Samenvatting We presenteren hier een model dat de kans op het detecteren van een prostaatkankerrecidief buiten de prostaatfossa op de prostaatspecifiek membraanantigeen (PSMA) positronemissietomografie/computertomografie (PET/CT)-scan voorspelt bij patiënten met een biochemisch recidief (BCR) na radicale prostatectomie (RP). 419 patiënten met een BCR prostaatspecifiek antigeen (PSA) < 2,0 ng/ml) na RP zonder hormoontherapie die een 68 Ga-PSMA PET/CT-scan ondergingen, werden geïncludeerd. Met multivariabele logistische regressieanalyse werden voorspellers voor de detectie van prostaatkankerrecidief buiten de prostaatfossa geïdentificeerd. Bij een mediane PSA-waarde van 0,40 ng/ml (interkwartielafstand 0,30–0,70) werd met PSMA PET/CT bij 174 (42%) patiënten een prostaatkankerrecidief buiten de prostaatfossa gedetecteerd. Significante voorspellers voor het detecteren van prostaatkankerrecidief buiten de prostaatfossa waren de PSA-waarde ten tijde van de PSMA PET/CT-scan en de Gleason-score, het lymfeklierstadium en het snijrandstadium van het RP-preparaat. De PSA-waarde ten tijde van de PSMA PET/CT en de Gleason-score, het lymfeklierstadium en het snijrandstadium van het RP-preparaat waren belangrijke voorspellers voor het vinden van prostaatkankerrecidief buiten de prostaatfossa met de PSMA PET/CT. Het dashboard ( https://psma.prostatecancer-riskcalculator.com/ ) kan gebruikt worden om het klinisch meest relevante moment voor het verrichten van een PSMA PET/CT-scan te bepalen.
Objectives To review the literature to determine the sensitivity and specificity of gallium‐68 prostate‐specific membrane antigen ( 68 Ga‐PSMA) positron‐emission tomography (PET) for detecting pelvic lymph node metastases in patients with primary prostate cancer (PCa), and the positive predictive value in patients with biochemical recurrence (BCR) after initial curative treatment, and, in addition, to determine the detection rate and management impact of 68 Ga‐PSMA PET in patients with BCR after radical prostatectomy (RP). Materials and Methods We performed a comprehensive literature search. Search terms used in MEDLINE, EMBASE and Science Direct were ‘(PSMA, 68 Ga‐PSMA, 68 Gallium‐PSMA, Ga‐68‐PSMA or prostate‐specific membrane antigen)’ and ‘(histology, lymph node, staging, sensitivity, specificity, positive predictive value, recurrence, recurrent or detection)’. Relevant abstracts were reviewed and full‐text articles obtained where possible. References to and from obtained articles were searched to identify further relevant articles. Results Nine retrospective and two prospective studies described the sensitivity and specificity of 68 Ga‐PSMA PET for detecting pelvic lymph node metastases before initial treatment, which ranged from 33.3% to 100% and 80% to 100%, respectively. In eight retrospective studies, the positive predictive value of 68 Ga‐PSMA PET in patients with BCR before salvage lymph node dissection ranged from 70% to 100%. The detection rate of 68 Ga‐PSMA PET in patients with BCR after RP in the PSA subgroups <0.2 ng/mL, 0.2–0.49 ng/mL and 0.5 to <1.0 ng/mL ranged from 11.3% to 50.0%, 20.0% to 72.7% and 25.0% to 87.5%, respectively. Conclusion The review results showed that 68 Ga‐PSMA PET had a high specificity for the detection of pelvic lymph node metastases in primary PCa. Furthermore, 68 Ga‐PSMA PET had a very high positive predictive value in detecting lymph node metastases in patients with BCR. By contrast, sensitivity was only moderate; therefore, based on the currently available literature, 68 Ga‐PSMA PET cannot yet replace pelvic lymph node dissection to exclude lymph node metastases. In the salvage phase, 68 Ga‐PSMA PET had both a high detection rate and impact on radiotherapy planning in early BCR after RP.
Abstract Background International guidelines recommend germline genetic testing for men with metastatic prostate cancer. If offered to all patients by genetic healthcare professionals, there will be insufficient capacity to cope with the high patient numbers. In a mainstreaming pathway, non-genetic healthcare professionals (ngHCPs) discuss and order germline genetic testing instead of referring patients to genetic healthcare professionals. We aimed to evaluate the experience of ngHCPs with pre-test genetic counselling and to explore the feasibility from the ngHCPs’ perspective. Methods We carried out a prospective cohort study in 15 hospitals in the Netherlands. All participating ngHCPs (i.e. urologists, medical oncologists, specialist nurses and nurse practitioners) completed an online training module of 45 min. The ngHCPs completed a questionnaire both before the training and at three and nine months after it. Paired analyses were used to compare the first with the last questionnaires on attitude, confidence in the ability to discuss and order germline genetic testing, and perceived and actual knowledge of genetics and genetic testing. Results 167 ngHCPs were invited to participate of whom 69 completed the first questionnaire and started or completed the last one. They had a positive attitude towards offering genetic testing themselves. After nine months of providing pre-test genetic counselling, significantly more ngHCPs considered mainstreaming helpful (94% after versus 81% before, p = 0.01). Both perceived and actual knowledge increased significantly. Pre-test genetic counselling took less than 10 minutes for 82% of ngHCPs and the majority (88%) were in favour of continuing the mainstream pathway. Only six participating ngHCPs considered mainstreaming possible without completing a training module beforehand. Conclusions After completing a short online training module, ngHCPs feel well-prepared to discuss germline genetic testing with metastatic prostate cancer patients.
To determine the effect of radical prostatectomy (RP) hospital volume on the probability of post-RP incontinence.Retrospective research based on claims-based data of health insurers.For every patient with RP the probability of incontinence was determined, based on the definition of claims of one or more incontinence pads per day. Casemix corrections were made based on indicators available in claims-data: age, lymph node dissection, and radiotherapy. No casemix corrections could be made for tumour stage and surgical technique.A total of 1590 patients were included in this study; for 26.0% of these patients, an average of one or more incontinence pads per day were claimed for. A significant relation between the volume of RP per hospital and the claims of incontinence material was observed. The probability of incontinence was significantly lower in hospitals with a volume of more than 100 RP patients per year when compared to hospitals with less than 100 RP patients per year.The probability of post-RP incontinence decreases as hospitals conduct more RP procedures. The casemix factors included in the analysis only had a limited impact on this observation.
The gastrin-releasing peptide receptor (GRPR) is expressed in high numbers in a variety of human tumors, including the frequently occurring prostate and breast cancers, and therefore provides the rationale for directing diagnostic or therapeutic radionuclides on cancer lesions after administration of anti-GRPR peptide analogs. This concept has been initially explored with analogs of the frog 14-peptide bombesin, suitably modified at the N-terminus with a number of radiometal chelates. Radiotracers that were selected for clinical testing revealed inherent problems associated with these GRPR agonists, related to low metabolic stability, unfavorable abdominal accumulation, and adverse effects. A shift toward GRPR antagonists soon followed, with safer analogs becoming available, whereby, metabolic stability and background clearance issues were gradually improved. Clinical testing of three main major antagonist types led to promising outcomes, but at the same time brought to light several limitations of this concept, partly related to the variation of GRPR expression levels across cancer types, stages, previous treatments, and other factors. Currently, these parameters are being rigorously addressed by cell biologists, chemists, nuclear medicine physicians, and other discipline practitioners in a common effort to make available more effective and safe state-of-the-art molecular tools to combat GRPR-positive tumors. In the present review, we present the background, current status, and future perspectives of this endeavor.
European Association of Urology guidelines recommend a risk-adjusted biopsy strategy for early detection of prostate cancer in biopsy-naïve men. It remains unclear which strategy is most effective. Therefore, we evaluated two risk assessment pathways commonly used in clinical practice.To compare the diagnostic performance of a risk-based ultrasound (US)-directed pathway (Rotterdam Prostate Cancer Risk Calculator [RPCRC] #3; US volume assessment) and a magnetic resonance imaging (MRI)-directed pathway.This was a prospective multicenter study (MR-PROPER) with 1:1 allocation among 21 centers (US arm in 11 centers, MRI arm in ten). Biopsy-naïve men with suspicion of prostate cancer (age ≥50 yr, prostate-specific antigen 3.0-50 ng/ml, ± abnormal digital rectal examination) were included.Biopsy-naïve men with elevated risk of prostate cancer, determined using RPCRC#3 in the US arm and Prostate Imaging Reporting and Data System scores of 3-5 in the MRI arm, underwent systematic biopsies (US arm) or targeted biopsies (MRI arm).The primary outcome was the proportion of men with grade group (GG) ≥2 cancer. Secondary outcomes were the proportions of biopsies avoided and GG 1 cancers detected. Categorical (nonparametric) data were assessed using the Mann-Whitney U test and χ2 tests.A total of 1965 men were included in the intention-to-treat population (US arm n = 950, MRI arm n = 1015). The US and MRI pathways detected GG ≥2 cancers equally well (235/950, 25% vs 239/1015, 24%; difference 1.2%, 95% confidence interval [CI] -2.6% to 5.0%; p = 0.5). The US pathway detected more GG 1 cancers than the MRI pathway (121/950, 13% vs 84/1015, 8.3%; difference 4.5%, 95% CI 1.8-7.2%; p < 0.01). The US pathway avoided fewer biopsies than the MRI pathway (403/950, 42% vs 559/1015, 55%; difference -13%, 95% CI -17% to -8.3%; p < 0.01). Among men with elevated risk, more GG ≥2 cancers were detected in the MRI group than in the US group (52% vs 43%; difference 9.2%, 95% CI 3.0-15%; p < 0.01).Risk-adapted US-directed and MRI-directed pathways detected GG ≥2 cancers equally well. The risk-adapted US-directed pathway performs well for prostate cancer diagnosis if prostate MRI capacity and expertise are not available. If prostate MRI availability is sufficient, risk assessment should preferably be performed using MRI, as this avoids more biopsies and detects fewer cases of GG 1 cancer.Among men with suspected prostate cancer, relevant cancers were equally well detected by risk-based pathways using either ultrasound or magnetic resonance imaging (MRI) to guide biopsy of the prostate. If prostate MRI availability is sufficient, risk assessment should be performed with MRI to reduce unnecessary biopsies and detect fewer irrelevant cancers.
