatment of cancer.” (Quoted in Precision Medicine News, 2023).

The study was based on “digitized pathology images of pretreatment prostate tissue and clinical data of 5727 patients enrolled in 5 phase 3 randomized trials in which treatment was radiotherapy with or without ADT.” The goal was to develop a binary model to predict the benefit from short-term ADT regarding the likelihood of developing distant metastases.

The article notes that androgen deprivation therapy (ADT) is customarily combined with radiation treatment in this setting. These were trials of radiation treatment for higher grades of prostate cancer, in which there are “no validated predictive models to guide its use.”

Spratt’s colleagues endeavored to establish such a guide – a binary determinant for men with localized intermediate-risk cancer predicting whether “a given patient will benefit from ADT or not“ based on the risk of time to developing distant metastases. They generated such a model by analyzing 4 major randomized clinical trials comparing radiation therapy alone or combined with ADT.

“Data from these trials were acquired and digitized and then were used to train a predictive AI model” to predict the differential benefit of ADT according to their biomarker status. Their image extraction method was described: “For each patient, the tissue across all available digital slides was divided into 256 x 256-pixel patches. … [and the] model was trained on image patches using self-supervised learning. Over 2.5 million tissue patches across four trials … were fed through the model 200 times to train the model.”

The next step was to take this predictive model and validate it using data from RTOG trial 9408 which randomized men with intermediate-risk cancer to radiation treatment plus or minus 4 months of ADT. By applying the AI-derived model, the 15-year estimate for developing distant metastases for biomarker-positive patients treated with ADT was 4% v 14.4% for biomarker-negative ADT patients. In developing their biomarker, they found the best cut-point was 67% for segregating biomarker-positive from biomarker-negative.

By applying the biomarker established in the development model, 543 men were biomarker-positive, indicating that ADT “significantly reduced (by 10.5 percentage points) the risk of distant metastases at 15 years compared to radiotherapy alone.” For 1051 biomarker-negative patients ADT conferred minimal benefit (percentage point benefit 0.5%). For prostate cancer-specific mortality, the comparison of benefits was 10.2% and 1.2%, respectively.

Dr. Spratt concluded, “Our AI-based predictive model was able to identify patients with a predominantly intermediate risk for prostate cancer likely to benefit from short-term ADT.” In an interview with ‘News Wise’ Dr. Spratt said: “We are fortunate to be already offering this test at UH Seidman Cancer Center, Case Western Reserve University, to our patients from Northwest Ohio, our nation, and around the world.” (Quoted in News Wise, June 2023)

BOTTOM LINE

The article reviewed in this Commentary is a prime example of how Artificial Intelligence can benefit the clinical management of prostate cancer.

From Artera.ai: “The ArteraAI Prostate Test is a Laboratory Developed Test that is now clinically available through a single CLIA-certified laboratory in Jacksonville, FL. Clinicians who would like to order the ArteraAI Prostate Test can contact us at support@artera.ai. Soon after, a member of our Customer Success team will reach out to set up an account in the ArteraAI Portal to enable order submission.”

PCa Commentary | Volume 179 – July 2023

by Edward Weber, MD | Jul 2023

Background
Although neuroendocrine cancer (NEPC) infrequently (<2%) presents elusively in the prostate, much more commonly it develops late in the course of the disease admixed in varying extent in metastatic lesions with standard adenocarcinoma. In this situation, it is termed “treatment-emergent t-NEPC” postulated to have “transdifferentiated” from adenocarcinoma. Its development is thought to be induced by mutations that have occurred during treatment due to increased therapeutic pressure from androgen suppressive therapy on the androgen signaling pathway. The genomic characteristics of the neuroendocrine components at the various metastatic sites are heterogeneous, making it challenging to craft a single targeted therapy. The transdifferentiated cells do not express PSA or the prostate-specific membrane antigen (PSMA) and hence are negative on PSMA PET scans. t-NEPC is aggressive, and difficult to diagnose, and effective treatment is lacking. Merkens et al., J Exp Clin Cancer Res. 2022, reviewed the underlying mechanisms of neuroendocrine transdifferentiation. t-NEPC associates with an inappropriately low PSA. Clues to its presence are bulky disease in viscera (especially liver) and lymph nodes, lytic bone metastases, a PSA doubling time of <6 months and an elevated serum calcium. t-NEPC in mCRPC tissue biopsies from patients treated with, for example, Zytiga and Xtandi rose to 10.5% compared to 2.3% in patients naive to these second-generation agents. During the period from 1998 to 2011 the incidence of t-NEPC was 6.3%; in 2012-2016 after introduction of Zytiga and Xtandi the rate was 13.3%. Diagnosis Appropriate management of t-NEPC is hampered by delayed diagnoses in part due to the lack of diagnostic serum biomarkers. The best candidate biomarker (but inconsistently elevated) is chromogranin A (CgA), the main component contained in secretory granules released from NEPC cells. Plasma values less than or equal to 85-100 ng/mL are normal; values >360 suggest significant t-NEPC. A suggested strategy is to check a baseline CgA in the early treatment phase of advanced cancer, and if the disease is objectively progressing without a commensurate rise in PSA, say, 4 – 10 ng/mL, obtain an 18F-FDG PET/CT scan (which can image aggressive cancer that is negative on PSMA PET scans (Spratt et al, Prostate 2015). “CgA should be included as a tool to monitor the evolution of [t-NE]PC, wherein it may be 2-3 times above normal levels,” reviewed in “Chromogranin A:” a useful biomarker in castration-resistant prostate cancer.” Poussard et al, World Journal of Urology, 2023.

Currently, the diagnosis of t-NEPC is based on biopsies of metastatic lesions performed when there is high suspicion for this transformation. But because of the heterogeneity among lesions, a biopsy may be misleading or inconclusive. The location of the projected biopsy may present difficulty or cause harm.

Because of these issues, an initial assay of circulating tumor cell histology may be useful (CTC, Epic Sciences), as discussed by Beltran et al, in “The Initial Detection and Partial Characterization of Circulating Tumor Cells in Neuroendocrine Prostate Cancer,” Clin Cancer Res 2016. PET Imaging targeting the delta-like ligand (DLL), a protein surface marker on NEPC cells, is under development, as is therapy with a Lutetium 177 nucleotide conjugate targeting the DLL protein.

An elevated neuron-specific enolase (NSE) above 16 ng/ml is often, but also inconsistently, found in t-NEPC. An elevated carcinoembryonic antigen (CEA) is a commonly available serum marker associated with t-NEPC. CEACAM5, a CEA-related “cell adhesion molecule 5, is a promising t-NEPC cell surface antigen” for which the CEACAM5 directed antibody-drug conjugate labetuzumab govitecan therapy is under development, DeLucia et al. (Fred Hutchinson Cancer Research Center, Clin Cancer Res. 2021)

Treatment
Chemotherapy offers a modest benefit in metastatic t-NEPC. The outcome of various regimens is discussed by Yamada and Beltram, Curr Oncol Rep.2021. Combination therapy with carboplatin (Paraplatin) and cabazitaxel (JEFTANA) yields objective responses of 50 – 60% with a median progression-free survival of 5.1 months and a median overall survival of 16 months. However, the management decision as to when to initiate chemotherapy in response to rising serum markers is challenging.

In an attempt to address the genomic heterogeneity of metastases, there is an ongoing trial at MD Anderson Cancer Center (NCT04592237) combining chemotherapy with carboplatin and cabazitaxel with PARP inhibition and anti-PD1 immunotherapy. A 29% rate of mutations in the BRCA family in NEPC explains the inclusion of PARP inhibitors in this regimen (Chedgy et al, J Pathol. 2018). The cell surface marker CD46 is overexpressed on NEPC cells and radioimmune therapy with an alpha-emitting Actinium 225 isotope conjugate is being developed (Bidkar et al, Clin Cancer Res. 2023).

Perspective
Androgen suppression by various means has been the mainstay of prostate cancer treatment since 1911. Even then the downside of ADT was recognized i.e., the induction of resistance to treatment through alterations of the androgen receptor.

More recently, therapy-induced NEPC has been added to the list of adverse developments. Until an effective strategy is developed to avoid the induction of t-NRPC, the only practical ways of addressing this induction are delaying the onset of ADT until a worrisome rise in the PSA doubling time is evidenced, limiting adjuvant ADT when the gain is minimal compared to no ADT (as can be assessed by using Decipher), and employing metastases directed therapy in oligometastatic relapse without accompanying ADT.

BOTTOM LINE
Successful management of treatment-induced neuroendocrine prostate cancer is limited by difficulty in diagnosis and a lack of effective therapy. Intense research is underway to address this important deficiency.

Identification of Localized Disease

by Peter F. Orio III, DO, MS | Jul 2023

Peter F. Orio III, DO, MS, discusses the process of identifying localized prostate cancer. Dr. Orio emphasizes that prostate cancer is a spectrum of disease, rather than a binary, as prostate cancer is not necessarily confined to the prostate organ alone, and that the ultimate goal of treatment is reduction of harm to the patient’s future self.

Dr. Orio reviews the current screening, imaging, and testing steps to identifying localized prostate cancer, including the best candidates for screening. He notes that mandatory DREs discourages patients from coming in to the urologist, and suggests that screening should eliminate them.

Dr. Orio offers the more sensitive and less invasive PSA tests in combination with MRIs as an alternative first step in screening. He concludes by offering PSA – MRI – Fusion Biopsy – Germline Testing – FHX – FNX Imaging as the new path for screening and identifying localized prostate cancer.

Multidisciplinary Approach to the Management of Advanced Prostate Cancer

by Daniel P. Petrylak, MD | Jul 2023

Daniel P. Petrylak, MD, discusses the benefits of a multidisciplinary approach for prostate cancer survival rates and increased clinical efficiency. He emphasizes the need for a prostate cancer management approach involving urologists, medical oncologists, radiation oncologists, and primary care physicians, with references to nutritionists, mental health professionals, and pain management experts.

Dr. Petrylak highlights existing SEER data results, indicating that men with locally advanced and high-risk prostate cancer experience better outcomes when treated with a multidisciplinary approach. He also reviews the University of Colorado’s data on multidisciplinary teams, noting an increased survival rate at each stage of prostate cancer when compared with regional and state data.

Dr. Petrylak then analyzes the benefits of a multidisciplinary approach for other disease states, including optimized patient outcomes, increased access to specialty therapies, more efficient clinician and patient scheduling, better care coordination, and improved communication. Dr. Petrylak concludes by offering considerations pertaining to healthcare challenges, and advocating for a multidisciplinary approach.

Implementation of Markers in Clinical Practice

by David S. Morris, MD, FACS | Jun 2023

David S. Morris, MD, FACS, discusses implementation of various markers in screening, diagnosing, and treating prostate cancer in community practice. He discusses the G-Minor (Genomics in Michigan ImpactiNg Observation or Radiation) trial and a retrospective analysis of the STAMPEDE (Systemic Therapy in Advancing or Metastatic Prostate Cancer: Evaluation of Drug Efficacy) trial, wherein certain markers were able to predict both metastasis-free survival and overall survival.

Radioligand Therapy in Prostate Cancer

by Geoffrey B. Johnson, MD, PhD | Jun 2023

Geoffrey B. Johnson, MD, PhD, Chair of the Division of Nuclear Medicine at the Mayo Clinic in Rochester, MN, discusses radioligand therapy in prostate cancer. Dr. Johnson briefly reviews the specific activity of this therapy, with a focus on Lutetium-177-PSMA-617.
Dr. Johnson highlights the benefits and tolerable side-effects of Lutetium-177-PSMA-617, and mentions the therapy is approved for patients with metastatic castrate-resistant prostate cancer who have been previously treated with androgen receptor pathway inhibition and taxane-based therapy.

The presentation further explores the process of patient selection for PSMA imaging, with the requirement of at least one lesion that shows higher PSMA expression than the liver. Dr. Johnson showcases post-therapy imaging examples, and discusses the potential of advanced scanning techniques, such as CZT-based scanners, which offer higher sensitivity and faster scans for accurate tracking of therapy response.

Dr. Johnson emphasizes the promising future of radionuclide therapy. He mentions the potential combinations of PSMA therapy with hormonal therapy, chemotherapy, immunotherapy, and external radiation. Additionally, he mentions ongoing trials exploring the use of alpha and beta emitters and the incorporation of different targets.

PSA Screening in 2023

by Gerald L. Andriole, Jr., MD | Jun 2023

Gerald L. Andriole, Jr., reviews evidence supporting a more comprehensive family history and biomarkers in screening and treating prostate cancer. Andriole underscores the power of a well-taken family history. He suggests doctors counsel patients on their hereditary risk of prostate cancer, emphasizing the importance of one diagnosed high risk family member, to reduce the rate of mortality.

Describing the Germline Mutations in Metastatic PCa, Andriole recommends all patients with prostate cancer who have certain characteristics be encouraged to speak to their physicians about whether they may need genetic testing for an inherited mutation. When looking in detail at polygenic risk scores (GRS,) knowledge of high GRS decreased mortality rate.

Andriole highlights the Prompt Test, the direct to consumer, poly-genomic test in the US. In comparison, the UK Biobank data compares prevalence and hazard ratio to show the frequency is higher, some predict cancer aggressiveness. He expects to hear a lot about the prompt test in future.

Dr. Andriole recommends identifying patients with clinically significant PCa earlier through a lower PSA cutpoint. He suggests using image guided Micro US or MRI, or a transperineal biopsy to show potentially indicative biomarkers.

Results From TRITON3

by Alan H. Bryce, MD | Jun 2023

Alan H. Bryce, MD, presents results from the TRITON3 study comparing the efficacy of a PARP inhibitor (rucaparib) against docetaxel in mCRPC treatment. Dr. Bryce reviews the study design, emphasizing the options presented to the study participants in both treatment arms. The study yielded evidence that rucaparib might be superior to docetaxel-containing treatments.

Review of the New Standard in Treatment and Global Issues: Androgen Deprivation Treatment (ADT), Chemotherapy, Androgen Receptors Inhibitors, and Androgen Synthesis Inhibitors

by Marc B. Garnick, MD | May 2023

Marc B. Garnick, MD, Gorman Brothers Professor of Medicine at Harvard Medical School and the Beth Israel Deaconess Medical Center, reviews current literature on the treatment of prostate cancer. Dr. Garnick focuses specifically on Androgen Deprivation Therapy (ADT,) Chemotherapy, Androgen Receptor Inhibitors, and Androgen Synthesis Inhibitors.

In this presentation, Dr. Garnick explores the current landscape of Advanced Prostate Cancer Treatments, the use of triplet therapies in combating metastatic Castration-Sensitive Prostate Cancer (mCSPC), and the possibility of avoiding ADT by combining advanced imaging techniques with Metastases-Directed Therapy (MDT).

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