Cost-utility Analysis of Navigate, a Treatment Decision Aid for Men with Prostate Cancer and Their Partners, in Comparison to Usual Care.

BACKGROUND AND OBJECTIVE: Evidence on the cost effectiveness of decision aids to guide management decisions for men with prostate cancer is limited. We examined the cost utility of the Navigate online decision aid for men with prostate cancer in comparison to usual care (no decision aid). METHODS: A Markov model with a 10-yr time horizon was constructed from a government health care perspective. Data from the Navigate trial (n = 302) and relevant published studies were used for model inputs. Incremental costs and quality-adjusted life-years (QALYs) were calculated for the two strategies. One-way and probabilistic sensitivity analyses were undertaken to address model uncertainty. KEY FINDINGS AND LIMITATIONS: On average, the Navigate strategy was estimated to cost AU$8899 (95% uncertainty interval [UI] AU$7509-AU$10438) and produce 7.08 QALYs (95% UI 6.73-7.36) in comparison to AU$9559 (95% UI AU$8177-AU$11017) and 7.03 QALYs (95% UI 6.67-7.31) or usual care. The Navigate strategy dominated usual care as it produced cost-savings and higher QALYs, although differences for both outcomes were small over 10 yr. The likelihood of Navigate being cost effective at a conventionally acceptable threshold of AU$50000 per QALY gained was 99.7%. This study is limited by the availability, quality, and choice of the data used in the model. CONCLUSIONS AND CLINICAL IMPLICATIONS: Use of an online decision aid for men with prostate cancer appears to be cost effective relative to usual care in Australia, driven by the higher acceptance and uptake of active surveillance. Wider implementation of decision aids may better inform men diagnosed with prostate cancer about their management options. PATIENT SUMMARY: We looked at the cost effectiveness of an online decision aid for guiding Australian men with prostate cancer in choosing a management option. We found that this decision aid was cost effective, mainly because more men chose active surveillance. Decision aids that inform patients about their management options should be more widely used in health care.

Standardized template for clinical reporting of PSMA PET/CT scans.

PURPOSE: Accurate diagnosis and staging of prostate cancer are crucial to improving patient care. Prostate-specific membrane antigen (PSMA)-targeted positron emission tomography with computed tomography (PET/CT) imaging has demonstrated superiority for initial staging and restaging in patients with prostate cancer. Referring physicians and PET/CT readers must agree on a consistent communication method and application of information derived from this imaging modality. While several guidelines have been published, a single PSMA PET/CT reporting template has yet to be widely adopted. Based on the consensus from community and academic physicians, we developed a standardized PSMA PET/CT reporting template for radiologists and nuclear medicine physicians to report and relay key imaging findings to referring physicians. The aim was to improve the quality, clarity, and utility of imaging results reporting to facilitate patient management decisions. METHODS: Based on community and expert consensus, we developed a standardized PSMA PET/CT reporting template to deliver key imaging findings to referring clinicians. RESULTS: Core category components proposed include a summary of any prior treatment history; presence, location, and degree of PSMA radiopharmaceutical uptake in primary and/or metastatic tumor(s), lesions with no uptake, and incidentally found lesions with positive uptake on PET/CT. CONCLUSIONS: This article provides recommendations on best practices for standardized reporting of PSMA PET/CT imaging. The generated reporting template is a proposed supplement designed to educate and improve data communication between imaging experts and referring physicians.

Has Active Surveillance for Prostate Cancer Become Safer? Lessons Learned from a Global Clinical Registry.

BACKGROUND AND OBJECTIVE: Active surveillance (AS) has evolved into a widely applied treatment strategy for many men around the world with low-risk prostate cancer (or in selected cases intermediate-risk disease). Here, we report on the safety and acceptability of AS, and treatment outcomes for low- and intermediate-risk tumours over time in 14 623 men with follow-up of over 6 yr. METHODS: Clinical data from 26 999 men on AS from 25 cohorts in 15 countries have been collected in an international database from 2000 onwards. KEY FINDINGS AND LIMITATIONS: Across our predefined four time periods of 4 yr each (covering the period 2000-2016), there was no significant change in overall survival (OS). However, metastasis-free survival (MFS) rates have improved since the second period and were excellent (>99%). Treatment-free survival rates for earlier periods showed a slightly more rapid shift to radical treatment. Over time, there was a constant proportion of 5% of men for whom anxiety was registered as the reason for treatment alteration. There was, however, also a subset of 10-15% in whom treatment was changed, for which no apparent reason was available. In a subset of men (10-15%), tumour progression was the trigger for treatment. In men who opted for radical treatment, surgery was the most common treatment modality. In those men who underwent radical treatment, 90% were free from biochemical recurrence at 5 yr after treatment. CONCLUSIONS AND CLINICAL IMPLICATIONS: Our study confirms that AS was a safe management option over the full duration in this large multicentre cohort with long-term follow-up, given the 84.1% OS and 99.4% MFS at 10 yr. The probability of treatment at 10 yr was 20% in men with initial low-risk tumours and 31% in men with intermediate-risk tumours. New diagnostic modalities may improve the acceptability of follow-up using individual risk assessments, while safely broadening the use of AS in higher-risk tumours. PATIENT SUMMARY: Active surveillance (AS) has evolved into a widely applied treatment strategy for many men with prostate cancer around the world. In this report, we show the long-term safety of following AS for men with low- and intermediate-risk prostate cancer. Our study confirms AS as a safe management option for low- and intermediate-risk prostate cancer. New diagnostic modalities may improve the acceptability of follow-up using individual risk assessments, while safely broadening the use of AS in higher-risk tumours.

Five-year outcomes of fractionated stereotactic body radiotherapy for oligometastatic prostate cancer from the TRANSFORM phase II trial.

Metastasis-directed therapy (MDT) for oligometastatic prostate cancer (PCa), including stereotactic body radiotherapy (SBRT), has shown promise but is still considered investigational. This is the 5-year analysis of the TRANSFORM trial, the largest prospective cohort of men with oligometastatic PCa treated with SBRT-based MDT. The primary endpoint was 5-year treatment escalation-free survival (TE-FS), defined as freedom from any new cancer therapy other than further SBRT. In total, 199 men received SBRT; 76.4% were hormone-naïve at baseline. The rate of 5-year TE-FS was 21.7% (95% confidence interval [CI]: 15.7%-28.7%) overall and 25.4% (95% CI: 18.1%-33.9%) in the hormone-naïve subgroup. The subgroups with International Society of Urological Pathology Grade Groups 4-5 disease (hazard ratio [HR] = 1.48, 95% CI: 1.05-2.01, p = .026), a higher baseline prostate-specific antigen (PSA) (HR = 1.06, 95% CI: 1.03-1.09, p < .001) and those who received prior androgen deprivation therapy (ADT) (HR = 2.13, 95% CI: 1.40-3.26, p < .001), were at greater risk of treatment escalation. Outcomes for participants with four or five initial lesions were comparable to those with one to three lesions. At last follow-up, 18.9% (95% CI: 13.2%-25.7%) of participants were free from treatment escalation (median follow-up of 67.9 months) and two participants had an undetectable PSA level. No treatment-related grade three or higher adverse events were reported. The findings of this study demonstrate that SBRT-based MDT is an effective option for delaying systemic treatment escalation in the context of oligometastatic PCa. Future randomised trials comparing SBRT-based MDT to standard-of-care ADT-based approaches are required to evaluate the impact of delaying ADT on survival.

Beyond Prostate Imaging Reporting and Data System: Combining Magnetic Resonance Imaging Prostate Imaging Reporting and Data System and Prostate-Specific Membrane Antigen-Positron Emission Tomography/Computed Tomography PRIMARY Score in a Composite (P) Score for More Accurate Diagnosis of Clinically Significant Prostate Cancer.

PURPOSE: The Prostate Imaging Reporting and Data System (PI-RADS) score is standard of care for clinically significant prostate cancer (csPCa) diagnosis. The PRIMARY score (prostate-specific membrane antigen [PSMA]-positron emission tomography [PET]/CT) also has high diagnostic accuracy for csPCa. This study aimed to develop an easily calculated combined (P) score for csPCa detection (International Society of Urological Pathology [ISUP] ≥2) incorporating separately read PI-RADS and PRIMARY scores, with external validation. MATERIALS AND METHODS: Two datasets of men with suspected PCa, no prior biopsy, recent MRI and 68Ga-PSMA-11-PET/CT, and subsequent transperineal biopsy were evaluated. These included the development sample (n = 291, 56% csPCa) a prospective trial and the validation sample (n = 227, 67% csPCa) a multicenter retrospective database. Primary outcome was detection of csPCa (ISUP ≥2), with ISUP ≥ 3 cancer detection a secondary outcome. Score performance was evaluated by area under the curve, sensitivity, specificity, and decision curve analysis. RESULTS: The 5-point combined (P) score was developed in a prospective dataset. In the validation dataset, csPCa was identified in 0%, 20%, 52%, 96%, and 100% for P score 1 to 5. The area under the curve was 0.93 (95% CI: 0.90-0.96), higher than PI-RADS 0.89 (95% CI: 0.85-0.93, P = .039) and PRIMARY score alone 0.84 (95% CI: 0.79-0.89, P < .001). Splitting scores at 1/2 (negative) vs 3/4/5 (positive), P score sensitivity was 94% (95% CI: 89-97) compared to PI-RADS 89% (95% CI: 83-93) and PRIMARY score 86% (95% CI: 79-91). For ISUP ≥ 3, P score sensitivity was 99% (95% CI: 95-100) vs 94% (95% CI: 88-98) and 92% (95% CI: 85-97) for PI-RADS and PRIMARY scores respectively. A maximum standardized uptake value > 12 (P score 5) was ISUP ≥ 2 in all cases with 93% ISUP ≥ 3. CONCLUSIONS: The P score is easily calculated and improves accuracy for csPCa over both PI-RADS and PRIMARY scores. It should be considered when PSMA-PET is undertaken for diagnosis.

The impact of management option on out-of-pocket costs and perceived financial burden among men with localised prostate cancer in Australia within 6 months of diagnosis.

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.

Co-designing an online treatment decision aid for men with low-risk prostate cancer: Navigate.

Objectives: To develop an online treatment decision aid (OTDA) to assist patients with low-risk prostate cancer (LRPC) and their partners in making treatment decisions. Patients and methods: Navigate, an OTDA for LRPC, was rigorously co-designed by patients with a confirmed diagnosis or at risk of LRPC and their partners, clinicians, researchers and website designers/developers. A theoretical model guided the development process. A mixed methods approach was used incorporating (1) evidence for essential design elements for OTDAs; (2) evidence for treatment options for LRPC; (3) an iterative co-design process involving stakeholder workshops and prototype review; and (4) expert rating using the International Patient Decision Aid Standards (IPDAS). Three co-design workshops with potential users (n = 12) and research and web-design team members (n = 10) were conducted. Results from each workshop informed OTDA modifications to the OTDA for testing in the subsequent workshop. Clinician (n = 6) and consumer (n = 9) feedback on usability and content on the penultimate version was collected. Results: The initial workshops identified key content and design features that were incorporated into the draft OTDA, re-workshopped and incorporated into the penultimate OTDA. Expert feedback on usability and content was also incorporated into the final OTDA. The final OTDA was deemed comprehensive, clear and appropriate and met all IPDAS criteria. Conclusion: Navigate is an interactive and acceptable OTDA for Australian men with LRPC designed by men for men using a co-design methodology. The effectiveness of Navigate in assisting patient decision-making is currently being assessed in a randomised controlled trial with patients with LRPC and their partners.

Reproducibility and Accuracy of the PRIMARY Score on PSMA PET and of PI-RADS on Multiparametric MRI for Prostate Cancer Diagnosis Within a Real-World Database.

The PRIMARY score is a 5-category scale developed to identify clinically significant intraprostate malignancy (csPCa) on 68Ga-prostate-specific membrane antigen (PSMA)-11 PET/CT (68Ga-PSMA PET) using a combination of anatomic site, pattern, and intensity. Developed within the PRIMARY trial, the score requires evaluation in external datasets. This study aimed to assess the reproducibility and diagnostic accuracy of the PRIMARY score in a cohort of patients who underwent multiparametric MRI (mpMRI) and 68Ga-PSMA PET before prostate biopsy for the diagnosis of prostate cancer. Methods: In total, data from 242 men who had undergone 68Ga-PSMA PET and mpMRI before transperineal prostate biopsy were available for this ethics-approved retrospective study. 68Ga-PSMA PET and mpMRI data were centrally collated in a cloud-based deidentified image database. Six experienced prostate-focused nuclear medicine specialists were trained (1 h) in applying the PRIMARY score with 30 sample images. Six radiologists experienced in prostate mpMRI read images as per the Prostate Imaging-Reporting and Data System (PI-RADS), version 2.1. All images were read (with masking of clinical information) at least twice, with discordant findings sent to a masked third (or fourth) reader as necessary. Cohen κ was determined for both imaging scales as 5 categories and then collapsed to binary (negative and positive) categories (score 1 or 2 vs. 3, 4, or 5). Diagnostic performance parameters were calculated, with an International Society of Urological Pathology grade group of at least 2 (csPCa) on biopsy defined as the gold standard. Combined-imaging-positive results were defined as any PI-RADS score of 4 or 5 or as a PI-RADS score of 1-3 with a PRIMARY score of 3-5. Results: In total, 227 patients with histopathology, 68Ga-PSMA PET, and mpMRI imaging before prostate biopsy were included; 33% had no csPCa, and 67% had csPCa. Overall interrater reliability was higher for the PRIMARY scale (κ = 0.70) than for PI-RADS (κ = 0.58) when assessed as a binary category (benign vs. malignant). This was similar for all 5 categories (κ = 0.65 vs. 0.48). Diagnostic performance to detect csPCa was comparable between PSMA PET and mpMRI (sensitivity, 86% vs. 89%; specificity, 76% vs. 74%; positive predictive value, 88% vs. 88%; negative predictive value, 72% vs. 76%). Using combined imaging, sensitivity was 94%, specificity was 68%, positive predictive value was 86%, and negative predictive value was 85%. Conclusion: The PRIMARY score applied by first-user nuclear medicine specialists showed substantial interrater reproducibility, exceeding that of PI-RADS applied by mpMRI-experienced radiologists. Diagnostic performance was similar between the 2 modalities. The PRIMARY score should be considered when interpreting intraprostatic PSMA PET images.

Clinical Trial Protocol for PRIMARY2: A Multicentre, Phase 3, Randomised Controlled Trial Investigating the Additive Diagnostic Value of [68Ga]Ga-PSMA-11 Positron Emission Tomography/Computed Tomography in Men with Negative or Equivocal Multiparametric Magnetic Resonance Imaging for the Diagnosis of Clinically Significant Prostate Cancer.

BACKGROUND: Multiparametric magnetic resonance imaging (mpMRI) has an established role for the diagnosis of clinically significant prostate cancer (sPCa). The PRIMARY trial demonstrated that [68Ga]Ga-PSMA-11 positron emission tomography/computed tomography (PET/CT) was associated with a significant improvement in sensitivity and negative predictive value for sPCa detection. OBJECTIVE: To demonstrate that addition of prostate-specific membrane antigen (PSMA) radioligand PET/CT will enable some men to avoid transperineal prostate biopsy without missing sPCa, and will facilitate biopsy targeting of PSMA-avid sites. DESIGN, SETTING, AND PARTICIPANTS: This multicentre, two-arm, phase 3, randomised controlled trial will recruit 660 participants scheduled to undergo biopsy. Eligible participants will have clinical suspicion of sPCa with a Prostate Imaging-Reporting and Data System (PI-RADS) score of 2 and red flags, or a PI-RADS score of 3 on mpMRI (PI-RADS v2). Participants will be randomised at a 1:1 ratio in permuted blocks stratified by centre. The trial is registered on ClinicalTrials.gov as NCT05154162. INTERVENTION: In the experimental arm, participants will undergo pelvic PSMA PET/CT. Local and central reviewers will interpret scans independently using the PRIMARY score. Participants with a positive result will undergo targeted transperineal prostate biopsies, whereas those with a negative result will undergo prostate-specific antigen monitoring alone. In the control arm, all participants undergo template transperineal prostate biopsies. Participants will be followed for subsequent clinical care for up to 2 yr after randomisation. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: sPCa is defined as Gleason score 3 + 4 (≥10%) = 7 disease (grade group 2) or higher on transperineal prostate biopsy. Avoidance of transperineal prostate biopsy will be measured at 6 mo from randomisation. The primary endpoints will be analysed on an intention-to-treat basis. CONCLUSIONS: Patient enrolment began in March 2022, with recruitment expected to take 36 mo. PATIENT SUMMARY: For patients with suspected prostate cancer who have nonsuspicious or unclear MRI (magnetic resonance imaging) scan findings, a different type of scan (called PSMA PET/CT; prostate-specific membrane antigen positron emission tomography/computed tomography) may identify men who could avoid an invasive prostate biopsy. This type of scan could also help urologists in better targeting of samples from suspicious lesions during prostate biopsies.

Disease mapping: Geographic differences in population rates of interventional treatment for prostate cancer in Australia.

BACKGROUND: Treatment decisions for men diagnosed with prostate cancer depend on a range of clinical and patient characteristics such as disease stage, age, general health, risk of side effects and access. Associations between treatment patterns and area-level factors such as remoteness and socioeconomic disadvantage have been observed in many countries. OBJECTIVE: To model spatial differences in interventional treatment rates for prostate cancer at high spatial resolution to inform policy and decision-making. METHODS: Hospital separations data for interventional treatments for prostate cancer (radical prostatectomy, low dose rate and high dose rate brachytherapy) for men aged 40 years and over were modelled using spatial models, generalised linear mixed models, maximised excess events tests and k-means statistical clustering. RESULTS: Geographic differences in population rates of interventional treatments were found (p<0.001). Separation rates for radical prostatectomy were lower in remote areas (12.2 per 10 000 person-years compared with 15.0-15.9 in regional and major city areas). Rates for all treatments decreased with increasing socioeconomic disadvantage (radical prostatectomy 19.1 /10 000 person-years in the most advantaged areas compared with 12.9 in the most disadvantaged areas). Three groups of similar areas were identified: those with higher rates of radical prostatectomy, those with higher rates of low dose brachytherapy, and those with low interventional treatment rates but higher rates of excess deaths. The most disadvantaged areas and remote areas tended to be in the latter group. CONCLUSIONS: The geographic differences in treatment rates may partly reflect differences in patients' physical and financial access to treatments. Treatment rates also depend on diagnosis rates and thus reflect variation in investigation rates for prostate cancer and presentation of disease. Spatial variation in interventional treatments may aid identification of areas of under-treatment or over-treatment.

68Ga-PSMA-PET/CT in addition to mpMRI in men undergoing biopsy during active surveillance for low- to intermediate-risk prostate cancer: study protocol for a prospective cross-sectional study.

Background: In active surveillance there is significant interest in whether imaging modalities such as multiparametric magnetic resonance imaging (mpMRI) or 68Gallium prostate-specific membrane antigen positron emission tomography/computerized tomography (68Ga-PSMA-PET/CT) can improve the detection of progression to clinically significant prostate cancer (csPCa) and thus reduce the frequency of prostate biopsies and associated morbidity. Recent studies have demonstrated the value of mpMRI in active surveillance; however, mpMRI does miss a proportion of disease progression and thus alone cannot replace biopsy. To date, prostate-specific membrane antigen positron emission tomography (PSMA-PET) has shown additive value to mpMRI in its ability to detect prostate cancer (PCa) in the primary diagnostic setting. Our objective is to evaluate the diagnostic utility of PSMA-PET to detect progression to csPCa in active surveillance patients. Methods: We will perform a prospective, cross-sectional, partially blinded, multicentre clinical trial evaluating the additive value of PSMA-PET with mpMRI against saturation transperineal template prostate biopsy. Two hundred and twenty-five men will be recruited who have newly diagnosed PCa which is suitable for active surveillance. Following enrolment, patients will undergo a PSMA-PET and mpMRI within 3 months of a repeat 12-month confirmatory biopsy. Patients who remain on active surveillance after confirmatory biopsy will then be planned to have a further mpMRI and PSMA-PET prior to a repeat biopsy in 3-4 years. The primary outcome is to assess the ability of PSMA-PET to detect or exclude significant malignancy on repeat biopsy. Secondary outcomes include (I) assess the comparative diagnostic accuracies of mpMRI and PSMA-PET alone [sensitivity/specificity/negative predictive value (NPV)/positive predictive value (PPV)] to detect progression on biopsy based on predefined histologic criteria for progression; (II) comparison of index lesion identification by template biopsies vs. MRI targeted lesions vs. PSMA targeted lesions; (III) evaluation of concordance of lesions identified on final histopathology and each imaging modality (PSMA-PET and/or mpMRI) in the subset of patients proceeding to RP. Discussion: The results of this trial will define the role of PSMA-PET in active surveillance and potentially reduce the number of biopsies needed to detect progression to csPCa. Trial Registration: The current trial was registered with the ANZCTR on the 3/2/2022 with the trial ID ACTRN12622000188730, it is accessible at https://www.anzctr.org.au/.

A Novel Risk Calculator Incorporating Clinical Parameters, Multiparametric Magnetic Resonance Imaging, and Prostate-Specific Membrane Antigen Positron Emission Tomography for Prostate Cancer Risk Stratification Before Transperineal Prostate Biopsy.

Background: Prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) can detect multiparametric magnetic resonance imaging (mpMRI)-invisible prostate tumours and improve the sensitivity of detection of prostate cancer (PCa) in comparison to mpMRI alone. Numerous risk calculators have been validated as tools for stratification of men at risk of being diagnosed with clinically significant (cs)PCa. Objective: To develop a novel risk calculator using clinical parameters and imaging parameters from mpMRI and PSMA PET/CT in a cohort of patients undergoing mpMRI and PSMA PET/CT before biopsy. Design setting and participants: A total of 291 men from the PRIMARY prospective trial underwent mpMRI and PSMA PET/CT before transperineal prostate biopsy with sampling of systematic and targeted cores. Outcome measurements and statistical analysis: Novel risk calculators were developed using multivariable logistic regression analysis to predict detection of overall PCa (International Society of Urological Pathology grade group [GG] ≥1) and csPCa (GG ≥2). The risk calculators were then compared with the European Randomised Study of Screening for Prostate Cancer risk calculator incorporating mpMRI (ERSPC-MRI). Resampling methods were used to evaluate the discrimination and calibration of the risk calculators and to perform decision curve analysis. Results and limitations: Age, prostate-specific antigen, prostate volume, and mpMRI Prostate Imaging-Reporting and Data System scores were included in the MRI risk calculator, resulting in area under the receiver operating characteristic curve (AUC) values of 0.791 for overall PCa (GG ≥1) and 0.812 for csPCa (GG ≥2). Addition of the maximum standardised uptake value (SUVmax) on PSMA PET/CT for the prostate lesion, and of SUVmax for the mpMRI lesions for the MRI-PSMA risk calculator resulted in AUCs of 0.831 for overall PCa and 0.876 for csPCa (≥ISUP2).The ERSPC-MRI risk calculator had AUCs of 0.758 (p = 0.02) for overall PCa and 0.805 (p = 0.001) for csPCa. Both the MRI and MRI-PSMA risk calculators were superior to the ERSPC-MRI for both overall PCa and csPCa. Conclusions: These novel risk calculators incorporate clinical and radiological parameters for stratification of men at risk of csPCa. The risk calculator including PSMA PET/CT data is superior to a calculator incorporating mpMRI data alone. Patient summary: We evaluated a new risk calculator that uses clinical information and results from two types of scan to predict the risk of clinically significant prostate cancer on prostate biopsy. This risk model can guide patients and clinicians in shared decision-making and may help in avoiding unnecessary prostate biopsies.

Can 68 Ga-PSMA positron emission tomography and multiparametric MRI guide treatment for biochemical recurrence after radical prostatectomy?

OBJECTIVE: To evaluate the role of multiparametric magnetic resonance imaging (mpMRI) and Gallium-68 (68 Ga)-prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) in guiding salvage therapy for patients with biochemical recurrence (BCR) post-radical prostatectomy. PATIENTS AND METHODS: Patients were evaluated with paired mpMRI and 68 Ga-PSMA PET/CT scans for BCR (prostate-specific antigen [PSA] >0.2 ng/mL). Patient, tumour, PSA and imaging characteristics were analysed with descriptive statistics. RESULTS: A total of 117 patients underwent paired scans to investigate BCR, of whom 53.0% (62/117) had detectable lesions on initial scans and 47.0% (55/117) did not. Of those without detectable lesions, 8/55 patients proceeded to immediate salvage radiotherapy (sRT) and 47/55 were observed. Of patients with negative imaging who were initially observed, 46.8% (22/47) did not reach threshold for repeat imaging, while 53.2% were rescanned due to rising PSA levels. Of these rescanned patients, 31.9% (15/47) were spared sRT due to proven distant disease, or due to absence of disease on repeat imaging. Of the original 117 patients, 53 (45.3%) were spared early sRT due to absence of disease on imaging or presence of distant disease, while those undergoing delayed sRT still maintained good PSA responses. Of note, patients with high-risk features who underwent sRT despite negative imaging demonstrated satisfactory PSA responses to sRT. Study limitations include the observational design and absence of cause-specific or overall survival data. CONCLUSION: Our findings support the use of mpMRI and 68 Ga-PSMA PET/CT in guiding timing and necessity of salvage therapy tailored to detected lesions, with potential to reduce unnecessary sRT-related morbidity. Larger or randomized trials are warranted to validate this.

Trends and variation in prostate cancer diagnosis via transperineal biopsy in Australia and New Zealand.

BACKGROUND: To describe changes in the use of prostate biopsy techniques among men diagnosed with prostate cancer in Australia and New Zealand and examine factors associated with these changes. METHODS: We extracted data between 2015 and 2019 from 7 jurisdictions of the Australia and New Zealand Prostate Cancer Outcomes Registry (PCOR-ANZ). Distribution and time trend of transrectal (TR) vs. transperineal (TP) biopsy type, differences in the proportion of biopsy type by geographic jurisdiction, diagnosing institute characteristics (public vs. private, metropolitan vs. regional, case volume) and patient characteristics such as socio-economic status (SES), and location of residence were analyzed. RESULTS: We analyzed data from 37,638 patients. The overall proportion of prostate cancer diagnosed by TP increased from 26% to 57% between 2015 and 2019. Patients living in a major city, a more socioeconomically advantaged area or who were diagnosed in a metropolitan or private hospital were more likely to have TP than TR. While all subgroups were observed to increase their use of TP over the study period, uptake grew faster for men from low SES areas and those diagnosed at a regional or low-volume hospital but slower for men living in outer regional/remote areas or treated at a public hospital. CONCLUSIONS: In this binational registry, prostate cancer is now more commonly diagnosed by TP than the TR approach. While the gap between uptakes of TP has diminished for patients with low vs. high SES, disparity has widened for patients from outer regional areas vs major cities and public vs. private hospitals.

Management of patients with advanced prostate cancer-metastatic and/or castration-resistant prostate cancer: Report of the Advanced Prostate Cancer Consensus Conference (APCCC) 2022.

BACKGROUND: Innovations in imaging and molecular characterisation together with novel treatment options have improved outcomes in advanced prostate cancer. However, we still lack high-level evidence in many areas relevant to making management decisions in daily clinical practise. The 2022 Advanced Prostate Cancer Consensus Conference (APCCC 2022) addressed some questions in these areas to supplement guidelines that mostly are based on level 1 evidence. OBJECTIVE: To present the voting results of the APCCC 2022. DESIGN, SETTING, AND PARTICIPANTS: The experts voted on controversial questions where high-level evidence is mostly lacking: locally advanced prostate cancer; biochemical recurrence after local treatment; metastatic hormone-sensitive, non-metastatic, and metastatic castration-resistant prostate cancer; oligometastatic prostate cancer; and managing side effects of hormonal therapy. A panel of 105 international prostate cancer experts voted on the consensus questions. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The panel voted on 198 pre-defined questions, which were developed by 117 voting and non-voting panel members prior to the conference following a modified Delphi process. A total of 116 questions on metastatic and/or castration-resistant prostate cancer are discussed in this manuscript. In 2022, the voting was done by a web-based survey because of COVID-19 restrictions. RESULTS AND LIMITATIONS: The voting reflects the expert opinion of these panellists and did not incorporate a standard literature review or formal meta-analysis. The answer options for the consensus questions received varying degrees of support from panellists, as reflected in this article and the detailed voting results are reported in the supplementary material. We report here on topics in metastatic, hormone-sensitive prostate cancer (mHSPC), non-metastatic, castration-resistant prostate cancer (nmCRPC), metastatic castration-resistant prostate cancer (mCRPC), and oligometastatic and oligoprogressive prostate cancer. CONCLUSIONS: These voting results in four specific areas from a panel of experts in advanced prostate cancer can help clinicians and patients navigate controversial areas of management for which high-level evidence is scant or conflicting and can help research funders and policy makers identify information gaps and consider what areas to explore further. However, diagnostic and treatment decisions always have to be individualised based on patient characteristics, including the extent and location of disease, prior treatment(s), co-morbidities, patient preferences, and treatment recommendations and should also incorporate current and emerging clinical evidence and logistic and economic factors. Enrolment in clinical trials is strongly encouraged. Importantly, APCCC 2022 once again identified important gaps where there is non-consensus and that merit evaluation in specifically designed trials. PATIENT SUMMARY: The Advanced Prostate Cancer Consensus Conference (APCCC) provides a forum to discuss and debate current diagnostic and treatment options for patients with advanced prostate cancer. The conference aims to share the knowledge of international experts in prostate cancer with healthcare providers worldwide. At each APCCC, an expert panel votes on pre-defined questions that target the most clinically relevant areas of advanced prostate cancer treatment for which there are gaps in knowledge. The results of the voting provide a practical guide to help clinicians discuss therapeutic options with patients and their relatives as part of shared and multidisciplinary decision-making. This report focuses on the advanced setting, covering metastatic hormone-sensitive prostate cancer and both non-metastatic and metastatic castration-resistant prostate cancer. TWITTER SUMMARY: Report of the results of APCCC 2022 for the following topics: mHSPC, nmCRPC, mCRPC, and oligometastatic prostate cancer. TAKE-HOME MESSAGE: At APCCC 2022, clinically important questions in the management of advanced prostate cancer management were identified and discussed, and experts voted on pre-defined consensus questions. The report of the results for metastatic and/or castration-resistant prostate cancer is summarised here.

Decade-long trends in prostate cancer biopsy grade groups and treatment within a population-based registry.

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.

Testosterone suppression plus enzalutamide versus testosterone suppression plus standard antiandrogen therapy for metastatic hormone-sensitive prostate cancer (ENZAMET): an international, open-label, randomised, phase 3 trial.

BACKGROUND: The interim analysis of the ENZAMET trial of testosterone suppression plus either enzalutamide or standard nonsteroidal antiandrogen therapy showed an early overall survival benefit with enzalutamide. Here, we report the planned primary overall survival analysis, with the aim of defining the benefit of enzalutamide treatment in different prognostic subgroups (synchronous and metachronous high-volume or low-volume disease) and in those who received concurrent docetaxel. METHODS: ENZAMET is an international, open-label, randomised, phase 3 trial conducted at 83 sites (including clinics, hospitals, and university centres) in Australia, Canada, Ireland, New Zealand, the UK, and the USA. Eligible participants were males aged 18 years or older with metastatic, hormone-sensitive prostate adenocarcinoma evident on CT or bone scanning with 99mTc and an Eastern Cooperative Oncology Group performance status score of 0-2. Participants were randomly assigned (1:1), using a centralised web-based system and stratified by volume of disease, planned use of concurrent docetaxel and bone antiresorptive therapy, comorbidities, and study site, to receive testosterone suppression plus oral enzalutamide (160 mg once per day) or a weaker standard oral non-steroidal antiandrogen (bicalutamide, nilutamide, or flutamide; control group) until clinical disease progression or prohibitive toxicity. Testosterone suppression was allowed up to 12 weeks before randomisation and for up to 24 months as adjuvant therapy. Concurrent docetaxel (75 mg/m2 intravenously) was allowed for up to six cycles once every 3 weeks, at the discretion of participants and physicians. The primary endpoint was overall survival in the intention-to-treat population. This planned analysis was triggered by reaching 470 deaths. This study is registered with ClinicalTrials.gov, NCT02446405, ANZCTR, ACTRN12614000110684, and EudraCT, 2014-003190-42. FINDINGS: Between March 31, 2014, and March 24, 2017, 1125 participants were randomly assigned to receive non-steroidal antiandrogen (n=562; control group) or enzalutamide (n=563). The median age was 69 years (IQR 63-74). This analysis was triggered on Jan 19, 2022, and an updated survival status identified a total of 476 (42%) deaths. After a median follow-up of 68 months (IQR 67-69), the median overall survival was not reached (hazard ratio 0·70 [95% CI 0·58-0·84]; p<0·0001), with 5-year overall survival of 57% (0·53-0·61) in the control group and 67% (0·63-0·70) in the enzalutamide group. Overall survival benefits with enzalutamide were consistent across predefined prognostic subgroups and planned use of concurrent docetaxel. The most common grade 3-4 adverse events were febrile neutropenia associated with docetaxel use (33 [6%] of 558 in the control group vs 37 [6%] of 563 in the enzalutamide group), fatigue (four [1%] vs 33 [6%]), and hypertension (31 [6%] vs 59 [10%]). The incidence of grade 1-3 memory impairment was 25 (4%) versus 75 (13%). No deaths were attributed to study treatment. INTERPRETATION: The addition of enzalutamide to standard of care showed sustained improvement in overall survival for patients with metastatic hormone-sensitive prostate cancer and should be considered as a treatment option for eligible patients. FUNDING: Astellas Pharma.

Is There an Impact of Transperineal Versus Transrectal Magnetic Resonance Imaging-targeted Biopsy on the Risk of Upgrading in Final Pathology in Prostate Cancer Patients Undergoing Radical Prostatectomy? An European Association of Urology-Young Academic Urologists Prostate Cancer Working Group Multi-institutional Study.

BACKGROUND: The concordance rates of transperineal (TP) versus transrectal (TR) prostate biopsies with radical prostatectomy (RP) specimen have been assessed poorly in men diagnosed with magnetic resonance imaging (MRI)-targeted biopsy (TBx). OBJECTIVE: To evaluate International Society of Urological Pathology (ISUP) concordance rates between the final pathology at RP and MRI-TBx or MRI-TBx + random biopsy (RB) according to the biopsy approach. DESIGN, SETTING, AND PARTICIPANTS: A multi-institutional database included patients diagnosed with TP or TR treated with RP. INTERVENTION: TP-TBx or TR-TBx of the prostate. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The ISUP grade at biopsy was compared with the final pathology. A multivariable logistic regression analysis (MVA) was performed to assess the association between the biopsy approach (TP-TBx vs TR-TBx) and ISUP upgrading, downgrading, concordance, and clinically relevant increase (CRI). RESULTS AND LIMITATIONS: Overall, 752 (59%) versus 530 (41%) patients underwent TR versus TP. At the MVA, TP-TBx was an independent predictor of upgrading (odds ratio [OR] 0.6, 95% confidence interval [CI] 0.4-0.9, p < 0.01) and improved concordance relative to the final pathology (OR 1.7, 95% CI 1.2-2.5, p < 0.01) after adjusting for age, cT stage, Prostate Imaging Reporting and Data System, number of targeted cores, prostate-specific antigen, and prostate volume. Moreover, TP-TBx was associated with a lower risk of CRI than TR-TBx (OR 0.7, p < 0.01). This held true when considering patients who underwent MRI-TBx + RB (OR 0.6, p < 0.01). The inclusion of men who had RP represents a potential selection bias. CONCLUSIONS: The adoption of TP-TBx compared with TR-TBx may reduce the risk of upgrading and improve the concordance of biopsy grade with the final pathology. The TP approach decreases the odds of CRI with improved patient selection for the correct active treatment. PATIENT SUMMARY: In this report, we evaluated whether transperineal (TP) targeted biopsy (TBx) may improve the concordance of clinically significant prostate cancer with the final pathology in comparison with transrectal (TR) TBx in a large worldwide population. We found that TP-TBx might increase concordance compared with TR-TBx. Adding random biopsies to target one increases accuracy; however, concordance with the final pathology is overall suboptimal even with the TP approach.