Search

Background: Active surveillance (AS) is recommended for low-risk and some intermediate-risk prostate cancer. Uptake and practice of AS vary significantly across different settings, as does the experience of surveillance-from which tests are offered, and to the levels of psychological support., Objective: To explore the current best practice and determine the most important research priorities in AS for prostate cancer., Design, Setting, and Participants: A formal consensus process was followed, with an international expert panel of purposively sampled participants across a range of health care professionals and researchers, and those with lived experience of prostate cancer. Statements regarding the practice of AS and potential research priorities spanning the patient journey from surveillance to initiating treatment were developed., Outcome Measurements and Statistical Analysis: Panel members scored each statement on a Likert scale. The group median score and measure of consensus were presented to participants prior to discussion and rescoring at panel meetings. Current best practice and future research priorities were identified, agreed upon, and finally ranked by panel members., Results and Limitations: There was consensus agreement that best practice includes the use of high-quality magnetic resonance imaging (MRI), which allows digital rectal examination (DRE) to be omitted, that repeat standard biopsy can be omitted when MRI and prostate-specific antigen (PSA) kinetics are stable, and that changes in PSA or DRE should prompt MRI ± biopsy rather than immediate active treatment. The highest ranked research priority was a dynamic, risk-adjusted AS approach, reducing testing for those at the least risk of progression. Improving the tests used in surveillance, ensuring equity of access and experience across different patients and settings, and improving information and communication between and within clinicians and patients were also high priorities. Limitations include the use of a limited number of panel members for practical reasons., Conclusions: The current best practice in AS includes the use of high-quality MRI to avoid DRE and as the first assessment for changes in PSA, with omission of repeat standard biopsy when PSA and MRI are stable. Development of a robust, dynamic, risk-adapted approach to surveillance is the highest research priority in AS for prostate cancer., Patient Summary: A diverse group of experts in active surveillance, including a broad range of health care professionals and researchers and those with lived experience of prostate cancer, agreed that best practice includes the use of high-quality magnetic resonance imaging, which can allow digital rectal examination and some biopsies to be omitted. The highest research priority in active surveillance research was identified as the development of a dynamic, risk-adjusted approach., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Purpose: Lutetium labelled prostate-specific membrane antigen radioligand therapy (Lu-PSMA RLT) has shown pleasing early results in management of high-volume metastatic castration resistant prostate cancer (mCRPC), but its role in the early treatment of men with only lymph node metastasis (LNM) is unknown. The aim was to assess the outcome of Lu-PSMA RLT earlier in the treatment of men with only LNM., Materials and Methods: Single institution retrospective review of men with only LNM on staging Ga-PSMA PET PSMA who proceeded with Lu-PSMA RLT., Results: There were 17 men with only LNM, including 13 with mCRPC and 3 who were both hormone and chemotherapy naïve. The median PSA was 3.7 (0.46-120 ng/mL). A PSA decline of ≥50% occurred in 10/17 (58.8%), decreasing to <0.2 ng/mL in 35.3% (6/17). The PSA continues to decline or remain stable in 10/17 (58.8%) with a median follow-up of 13 months, and 8/17 (47.1%) have not reached their pre-treatment levels. There were no significant side effects. There was a better PSA response in men without prior chemotherapy (p=0.05). The prostate cancer specific and overall survival is 82.4% (14/17)., Conclusions: Our results identify improved PSA response to Lu-PSMA RLT in men with only LNM, especially in the chemotherapy naïve cohort, compared to previous series with more advanced mCRPC. These findings provide important proof of principle to aid with planning of future prospective randomized trials evaluating the role of Lu-PSMA RLT earlier in the management of node metastatic prostate cancer, including men naïve of ADT and chemotherapy., Competing Interests: The authors have nothing to disclose., (© The Korean Urological Association, 2021.)

Background: Careful assessment of the reasons for discontinuation of active surveillance (AS) is required for men with prostate cancer (PCa)., Objective: Using Movember's Global Action Plan Prostate Cancer Active Surveillance initiative (GAP3) database, we report on reasons for AS discontinuation., Design, Setting, and Participants: We compared data from 10296 men on AS from 21 centres across 12 countries., Outcome Measurements and Statistical Analysis: Cumulative incidence methods were used to estimate the cumulative incidence rates of AS discontinuation., Results and Limitations: During 5-yr follow-up, 27.5% (95% confidence interval [CI]: 26.4-28.6%) men showed signs of disease progression, 12.8% (95% CI: 12.0-13.6%) converted to active treatment without evidence of progression, 1.7% (95% CI: 1.5-2.0%) continued to watchful waiting, and 1.7% (95% CI: 1.4-2.1%) died from other causes. Of the 7049 men who remained on AS, 2339 had follow-up for >5yr, 4561 had follow-up for <5yr, and 149 were lost to follow-up. Cumulative incidence of progression was 27.5% (95% CI: 26.4-28.6%) at 5yr and 38.2% (95% CI: 36.7-39.9%) at 10yr. A limitation is that not all centres were included due to limited information on the reason for discontinuation and limited follow-up., Conclusions: Our descriptive analyses of current AS practices worldwide showed that 43.6% of men drop out of AS during 5-yr follow-up, mainly due to signs of disease progression. Improvements in selection tools for AS are thus needed to correctly allocate men with PCa to AS, which will also reduce discontinuation due to conversion to active treatment without evidence of disease progression., Patient Summary: Our assessment of a worldwide database of men with prostate cancer (PCa) on active surveillance (AS) shows that 43.6% drop out of AS within 5yr, mainly due to signs of disease progression. Better tools are needed to select and monitor men with PCa as part of AS., (Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Purpose: This study aimed to evaluate (1) the time interval between a decision to commence on active surveillance (AS) and grade progression in community practice; (2) factors predicting grade progression in localised prostate cancer (CaP) patients apparently undergoing AS., Methods: Data from the Prostate Cancer Outcomes Registry-Victoria were used to analyze men with Gleason 3 + 3 CaP or less who had at least one repeat biopsy. Unadjusted and adjusted 5-year Kaplan-Meier survival curves were used to assess the time to grade progression. Both univariate and multivariate analyses for grade progression were performed using Cox proportional hazards., Results: The cohort included 951 men. Overall, 39% of men had Gleason grade reclassified to a higher risk disease state with median of 2.2 years [IQR 1.2-3.7 years]. Men who harboured cT2 disease were 30% more likely to have upgrading compared to men with cT1 disease (adjusted HR: 1.3, 95% CI 1.0-1.6, p = 0.048). Half of the men with cT2 in our cohort had their Gleason grade reclassified within 1.6 years from diagnosis as compared with 2.7 years for the cT1 group. The presence of percentage of core involvement >25.0% and a PSA velocity of >1.01 ng/mL/year remained significant for a higher progression rate. The adjusted HR: 1.6; 95% CI [1.2-2.3], p = 0.004; adjusted HR: 1.6, 95% CI [1.2-2.4], p = 0.021, for percent of core involvement of 25.1-37.5%, and ≥37.6%, respectively. The adjusted HRs and p value associated with PSA velocity were 1.5; 95% CI [1.1-2.1], p = 0.016 and 1.6; 95% CI [1.2-2.3], p = 0.003 for PSA velocity values of 1.01-2 ng/mL per year and >2 ng/mL per year, respectively. Men who were diagnosed in regional hospital and subsequently had biopsy in metropolitan hospital were twice at risk of having Gleason upgrade compared to those whom both diagnostic and surveillance biopsies were carried out in metropolitan hospitals (adjusted HR: 1.9; 95% CI 1.1-3.3, p = 0.029)., Conclusions: When placing men on AS and considering time to histologic progression, clinicians should pay particular attention to the likely accuracy of the diagnostic specimen, their tumour stage, volume of tumour (percent of core involvement), and rising PSA. Those diagnosed with T2 disease and had >25.0% of core involvement, and a PSA velocity greater than 1 ng/mL per year is at particular risk for more rapid disease progression and, for this reason, should be counselled on the importance of following the recommended surveillance regimen. For half of these men, their disease will have 'progressed' according to biopsy results in 2 years.

Prostate-specific antigen (PSA) testing of men at normal risk of prostate cancer is one of the most contested issues in cancer screening. There is no formal screening program, but testing is common - arguably a practice that ran ahead of the evidence. Public and professional communication about PSA screening has been highly varied and potentially confusing for practitioners and patients alike. There has been much research and policy activity relating to PSA testing in recent years. Landmark randomised controlled trials have been reported; authorities - including the 2013 Prostate Cancer World Congress, the Prostate Cancer Foundation of Australia, Cancer Council Australia, and the National Health and Medical Research Council - have made or endorsed public statements and/or issued clinical practice guidelines; and the US Preventive Services Task Force is revising its recommendations. But disagreement continues. The contention is partly over what the new evidence means. It is also a result of different valuing and prioritisation of outcomes that are hard to compare: prostate cancer deaths prevented (a small and disputed number); prevention of metastatic disease (somewhat more common); and side-effects of treatment such as incontinence, impotence and bowel trouble (more common again). A sizeable proportion of men diagnosed through PSA testing (somewhere between 20% and 50%) would never have had prostate cancer symptoms sufficient to prompt investigation; many of these men are older, with competing comorbidities. It is a complex picture. Below are four viewpoints from expert participants in the evolving debate, commissioned for this cancer screening themed issue of Public Health Research & Practice. We asked the authors to respond to the challenge of PSA testing of asymptomatic, normal-risk men. They raise important considerations: uncertainty, harms, the trustworthiness and interpretation of the evidence, cost (e.g. of using multiparametric magnetic resonance imaging to triage patients with elevated PSA), a likely bias towards intervention (particularly for cancer), and the potential to limit harm by treating more conservatively (although this may not occur consistently). They provide important insights, and disagree on some issues, but generally concur that men should decide for themselves whether to be tested. It seems reasonable to support men's autonomy to make their own decisions based on their own values. However, the support men might require to decide is likely to be considerable, and this needs to be taken seriously in policy making., Competing Interests: BA’s then-employer, the Sax Institute, was reimbursed by the PCFA for remunerated time spent advising the systematic evidence review team for the PSA testing guideline and on writing parts of the guideline document. BA chairs the PCFA’s Research Advisory Committee and is an ex officio member of its National Board. BA receives no remuneration for either of these memberships, but all expenses for attending meetings are paid for by the PCFA, and he attends Committee and Board dinners hosted by the PCFA. BA is an Associate Investigator of a PCFA-funded randomised controlled trial of vitamin D in the prevention of progression of prostate cancer managed by active surveillance. He was one of the initiators of the process to develop an Australian guideline for PSA testing and the early management of test-detected prostate cancer, and was a member of the expert advisory panel that oversaw development of the guideline and agreed on its final text. MB is a member of the USPSTF. His viewpoint does not necessarily represent the views and policies of the USPSTF. MB received salary support from the nonprofit organisation Healthwise as Chief Science Officer, and Healthwise provided grants to Massachusetts General Hospital for MB’s prostate-related and shared decision making research. RG is a member of the Andrology Australia Advisory Board and is also involved in NHMRC- and Movember-supported research into management of men with prostate cancer. RG and MF were members of the expert advisory panel for the NHMRC-approved Australian guidelines for PSA testing. IH is a consultant oncologist who sees men in paid consultations who want second opinions about how to proceed with their PSA or biopsy results.

Background: Androgen-deprivation therapy is offered to men with prostate cancer who have a rising prostate-specific antigen after curative therapy (PSA relapse) or who are considered not suitable for curative treatment; however, the optimal timing for its introduction is uncertain. We aimed to assess whether immediate androgen-deprivation therapy improves overall survival compared with delayed therapy., Methods: In this randomised, multicentre, phase 3, non-blinded trial, we recruited men through 29 oncology centres in Australia, New Zealand, and Canada. Men with prostate cancer were eligible if they had a PSA relapse after previous attempted curative therapy (radiotherapy or surgery, with or without postoperative radiotherapy) or if they were not considered suitable for curative treatment (because of age, comorbidity, or locally advanced disease). We used a database-embedded, dynamically balanced, randomisation algorithm, coordinated by the Cancer Council Victoria, to randomly assign participants (1:1) to immediate androgen-deprivation therapy (immediate therapy arm) or to delayed androgen-deprivation therapy (delayed therapy arm) with a recommended interval of at least 2 years unless clinically contraindicated. Randomisation for participants with PSA relapse was stratified by type of previous therapy, relapse-free interval, and PSA doubling time; randomisation for those with non-curative disease was stratified by metastatic status; and randomisation in both groups was stratified by planned treatment schedule (continuous or intermittent) and treatment centre. Clinicians could prescribe any form and schedule of androgen-deprivation therapy and group assignment was not masked. The primary outcome was overall survival in the intention-to-treat population. The trial closed to accrual in 2012 after review by the independent data monitoring committee, but data collection continued for 18 months until Feb 26, 2014. It is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12606000301561) and ClinicalTrials.gov (NCT00110162)., Findings: Between Sept 3, 2004, and July 13, 2012, we recruited 293 men (261 with PSA relapse and 32 with non-curable disease). We randomly assigned 142 men to the immediate therapy arm and 151 to the delayed therapy arm. Median follow-up was 5 years (IQR 3·3-6·2) from the date of randomisation. 16 (11%) men died in the immediate therapy arm and 30 (20%) died in the delayed therapy arm. 5-year overall survival was 86·4% (95% CI 78·5-91·5) in the delayed therapy arm versus 91·2% (84·2-95·2) in the immediate therapy arm (log-rank p=0·047). After Cox regression, the unadjusted HR for overall survival for immediate versus delayed arm assignment was 0·55 (95% CI 0·30-1·00; p=0·050). 23 patients had grade 3 treatment-related adverse events. 105 (36%) men had adverse events requiring hospital admission; none of these events were attributable to treatment or differed between treatment-timing groups. The most common serious adverse events were cardiovascular, which occurred in nine (6%) patients in the delayed therapy arm and 13 (9%) in the immediate therapy arm., Interpretation: Immediate receipt of androgen-deprivation therapy significantly improved overall survival compared with delayed intervention in men with PSA-relapsed or non-curable prostate cancer. The results provide benchmark evidence of survival rates and morbidity to discuss with men when considering their treatment options., Funding: Australian National Health and Medical Research Council and Cancer Councils, The Royal Australian and New Zealand College of Radiologists, Mayne Pharma Australia., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

• Currently there is significant confusion and polarisation about prostate cancer screening for both patients and physicians alike. • We propose a risk-adjusted testing programme, which would lead to fewer patients who need to be tested and treated to save a life and also eliminate inappropriate prostate-specific antigen testing in the elderly and patients with severe co-morbidities where there is no clear benefit., (© 2012 THE AUTHORS. BJU INTERNATIONAL © 2012 BJU INTERNATIONAL.)

Objectives: To determine the effects of diets rich in soy and linseed compared with a control diet on biochemical markers of prostate cancer in men diagnosed with prostate cancer., Methods: Twenty-nine men diagnosed with prostate cancer and scheduled to undergo a radical prostatectomy were randomized to one of three groups: soy (high phytoestrogen), soy and linseed (high phytoestrogen), or wheat (low phytoestrogen). A bread was specially manufactured to incorporate 50 g of heat-treated (HT) soy grits or 50 g of HT soy grits and 20 g of linseed as part of the study participant's daily diet. Baseline and preoperative levels of prostate-specific antigen (PSA), free PSA, testosterone, sex hormone-binding globulin, free androgen index, and dihydrotestosterone were measured., Results: Statistically significant differences were detected between the HT soy grits group and the control wheat group for the percentage of change in total PSA (-12.7% versus 40%, P = 0.02) and the percentage of change in free/total PSA ratio (27.4% versus -15.6%, P = 0.01); and between the HT soy grits group and the HT soy grits and linseed group for the percentage of change in free androgen index (16.4% versus -15.5%, P = 0.04) and the percentage of change in free/total PSA ratio (27.4% versus -10%, P = 0.007)., Conclusions: The data from this study indicate that a daily diet containing four slices of a bread rich in HT soy grits favorably influences the PSA level and the free/total PSA ratio in patients with prostate cancer. This work provides some evidence to support epidemiologic studies claiming that male populations who consume high phytoestrogen diets have a reduced risk of prostate cancer development and progression.

Epidemiological evidence suggests a geographical basis for the incidence of prostate cancer and dietary factors, including isoflavone consumption, may be linked to this phenomenon. This paper reports a nonrandomized, nonblinded trial with historically matched controls from archival tissue designed to determine the effects of acute exposure to a dietary supplement of isoflavones in men with clinically significant prostate cancer before radical prostatectomy. Thirty-eight patients were recruited to the study upon diagnosis of prostate cancer. Before surgery, 20 men consumed 160 mg/day of red clover-derived dietary isoflavones, containing a mixture of genistein, daidzein, formononetin, and biochanin A. Serum PSA, testosterone, and biochemical factors were measured, and clinical and pathological parameters were recorded. The incidence of apoptosis in prostate tumor cells from radical prostatectomy specimens was compared between 18 treated and 18 untreated control tissues. There were no significant differences between pre- and posttreatment serum PSA, Gleason score, serum testosterone, or biochemical factors in the treated patients (P > 0.05). Apoptosis in radical prostatectomy specimens from treated patients was significantly higher than in control subjects (P = 0.0018), specifically in regions of low to moderate-grade cancer (Gleason grade 1-3). No adverse events related to the treatment were reported. This report suggests that dietary isoflavones may halt the progression of prostate cancer by inducing apoptosis in low to moderate-grade tumors, potentially contributing to the lower incidence of clinically significant disease in Asian men. The assessment of new prostatic therapies aimed at increasing apoptosis should control for intake of dietary isoflavones.

BackgroundThe optimal interval for repeat biopsy during active surveillance (AS) for prostate cancer is yet to be defined. This study examined whether risk of upgrading (to grade group ≥ 2) or risk of converting to treatment varied according to intensity of repeat biopsy using data from the GAP3 consortium's global AS database.Materials and methodsIntensity of surveillance biopsy schedules was categorized according to centers' protocols: (a) Prostate Cancer Research International Active Surveillance project (PRIAS) protocols with biopsies at years 1, 4, and 7 (10 centers; 7532 men); (b) biennial biopsies, that is, every other year (8 centers; 4365 men); and (c) annual biopsy schedules (4 centers; 1602 men). Multivariable Cox regression was used to compare outcomes according to biopsy intensity.ResultsOut of the 13,508 eligible participants, 56% were managed according to PRIAS protocols (biopsies at years 1, 4, and 7), 32% via biennial biopsy, and 12% via annual biopsy. After adjusting for baseline characteristics, risk of converting to treatment was greater for those on annual compared with PRIAS biopsy schedules (hazard ratio [HR] = 1.66; 95% confidence interval [CI] = 1.51-1.83; p

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.

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. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the role of multiparametric magnetic resonance imaging (mpMRI) and Gallium‐68 (68Ga)‐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 68Ga‐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 68Ga‐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. [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]

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]

Stereotactic body radiotherapy (SBRT) can delay escalation to systemic treatment in men with oligometastatic prostate cancer (PCa). However, large, prospective studies are still required to evaluate the efficacy of this approach in different patient groups. This is the interim analysis of a prospective, single institution study of men relapsing with up to five synchronous lesions following definitive local treatment for primary PCa. Our aim was to determine the proportion of patients not requiring treatment escalation following SBRT. In total, 199 patients were enrolled to receive fractionated SBRT (50 Gray in 10 fractions) to each visible lesion. Fourteen patients were castration resistant at enrolment. The proportion of patients not requiring treatment escalation 2 years following SBRT was 51.7% (95% CI: 44.1–59.3%). The median length of treatment escalation‐free survival over the entire follow‐up period was 27.1 months (95% CI; 21.8–29.4 months). Prior androgen deprivation therapy (ADT) predicted a significantly lower rate of freedom from treatment escalation at 2 years compared to no prior ADT (odds ratio = 0.21, 95% CI: 0.08–0.54, p = 0.001). There was no difference in the efficacy of SBRT when treating 4–5 vs. 1–3 initial lesions. A prostate‐specific antigen (PSA) decline was induced in 75% of patients, with PSA readings falling to an undetectable level in six patients. No late grade three toxicities were observed. These interim results suggest that SBRT can be used to treat up to five synchronous PCa oligometastases to delay treatment escalation. What's new? Metastasis‐directed therapy (MDT), involving surgery or stereotactic ablative radiotherapy, is a promising alternative treatment strategy for prostate cancer patients with metastatic disease. It remains unclear, however, which subsets of patients most benefit from MDT. Here, interim analysis of a large prospective trial involving fractionated stereotactic body radiotherapy (SBRT) for prostate cancer patients with up to five synchronous oligometastases shows that 2 years following SBRT, about half of patients did not require treatment escalation. In addition, nearly one‐quarter of patients had prostate‐specific antigen levels below baseline. The findings highlight the promise of SBRT for long‐term suppression of oligometastatic prostate cancer. [ABSTRACT FROM AUTHOR]

While measurement of serum prostate specific antigen (PSA) is an important screening tool for prostate cancer, new biomarkers are necessary for better discrimination between presence and absence of disease. The MIL-38 monoclonal antibody is specific for the membrane glycoprotein glypican 1 (GPC-1) and binds to prostate cancer tissue. Urine is known to be a source of cellular material. Thus, we hypothesized that detection of GPC-1 in urine cellular material may identify individuals with prostate cancer. Urine samples from patients with prostate cancer, benign prostatic hyperplasia (BPH), or normal controls were collected and cell sediments prepared. GPC-1-positive cells were detected using a MIL-38 immunofluorescence assay (IFA) and samples were classed positive or negative for GPC-1 expressing cells. Assay sensitivity and specificity, stratified by PSA, was reported. A total of 125 patient samples were analyzed (N = 41 prostate cancer; N = 37 BPH; N = 47 normal controls). The use of MIL-38 to detect GPC-1 by IFA discriminated between prostate cancer and BPH urine specimens with a sensitivity and specificity of 71% and 76%, respectively. Assay specificity increased with increasing PSA, with the highest specificity (89%) for patients with PSA ≥4 ng/ml. At lower PSA (<2 ng/ml) specificity decreased, as evidenced by a greater number of false positives in this concentration range. The odds ratio (OR) and 95% confidence intervals (CIs) for GPC-1-positive cells in patients with prostate cancer, adjusted for PSA, was greatest at the lowest serum PSA (<2 ng/ml; OR = 13.4; 95% CI: 4.0–44.7) compared with no adjustment for PSA (OR = 6.4; 95% CI: 2.8–14.9). The use of MIL-38 for detection of GPC-1 may be a useful tool for detection of prostate cancer. [ABSTRACT FROM AUTHOR]

Background: To describe trajectories of health-related quality of life (QoL), life satisfaction, and psychological adjustment for men with prostate cancer over the medium to long term and identify predictors of poorer outcomes using growth mixture models.Methods: One-thousand sixty-four (82.4% response) men diagnosed with prostate cancer were recruited close to diagnosis and assessed over a 72-month (6-year) period with self-report assessment of health-related QoL, life satisfaction, cancer-related distress, and prostate specific antigen anxiety. Urinary, bowel, and sexual function were also assessed using validated questionnaires.Results: Poorer physical QOL was predicted by older age, lower education, lower income, comorbidities, and receiving hormone therapy. Lower life satisfaction was related to younger age, lower income, not being partnered, and comorbidities. Poorer psychological trajectories were predicted by younger age, lower income, comorbidities, and receiving radical prostatectomy or brachytherapy. Better urinary, bowel, and sexual function were related to better global outcomes over time. Anxiety about prostate specific antigen testing was rare.Conclusions: Distinct trajectories exist for medium- to long-term QoL, life satisfaction, and psychological adjustment after prostate cancer; with age and socioeconomic deprivation playing a differential role in men's survivorship profile and the impact of functional status on outcomes increasing over time. These results reinforce the need for an appraisal of men's life course in addition to treatment side effects when planning survivorship care after cancer. [ABSTRACT FROM AUTHOR]

The authors offer a systematic review of studies on the psychological interventions for prostate cancer survivors and their partners. Topics include the change in the medical and social context of prostate cancer since the introduction of prostate-specific antigen (PSA) testing, clinical questions that guided the review, and effects of psychosocial and psychosexual intervention on men with prostate cancer.

Background The diagnosis of prostate cancer has long been plagued by the absence of an imaging tool that reliably detects and localises significant tumours. Recent evidence suggests that multi-parametric MRI could improve the accuracy of diagnostic assessment in prostate cancer. This review serves as a background to a recent USANZ position statement. It aims to provide an overview of MRI techniques and to critically review the published literature on the clinical application of MRI in prostate cancer., Technical Aspects The combination of anatomical (T2-weighted) MRI with at least two of the three functional MRI parameters - which include diffusion-weighted imaging, dynamic contrast-enhanced imaging and spectroscopy - will detect greater than 90% of significant (moderate to high risk) tumours; however MRI is less reliable at detecting tumours that are small (<0.5 cc), low grade (Gleason score 6) or in the transitional zone. The higher anatomical resolution provided by 3-Tesla magnets and endorectal coils may improve the accuracy, particularly in primary tumour staging., Screening The use of mpMRI to determine which men with an elevated PSA should undergo biopsy is currently the subject of two large clinical trials in Australia. MRI should be used with caution in this setting and then only in centres with established uro-radiological expertise and quality control mechanisms in place. There is sufficient evidence to justify using MRI to determine the need for repeat biopsy and to guide areas in which to focus repeat biopsy., Image-Directed Biopsy MRI-directed biopsy is an exciting concept supported by promising early results, but none of the three proposed techniques have so far been proven superior to standard biopsy protocols. Further evidence of superior accuracy and core-efficiency over standard biopsy is required, before their costs and complexities in use can be justified., Treatment Selection and Planning When used for primary-tumour staging (T-staging), MRI has limited sensitivity for T3 disease, but its specificity of greater than 95% may be useful in men with intermediate-high risk disease to identify those with advanced T3 disease not suitable for nerve sparing or for surgery at all. MRI appears to be of value in planning dosimetry in men undergoing radiotherapy, and in guiding selection for and monitoring on active surveillance. [ABSTRACT FROM AUTHOR]

Objective: To analyse the performance of the quality of prostate cancer (CaP) care over a 5-year period with reference to three quality indicators (QIs) reported by the Prostate Cancer Outcomes Registry-Victoria (PCOR-Vic):QI-1: Alignment with the modified Prostate Cancer Research International Active Surveillance (PRIAS) protocol guideline;QI-2: Timeliness of CaP care for men with high risk and locally advanced disease;QI-3: Positive surgical margins (PSMs) for organ-confined pathological T2 disease.Design, Setting and Participants: Between 1 January 2009 and 31 December 2013, 4708 men diagnosed with CaP who met the QI-1, QI-2 or QI-3 inclusion criteria were recruited from Victorian hospitals.Outcome measures and statistical analysis: Trend analysis was conducted to monitor performance according to QI-1, QI-2 and QI-3. We used the autoregressive integrated moving average (ARIMA) model to account for any inherent autocorrelation in the data when analysing the monthly incidence of each indicator. Differences in the annual figures for the indicators across years were also analysed by aggregating data by year and applying the ARIMA model.Results and Limitations: There was a downward trend over the 5 years in the percentage of men with low risk disease who underwent active treatment (45% to 34%; P = 0.024), an upward trend in the percentage of those with high risk and locally advanced disease who received active treatment within 12 months of diagnosis (88% to 93%; P = 0.181), and a decline in PSM rate in men with pathological T2 disease after radical prostatectomy (21% to 12%; P = 0.036). Limitations of the study include the fact that the improvement in the QIs was detected using PCOR-Vic as a single population, but there may be institutional variations in quality improvement.Conclusions: Over 2009-2013, the performance of the Victorian health system improved according to the three processes of care indicators reported by the PCOR-Vic. [ABSTRACT FROM AUTHOR]

Background: Adjuvant radiotherapy has been shown to halve the risk of biochemical progression for patients with high-risk disease after radical prostatectomy. Early salvage radiotherapy could result in similar biochemical control with lower treatment toxicity. We aimed to compare biochemical progression between patients given adjuvant radiotherapy and those given salvage radiotherapy.Methods: We did a phase 3, randomised, controlled, non-inferiority trial across 32 oncology centres in Australia and New Zealand. Eligible patients were aged at least 18 years and had undergone a radical prostatectomy for adenocarcinoma of the prostate with pathological staging showing high-risk features defined as positive surgical margins, extraprostatic extension, or seminal vesicle invasion; had an Eastern Cooperative Oncology Group performance status of 0-1, and had a postoperative prostate-specific antigen (PSA) concentration of 0·10 ng/mL or less. Patients were randomly assigned (1:1) using a minimisation technique via an internet-based, independently generated allocation to either adjuvant radiotherapy within 6 months of radical prostatectomy or early salvage radiotherapy triggered by a PSA of 0·20 ng/mL or more. Allocation sequence was concealed from investigators and patients, but treatment assignment for individual randomisations was not masked. Patients were stratified by radiotherapy centre, preoperative PSA, Gleason score, surgical margin status, and seminal vesicle invasion status. Radiotherapy in both groups was 64 Gy in 32 fractions to the prostate bed without androgen deprivation therapy with real-time review of plan quality on all cases before treatment. The primary endpoint was freedom from biochemical progression. Salvage radiotherapy would be deemed non-inferior to adjuvant radiotherapy if freedom from biochemical progression at 5 years was within 10% of that for adjuvant radiotherapy with a hazard ratio (HR) for salvage radiotherapy versus adjuvant radiotherapy of 1·48. The primary analysis was done on an intention-to-treat basis. This study is registered with ClinicalTrials.gov, NCT00860652.Findings: Between March 27, 2009, and Dec 31, 2015, 333 patients were randomly assigned (166 to adjuvant radiotherapy; 167 to salvage radiotherapy). Median follow-up was 6·1 years (IQR 4·3-7·5). An independent data monitoring committee recommended premature closure of enrolment because of unexpectedly low event rates. 84 (50%) patients in the salvage radiotherapy group had radiotherapy triggered by a PSA of 0·20 ng/mL or more. 5-year freedom from biochemical progression was 86% (95% CI 81-92) in the adjuvant radiotherapy group versus 87% (82-93) in the salvage radiotherapy group (stratified HR 1·12, 95% CI 0·65-1·90; pnon-inferiority=0·15). The grade 2 or worse genitourinary toxicity rate was lower in the salvage radiotherapy group (90 [54%] of 167) than in the adjuvant radiotherapy group (116 [70%] of 166). The grade 2 or worse gastrointestinal toxicity rate was similar between the salvage radiotherapy group (16 [10%]) and the adjuvant radiotherapy group (24 [14%]).Interpretation: Salvage radiotherapy did not meet trial specified criteria for non-inferiority. However, these data support the use of salvage radiotherapy as it results in similar biochemical control to adjuvant radiotherapy, spares around half of men from pelvic radiation, and is associated with significantly lower genitourinary toxicity.Funding: New Zealand Health Research Council, Australian National Health Medical Research Council, Cancer Council Victoria, Cancer Council NSW, Auckland Hospital Charitable Trust, Trans-Tasman Radiation Oncology Group Seed Funding, Cancer Research Trust New Zealand, Royal Australian and New Zealand College of Radiologists, Cancer Institute NSW, Prostate Cancer Foundation Australia, and Cancer Australia. [ABSTRACT FROM AUTHOR]

Background: Androgen-deprivation therapy in patients with prostate cancer who have relapsed with rising prostate-specific antigen concentration only (PSA-only relapse), or with non-curable but asymptomatic disease at diagnosis, could adversely affect quality of life at a time when the disease itself does not. We aimed to compare the effect of immediate versus delayed androgen-deprivation therapy on health-related quality of life over 5 years in men enrolled in the TOAD (Timing of Androgen Deprivation) trial.Methods: This randomised, multicentre, open-label, phase 3 trial done in 29 public and private cancer centres across Australia, New Zealand, and Canada compared immediate with delayed androgen-deprivation therapy in men with PSA-only relapse after definitive treatment, or de-novo non-curable disease. Patients were randomly assigned (1:1) with a database-embedded, dynamically balanced algorithm to immediate androgen-deprivation therapy (immediate therapy group) or to delayed androgen-deprivation therapy (delayed therapy group). Any type of androgen-deprivation therapy was permitted, as were intermittent or continuous schedules. The European Organisation for Research and Treatment of Cancer (EORTC) quality-of-life questionnaires QLQ-C30 and PR25 were completed before randomisation, every 6 months for 2 years, and annually for a further 3 years. The primary outcome of the trial, reported previously, was overall survival, with global health-related quality of life at 2 years as a secondary endpoint. Here we report prespecified secondary objectives of the quality-of-life endpoint. Analysis was by intention to treat. Statistical significance was set at p=0·0036. The trial was registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12606000301561, and ClinicalTrials.gov, number NCT00110162.Findings: Between Sept 3, 2004, and July 13, 2012, 293 men were recruited and randomly assigned; 151 to the delayed therapy group and 142 to the immediate therapy group. There was no difference between the two groups in global health-related quality of life over 2 years from randomisation. There were no statistically significant differences in global quality of life, physical functioning, role functioning, or emotional functioning, fatigue, dyspnoea, insomnia, or feeling less masculine over the entire 5 years after randomisation. Sexual activity was lower in the immediate therapy group than in the delayed group at 6 and 12 months (at 6 months mean score 29·20 [95% CI 24·59-33·80] in the delayed group vs 10·40 [6·87-13·93] in the immediate group, difference 18·80 [95% CI 13·00-24·59], p<0·0001; at 12 months 28·63 [24·07-33·18] vs 13·76 [9·94-17·59], 14·86 [8·95-20·78], p<0·0001), with the differences exceeding the clinically significant threshold of 10 points until beyond 2 years. The immediate therapy group also had more hormone-treatment-related symptoms at 6 and 12 months (at 6 months mean score 8·48 [95% CI 6·89-10·07] in the delayed group vs 15·97 [13·92-18·02] in the immediate group, difference -7·49 [-10·06 to -4·93], p<0·0001; at 12 months 9·32 [7·59-11·05] vs 17·07 [14·75-19·39], -7·75 [-10·62 to -4·89], p<0·0001), but with differences below the threshold of clinical significance. For the individual symptoms, hot flushes were clinically significantly higher in the immediate group (adjusted proportion 0·31 for delayed therapy vs 0·55 for immediate therapy, adjusted odds ratio 2·87 [1·96-4·21], p<0·0001) over the 5-year period, as were nipple or breast symptoms (0·06 vs 0·14, 2·64 [1·61-4·34], p=0·00013).Interpretation: Immediate use of androgen-deprivation therapy was associated with early detriments in specific hormone-treatment-related symptoms, but with no other demonstrable effect on overall functioning or health-related quality of life. This evidence can be used to help decision making about treatment initiation for men at this disease stage.Funding: Australian National Health and Medical Research Council and Cancer Councils, The Royal Australian and New Zealand College of Radiologists, Mayne Pharma Australia, Tolmar Australia. [ABSTRACT FROM AUTHOR]