Investigating PSMA-PET/CT to resolve prostate MRI PIRADS4-5 and negative biopsy discordance.

BACKGROUND: To determine the utility of diagnostic 18F-DCPyL PSMA-PET/CT to aid management of men with highly suspicious multiparametric MRI prostate (PIRAD 4-5 lesions) and discrepant negative prostate biopsy. METHODS: A multicentre prospective consecutive case series was conducted (2018-2021), recruiting men with prior mpMRI prostate PIRADS 4-5 lesions and negative prostate biopsy. All men had 18F-DCPyL PSMA-PET/CT with subsequent management based on the concordance between MRI and PET: (1) Concordant lesions were biopsied using in-bore MRI targeting; (2) PSMA-PET/CT avidity without MRI correlate were biopsied using cognitive/software targeting with ultrasound guidance and (3) Patients with negative PET/CT were returned to standard of care follow-up. RESULTS: 29 patients were recruited with 48% (n = 14) having concordant MRI/PET abnormalities. MRI targeted biopsy found prostate cancer in six patients, with grade groups GG3 (n = 1), GG2 (n = 1), GG1 (n = 4) found. Of the 20 men who PSMA-PET/CT avidity and biopsy, analysis showed higher SUVmax (20.1 vs 6.8, p = 0.036) predicted prostate cancer. Of patients who had PSMA-PET avidity without MRI correlate, and those with no PSMA-PET avidity, only one patient was subsequently found to have prostate cancer (GG1). The study is limited by small size and short follow-up of 17 months (IQR 12.5-29.9). CONCLUSIONS: PSMA-PET/CT is useful in this group of men but requires further investigation. Avidity (higher SUVmax) that correlates to the mpMRI prostate lesion should be considered for targeted biopsy.

Patterns of disease detection using [18F]DCFPyL PET/CT imaging in patients with detectable PSA post prostatectomy being considered for salvage radiotherapy: a prospective trial.

PURPOSE: Prostate-specific membrane antigen (PSMA) PET/CT is increasingly used in patients with biochemical recurrence post prostatectomy to detect local recurrence and metastatic disease at low PSA levels. The aim of this study was to assess patterns of disease detection, predictive factors and safety using [18F]DCFPyL PET/CT versus diagnostic CT in patients being considered for salvage radiotherapy with biochemical recurrence post prostatectomy. METHODS: We conducted a prospective trial recruiting 100 patients with detectable PSA post prostatectomy (PSA 0.2-2.0 ng/mL) and referred for salvage radiotherapy from August 2018 to July 2020. All patients underwent a PSMA PET/CT using the [18F]DCFPyL tracer and a diagnostic CT. The detection rates of [18F]DCFPyL PET/CT vs diagnostic CT were compared and patterns of disease are reported. Clinical patient and tumour characteristics were analysed for predictive utility. Thirty-day post-scan safety is reported. RESULTS: Of 100 patients recruited, 98 were suitable for analysis with a median PSA of 0.32 ng/mL. [18F]DCFPyL PET/CT was positive 46.4% and equivocal 5.2%, compared to 15.5% positivity for diagnostic CT. Local recurrence was detected on [18F]DCFPyL PET/CT in 28.5%, nodal disease in 27.5% and bony metastases in 6.1% of patients. Both ISUP grade group (p < 0.001) and pre-scan PSA (p = 0.029) were significant predictors of [18F]DCFPyL PET/CT positivity, and logistic regression generated probabilities combining the two showed improved prediction rates. No significant safety events were reported post [18F]DCFPyL administration. CONCLUSIONS: [18F]DCFPyL PET/CT increases detection of disease in patients with biochemical recurrence post prostatectomy compared to diagnostic CT. Patients being considered for salvage radiotherapy with a PSA >0.2 ng/mL should be considered for [18F]DCFPyL PET/CT scan. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry Number: ACTRN12618001530213 ( http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=375932&isReview=true ).

The application of theranostics in different stages of prostate cancer.

Despite the remarkable achievements in treating metastatic prostate cancer over the last two decades, castrate-resistant status is still considered the lethal stage of the disease. Theranostics combines a targeting compound (ligand) with a therapeutic radioisotope (radioactive particle) injected into the blood to target the cancer cells. The most studied radioligand is 177Lu-PSMA-617, which targets PSMA, a protein found in prostate cancer cells. This new approach has shown promising results in treating metastatic castration-resistant prostate cancer. Currently, many trials are using PSMA-targeting radioligands in combination with conventional therapies in advanced prostate cancer or even in the earlier stages of the disease. Other preclinical trials are exploring the possibility of using newer ligands or radioisotopes to treat prostate cancer to increase the specificity and efficacy of this treatment.

Prostate-specific membrane antigen theranostics in advanced prostate cancer: an evolving option.

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

PET imaging in urology: a rapidly growing successful collaboration.

PURPOSE OF REVIEW: To discuss and highlight the recent findings in urological oncology focusing on nuclear medicine advances on imaging and therapy. RECENT FINDINGS: Testicular tumors: F-FDG as the standard positron emission tomography (PET) tracer with proven good accuracy in detecting metastatic testicular cancer; urothelial cancer: good accuracy of F-FDG PET in detecting distant metastases but poor results in detecting local disease; prostate cancer: prostate-specific membrane antigen (PSMA) is a promising target for imaging prostate cancer with unprecedented accuracy in both staging and restaging and prospective studies were recently published. In castration-resistant prostate cancer, PSMA-targeting radionuclide therapy is showing potential as a curative possibility (e.g. using Lu-PSMA); renal cell cancer (RCC): besides FDG other PET radiotracers are under clinical evaluation (e.g. antibody-based molecular imaging, metabolic radiotracers and PSMA-based tracers). PSMA-based imaging may have applications in staging clear-cell RCC and in the selection and in the antiangiogenic treatment's response assessment. Possible role of PSMA-targeting radionuclide therapy? SUMMARY: In urological oncology, the use of F-FDG has been limited by a generally low tumor uptake and physiological F-FDG excretion by the urinary system. Other radiotracers are increasing the urologist's portfolio allowing imaging of several biochemical pathways. Theragnostic possibilities are also under investigation thanks to PSMA-based tracers.

Evaluation of the accuracy of multiparametric MRI for predicting prostate cancer pathology and tumour staging in the real world: an multicentre study.

OBJECTIVES: To assess the accuracy of multiparametric magnetic resonance imaging (mpMRI) for the detection of significant prostate cancer in men undergoing radical prostatectomy (RP) in an Australian multicentre setting, and to assess concordance between mpMRI and RP for local tumour staging and index lesion locations. PATIENTS AND METHODS: Men who underwent mpMRI within 12 months of RP between January 2013 and August 2016 at three Australian sites were included (Central Coast, NSW, St Vincents Hospital, Melbourne, Vic., and Bendigo Hospital, Vic.). The results of mpMRI were compared with the final RP specimen to analyse the performance of mpMRI for significant prostate cancer detection, index lesion localization, prediction of T3 disease and lymph node metastasis. A comparison between mpMRI cases performed using the technical and reporting specifications of Prostate Imaging Reporting and Data System (PI-RADS) version 1 and version 2 was also performed. Data analysis was performed using spss 24.0. RESULTS: A total of 235 cases were included for analysis. mpMRI PI-RADS score ≥3 had a 91% sensitivity and 95% positive predictive value (PPV) for significant prostate cancer at RP. The overall concordance between index lesion location on mpMRI and RP specimen was 75%. The sensitivity for predication of significant prostate cancer was higher in the PI-RADS version 2 cases compared with PI-RADS version 1 (87-99%; P = 0.005). Index lesion concordance was higher in the PI-RADS version 2 group (68% vs 91%; P = 0.002). mpMRI had a 38% sensitivity, 95% specificity, 90% PPV and 57% negative predictive value for extraprostatic disease. Sensitivity for prediction of T3 disease improved from 30% to 62% (P = 0.008) with PI-RADS version 2. CONCLUSIONS: In patients undergoing RP, an abnormal mpMRI is highly predictive (95% PPV) of significant prostate cancer, with an index lesion concordance of 75%. There has been a significant improvement in accuracy after the adoption of PI-RADS version 2 technical specifications and reporting criteria; however; further study is required to determine if this is attributable to improved experience with mpMRI or changes in the PI-RADS system.

The role of prostate-specific membrane antigen PET/computed tomography in primary staging of prostate cancer.

PURPOSE OF REVIEW: Functional imaging with PET combined with computed tomography (CT) is of emerging interest in prostate cancer (PCa). Development of prostate-specific membrane antigen (PSMA) radiolabelled ligands has thrust PET/CT into the limelight as an alternative to conventional imaging techniques, and the evidence base to support its utility in primary staging of newly diagnosed PCa is rapidly growing. This review focuses on the most recent and important publications evaluating PSMA PET/CT in primary staging of PCa. RECENT FINDINGS: Three recent meta-analyses have reported Ga-PSMA PET/CT to demonstrate superior sensitivity and specificity for pelvic lymph node detection than conventional imaging. A recent systematic review also suggests Ga-PSMA PET/CT to be superior to bone scan for identifying bone metastases. However, the majority of studies are of a retrospective nature, and few provide histopathological correlation of PSMA PET/CT findings. Data from prospective studies are awaited to determine accuracy and management impact of PSMA PET/CT in primary staging. SUMMARY: PSMA PET/CT is rapidly altering the landscape of primary staging in PCa. It appears to be superior to conventional imaging for detecting regional and distant metastasis, though caution should be applied given the lack of prospective studies assessing how significant findings should be integrated into patient management. PSMA PET/CT could potentially become the gold standard for primary staging of high-risk PCa if future prospective data can prove its validity in this space.

Patient-centred pathology reporting improves patient experience and understanding of disease in prostate cancer care.

Introduction and Objectives: Patient-centred (PC) and holistic care improves patient satisfaction and health outcomes. We sought to investigate the benefit of utilising a PC pathology report in patients undergoing radical prostatectomy (RP) for prostate cancer (PCa). Our study aimed to evaluate and compare patient understanding of their PCa diagnosis after RP, upon receiving either a standard histopathology report or a personalised and PC report (PCR). Moreover, we evaluated knowledge retention at 4 weeks after the initial consultation. Methods: We invited patients undergoing RP at three metropolitan Urology clinics to participate in our randomised controlled study. Patients were randomised to receive either a PCR or standard pathology report. Patient satisfaction questionnaires (Perceived Efficacy in Patient-Physician Interactions [PEPPI], Consultation and Relational Empathy [CARE] and Communication Assessment Tool [CAT]) and a knowledge test were conducted within 72 h of the initial appointment and again at 4 weeks. Accurate recollection of Gleason grade group (GGG) and extracapsular extension (ECE) were classified as 'correct'. Baseline demographic data included age, education, marital and employment status, pre-op prostate specific antigen (PSA) and clinical stage. Baseline data were tested for differences between groups using the Student's t test, chi-squared test or Fisher's exact test depending on whether data were continuous, categorical or sparse. Comparison of correctly answered 'knowledge' questions was analysed using chi-squared test. A significance level of p ≤ 0.05 was used. Results: Data from 62 patients were analysed (30 standard vs. 32 PCR). No significant differences in baseline demographics were found between groups. Both groups reported high levels of satisfaction with their healthcare experiences in all domains of patient-physician rapport, empathy and communication. There were no significant differences between groups in PEPPI (p = 0.68), CAT (p = 0.39) and CARE (p = 0.66) scores, at baseline and 4 weeks. Ninety-three per cent of patients who received the PCR understood the report while 90% felt the report added to their understanding of their PCa. Regarding patient knowledge, the PCR group had significantly more correct answers on GGG and ECE as compared with the standard report group at baseline and 4 weeks (p < 0.001 and 0.001, respectively). Conclusions: Our findings demonstrate that PC pathology reports improve patient knowledge and understanding of their PCa that is retained for at least 4 weeks after initial receipt of results.

Radical inguinal orchidectomy: the gold standard for initial management of testicular cancer.

Radical inguinal orchidectomy with division of the spermatic cord at the internal inguinal ring is the gold standard for diagnosis and local treatment of testicular malignancies. The technique is well established and described in detail in this paper, collating methods from various surgical textbooks and articles. We also discuss pre-operative considerations including fertility counselling and potential testicular prosthesis at time of orchidectomy, and the importance of contemplating differential diagnoses such as para-testicular sarcoma and primary testicular lymphoma (PTL) prior to performing radical orchidectomy (RO). The evidence and indications for new surgical techniques to treat local testicular malignancies are also described, including testis sparing surgery (TSS) and spermatic cord sparing orchidectomy.

Quantifying the Effect of Location Matching on Accuracy of Multiparametric Magnetic Resonance Imaging Prior to Prostate Biopsy-A Multicentre Study.

BACKGROUND: Multiparametric magnetic resonance imaging (mpMRI) has shown promise to improve detection of prostate cancer over conventional methods. However, most studies do not describe whether the location of mpMRI lesions match that of cancer found at biopsy, which may lead to an overestimation of accuracy. OBJECTIVE: To quantitate the effect of mapping locations of mpMRI lesions to locations of positive biopsy cores on the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of mpMRI. DESIGN SETTING AND PARTICIPANT: We retrospectively identified patients having mpMRI of the prostate preceding prostate biopsy at three centres from 2013 to 2016. Men with targetable lesions on imaging underwent directed biopsy in addition to systematic biopsy. We correlated locations of positive mpMRI lesions with those of positive biopsy cores, defining a match when both were in the same sector of the prostate. We defined positive mpMRI as Prostate Imaging Reporting and Data System (PI-RADS) score ≥4 and significant cancer at biopsy as grade group ≥2. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Sensitivity, specificity, PPV, and NPV were calculated with and without location matching. RESULTS AND LIMITATIONS: Of 446 patients, 247 (55.4%) had positive mpMRI and 232 (52.0%) had significant cancer at biopsy. Sensitivity and NPV for detecting significant cancer with location matching (both 63.4%) were decreased compared with those without location matching (77.6% and 73.9%, respectively). Of the 85 significant cancers not detected by mpMRI, most were of grade group 2 (64.7%, 55/85). CONCLUSIONS: We report a 10-15% decrease in sensitivity and NPV when location matching was used to detect significant prostate cancer by mpMRI. False negative mpMRI remains an issue, highlighting the continued need for biopsy and for improving the standards around imaging quality and reporting. PATIENT SUMMARY: The true accuracy of multiparametric magnetic resonance imaging (mpMRI) must be determined to interpret results and better counsel patients. We mapped the location of positive mpMRI lesions to where cancer was found at biopsy and found, when compared with matching to cancer anywhere in the prostate, that the accuracy of mpMRI decreased by 10-15%.

Indirect Comparisons of Efficacy between Combination Approaches in Metastatic Hormone-sensitive Prostate Cancer: A Systematic Review and Network Meta-analysis.

CONTEXT: There have been substantial changes in the management of men with metastatic hormone-sensitive prostate cancer (mHSPC) over the past 5 yr, with upfront combination therapies replacing androgen-deprivation therapy (ADT) alone. A range of therapies have entered the space with no clear answer regarding their comparative efficacy. OBJECTIVE: To perform a systematic review and network meta-analysis to characterise the comparative efficacy of combination approaches in men with mHSPC. EVIDENCE ACQUISITION: We searched multiple databases and abstracts of major meetings up to June 2019 for randomised trials of patients receiving first-line therapy for metastatic disease, a combination of ADT and one (or more) of taxane-based chemotherapy, and androgen receptor-targeted therapies. The primary endpoint was overall survival (OS) and we evaluated progression-free survival as a secondary outcome. We performed subgroup analysis based on the volume of disease. EVIDENCE SYNTHESIS: We found seven trials that met our eligibility criteria using either docetaxel, abiraterone acetate, enzalutamide, or apalutamide in combination with ADT. All agents in combination with ADT were shown to be superior to ADT alone; enzalutamide + ADT had the lowest absolute hazard ratio compared with ADT only (hazards ratio 0.53, 95% confidence interval 0.37-0.75), and an estimated 76.9% probability that it is the preferred treatment to prolong OS compared with other combination treatments, or with ADT alone. Enzalutamide appeared to have better OS compared with docetaxel in men with low-volume disease, but there was no difference in other comparisons. CONCLUSIONS: Combination therapy with any of docetaxel, abiraterone acetate, enzalutamide, or apalutamide provides a significant OS benefit when compared with ADT alone. We did not identify significant differences in OS between different combination therapies. Subtle differences between these options provide clinicians considerable flexibility when selecting options for individual patients. PATIENT SUMMARY: Many men with metastatic, hormone-sensitive prostate cancer should be managed with upfront combination therapy instead of androgen-deprivation therapy alone. Clinicians may consider many factors during the decision-making process, and thus management should be tailored for patients individually.