Expert Perspectives on Controversies in Castration-Sensitive Prostate Cancer Management: Narrative Review and Report of the First US Prostate Cancer Conference Part 1.

Purpose: Castration-sensitive prostate cancer (CSPC) is a complex and heterogeneous condition encompassing a range of clinical presentations. As new approaches have expanded management options, clinicians are left with myriad questions and controversies regarding the optimal individualized management of CSPC. Materials and Methods: The US Prostate Cancer Conference (USPCC) multidisciplinary panel was assembled to address the challenges of prostate cancer management. The first annual USPCC meeting included experts in urology, medical oncology, radiation oncology, and nuclear medicine. USPCC co-chairs and session moderators identified key areas of controversy and uncertainty in prostate cancer management and organized the sessions with multidisciplinary presentations and discussion. Throughout the meeting, experts responded to questions prepared by chairs and moderators to identify areas of agreement and controversy. Results: The USPCC panel discussion and question responses for CSPC-related topics are presented. Key advances in CSPC management endorsed by USPCC experts included the development and clinical utilization of gene expression classifiers and artificial intelligence (AI) models for risk stratification and treatment selection in specific patient populations, the use of advanced imaging modalities in patients with clinically localized unfavorable intermediate or high-risk disease and those with biochemical recurrence, recommendations of doublet or triplet therapy for metastatic CSPC (mCSPC), and consideration of prostate and/or metastasis-directed radiation therapy in select patients with mCSPC. Conclusions: CSPC is a diverse disease with many therapeutic options and the potential for adverse outcomes associated with either undertreatment or overtreatment. Future studies are needed to validate and clinically integrate novel technologies, including genomics, AI, and advanced imaging, to optimize outcomes among patients with CSPC.

Expert Perspectives on Controversies in Metastatic Castration-Resistant Prostate Cancer Management: Narrative Review and Report of the First US Prostate Cancer Conference Part 2.

Background: Management strategies for metastatic castration-resistant prostate cancer (mCRPC) have rapidly shifted in recent years. As novel imaging and therapeutic approaches have made their way to the clinic, providers are encountering increasingly challenging clinical scenarios, with limited guidance from the current literature. Materials and Methods: The US Prostate Cancer Conference (USPCC) is a multidisciplinary meeting of prostate cancer experts intended to address the many challenges of prostate cancer management. At the first annual USPCC meeting, areas of controversy and consensus were identified during a 2-day meeting that included expert presentations, full-panel discussions, and postdiscussion responses to questions developed by the USPCC cochairs and session moderators. Results: This narrative review covers the USPCC expert discussion and perspectives relevant to mCRPC, including neuroendocrine/aggressive-variant prostate cancer (NEPC/AVPC). Areas of broad agreement identified among USPCC experts include the benefits of poly (ADP-ribose) polymerase (PARP) inhibitors for patients with BRCA1/2 mutations, the use of radioligand therapy in patients with prostate-specific membrane antigen (PSMA)-positive mCRPC, and the need for clinical trials that address real-world clinical questions, including the performance of novel therapies when compared with modern standard-of-care treatment. Ongoing areas of controversy and uncertainty included the appropriateness of PARP inhibitors in patients with non-BRCA1/2 mutations, the optimal definition of PSMA positivity, and systemic therapies for patients with NEPC/AVPC after progression on platinum-based therapies. Conclusions: The first annual USPCC meeting identified several areas of controversy in the management of mCRPC, highlighting the urgent need for clinical trials designed to facilitate treatment selection and sequencing in this heterogeneous disease state.

Adolescent Young Adult Acute Lymphoblastic Leukemia Survivors Develop Innovative Solutions for Unmet Needs.

Adolescent young adult (AYA) cancer survivors continue to have substantive unmet needs. Literature and insights from a task force of survivors, caregivers, and survivor advocates convened by Servier Pharmaceuticals indicate desires for peer created and provided support. This secondary data analysis of information from the task force identified unmet needs in five domains and solutions explored for four prioritized needs. Ultimately, four actionable solution concepts were selected by the task force for further development. Through their work, many key insights about including survivors in creating solutions and the many approaches for best serving AYAs with cancer were revealed.

Assessment of high-grade prostate cancer risk using prostate cancer biomarkers.

INTRODUCTION: To identify patients at risk of high-grade prostate cancer using prostate cancer biomarkers. MATERIALS AND METHODS: A total of 601 men were screened for prostate cancer in 2012, 2015, and 2016 using prostate cancer biomarkers: prostate health index (phi), 4KScore, and SelectMDx. The first two are blood tests that incorporate several PSA isoforms; SelectMDx measures mRNA levels of homeobox C6 and distal-less homeobox 1 in post-digital rectal examination urine samples. The performance of each biomarker was evaluated using cut off values based on published literature. Gleason Grade Group (GG) ≥ 2 is considered as high-grade prostate cancer. RESULTS: For patients with PSA < 1.5 ng/mL, none were at risk for GG ≥ 2 cancer based on SelectMDx > 0%, whereas 17.1% were at intermediate to high risk of finding GG ≥ 2 cancer with 4KScore ≥ 7.5%, and 3.5% were at risk of finding any prostate cancer with phi ≥ 36 at biopsy. For cut offs revised for finding men at high risk for GG ≥ 2 cancer at biopsy, only one patient with PSA < 1.5 ng/mL would be at risk with 4KScore ≥ 20% and none with phi ≥ 52.7. For patients with PSA 1.5 to 3.99 ng/mL, 2%, 8%, and 1% were at high risk for finding GG ≥ 2 cancer at biopsy based on phi, 4KScore, and SelectMDx, respectively. CONCLUSIONS: Men with PSA < 1.5 ng/mL are at very low risk of finding high-grade prostate cancer at biopsy. However, some men with PSA between 1.5 to 3.99 ng/mL may be at intermediate to high risk for high-grade prostate cancer. Thus, primary care physicians could run biomarkers test and refer those with positive biomarker results to a specialist for further evaluation.

The effect of digital rectal exam on the 4Kscore for aggressive prostate cancer.

BACKGROUND: The 4Kscore is a new commercially available blood-based diagnostic test which predicts risk for aggressive, clinically significant prostate cancer on prostate biopsy. The 4Kscore is currently restricted to patients who have not had a digital rectal exam (DRE) in the previous 96 h, owing to prior mixed data suggesting that prostate specific antigen (PSA) isoforms may increase by a statistically significant-if not necessarily clinically significant-amount shortly after DRE. Our primary objective was to determine if 4Kscore test results are affected by a preceding DRE. METHODS: Participants at a Prostate Cancer Awareness Week screening event sponsored by the Prostate Conditions Education Council filled out clinical history questionnaires and had blood samples for 4Kscore testing drawn prior to DRE, then 15-45 min following DRE. Patients with prior cancer diagnosis, 5-alpha reductase inhibitor medication use, or lower urinary tract procedures in the prior 6 months were excluded, resulting in a population of 162 participants for analysis. Values were then compared to determine if there was a significant difference in 4Kscore following DRE. RESULTS: A statistically significant increase was seen in levels of 3 kallikreins measured (total PSA, free PSA, and intact PSA; median <0.03 ng/mL for all). This resulted in a small but statistically significant decrease in post-DRE 4Kscore (median absolute score decrease 0.43%). Using a 4Kscore cutoff of 7.5% resulted in reclassification of 10 patients (6.2%), nine of whom were "downgraded" from above the cutoff to below. CONCLUSIONS: If the blood draw for the 4 K score is performed after a screening DRE, there is a statistically significant difference in the 4 K score results, but in the vast majority of cases it would not affect clinical decision making.

Role of Genetic Testing for Inherited Prostate Cancer Risk: Philadelphia Prostate Cancer Consensus Conference 2017.

Purpose Guidelines are limited for genetic testing for prostate cancer (PCA). The goal of this conference was to develop an expert consensus-driven working framework for comprehensive genetic evaluation of inherited PCA in the multigene testing era addressing genetic counseling, testing, and genetically informed management. Methods An expert consensus conference was convened including key stakeholders to address genetic counseling and testing, PCA screening, and management informed by evidence review. Results Consensus was strong that patients should engage in shared decision making for genetic testing. There was strong consensus to test HOXB13 for suspected hereditary PCA, BRCA1/2 for suspected hereditary breast and ovarian cancer, and DNA mismatch repair genes for suspected Lynch syndrome. There was strong consensus to factor BRCA2 mutations into PCA screening discussions. BRCA2 achieved moderate consensus for factoring into early-stage management discussion, with stronger consensus in high-risk/advanced and metastatic setting. Agreement was moderate to test all men with metastatic castration-resistant PCA, regardless of family history, with stronger agreement to test BRCA1/2 and moderate agreement to test ATM to inform prognosis and targeted therapy. Conclusion To our knowledge, this is the first comprehensive, multidisciplinary consensus statement to address a genetic evaluation framework for inherited PCA in the multigene testing era. Future research should focus on developing a working definition of familial PCA for clinical genetic testing, expanding understanding of genetic contribution to aggressive PCA, exploring clinical use of genetic testing for PCA management, genetic testing of African American males, and addressing the value framework of genetic evaluation and testing men at risk for PCA-a clinically heterogeneous disease.

Genomic testing in oncology to improve clinical outcomes while optimizing utilization: the evolution of diagnostic testing.

Cancer care is costly, particularly when chemotherapy and its supportive costs are considered. Yet, chemotherapy is not the right course for every patient. Patients with cancer need appropriate treatment that will give them the best possible outcome. Personalized medicine has become an important area of oncology. In addition to genetic testing, genomic testing has become a useful tool in diagnostics. For genomic assays to be viable, they must have clinical validity, analytic validity, and clinical utility. Stakeholders are willing to provide coverage for such testing through medical policy when there is strong evidence the tests are effective. Genomic testing can be used in decision making to rule out chemotherapy or other treatment options that would not be effective for the care of an individual patient. The use of genomic testing to help eliminate ineffective or possible harmful treatment options and determine appropriate care will benefit the patient while reducing healthcare utiliztion and costs.

Effects of Testosterone Level on Lower Urinary Tract Symptoms.

Lower urinary tract symptoms (LUTS) are common in older men and are frequently associated with benign prostatic hyperplasia (BPH). The relationship between BPH and endogenous total testosterone (TT) levels has been widely studied. The aim of this post hoc analysis was to determine the association between LUTS and endogenous TT levels in a subset of men participating in the 2013 Prostate Cancer Awareness Week, a U.S. community-based prostate cancer screening program. Men completed the International Prostate Symptom Score (I-PSS) questionnaire, prostate size was estimated by a digital rectal examination, and serum TT and prostate-specific antigen levels were measured. Mean TT levels (ng/dl) did not significantly correlate with prostate size category (r = +.03, p = .69): normal, 419.2 (n = 106); enlarged, 394.7 (n = 71); abnormal, 416.4 (n = 7); and abnormal/suspicious, 515.2 (n = 19). Mean TT levels (ng/dl) did not significantly correlate with I-PSS category (r = -.06, p = .40): none, 468.5 (n = 15); mild, 414.0 (n = 138); moderate, 397.4 (n = 66); and severe, 437.9 (n = 7). Mean TT levels (ng/dl) did not significantly correlate with I-PSS quality of life rating (r = -.13, p = .055): delighted, 474.5 (n = 43); pleased, 424.6 (n = 65); mostly satisfied, 361.2 (n = 63); mixed, 448.2 (n = 29); mostly dissatisfied, 337.2 (n = 17); and unhappy, 435.8 (n = 6). Adjustment for prostate size or prostate-specific antigen levels yielded similar findings. In conclusion, endogenous TT levels did not correlate with LUTS or prostate size, and these findings support the saturation theory in which TT is not able to induce further androgen-stimulated prostate tissue growth due to receptor saturation. Any worsening of LUTS following testosterone replacement therapy in hypogonadal men may be related to stimulation of prostatic cells previously deprived of testosterone.

Measurement of testosterone: how important is a morning blood draw?

OBJECTIVE: Since testosterone levels exhibit a circadian variation with peak levels in the morning, evidence-based guidelines recommend measuring morning total testosterone (TT) levels as the initial diagnostic test for androgen deficiency. However, it has been suggested that morning blood draw may not be necessary in older men due to a blunted circadian rhythm. We sought to determine whether it is possible to expand the morning sampling window for measurement of TT. RESEARCH DESIGN AND METHODS: TT levels were measured in a subset of men (mean age of 61 years) participating in the 2013 Prostate Cancer Awareness Week. RESULTS: TT levels measured in blood drawn from 8 to 11 AM (n = 229) differed significantly from those drawn outside this window (n = 442) (411.7 vs 368.3 ng/dl; p = 0.0003). Differences in TT levels were evident across five blood draw time windows (p = < 0.0001) and persisted after adjustment for age and BMI. TT levels in blood drawn from 2 to 5 PM (344.3 ng/dl) and 5 to 8 PM (334.4 ng/dl) differed significantly from that drawn from 8 to 11 AM (p < 0.05), while TT levels from 11 AM to 2 PM (396.5 ng/dl) and 8 PM to 8 AM (373.4 ng/dl) did not (p = 0.90 and 0.73, respectively). CONCLUSION: Based on these findings, it may be possible to expand the blood draw time window for measurement of serum TT. This community-based study was not prospectively design to determine the most appropriate blood draw window for TT measurement. Only a single TT measurement was made without consideration for day-to-day variability, and TT levels were not measured in the same men at different blood draw times.