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Multiparametric MRI (mpMRI) is validated for the diagnosis of clinically significant prostate cancer (csPCa). 68Ga-PSMA-11 PET/CT (68Ga-PSMA PET/CT) combined with mpMRI has improved negative predictive value over mpMRI alone for csPCa. The aim of this post hoc analysis of the PRIMARY study was to evaluate the clinical significance of patterns of intraprostatic PSMA activity, proposing a 5-point PRIMARY score to optimize the accuracy of 68Ga-PSMA PET/CT for csPCa in a low-prevalence population. Methods: The PRIMARY trial was a prospective multicenter phase II imaging trial that enrolled men with suspected PCa, no prior biopsy, and a recent mpMRI examination (6 mo) and for whom prostate biopsy was planned. In total, 291 men underwent mpMRI, 68Ga-PSMA PET/CT, and systematic biopsy with or without targeted biopsy. The mpMRI was read separately using the Prostate Imaging Reporting and Data System (PI-RADS) (version 2). 68Ga-PSMA PET/CT (pelvis only) was acquired a minimum of 60 min after injection. 68Ga-PSMA PET/CT was centrally read for pattern (diffuse transition zone [TZ], symmetric central zone [CZ], focal TZ, or focal peripheral zone [PZ]) and intensity (SUVmax). In this post hoc analysis, a 5-level PRIMARY score was assigned on the basis of analysis of the central read: no pattern (score of 1), diffuse TZ or CZ (not focal) (score of 2), focal TZ (score of 3), focal PZ (score of 4), or an SUVmax of at least 12 (score of 5). Two further readers independently assigned a PRIMARY score to 118 scans to determine interrater agreement. Associations between PRIMARY score and csPCa (International Society of Urological Pathology grade group ≥ 2) were evaluated. Results: Of the 291 men enrolled, 162 (56%) had csPCa. A PRIMARY score of 1 was present in 16% (47); a score of 2, in 19% (55); a score of 3, in 10% (29); a score of 4 in 40% (117); and a score of 5, in 15% (43). The proportion of patients with csPCa and a PRIMARY score of 1, 2, 3, 4, and 5 was 8.5% (4/47), 27% (15/55), 38% (11/29), 76% (89/117), and 100% (43/43), respectively. Sensitivity, specificity, positive predictive value, and negative predictive value for a PRIMARY score of 1 or 2 (low-risk patterns) versus a PRIMARY score of 3-5 (high-risk patterns) were 88%, 64%, 76%, and 81%, respectively, compared with 83%, 53%, 69%, and 72%, respectively, for a PI-RADS score of 2 versus 3-5 on mpMRI. The Cohen κ for a PRIMARY score of 1 of 2 versus a PRIMARY score of 3-5 was 0.76 (95% CI, 0.64-0.88) for reader 1 and 0.64 (95% CI, 0.49-0.78) for reader 2. Conclusion: A PRIMARY score incorporating intraprostatic pattern and intensity on 68Ga-PSMA PET/CT shows potential, with high diagnostic accuracy for csPCa. Further validation is warranted before implementation.

BackgroundInnovations in treatments, imaging, and molecular characterisation in advanced prostate cancer have improved outcomes, but there are still many aspects of management that lack high-level evidence to inform clinical practice. The Advanced Prostate Cancer Consensus Conference (APCCC) 2019 addressed some of these topics to supplement guidelines that are based on level 1 evidence.ObjectiveTo present the results from the APCCC 2019.Design, setting, and participantsSimilar to prior conferences, experts identified 10 important areas of controversy regarding the management of advanced prostate cancer: locally advanced disease, biochemical recurrence after local therapy, treating the primary tumour in the metastatic setting, metastatic hormone-sensitive/naïve prostate cancer, nonmetastatic castration-resistant prostate cancer, metastatic castration-resistant prostate cancer, bone health and bone metastases, molecular characterisation of tissue and blood, inter- and intrapatient heterogeneity, and adverse effects of hormonal therapy and their management. A panel of 72 international prostate cancer experts developed the programme and the consensus questions.Outcome measurements and statistical analysisThe panel voted publicly but anonymously on 123 predefined questions, which were developed by both voting and nonvoting panel members prior to the conference following a modified Delphi process.Results and limitationsPanellists voted based on their opinions rather than a standard literature review or formal meta-analysis. The answer options for the consensus questions had varying degrees of support by the panel, as reflected in this article and the detailed voting results reported in the Supplementary material.ConclusionsThese voting results from a panel of prostate cancer experts can help clinicians and patients navigate controversial areas of advanced prostate management for which high-level evidence is sparse. However, diagnostic and treatment decisions should always be individualised based on patient-specific factors, such as disease extent and location, prior lines of therapy, comorbidities, and treatment preferences, together with current and emerging clinical evidence and logistic and economic constraints. Clinical trial enrolment for men with advanced prostate cancer should be strongly encouraged. Importantly, APCCC 2019 once again identified important questions that merit assessment in specifically designed trials.Patient summaryThe Advanced Prostate Cancer Consensus Conference provides a forum to discuss and debate current diagnostic and treatment options for patients with advanced prostate cancer. The conference, which has been held three times since 2015, aims to share the knowledge of world experts in prostate cancer management with health care providers worldwide. At the end of the conference, an expert panel discusses and votes on predefined consensus questions that target the most clinically relevant areas of advanced prostate cancer treatment. The results of the voting provide a practical guide to help clinicians discuss therapeutic options with patients as part of shared and multidisciplinary decision making.

The Asian Prostate Cancer (A-CaP) study is an Asia-wide initiative that was launched in December 2015 in Tokyo, Japan, with the objective of surveying information about patients who have received a histopathological diagnosis of prostate cancer (PCa) and are undergoing treatment and clarifying distribution of staging, the actual status of treatment choices, and treatment outcomes. The study aims to clarify the clinical situation for PCa in Asia and use the outcomes for the purposes of international comparison. Following the first meeting in Tokyo in December 2015, the second A-CaP meeting was held in Seoul, Korea, in September 2016. This, the third A-CaP meeting, was held on October 14, 2017, in Chiang Mai, Thailand, with the participation of members and collaborators from 12 countries and regions. In the meeting, participating countries and regions presented the current status of data collection, and the A-CaP office presented a preliminary analysis of the registered cases received from each country and region. Participants discussed ongoing challenges relating to data input and collection, institutional, and legislative issues that may present barriers to data sharing, and the outlook for further patient registrations through to the end of the registration period in December 2018. In addition to A-CaP-specific discussions, a series of special lectures were also delivered on the situation for health insurance in the United States, the correlation between insurance coverage and PCa outcomes, and the outlook for robotic surgery in the Asia-Pacific region. Members also confirmed the principles of authorship in collaborative studies, with a view to publishing original articles based on A-CaP data in the future.

Germline mutations in the BRCA2 tumour suppressor are associated with both an increased lifetime risk of developing prostate cancer (PCa) and increased risk of aggressive disease. To understand this aggression, here we profile the genomes and methylomes of localized PCa from 14 carriers of deleterious germline BRCA2 mutations (BRCA2-mutant PCa). We show that BRCA2-mutant PCa harbour increased genomic instability and a mutational profile that more closely resembles metastastic than localized disease. BRCA2-mutant PCa shows genomic and epigenomic dysregulation of the MED12L/MED12 axis, which is frequently dysregulated in metastatic castration-resistant prostate cancer (mCRPC). This dysregulation is enriched in BRCA2-mutant PCa harbouring intraductal carcinoma (IDC). Microdissection and sequencing of IDC and juxtaposed adjacent non-IDC invasive carcinoma in 10 patients demonstrates a common ancestor to both histopathologies. Overall we show that localized castration-sensitive BRCA2-mutant tumours are uniquely aggressive, due to de novo aberration in genes usually associated with metastatic disease, justifying aggressive initial treatment.

The Asian Prostate Cancer (A-CaP) Study is an Asia-wide initiative that has been developed over the course of 2 years. The A-CaP Study is scheduled to begin in 2016, when each participating country or region will begin registration of newly diagnosed prostate cancer patients and conduct prognosis investigations. From the data gathered, common research themes will be identified, such as comparisons among Asian countries of background factors in newly diagnosed prostate cancer patients. This is the first Asia-wide study of prostate cancer and has developed from single country research efforts in this field, including in Japan and Korea. The inaugural Board Meeting of A-CaP was held on December 11, 2015 at the Research Center for Advanced Science and Technology, The University of Tokyo, attended by representatives of all participating countries and regions, who signed a memorandum of understanding concerning registration for A-CaP. Following the Board Meeting an A-CaP Launch Symposium was held. The symposium was attended by representatives of countries and regions participating in A-CaP, who gave presentations. Presentations and a keynote address were also delivered by representatives of the University of California San Francisco, USA, and the Peter MacCallum Cancer Centre, Australia, who provided insight and experience on similar databases compiled in their respective countries.

Aim Methods Results Conclusion The aim of the third Asia‐Pacific Advanced Prostate Cancer Consensus Conference (APAC APCCC 2023) was to discuss the application in the Asia‐Pacific (APAC) region of consensus statements from the 4th Advanced Prostate Cancer Consensus Conference (APCCC 2022).The one‐day meeting in July 2023 brought together 27 experts from 14 APAC countries. The meeting covered five topics: (1) Intermediate‐ and high‐risk and locally advanced prostate cancer; (2) Management of newly diagnosed metastatic hormone‐sensitive prostate cancer; (3) Management of non‐metastatic castration‐resistant prostate cancer; (4) Homologous recombination repair mutation testing; (5) Management of metastatic castration‐resistant prostate cancer. Pre‐ and post‐symposium polling gathered APAC‐specific responses to APCCC consensus questions and insights on current practices and challenges in the APAC region.APAC APCCC highlights APAC‐specific considerations in an evolving landscape of diagnostic technologies and treatment innovations for advanced prostate cancer. While new technologies are available in the region, cost and reimbursement continue to influence practice significantly. Individual patient considerations, including the impact of chemophobia on Asian patients, also influence decision‐making.The use of next‐generation imaging, genetic testing, and new treatment combinations is increasing the complexity and duration of prostate cancer management. Familiarity with new diagnostic and treatment options is growing in the APAC region. Insights highlight the continued importance of a multidisciplinary approach that includes nuclear medicine, genetic counseling, and quality‐of‐life expertise. The APAC APCCC meeting provides an important opportunity to share practice and identify APAC‐specific issues and considerations in areas of low evidence where clinical experience is growing. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to quantify the out-of-pocket (OOP) costs and perceived financial burden among Australian men with localised prostate cancer in the first 6 months after diagnosis, by primary management option. Methods: This cost-analysis quantified OOP costs using administrative claims data and self-reported survey data. Financial burden was assessed using the COmprehensive Score for financial Toxicity–Functional Assessment of Chronic Illness Therapy (COST-FACIT) tool. Participants were recruited into a randomised control trial from public or private treatment centres in Victoria and Queensland. Generalised linear models were used to predict OOP costs and COST-FACIT scores. Results: Median total OOP costs within 6 months of diagnosis for 256 Australian patients with localised prostate cancer was A$1172 (A$343–2548). Up to 50% of the sample reported A$0 costs for most medical services. Compared with those managed with active surveillance, men having active treatment had 6.4 (95% CI: 3.2–12.7) times greater total OOP costs. Management option, higher Gleason score at diagnosis and having multiple comorbidities were significant predictors of higher OOP costs. Overall high scores on the COST-FACIT indicated low levels of financial burden for the entire sample. Conclusion: Largely attributable to being managed with active surveillance, Australian men diagnosed with localised prostate cancer reported relatively low OOP costs and financial burden in the first 6 months post-diagnosis. Together with clinical outcomes, clinicians can use this up to date evidence on costs and perceived financial burdens to assist localised prostate cancer patients and their families make informed decisions about their preferred management option. What is known about the topic? International evidence suggests that men with low-risk prostate cancer managed with active surveillance initially incur lower out-of-pocket costs than those managed with active treatment. What does this paper add? Australian men with low-risk prostate cancer report low out-of-pocket costs and financial burden in the first 6 months post-diagnosis. Compared with those managed with active surveillance, men having active treatment had 6–7 times greater out-of-pocket expenses. What are the implications for practitioners? Being managed by active surveillance as the primary management option for low-risk prostate cancer reduces the financial burdens associated with a cancer diagnosis. [ABSTRACT FROM AUTHOR]

ContextDisease-specific registries that enroll a considerable number of patients play a major role in prostate cancer (PCa) research.ObjectiveTo evaluate available registries, describe their strengths and limitations, and discuss the potential future role of PCa registries in outcomes research.Evidence acquisitionWe performed a literature review of the Medline, Embase, and Web of Science databases. The search strategy included the terms prostate cancer, outcomes, statistical approaches, population-based cohorts, registries of outcomes, and epidemiological studies, alone or in combination. We limited our search to studies published between January 2005 and January 2015.Evidence synthesisSeveral population-based and prospective disease-specific registries are currently available for prostate cancer. Studies performed using these data sources provide important information on incidence and mortality, disease characteristics at presentation, risk factors, trends in utilization of health care services, disparities in access to treatment, quality of care, long-term oncologic and health-related quality of life outcomes, and costs associated with management of the disease. Although data from these registries have some limitations, statistical methods are available that can address certain biases and increase the internal and external validity of such analyses. In the future, improvements in data quality, collection of tissue samples, and the availability of data feedback to health care providers will increase the relevance of studies built on population-based and disease-specific registries.ConclusionsThe strengths and limitations of PCa registries should be carefully considered when planning studies using these databases. Although randomized controlled trials still provide the highest level of evidence, large registries play an important and growing role in advancing PCa research and care.Patient summarySeveral population-based and prospective disease-specific registries for prostate cancer are currently available. Analyses of data from these registries yield information that is clinically relevant for the management of patients with prostate cancer.

Various conflicting guidelines and recommendations about prostate cancer screening and early detection have left both clinicians and their patients quite confused. At the Prostate Cancer World Congress held in Melbourne in August 2013, a multidisciplinary group of the world's leading experts in this area gathered together and generated this set of consensus statements to bring some clarity to this confusion. The five consensus statements provide clear guidance for clinicians counselling their patients about the early detection of prostate cancer.

Active surveillance remains a treatment option for low- to intermediate-risk prostate cancer (PCa) patients. Prostate-specific membrane antigen positron emission tomography and computed tomography (PSMA PET/CT) has emerged as a useful modality to assess intraprostatic lesions. This systematic review aims to evaluate PSMA PET/CT in localized low- to intermediate-risk PCa to determine its role in active surveillance. Following PRISMA guidelines, a search was performed on Medline, Embase, and Scopus. Only studies evaluating PSMA PET/CT in localized low- to intermediate-risk PCa were included. Studies were excluded if patients received previous treatment, or if they included high-risk PCa. The search yielded 335 articles, of which only four publications were suitable for inclusion. One prospective study demonstrated that PSMA PET/CT-targeted biopsy has superior diagnostic accuracy when compared to mpMRI. One prospective and one retrospective study demonstrated MRI occult lesions in 12.3–29% of patients, of which up to 10% may harbor underlying unfavorable pathology. The last retrospective study demonstrated the ability of PSMA PET/CT to predict the volume of Gleason pattern 4 disease. Early evidence demonstrated the utility of PSMA PET/CT as a tool in making AS safer by detecting MRI occult lesions and patients at risk of upgrading of disease. [ABSTRACT FROM AUTHOR]

New and very expensive forms of radiotherapy, such as intensity-modulated radiation therapy and proton therapy, have taken over the localized prostate cancer market. But is there enough evidence to justify their increased utilization and if so, how can we possibly afford them?

Objective: To assess changes in diagnosis prostate cancer (PCa) grade, biopsy and treatment approach over a decade (2011–2020) at a population level within a clinical quality cancer registry. Patients and Methods: Patients diagnosed by prostate biopsy between 2011 and 2020 were retrieved from the Victorian Prostate Cancer Outcomes Registry, a prospective, state‐wide clinical quality registry in Australia. Distributions of each grade group (GG) proportion over time were modelled with restricted cubic splines, separately by biopsy technique, age group and subsequent treatment method. Results: From 2011 to 2020, 24 308 men were diagnosed with PCa in the registry. The proportion of GG 1 disease declined from 36–23%, with commensurate rises in GG 2 (31–36%), GG 3 (14–17%) and GG 5 (9.3–14%) disease. This pattern was similar for men diagnosed by transrectal ultrasonography or transperineal biopsy. Patients aged <55 years had the largest absolute reduction in GG 1 PCa, from 56–35%, compared to patients aged 55–64 (41–31%), 65–74 (31–21%), and ≥75 years (12–10%). The proportion of prostatectomies performed for patients with GG 1 disease fell from 28% to 7.1% and, for primary radiation therapy, the proportion fell from 22% to 3.5%. Conclusion: From 2011 to 2020, there has been a substantial decrease in the proportion of GG 1 PCa diagnosed, particularly in younger men. The percentage of interventional management performed in GG 1 disease has fallen to very low levels. These results reflect the implementation of major changes to diagnostic and treatment guidelines and inform the future allocation of treatment methods. [ABSTRACT FROM AUTHOR]

Reported here is a case of rapidly progressive metastatic castration-resistant prostate cancer treated with [177Lu]Lu-PSMA-617 in the setting of severe renal impairment and impending ureteric obstruction. PSMA is expressed on renal tubular cells, raising the possibility of radiation-induced nephrotoxicity, and this level of renal impairment would typically exclude the patient from [177Lu]Lu-PSMA-617 therapy. Multidisciplinary input, individualized dosimetry, and patient-specific dose reduction were used to ensure the cumulative dose to the kidneys remained within acceptable limits. He was initially planned for treatment with six cycles of [177Lu]Lu-PSMA-617. However, he had an excellent response to therapy following four cycles of treatment and the last two cycles were omitted. He has been followed for 1-year posttherapy without evidence of disease recurrence. No acute or chronic nephrotoxicity was observed. This case report highlights the utility of [177Lu]Lu-PSMA-617 therapy in severe renal impairment and provides evidence of relative safety in patients who would otherwise not be considered candidates for therapy. Plain language summary: This report presents a case of a man with aggressive metastatic prostate cancer who received [177Lu]Lu-PSMA-617 therapy, despite having severely reduced kidney function and worsening ureter obstruction. This treatment could have potential side effects on kidney function, but the medical team used a personalized approach to reduce patient risk. The man was initially planned to have six cycles of therapy, but his excellent response to treatment after four cycles meant the last two cycles were not given. The man has been followed for 1 year after treatment and has not experienced any worsening kidney function. This case shows the safe and effective use of [177Lu]Lu-PSMA-617 therapy in a patient with severely reduced kidney function who would not normally qualify for this treatment. [ABSTRACT FROM AUTHOR]

Objectives: To identify whether synchronous reading of multiparametric magnetic resonance imaging (mpMRI) and 68Ga‐PSMA‐11 positron emission tomography (PET)/computed tomography (prostate‐specific membrane antigen [PSMA‐PET]) images can improve diagnostic performance and certainty compared with mpMRI/PSMA‐PET reported independently and synthesized, while also assessing concordance between imaging modalities and agreement with histopathology. Methods: This was a retrospective analysis of 100 patients randomly selected from the PRIMARY trial, a prospective Phase II multicentre imaging trial. Three dual‐trained radiologist/nuclear medicine physicians re‐reported the mpMRI and PSMA‐PET both independently and synchronously for the same patients in random order, blinded to previous results. Diagnostic performance was assessed for mpMRI/PSMA‐PET images read synchronously or independently and then synthesized. Agreement between imaging results and histopathology was examined. 'Concordance' between imaging modalities was defined as overlapping lesions. Reporting certainty was evaluated by the individual reporters for each modality. Results: International Society of Urological Pathology Grade Group ≥2 cancer was present in 60% of patients on biopsy. Synchronous reading of mpMRI/PSMA‐PET increased sensitivity compared to mpMRI or PSMA‐PET alone (93% vs 80% vs 88%, respectively), although specificity was not improved (63% vs 58% vs 78%, respectively). No significant difference in diagnostic performance was noted between mpMRI/PSMA‐PET read synchronously and mpMRI or PSMA‐PET reported independently and then synthesized. Most patients had concordant imaging (60%), while others had discordant lesions only (28%) or a mixture (concordant and discordant lesions; 12%). When mpMRI/PSMA‐PET findings were concordant and positive, 95% of patients had clinically significant prostate cancer (csPCa). When PSMA‐PET alone was compared to synchronous PSMA‐PET/MRI reads, there was an improvement in reader certainty in 20% of scans. Conclusion: Synchronous mpMRI/PSMA‐PET reading improves reader certainty and sensitivity for csPCa compared to mpMRI or PSMA‐PET alone. However, synthesizing the results of independently read PSMA‐PET and mpMRI reports provided similar diagnostic performance to synchronous PSMA‐PET/MRI reads. This may provide greater flexibility for urologists in terms of referral patterns, reducing healthcare system costs and improving efficiencies in prostate cancer diagnosis. [ABSTRACT FROM AUTHOR]

1 Table Comparison of salvage radiation treatment and surveillance as management strategies for low-risk biochemical recurrence with negative prostate-specific membrane antigen positron emission tomography/CT. Abbreviations ADT androgen deprivation therapy EAU European Association of Urology PET positron emission tomography PSMA prostate-specific membrane antigen RT radiation therapy Biochemical recurrence, or first detection of measurable serum PSA after radical prostatectomy, occurs in approximately one-third of patients [[1]] and is often the first indicator of residual or relapsed prostate cancer. As most potential sources of biochemical recurrence are located in the pelvis, treatment of biochemical recurrence largely relies on salvage radiation therapy (RT), including prostate bed/fossa with or without pelvic lymph node RT, sometimes with androgen deprivation therapy (ADT). [Extracted from the article]

Simple Summary: PSMA PET-CT is a new scan which has now been proven to be the most accurate in detecting prostate cancer outside the prostate gland. It is now recommended by international guidelines to be used before treatment is commenced for prostate cancer. However, we still do not know the true impact the information from these scans has on the treatment that we give the patients. In this study, we look at whether men who had a PSMA PET-CT scans before their treatment for prostate cancer needed any further treatment for their prostate cancer within the first 29 months of follow up. Our results found that 80% of men these men did not need any further treatment for their prostate cancer. We also found that if the prostate cancer was seen on PSMA PET-CT in lymph nodes outside of the pelvis, men were 5 times more likely to need another form of treatment within 29 months. PSMA PET-CT scans are now recommended in international urological guidelines for primary staging and re-staging of prostate cancer. However, there is little published literature on the clinical outcomes for patients after treatment decisions made using PSMA PET-CT results. This is a multisite, prospective cohort study investigating the clinical outcomes of men who received treatment plans based on PSMA PET-CT results for primary staging. Men with biopsy proven prostate cancer received a PSMA PET-CT scan for primary staging. Treatment plans were recommended by multidisciplinary teams (MDT). After treatment, these men were followed with 6 monthly PSA tests and imaging or biopsies if recommended by MDT. The primary outcome was treatment progression defined as the addition or change of any treatment modalities such as androgen deprivation therapy, radiation therapy or chemotherapy. In total, 80% of men did not have any treatment progression after enactment of treatment based on PSMA PET-CT primary staging results at 29 months of follow up. Men who had distant nodes seen on PSMA PET-CT had a 5 times increased risk of treatment progression. Larger studies with longer follow up are needed to validate our results and optimise the way clinicians use PSMA PET-CT results to guide management. [ABSTRACT FROM AUTHOR]

Aim: The second Asia‐Pacific Advanced Prostate Cancer Consensus Conference (APAC APCCC 2020) gathered insights into the real‐world application in the Asia‐Pacific (APAC) region of consensus statements from the 3rd Advanced Prostate Cancer Consensus Conference (APCCC 2019). Methods: The 4‐h our virtual meeting in October 2020 brought together 26 experts from 14 APAC countries to discuss APCCC 2019 recommendations. Presentations were prerecorded and viewed prior to the meeting. A postmeeting survey gathered views on current practice. Results: The meeting and survey highlighted several developments since APAC APCCC 2018. Increased access and use in the region of PSMA PET/CT imaging is providing additional diagnostic and staging information for advanced prostate cancer and influencing local and systemic therapy choices. Awareness of oligometastatic disease, although not clearly defined, is increasing. Novel androgen receptor pathway antagonists are expanding treatment options. Cost and access to contemporary treatments and technologies continue to be a significant factor influencing therapeutic decisions in the region. With treatment options increasing, multidisciplinary treatment planning, shared decision making, and informed choice remain critical. A discussion on the COVID‐19 pandemic highlighted challenges for diagnosis, treatment, and clinical trials and new service delivery models that will continue beyond the pandemic. Conclusion: APAC‐specific prostate cancer research and data are important to ensure that treatment guidelines and recommendations reflect local populations and resources. Facilitated approaches to collaboration across the region such as that achieved through APAC APCCC meetings continue to be a valuable mechanism to ensure the relevance of consensus guidelines within the region. [ABSTRACT FROM AUTHOR]

Summary: Early detection and management of prostate cancer has evolved over the past decade, with a focus now on harm minimisation and reducing overdiagnosis and overtreatment, given the proven improvements in survival from randomised controlled trials.Multiparametric magnetic resonance imaging (mpMRI) is now an important aspect of the diagnostic pathway in prostate cancer, improving the detection of clinically significant prostate cancer, enabling accurate localisation of appropriate sites to biopsy, and reducing unnecessary biopsies in most patients with normal magnetic resonance imaging scans.Biopsies are now performed transperineally, substantially reducing the risk of post‐procedure sepsis.Australian‐led research has shown that prostate‐specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) has superior accuracy in the staging of prostate cancer than conventional imaging (CT and whole‐body bone scan).Localised prostate cancer that is low risk (International Society for Urological Pathology [ISUP] grade 1, Gleason score 3 + 3 = 6; and ISUP grade group 2, Gleason score 3 + 4 = 7 with less than 10% pattern 4) can be offered active surveillance, reducing harms from overtreatment.Prostatectomy and definitive radiation remain the gold standard for localised intermediate and high risk disease. However, focal therapy is an emerging experimental treatment modality in Australia in carefully selected patients.The management of advanced prostate cancer treatment has evolved to now include several novel agents both in the metastatic hormone‐sensitive and castration‐resistant disease settings. Multimodal therapy with androgen deprivation therapy, additional systemic therapy and radiotherapy are often recommended.PSMA‐based radioligand therapy has emerged as a treatment option for metastatic castration‐resistant prostate cancer and is currently being evaluated in earlier disease states. [ABSTRACT FROM AUTHOR]

Simple Summary: In this study, we identified germline mutations that contribute to prostate cancer development in men who have multiple relatives with prostate cancer (and other cancers). We correlated the genetic mutations found in each patient with the resulting prostate cancer characteristics. Mutations found in ATM and CHEK2 genes were associated with aggressive prostate cancer. More data is needed to confirm the prevalence and impact of these germline mutations in prostate cancer. Background: Germline mutations in BRCA2 are associated with aggressive prostate cancer. Additional information regarding the clinical phenotype of germline pathogenic variants in other prostate cancer predisposition genes is required. Clinical testing has been limited by evidence, further restricting knowledge of variants that contribute to prostate cancer development. Objective: Prostate cancer patients who were first- and second-degree relatives from multi-case prostate cancer families underwent a gene panel screen to identify novel (non-BRCA) germline pathogenic variants in cancer predisposition genes and define clinical phenotypes associated with each gene. Methods: The germline genomic DNA (gDNA) of 94 index cases with verified prostate cancer from families with a minimum of two verified prostate cancer cases was screened with an 84-cancer-gene panel. Families were recruited for multi-case breast/ovarian cancer (n = 66), or multi-case prostate cancer (n = 28). Prostate cancer characteristics associated with each gene were compared with prostate cancer cases of confirmed non-mutation carriers (BRCAX), also from multi-case prostate cancer families (n = 111), and with data from the Prostate Cancer Outcomes Registry (PCOR). Results: Ninety-four prostate cancer index cases underwent gene panel testing; twenty-two index cases (22/94; 23%) were found to carry a class 4–5 (C4/5) variant. Six of twenty-two (27%) variants were not clinically notifiable, and seven of twenty-two (31.8%) variants were in BRCA1/2 genes. Nine of twenty-two (40.9%) index cases had variants identified in ATM (n = 4), CHEK2 (n = 2) and HOXB13G84 (n = 3); gDNA for all relatives of these nine cases was screened for the corresponding familial variant. The final cohort comprised 15 confirmed germline mutation carriers with prostate cancer (ATM n = 9, CHEK2 n = 2, HOXB13G84 n = 4). ATM and CHEK2-associated cancers were D'Amico intermediate or high risk, comparable to our previously published BRCA2 and BRCAX prostate cancer cohort. HOXB13G84 carriers demonstrated low- to intermediate-risk prostate cancer. In the BRCAX cohort, 53.2% of subjects demonstrated high-risk disease compared with 25% of the PCOR cohort. Conclusions:ATM and CHEK2 germline mutation carriers and the BRCAX (confirmed non-mutation carriers) cohort demonstrated high risk disease compared with the general population. Targeted genetic testing will help identify men at greater risk of prostate-cancer-specific mortality. Data correlating rare variants with clinical phenotype and familial predisposition will strengthen the clinical validity and utility of these results and establish these variants as significant in prostate cancer detection and management. [ABSTRACT FROM AUTHOR]

Background: Docetaxel has emerged as a standard‐of‐care for metastatic hormone‐sensitive prostate cancer (mHSPC). Uptake of docetaxel for mHSPC in Australia has not previously been reported. Aims: To investigate the real‐world uptake of docetaxel in mHSPC and to identify predictors of utilisation of docetaxel in mHSPC. Methods: Men diagnosed from June 2014 to December 2018 and enrolled in the Prostate Cancer Outcomes Registry‐Victoria (PCOR‐Vic) were included. Data collected include demographics, diagnosis method and institution, staging investigations and treatments within 12 months of diagnosis. Wilcoxon rank‐sum, Chi‐squared and trend tests were used to identify predictors of docetaxel utilisation. All predictors were entered as covariates simultaneously into a multivariable logistic regression model. Statistical significance was set at 0.05 (two sided). Results: In all, 1014 men with mHSPC were analysed, 25% of whom received docetaxel with androgen deprivation therapy. Uptake of docetaxel increased from 20% in 2014 to 33% in 2018. Predictors of higher usage of docetaxel were younger age and treatment in a private hospital, with both remaining significant on multivariable analysis. Notably, the proportion of men aged <70 years receiving docetaxel increased from 54% in 2014–2015 to 64% in 2016–2018, while in men aged ≥70 years the comparative figures were 15% and 22% respectively. Conclusions: Although docetaxel was not used in the majority of cases, there was a clear increase in docetaxel uptake, especially in younger men following publication of the CHAARTED and STAMPEDE trials. Identifying barriers to real‐world implementation of pivotal clinical trial data is critical to improving outcomes in mHSPC. [ABSTRACT FROM AUTHOR]

Simple Summary: Prostate-specific membrane antigen (PSMA) positron emission tomography-computed tomography (PET-CT) is an essential imaging tool that is used to locate prostate cancer when it recurs. The results of this scan are used to guide clinical decisions for the management of cancer. However, the long-term effect of these clinical decisions is yet to be determined. In this study, we followed men with recurrent prostate cancer for 3 years after they had a clinical decision made based on a PSMA PET-CT. Our results showed that 75% of men had no addition or change in their treatment plan 3 years after their initial clinical decision was made. In men with a PSMA PET-CT that showed no suspected cancer, 85% had no addition or change to their treatment plan. This indicates that clinical decisions made using PSMA PET-CT in this setting can have a medium- to long-lasting effect. Prostate-specific membrane antigen (PSMA) positron emission tomography-computed tomography (PET-CT) is a novel imaging modality used to stage recurrent prostate cancer. It has the potential to improve prognostication and ultimately guide the timing of treatment for men with recurrent prostate cancer. This study aims to assess the clinical impact of PSMA PET-CT by analyzing its predictive value of treatment progression after 3 years of follow-up. In this prospective cohort study of 100 men, patients received a PSMA PET-CT for restaging of their disease which was used by a multi-disciplinary team to make a treatment decision. The primary endpoint was treatment progression. This was defined as the addition or change of any treatment modalities such as androgen deprivation therapy (ADT), radiation therapy or chemotherapy. The median follow-up time was 36 months (IQR 24–40 months). No treatment progression was found in 72 (75%) men and therefore 24 (25%) patients were found to have treatment progression. In men with a negative PSMA PET-CT result, 5/33 (15.1%) had treatment progression and 28/33 (84.8%) had no treatment progression. In conclusion, clinical decisions made with PSMA PET-CT results led to 75% of men having no treatment progression at 3 years of follow-up. In men with negative PSMA PET-CT results, this increased to 85% of men. [ABSTRACT FROM AUTHOR]

Objective: Feeling depressed and lethargic are common side effects of prostate cancer (PCa) and its treatments. We examined the incidence and severity of feeling depressed and lack of energy in patients in a population based PCa registry. Methods: We included men diagnosed with PCa between 2015 and 2019 in Victoria, Australia, and enrolled in the Prostate Cancer Outcomes Registry. The primary outcome measures were responses to two questions on the Expanded Prostate Cancer Index Composite (EPIC‐26) patient reported instrument: problems with feeling depressed and problems with lack of energy 12 months following treatment. We evaluated associations between these and age, cancer risk category, treatment type, and urinary, bowel, and sexual function. Results: Both outcome questions were answered by 9712 out of 12,628 (77%) men. 981 patients (10%) reported at least moderate problems with feeling depressed; 1563 (16%) had at least moderate problems with lack of energy and 586 (6.0%) with both. Younger men reported feeling depressed more frequently than older men. Lack of energy was more common for treatments that included androgen deprivation therapy than not (moderate/big problems: 31% vs. 13%), irrespective of disease risk category. Both outcomes were associated with poorer urinary, bowel, and sexual functional domain scores. Conclusions: Self‐reported depressive feelings and lack of energy were frequent in this population‐based registry. Problems with feeling depressed were more common in younger men and lack of energy more common in men having hormonal treatment. Clinicians should be aware of the incidence of these symptoms in these at‐risk groups and be able to screen for them. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate outcomes for men with biochemically recurrent prostate cancer who were selected for transponder-guided salvage radiotherapy (SRT) to the prostate bed alone by 68Ga-labelled prostate-specific membrane antigen positron emission tomography (68Ga-PSMA-PET). Methods: This is a single-arm, prospective study of men with a prostate-specific antigen (PSA) level rising to 0.1–2.5 ng/mL following radical prostatectomy. Patients were staged with 68Ga-PSMA-PET and those with a negative finding, or a positive finding localised to the prostate bed, continued to SRT only to the prostate bed alone with real-time target-tracking using electromagnetic transponders. The primary endpoint was freedom from biochemical relapse (FFBR, PSA > 0.2 ng/mL from the post-radiotherapy nadir). Secondary endpoints were time to biochemical relapse, toxicity and patient-reported quality of life (QoL). Results: Ninety-two patients (median PSA of 0.18 ng/ml, IQR 0.12–0.36), were screened with 68Ga-PSMA-PET and metastatic disease was found in 20 (21.7%) patients. Sixty-nine of 72 non-metastatic patients elected to proceed with SRT. At the interim (3-year) analysis, 32 (46.4%) patients (95% CI 34.3–58.8%) were FFBR. The median time to biochemical relapse was 16.1 months. The rate of FFBR was 82.4% for ISUP grade-group 2 patients. Rates of grade 2 or higher gastrointestinal and genitourinary toxicity were 0% and 15.2%, respectively. General health and disease-specific QoL remained stable. Conclusion: Pre-SRT 68Ga-PSMA-PET scans detect metastatic disease in a proportion of patients at low PSA levels but fail to improve FFBR. Transponder-guided SRT to the prostate bed alone is associated with a favourable toxicity profile and preserved QoL. Trial registration number: ACTRN12615001183572, 03/11/2015, retrospectively registered. [ABSTRACT FROM AUTHOR]

Introduction: There has been a growing body of evidence highlighting the improved sensitivity and specificity for prostate specific membrane antigen (PSMA) positron emission tomography (PET) in advanced prostate cancer imaging. We aimed to assess prostate cancer staging practice patterns in Australia using population‐based data. Subject and Methods: We extracted data on men diagnosed with prostate cancer between October 2016 and December 2018 from the Prostate Cancer Outcomes Registry‐Victoria (PCOR‐Vic). We evaluated trends and comparisons between patients receiving PET/CT (with or without conventional imaging (CImg)), and CImg alone, and analysed imaging modality as predictor of clinical regional node positive disease (cN1 vs cN0/X), metastatic disease (cM1 vs cM0/X), and treatment received. Results: In total, 6139 patients in the registry had either a staging PET scan (n = 889, 14%), CImg without PET scan (n = 2464, 40%), or no recorded PET or CImg (n = 2786, 45%). The proportion of allimaged patients who received staging PET increased from 19% to 36% from the first to last three‐month period, and in the high‐risk category the increase was 23–43%. After adjustment for grade group, PET vs CImg‐only patients were observed to have a higher proportion of cN1 disease (OR = 2.46, 95% CI: 1.90–3.20) but not cM1 disease (OR = 1.10, 95% CI: 0.84–1.44). Conclusions: Our registry data highlights the rapid uptake of PET imaging, particularly in high‐risk disease. Based on this data, we highlight the increased diagnosis of nodal disease, thus potentially optimizing patient selection prior to definitive treatment for prostate cancer. [ABSTRACT FROM AUTHOR]

Objective: To assess the activity and safety of sequential lutetium‐177 (177Lu)‐PSMA‐617 and docetaxel vs docetaxel on a background of androgen deprivation therapy (ADT) in men with de novo metastatic hormone‐naïve prostate cancer (mHNPC). Patients and Methods: UpFrontPSMA (NCT04343885) is an open‐label, randomized, multicentre, phase 2 trial, recruiting 140 patients at 12 Australian centres. Key eligibility criteria include: prostate cancer with a histological diagnosis within 12 weeks of screening commencement; prostate‐specific antigen (PSA) >10 ng/mL at diagnosis; ≤4 weeks on ADT; evidence of metastatic disease on computed tomography (CT) and/or bone scan; high‐volume prostate‐specific membrane antigen (PSMA)‐avid disease with a maximum standardized uptake value >15; and absence of extensive discordant fluorodeoxyglcuose (FDG)‐positive, PSMA‐negative disease. 68Ga‐PSMA‐11 and 18F‐FDG positron‐emission tomography (PET)/CT undergo central review to determine eligibility. Patients are randomized 1:1 to experimental treatment, Arm A (177Lu‐PSMA‐617 7.5GBq q6w × 2 cycles followed by docetaxel 75 mg/m2 q3w × 6 cycles), or standard‐of‐care treatment, Arm B (docetaxel 75 mg/m2 q3w × 6 cycles). All patients receive continuous ADT. Patients are stratified based on disease volume on conventional imaging and duration of ADT at time of registration. The primary endpoint is the proportion of patients with undetectable PSA (≤0.2 ng/L) at 12 months after study treatment commencement. Secondary endpoints include safety, time to castration resistance, overall survival, PSA and radiographic progression‐free survival, objective tumour response rate, early PSMA PET response, health‐related quality of life, and frequency and severity of adverse events. Enrolment commenced in April 2020. Results and Conclusions: The results of this trial will generate data on the activity and safety of 177Lu‐PSMA‐617 in men with de novo mHNPC in a randomized phase 2 design. [ABSTRACT FROM AUTHOR]

Prostate-specific membrane antigen (PSMA) PET/CT is a novel imaging technique for the detection and staging of either primary or recurrent prostate cancer. Early studies demonstrated its improved sensitivity and specificity over and in combination with other currently employed imaging techniques, such as multiparametric MRI, bone scan, PET and CT. However, the lack of strength and confidence in these studies has meant incorporation of PSMA PET/CT into clinical guidelines and practice has been limited to date. In response, a number of high-quality prospective studies have recently emerged and reflect exciting results seen in preceding publications. Here we recount some of the key earlier publications, report results from the latest studies and look to the future discussing some of the eagerly awaited ongoing clinical trials. [ABSTRACT FROM AUTHOR]

Objective: Coronavirus disease‐19 (COVID‐19) pandemic caused delays in definitive treatment of patients with prostate cancer. Beyond the immediate delay a backlog for future patients is expected. The objective of this work is to develop guidance on criteria for prioritisation of surgery and reconfiguring management pathways for patients with non‐metastatic prostate cancer who opt for surgical treatment. A second aim was to identify the infection prevention and control (IPC) measures to achieve a low likelihood of coronavirus disease 2019 (COVID‐19) hazard if radical prostatectomy (RP) was to be carried out during the outbreak and whilst the disease is endemic. Methods: We conducted an accelerated consensus process and systematic review of the evidence on COVID‐19 and reviewed international guidance on prostate cancer. These were presented to an international prostate cancer expert panel (n = 34) through an online meeting. The consensus process underwent three rounds of survey in total. Additions to the second‐ and third‐round surveys were formulated based on the answers and comments from the previous rounds. The Consensus opinion was defined as ≥80% agreement and this was used to reconfigure the prostate cancer pathways. Results: Evidence on the delayed management of patients with prostate cancer is scarce. There was 100% agreement that prostate cancer pathways should be reconfigured and measures developed to prevent nosocomial COVID‐19 for patients treated surgically. Consensus was reached on prioritisation criteria of patients for surgery and management pathways for those who have delayed treatment. IPC measures to achieve a low likelihood of nosocomial COVID‐19 were coined as 'COVID‐19 cold' sites. Conclusion: Reconfiguring management pathways for patients with prostate cancer is recommended if significant delay (>3–6 months) in surgical management is unavoidable. The mapped pathways provide guidance for such patients. The IPC processes proposed provide a framework for providing RP within an environment with low COVID‐19 risk during the outbreak or when the disease remains endemic. The broader concepts could be adapted to other indications beyond prostate cancer surgery. [ABSTRACT FROM AUTHOR]

Background: Active surveillance (AS) is the disease management option of choice for low-risk prostate cancer. Despite this, men with low-risk prostate cancer (LRPC) find management decisions distressing and confusing. We developed Navigate, an online decision aid to help men and their partners make management decisions consistent with their values. The aims are to evaluate the impact of Navigate on uptake of AS; decision-making preparedness; decisional conflict, regret and satisfaction; quality of illness communication; and prostate cancer-specific quality of life and anxiety. In addition, the healthcare cost impact, cost-effectiveness and patterns of use of Navigate will be assessed. This paper describes the study protocol.Methods: Three hundred four men and their partners are randomly assigned one-to-one to Navigate or to the control arm. Randomisation is electronically generated and stratified by site. Navigate is an online decision aid that presents up-to-date, unbiased information on LRPC tailored to Australian men and their partners including each management option and potential side-effects, and an interactive values clarification exercise. Participants in the control arm will be directed to the website of Australia's peak national body for prostate cancer. Eligible patients will be men within 3 months of being diagnosed with LRPC, aged 18 years or older, and who are yet to make a treatment decision, who are deemed eligible for AS by their treating clinician and who have Internet access and sufficient English to participate. The primary outcome is self-reported uptake of AS as the first-line management option. Secondary outcomes include self-reported preparedness for decision-making; decisional conflict, regret and satisfaction; quality of illness communication; and prostate cancer-specific quality of life. Uptake of AS 1 month after consent will be determined through patient self-report. Men and their partners will complete study outcome measures before randomisation and 1, 3 and 6 months after study consent.Discussion: The Navigate online decision aid has the potential to increase the choice of AS in LRPC, avoiding or delaying unnecessary radical treatments and associated side effects. In addition, Navigate is likely to reduce patients' and partners' confusion and distress in management decision-making and increase their quality of life.Trial Registration: Australian and New Zealand Clinical Trial Registry ACTRN12616001665426 . Registered on 2 December 2016. All items from the WHO Trial Registration Data set can be found in this manuscript. [ABSTRACT FROM AUTHOR]

Summary: Prostate cancer continues to be the most commonly diagnosed cancer, and the second leading cause of cancer death among Australian men.Prostate‐specific antigen testing is personalised (not dichotomous in nature) and its interpretation should take into account the patient's age, symptoms, previous results and medication (eg, 5‐α reductase inhibitors such as dutasteride).Multiparametric magnetic resonance imaging of the prostate has been proven to have a 93% sensitivity for detecting clinically significant prostate cancer. It has the potential to decrease unnecessary prostate biopsies by around 27%.International Society of Urological Pathology (ISUP) grade 1 (Gleason score 6) has been shown to have very little, if any, risk of metastasisISUP grade 1 (Gleason score 3 +3 = 6) and low percentage ISUP grade 2 (Gleason score 3 + 4 [< 10%] = 7) can be offered active surveillance. The goal of active surveillance is to defer treatment but is still curative when required.With better imaging (magnetic resonance imaging and emerging prostate‐specific membrane antigen positron emission tomography–computed tomography) and transperineal prostate biopsy, more men can be offered screening after discussion of risks and benefits, knowing that overdiagnosis has been minimised and radical treatment is reserved for only the most aggressive disease. [ABSTRACT FROM AUTHOR]

Objectives: To review current data for the role of prostate specific membrane antigen (PSMA) radioligand therapy (RLT) for patients with advanced prostate cancer. This review provides an update for multidisciplinary teams on the current and potential future applications of theranostics in prostate cancer. Methods: Narrative review focussing on PSMA as a target for RLT, and data using Results: RLT with PSMA is an exciting therapeutic alternative to the existing management options already in use for patients with metastatic castrate‐resistant prostate cancer (mCRPC). To date, most evidence exists regarding small‐molecule PSMA inhibitors bound to beta‐emitting radioisotopes such as 177Lu (Lu‐PSMA). Prospective phase II data supports the safety and efficacy of Lu‐PSMA in men with heavily pre‐treated progressive mCRPC, and several late‐phase randomised trials of Lu‐PSMA are underway, with many more in the pipeline. Early results are encouraging, indicating that the theranostic approach may play a vital role in management of advanced prostate cancer and perhaps even in much earlier disease states. Conclusions: PSMA RLT is a promising new treatment option for men with mCPRC, and may also have utility in less advanced prostate cancer. [ABSTRACT FROM AUTHOR]

Objective: To compare the accuracy of 68gallium prostate‐specific membrane antigen positron emission tomography/computed tomography (68Ga‐PSMA PET/CT) with multiparametric MRI (mpMRI) in detecting and localising primary prostate cancer when compared with radical prostatectomy (RP) specimen pathology. Patients and methods: Retrospective review of men who underwent 68Ga‐PSMA PET/CT and mpMRI for primary prostate cancer before RP across four centres between 2015 and 2018. Patients undergoing imaging for recurrent disease or before non‐surgical treatment were excluded. We defined pathological index tumour as the lesion with highest International Society of Urological Pathology Grade Group (GG) on RP specimen pathology. Our primary outcomes were rates of accurate detection and localisation of RP specimen pathology index tumour using 68Ga‐PSMA PET/CT or mpMRI. We defined tumour detection as imaging lesion corresponding with RP specimen tumour on any imaging plane, and localisation as imaging lesion matching RP specimen index tumour in all sagittal, axial, and coronal planes. Secondary outcomes included localisation of clinically significant and transition zone (TZ) index tumours. We defined clinically significant disease as GG 3–5. We used descriptive statistics and the Mann–Whitney U‐test to define and compare demographic and pathological characteristics between detected, missed and localised tumours using either imaging modality. We used the McNemar test to compare detection and localisation rates using 68Ga‐PSMA PET/CT and mpMRI. Results: In all, 205 men were included in our analysis, including 133 with clinically significant disease. There was no significant difference between 68Ga‐PSMA PET/CT and mpMRI in the detection of any tumour (94% vs 95%, P > 0.9). There was also no significant difference between localisation of all index tumours (91% vs 89%, P = 0.47), clinically significant index tumours (96% vs 91%, P = 0.15) or TZ tumours (85% vs 80%, P > 0.9) using 68Ga‐PSMA PET/CT and mpMRI. Limitations include retrospective study design and non‐central review of imaging and pathology. Conclusion: We found no significant difference in the detection or localisation of primary prostate cancer between 68Ga‐PSMA PET/CT and mpMRI. Further prospective studies are required to evaluate a combined PET/MRI model in minimising tumours missed by either modality. [ABSTRACT FROM AUTHOR]

Objectives: Primary objectives: To determine the additive value of gallium‐68 prostate‐specific membrane antigen (PSMA) positron emission topography (PET)/computed tomography (CT) when combined with multiparametric magnetic resonance imaging (mpMRI) detecting clinically significant prostate cancer (csPCa) in men undergoing initial biopsy for suspicion of PCa, and to determine the proportion of men who could have avoided prostate biopsy with positive mpMRI (PI‐RADS ≥3) but negative PSMA‐PET/CT. Secondary objectives: To determine the proportion of men who had csPCa detected only by PSMA‐PET/CT or only by systematic prostate biopsy; to compare index lesions by template biopsies vs targeted lesions identified on mpMRI or PSMA‐PET/CT; to assess whether there may be health economic benefit or harm if PSMA‐PET/CT is incorporated into the diagnostic algorithm; and to develop a nomogram which combines clinical, imaging and biomarker data to predict the likelihood of csPCa. Patients and Methods: The PRIMARY trial is a multicentre, prospective, cross‐sectional study that meets the criteria for level 1 evidence in diagnostic test evaluation. PRIMARY will investigate if a limited (pelvic‐only) PSMA‐PET/CT in combination with routine mpMRI can reliably discriminate men with csPCa from those without csPCa. We conducted a power calculation based on pilot data and will recruit up to 600 men who will undergo PSMA‐PET/CT (the index test), mpMRI (standard test) and transperineal template + targeted (PSMA‐PET/CT and/or mpMRI) biopsies (reference test). The conduct and reporting of the mpMRI and PSMA‐PET/CT will be blinded to each other. Results: The PRIMARY trial will measure and compare sensitivity, specificity, positive predictive value and negative predictive value of both mpMRI and PSMA‐PET/CT vs targeted prostrate biopsy. The results will be used to determine the proportion of men who could safely avoid biopsy without compromising detection of csPCa. Furthermore, we will assess whether there is a health economic benefit in incorporating PSMA‐PET/CT into the diagnostic algorithm. Conclusions: This trial will provide robust prospective data to determine the diagnostic ability of PSMA‐PET/CT used in addition to mpMRI. It will establish if certain patients can avoid biopsy in the investigation of PCa. [ABSTRACT FROM AUTHOR]

Historically, in a time when systemic therapy options were scarce, the responsibility of monitoring ADT efficacy fell squarely on urologists. Thus, urologists appropriately relinquished the management of eligible patients to their medical oncology colleagues - a paradigm shift away from urologists as the principal custodians of mHSPC. However, we propose that it is only through improved understanding and experience with these therapies that urologists can once again significantly contribute to shared decision-making alongside their medical oncology colleagues in the multidisciplinary management of patients with advanced prostate cancer. [Extracted from the article]

Abbreviations AS active surveillance NCCN National Comprehensive Cancer Network The management of low-risk prostate cancer in North America has recently seen some unexpected, surprising, and somewhat perplexing occurrences. Examples include recent imaging trials using prostate-specific membrane antigen positron emission tomography-CT to better target and provide more informed initial biopsy as found in the PRIMARY trial [4], or CONFIRM trial (Australian New Zealand Clinical Trials Registry [ACTRN]12621001648819 at https://www.anzctr.org.au) aiming to better select men for AS prior to confirmatory biopsy. This trial concluded that 'enzalutamide monotherapy was well-tolerated and demonstrated a significant treatment response in patients with low-risk or intermediate-risk localized prostate cancer', and that 'enzalutamide may provide an alternative treatment option for patients undergoing AS'. [Extracted from the article]

Objectives: To develop a registration framework for correlating positron emission tomography/computed tomography (PET/CT) images with multiparametric magnetic resonance imaging (mpMRI) and histology of the prostate, thereby enabling voxel‐wise analysis of imaging parameters. Patients and Methods: In this prospective proof‐of‐concept study, nine patients scheduled for radical prostatectomy underwent mpMRI and PET/CT imaging before surgery. One had PET imaging using 18F‐fluoromethylcholine, five using 68Ga‐labelled prostate‐specific membrane antigen (PSMA)‐HBED‐CC (PMSA‐11), and three using a trial 68Ga‐labelled THP‐PSMA tracer. PET/CT data were co‐registered with mpMRI via the CT scan and an in vivo three‐dimensional T2‐weighted (T2w) MRI, and then co‐registered with ground truth histology data using ex vivo MRI of the prostate specimen. Maximum and mean standardised uptake values (SUVmax and SUVmean) were extracted from PET data using tumour annotations from histology, and Kolmogorov–Smirnov tests were used to compare between tumour‐ and benign‐voxel values. Correlation analysis was performed between mpMRI and PET SUV tumour voxel values using Pearson's correlation coefficient and R2 statistics. Results: PET/CT data from all nine patients were successfully registered with mpMRI and histology data. SUVmax and SUVmean ranged from 2.21 to 12.11 and 1.08 to 4.21, respectively. All patients showed the PET SUV values in benign and tumour voxels were from statistically different distributions. Correlation analysis showed no consistent trend between the T2w or apparent diffusion coefficient values and PET SUV. However, parameters from dynamic contrast‐enhanced (DCE) MRI including the maximum enhancement, volume transfer constant (Ktrans), and the initial area under the contrast agent concentration curve for the first 60 s after injection (iAUGC60), showed consistent positive correlations with PET SUV. Furthermore, R2* values from blood oxygen level‐dependent (BOLD) MRI showed consistent negative correlations with PET SUV‐voxel values. Conclusion: We have developed a novel framework for registering and correlating PET/CT data at a voxel‐level with mpMRI and histology. Despite registration uncertainties, perfusion and oxygenation parameters from DCE MRI and BOLD imaging showed correlations with PET SUV. Further analysis will be performed on a larger patient cohort to quantify these proof‐of‐concept findings. Improved understanding of the correlation between mpMRI and PET will provide supportive information for focal therapy planning of the prostate. [ABSTRACT FROM AUTHOR]