The additional value of 68Ga-PSMA PET/CT SUVmax in predicting ISUP GG ≥ 2 and ISUP GG ≥ 3 prostate cancer in biopsy.

BACKGROUND: Prebiopsy magnetic resonance imaging (MRI) increases the detection rate of clinically significant prostate cancer (csPCa). Prostate-specific membrane antigen-positron emission tomography/computed tomography (PSMA PET/CT) maximum standardized uptake value (SUVmax) of the prostate may offer additional value in predicting the likelihood of csPCa in biopsy. METHODS: A single-center cohort study involving patients with biopsy-proven PCa who underwent both MRI and PSMA PET/CT between 2020 and 2021. Logistic regression models were developed for International Society of Urological Pathology (ISUP) Grade Group (GG) ≥ 2 and GG ≥ 3 using noninvasive prebiopsy parameters: age, (log-)prostate-specific antigen (PSA) density, PI-RADS 5 lesion presence, extraprostatic extension (EPE) on MRI, and SUVmax of the prostate. Models with and without SUVmax were compared using Likelihood ratio tests and area under the curve (AUC). DeLong's test was used to compare the AUCs. RESULTS: The study included 386 patients, with 262 (68%) having ISUP GG ≥ 2 and 180 (47%) having ISUP GG ≥ 3. Including SUVmax significantly improved both models' goodness of fit (p < 0.001). The GG ≥ 2 model had a higher AUC with SUVmax 89.16% (95% confidence interval [CI]: 86.06%-92.26%) than without 87.34% (95% CI: 83.93%-90.76%) (p = 0.026). Similarly, the GG ≥ 3 model had a higher AUC with SUVmax 82.51% (95% CI: 78.41%-86.6%) than without 79.33% (95% CI: 74.84%-83.83%) (p = 0.003). The SUVmax inclusion improved the GG ≥ 3 model's calibration at higher probabilities. CONCLUSION: SUVmax of the prostate on PSMA PET/CT potentially improves diagnostic accuracy in predicting the likelihood of csPCa in prostate biopsy.

Automated pelvic MRI measurements associated with urinary incontinence for prostate cancer patients undergoing radical prostatectomy.

BACKGROUND: Pelvic morphological parameters on magnetic resonance imaging (MRI), such as the membranous urethral length (MUL), can predict urinary incontinence after radical prostatectomy but are prone to interobserver disagreement. Our objective was to improve interobserver agreement among radiologists in measuring pelvic parameters using deep learning (DL)-based segmentation of pelvic structures on MRI scans. METHODS: Preoperative MRI was collected from 167 prostate cancer patients undergoing radical prostatectomy within our regional multicentric cohort. Two DL networks (nnU-Net) were trained on coronal and sagittal scans and evaluated on a test cohort using an 80/20% train-test split. Pelvic parameters were manually measured by three abdominal radiologists on raw MRI images and with the use of DL-generated segmentations. Automated measurements were also performed for the pelvic parameters. Interobserver agreement was evaluated using the intraclass correlation coefficient (ICC) and the Bland-Altman plot. RESULTS: The DL models achieved median Dice similarity coefficient (DSC) values of 0.85-0.97 for coronal structures and 0.87-0.98 for sagittal structures. When radiologists used DL-generated segmentations of pelvic structures, the interobserver agreement for sagittal MUL improved from 0.64 (95% confidence interval 0.28-0.83) to 0.91 (95% CI 0.84-0.95). Furthermore, there was an increase in ICC values for the obturator internus muscle from 0.74 (95% CI 0.42-0.87) to 0.86 (95% CI 0.75-0.92) and for the levator ani muscle from 0.40 (95% CI 0.05-0.66) to 0.61 (95% CI 0.31-0.78). CONCLUSIONS: DL-based automated segmentation of pelvic structures improved interobserver agreement in measuring pelvic parameters on preoperative MRI scans. RELEVANCE STATEMENT: The implementation of deep learning segmentations allows for more consistent measurements of pelvic parameters by radiologists. Standardized measurements are crucial for incorporating these parameters into urinary continence prediction models. KEY POINTS: • DL-generated segmentations improve interobserver agreement for pelvic measurements among radiologists. • Membranous urethral length measurement improved from substantial to almost perfect agreement. • Artificial intelligence enhances objective pelvic parameter assessment for continence prediction models.

Gallium-68 Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography in Active Surveillance for Prostate Cancer Trial (PASPoRT).

BACKGROUND: The use of clinical parameters, including prebiopsy magnetic resonance imaging (MRI), to decide between active surveillance (AS) and active therapy for prostate cancer (PCa) leads to imperfect selection. Additional prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) imaging may improve risk stratification. OBJECTIVE: To study risk stratification and patient selection for AS with the addition of PSMA PET/CT to standard practice. DESIGN, SETTING, AND PARTICIPANTS: A single-centre prospective cohort study (NL69880.100.19) enrolled patients recently diagnosed with PCa who started AS. At diagnosis, all participants had undergone prebiopsy MRI and targeted biopsy for visualised lesions. Patients underwent an additional [68Ga]-PSMA PET/CT and targeted biopsy of all PSMA lesions with a maximum standardised uptake value (SUVmax) of ≥4 not covered by previous biopsies. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was the number needed to scan (NNS) to detect one patient with upgrading. The study was powered to detect an NNS of 10. Regarding secondary outcomes, univariate logistic regressions analyses were performed on all patients and on the patients who received additional PSMA targeted biopsies on the likelihood of upgrading. RESULTS AND LIMITATIONS: A total of 141 patients were included. Additional PSMA targeted biopsies were performed in 45 (32%) patients. In 13 (9%) patients, upgrading was detected: nine grade group (GG) 2, two GG 3, one GG 4, and one GG 5. The NNS was 11 (95% confidence interval 6-18). Of all participants, PSMA PET/CT and targeted biopsies yielded upgrading most frequently in patients with negative MRI (Prostate Imaging Reporting and Data System [PI-RADS] 1-2). Of patients who received additional PSMA targeted biopsies, upgrading was most frequently found in those with higher prostate-specific antigen density and negative MRI. Limitations included the lack of comparison with standard repeat biopsy, no central review of MRI, and possibility of biopsy sampling error. CONCLUSIONS: PSMA PET/CT can further improve PCa risk stratification and selection for AS patients diagnosed after MRI and targeted biopsies. PATIENT SUMMARY: Prostate-specific membrane antigen positron emission tomography/computed tomography and additional targeted prostate biopsies can identify more aggressive prostate cancer cases previously missed in patients recently started with expectant management for favourable-risk prostate cancer.

The Development and External Validation of Artificial Intelligence-Driven MRI-Based Models to Improve Prediction of Lesion-Specific Extraprostatic Extension in Patients with Prostate Cancer.

Adequate detection of the histopathological extraprostatic extension (EPE) of prostate cancer (PCa) remains a challenge using conventional radiomics on 3 Tesla multiparametric magnetic resonance imaging (3T mpMRI). This study focuses on the assessment of artificial intelligence (AI)-driven models with innovative MRI radiomics in predicting EPE of prostate cancer (PCa) at a lesion-specific level. With a dataset encompassing 994 lesions from 794 PCa patients who underwent robot-assisted radical prostatectomy (RARP) at two Dutch hospitals, the study establishes and validates three classification models. The models were validated on an internal validation cohort of 162 lesions and an external validation cohort of 189 lesions in terms of discrimination, calibration, net benefit, and comparison to radiology reporting. Notably, the achieved AUCs ranged from 0.86 to 0.91 at the lesion-specific level, demonstrating the superior accuracy of the random forest model over conventional radiological reporting. At the external test cohort, the random forest model was the best-calibrated model and demonstrated a significantly higher accuracy compared to radiological reporting (83% vs. 67%, p = 0.02). In conclusion, an AI-powered model that includes both existing and novel MRI radiomics improves the detection of lesion-specific EPE in prostate cancer.

Outcomes of a Diagnostic Pathway for Prostate Cancer Based on Biparametric MRI and MRI-Targeted Biopsy Only in a Large Teaching Hospital.

BACKGROUND: Diagnostic pathways for prostate cancer (PCa) balance detection rates and burden. MRI impacts biopsy indication and strategy. METHODS: A prospectively collected cohort database (N = 496) of men referred for elevated PSA and/or abnormal DRE was analyzed. All underwent biparametric MRI (3 Tesla scanner) and ERSPC prostate risk-calculator. Indication for biopsy was PIRADS ≥ 3 or risk-calculator ≥ 20%. Both targeted (cognitive-fusion) and systematic cores were combined. A hypothetical full-MRI-based pathway was retrospectively studied, omitting systematic biopsies in: (1) PIRADS 1-2 but risk-calculator ≥ 20%, (2) PIRADS ≥ 3, receiving targeted biopsy-cores only. RESULTS: Significant PCa (GG ≥ 2) was detected in 120 (24%) men. Omission of systematic cores in cases with PIRADS 1-2 but risk-calculator ≥ 20%, would result in 34% less biopsy indication, not-detecting 7% significant tumors. Omission of systematic cores in PIRADS ≥ 3, only performing targeted biopsies, would result in a decrease of 75% cores per procedure, not detecting 9% significant tumors. Diagnosis of insignificant PCa dropped by 52%. PCa undetected by targeted cores only, were ipsilateral to MRI-index lesions in 67%. CONCLUSIONS: A biparametric MRI-guided PCa diagnostic pathway would have missed one out of six cases with significant PCa, but would have considerably reduced the number of biopsy procedures, cores, and insignificant PCa. Further refinement or follow-up may identify initially undetected cases. Center-specific data on the performance of the diagnostic pathway is required.

Deep learning for automated contouring of neurovascular structures on magnetic resonance imaging for prostate cancer patients.

Background and purpose: Manual contouring of neurovascular structures on prostate magnetic resonance imaging (MRI) is labor-intensive and prone to considerable interrater disagreement. Our aim is to contour neurovascular structures automatically on prostate MRI by deep learning (DL) to improve workflow and interrater agreement. Materials and methods: Segmentation of neurovascular structures was performed on pre-treatment 3.0 T MRI data of 131 prostate cancer patients (training [n = 105] and testing [n = 26]). The neurovascular structures include the penile bulb (PB), corpora cavernosa (CCs), internal pudendal arteries (IPAs), and neurovascular bundles (NVBs). Two DL networks, nnU-Net and DeepMedic, were trained for auto-contouring on prostate MRI and evaluated using volumetric Dice similarity coefficient (DSC), mean surface distances (MSD), Hausdorff distances, and surface DSC. Three radiation oncologists evaluated the DL-generated contours and performed corrections when necessary. Interrater agreement was assessed and the time required for manual correction was recorded. Results: nnU-Net achieved a median DSC of 0.92 (IQR: 0.90-0.93) for the PB, 0.90 (IQR: 0.86-0.92) for the CCs, 0.79 (IQR: 0.77-0.83) for the IPAs, and 0.77 (IQR: 0.72-0.81) for the NVBs, which outperformed DeepMedic for each structure (p < 0.03). nnU-Net showed a median MSD of 0.24 mm for the IPAs and 0.71 mm for the NVBs. The median interrater DSC ranged from 0.93 to 1.00, with the majority of cases (68.9%) requiring manual correction times under two minutes. Conclusions: DL enables reliable auto-contouring of neurovascular structures on pre-treatment MRI data, easing the clinical workflow in neurovascular-sparing MR-guided radiotherapy.

Real-world outcomes of first-line chemotherapy for unresectable stage III and IV bladder cancer.

PURPOSE: For many malignancies, considerable divergence between the efficacy found in clinical trials and effectiveness in routine practice have been reported (efficacy-effectiveness gap). The purpose of this study was to evaluate the efficacy-effectiveness gap in palliative first-line (1L) chemotherapy treatment (CTx) for urothelial carcinoma of the bladder. METHODS: From seven Dutch teaching hospitals, all patients diagnosed with unresectable stage III (cT2-4aN1-3M0) and IV (cT4b and/or cM1) disease, who received 1L-CTx (for both primary as recurrent disease after radical cystectomy) between 2008 and 2016, were captured. Results were compared with data from seven randomised trials that investigated 1L gemcitabine + cisplatin (GemCis) and/or gemcitabine + carboplatin (GemCarbo). RESULTS: Of the 835 included patients, 191 received 1L-CTx. Median overall survival (mOS) of GemCis patients (N = 88) was 10.4 months [95% CI 7.9-13.0], which was shorter compared to clinical trial findings (range mOS: 12.7-14.3 months) despite comparable clinical characteristics. The mOS of GemCarbo patients (N = 92) was 9.3 months [95% CI 7.5-11.1]. Patients who received GemCarbo had worse prognostic characteristics (higher age, impaired renal function and worse performance status (all P-values < 0.001)) compared to GemCis patients, but were equal in occurrence of dose reductions (24.4% vs. 29.5%, P-value = 0.453), early termination (55.7% vs. 54.1%, P-value = 0.839), clinical best response (P-value = 0.733), and toxicity (68.1% vs. 63.3%, P-value = 0.743). In multivariable regression, GemCis was not superior to GemCarbo (HR 0.90 [95% CI 0.55-1.47], P-value = 0.674). CONCLUSION: There seems to be an efficacy-effectiveness gap in 1L GemCis treatment, despite patients having similar baseline characteristics. Early termination of treatment occurred more often and dose reduction less often compared to clinical trials, hinting towards abandonment of treatment in case of adverse events. Patients treated with 1L GemCis did not have superior survival compared to GemCarbo patients, even though GemCarbo patients had worse baseline characteristics.

Patient preferences for treatment modalities for localised prostate cancer.

Objectives: To assess the patient preferences and utility scores for the different conventional and innovative treatment modalities for localised prostate cancer (PCa). Subjects and Methods: Patients treated for localised PCa and healthy volunteers were invited to fill out a treatment-outcome scenario questionnaire. Participants ranked six different treatments for localised PCa from most to least favourable, prior to information. In a next step, treatment procedures, toxicity, risk of biochemical recurrence and follow-up regimen were comprehensibly described for each of the six treatments (i.e. treatment-outcome scenarios), after which patients re-ranked the six treatments. Additionally, participants gave a visual analogue scale (VAS) and time trade-off (TTO) score for each scenario. Differences between utility scores were tested by Friedman tests with post hoc Wilcoxon signed-rank tests. Results: Eighty patients and twenty-nine healthy volunteers were included in the study. Before receiving treatment-outcome scenario information, participants ranked magnetic resonance-guided adaptive radiotherapy most often as their first choice (35%). After treatment information was received, active surveillance was most often ranked as the first choice (41%). Utility scores were significantly different between the six treatment-outcome scenarios, and active surveillance, non- and minimal-invasive treatments received higher scores. Conclusions: Active surveillance and non-invasive treatment for localised PCa were the most preferred options by PCa patients and healthy volunteers and received among the highest utility scores. Treatment preferences change after treatment information is received.

Active surveillance in renal transplant patients with prostate cancer: a multicentre analysis.

INTRODUCTION: Due to medical improvements leading to increased life expectancy after renal transplantation and widened eligibility criteria allowing older patients to be transplanted, incidence of (low-risk) prostate cancer (PCa) is increasing among renal transplant recipients (RTR). It remains to be established whether active surveillance (AS) for PCa represents a safe treatment option in this setting. Therefore, we aim to compare AS discontinuation and oncological outcomes of AS for PCa of RTR vs. non-transplant patients. METHODS: Multicentre study including RTR diagnosed with PCa between 2008 and 2018 in whom AS was initiated. A subgroup of non-RTR from the St. Antonius hospital AS cohort was used as a control group. Comparison of RTR vs. non-RTR was performed by 2:1 propensity score matched survival analysis. Outcome measures included tumour progression-free survival, treatment-free survival, metastasis rates, biochemical recurrence rates and overall survival. Patients were matched based on age, year of diagnosis, PSA, biopsy ISUP grade group, relative number of positive biopsy cores and clinical stage. RESULTS: A total of 628 patients under AS were evaluated, including 17 RTRs and 611 non-RTRs. A total of 13 RTR cases were matched with 24 non-RTR cases. Median overall follow-up for the RTR and non-RTR matched cases was, respectively, 5.1 (IQR 3.2-8.7) years and 5.7 (IQR 4.8-8.1) years. There were no events of metastasis and biochemical recurrence among matched cases. The matched-pair analysis results in a 1-year and 5-year survival of the RTR and non-RTR patients were, respectively, 100 vs. 92%, and 39 vs. 76% for tumour progression, 100 vs. 91% and 59 vs. 76% for treatment-free survival and, respectively, 100 vs. 100% and 88 vs. 100% for overall survival. No significant differences in tumour progression-free survival (p = 0.07) and treatment-free survival were observed (p = 0.3). However, there was a significant difference in overall survival comparing both groups (p = 0.046). CONCLUSIONS: AS may be carefully considered in RTR with low-risk PCa. In our preliminary analysis, no major differences were present in AS outcomes between RTR and non-RTR. Overall mortality was significantly higher in the RTR subgroup.

Incidence of significant prostate cancer after negative MRI and systematic biopsy in the FUTURE trial.

OBJECTIVES: To assess the proportion of clinically significant (cs) prostate cancer (PCa) found during follow-up in patients with negative systematic biopsy (SB) followed by non-suspicious multiparametric magnetic resonance imaging (mpMRI) and persistent clinical suspicion of PCa compared to the general population. PATIENTS AND METHODS: A prospective study in a subgroup of patients from a multicentre randomized controlled trial was conducted between 2014 and 2017, including 665 men with prior negative SB with a persistent elevated prostate-specific antigen and/or suspicious digital rectal examination undergoing mpMRI. All patients with negative SB and Prostate Imaging-Reporting and Data System (PI-RADS) ≤2 on mpMRI entered biochemical follow-up. Follow-up data until December 2021 were collected by reviewing institutional hospital records and the Dutch Pathology Registry (PALGA). The primary outcome was the observed number of csPCa (Gleason ≥3 + 4/International Society of Urological Pathology grade group ≥2) cases during follow-up compared to the expected number in the general population (standardized incidence ratio [SIR]). RESULTS: In total, 431 patients had non-suspicious mpMRI and entered biochemical follow-up. After a median (interquartile range) follow-up of 41 (23-57) months, 38 patients were diagnosed with PCa, of whom 13 (3.0%) had csPCa. The SIR for csPCa was 4.3 (95% confidence interval 2.3-7.4; total excess of eight cases). A higher risk of a positive biopsy for (cs)PCa based on the European Randomized Study of Screening for Prostate Cancer risk calculator and a suspicious repeat MRI (PI-RADS ≥3) were significant predictive factors for csPCa. CONCLUSION: After negative prior biopsy and non-suspicious mpMRI the risk of csPCa is low. However, compared to the general population, the risk of csPCa is increased despite the high negative predictive value of mpMRI. More research focusing on biochemical and image-guided risk-adapted diagnostic surveillance strategies is warranted.

Estetrol Prevents Hot Flushes and Improves Quality of Life in Patients with Advanced Prostate Cancer Treated with Androgen Deprivation Therapy: The PCombi Study.

Background: Androgen deprivation therapy (ADT) for prostate cancer (PCa) is accompanied by side effects affecting health-related quality of life (HRQL). Objective: To assess the effects of the fetal estrogen estetrol (E4) on symptoms related to estrogen and androgen deficiency, and on HRQL measured using the validated Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire. Design setting and participants: This was a phase 2, double-blind, randomized, placebo-controlled study in patients with advanced PCa. Intervention: Patients receiving ADT were randomly assigned at a 2:1 ratio to daily treatment with a high dose of E4 (HDE4; n = 41) or placebo (n = 21) for 24 wk. Outcome measurements and statistical analysis: The primary outcome was the effect of HDE4 cotreatment on hot flushes (HFs). Secondary outcomes were the Q-Man questionnaire for evaluation of the effect on estrogen and androgen deficiency symptoms, and the FACT-P questionnaire for evaluating HRQL. Results and limitations: At 24 wk, the number of patients experiencing HFs was significantly lower in the HDE4 group than in the placebo group (14.3% vs 60.0%; p < 0.001). HDE4 treatment was associated with lower incidence of night sweats, arthralgia, and fatigue, but more nipple tenderness and gynecomastia. At 24 wk, the mean HRQL score favored HDE4 over placebo for the FACT-P total score (122.2 ± 12.3 vs 118.7 ± 19.7) and for several other FACT subscales. Conclusions: Daily HDE4 coadministration almost completely prevented HFs in patients with advanced PCa treated with ADT. HDE4 also had positive effects on HRQL and counteracted other estrogen deficiency symptoms caused by ADT. These data support the dual efficacy concept of ADT and HDE4 to improve HRQL and increase the antitumor effect of ADT. Patient summary: For patients on androgen deprivation therapy for advanced prostate cancer, cotreatment with a high dose of estetrol almost completely prevents the occurrence of hot flushes and improves quality of life and well-being, but nipple sensitivity and an increase in breast size may occur.

A side-specific nomogram for extraprostatic extension may reduce the positive surgical margin rate in radical prostatectomy.

PURPOSE: Nomograms predicting side-specific extraprostatic extension (EPE) may be applied to reduce positive surgical margin (PSM) rates in patients planned for radical prostatectomy (RP). This study evaluates the impact of implementing an externally validated nomogram for side-specific EPE on PSM rate and degree of nerve-sparing. METHODS: In patients planned for RP, the side-specific nomogram predictions (based on MRI, ISUP grade group, and PSA density), with an advised threshold of 20% for safe nerve-sparing, were presented preoperatively to the urological surgeon. The surgeon completed a survey before RP about the planning with respect to side-specific nerve-sparing and change of management due to the result of the nomogram. PSM rates and degree of nerve-sparing were compared to a retrospective control group treated in the months prior to the introduction of the nomogram. RESULTS: A total of 100 patients were included, 50 patients in both groups representing 200 prostate lobes. Of the patients, 37% had histologically confirmed EPE, and 40% a PSM. In 12% of the 100 lobes planned after nomogram presentation, a change in management due to the nomogram was reported. A per-prostate lobe analysis of all the lobes showed comparable rates of full nerve-sparing (45% vs. 30%; p = 0.083) and lower rates of PSM on the lobes with histological EPE (45% vs. 85%; p < 0.05) in the intervention (nomogram) group versus the control group. CONCLUSION: Implementing a predictive nomogram for side-specific EPE in the surgical planning for nerve-sparing leads to lower rates PSM on the side of the histological EPE without compromising nerve-sparing.

Maintaining bone health by estrogen therapy in patients with advanced prostate cancer: a narrative review.

The purpose of androgen deprivation therapy (ADT) in prostate cancer (PCa), using luteinizing hormone-releasing hormone agonists (LHRHa) or gonadotrophin-releasing hormone antagonists, is to suppress the levels of testosterone. Since testosterone is the precursor of estradiol (E2), one of the major undesired effects of ADT is the concomitant loss of E2, causing among others an increased bone turnover and bone loss and an increased risk of osteoporosis and fractures. Therefore, the guidelines for ADT indicate to combine ADT routinely with bone-sparing agents such as bisphosphonates, denosumab or selective estrogen receptor modulators. However, these compounds may have side effects and some require inconvenient parenteral administration. Co-treatment with estrogens is an alternative approach to prevent bone loss and at the same time, to avoid other side effects caused by the loss of estrogens, which is the topic explored in the present narrative review. Estrogens investigated in PCa patients include parenteral or transdermal E2, diethylstilbestrol (DES), and ethinylestradiol (EE) as monotherapy, or high-dose estetrol (HDE4) combined with ADT. Cardiovascular adverse events have been reported with parenteral E2, DES and EE. Encouraging effects on bone parameters have been obtained with transdermal E2 (tE2) and HDE4, in the tE2 development program (PATCH study), and in the LHRHa/HDE4 co-treatment study (PCombi), respectively. Confirmation of the beneficial effects of estrogen therapy with tE2 or HDE4 on bone health in patients with advanced PCa is needed, with special emphasis on bone mass and fracture rate.

Superfast Magnetic Resonance Imaging-based Diagnostic Pathway for Prostate Cancer.

We describe a <36-h superfast diagnostic pathway for men at risk of prostate cancer (PCa) that was initiated in our centre in March 2022. Patients are scheduled to undergo a repeat prostate-specific antigen blood test, magnetic resonance imaging, a urology consultation, and, if indicated, prostate biopsies in a single morning. The histopathology report is available the next day, after which the biopsy results and treatment options are discussed via a telephone consultation. The project has included 122 patients so far. With a reduction to only one hospital visit per patient and just five appointments (4%) cancelled so far, this timely pathway seems to be efficient from a patient perspective. In addition, reducing the waiting time until histopathology diagnosis could decrease the anxiety and depression that patients may experience during the diagnostic workup for PCa. Therefore, we believe that this fast-track diagnostic pathway could be incorporated in the future European standard of care, bringing PCa care in line with other malignancies such as breast cancer. Patient summary: We describe a superfast diagnostic pathway for men at risk of prostate cancer. So far, this strategy seems to be an efficient and appropriate way to shorten time to diagnosis and to reduce the number of hospital visits for patients.

Cost-effectiveness of the implementation of [68Ga]Ga-PSMA-11 PET/CT at initial prostate cancer staging.

BACKGROUND: Despite its high specificity, PSMA PET/CT has a moderate to low sensitivity of 40-50% for pelvic lymph node detection, implicating that a negative PSMA PET/CT cannot rule out lymph node metastases. This study investigates a strategy of implementing PSMA PET/CT for initial prostate cancer staging and treatment planning compared to conventional diagnostics. In this PSMA PET/CT strategy, a bilateral extended pelvic lymph node dissection (ePLND) is only performed in case of a negative PSMA PET/CT; in case of a positive scan treatment planning is solely based on PSMA PET/CT results. METHOD: A decision table and lifetime state transition model were created. Quality-adjusted life years and health care costs were modelled over lifetime. RESULTS: The PSMA PET/CT strategy of treatment planning based on initial staging with [68Ga]Ga-PSMA-11 PET/CT results in cost-savings of €674 and a small loss in quality of life (QoL), 0.011 QALY per patient. The positive effect of [68Ga]Ga-PSMA-11 PET/CT was caused by abandoning both an ePLND and unnecessary treatment in iM1 patients, saving costs and resulting in higher QoL. The negative effect was caused by lower QoL and high costs in the false palliative state, due to pN1lim patients (≤ 4 pelvic lymph node metastases) being falsely diagnosed as iN1ext (> 4 pelvic lymph node metastases). These patients received subsequently palliative treatment instead of potentially curative therapy. CONCLUSION: Initial staging and treatment planning based on [68Ga]Ga-PSMA-11 PET/CT saves cost but results in small QALY loss due to the rate of false positive findings.

The first patient-reported outcomes from the Utrecht Prostate Cohort (UPC): the first platform facilitating 'trials within cohorts' (TwiCs) for the evaluation of interventions for prostate cancer.

PURPOSE: To describe the development and first outcomes of the Utrecht Prostate Cohort (UPC): the first 'trials within cohorts' (TwiCs) platform for prostate cancer (PCa). METHODS: All non-metastasized, histologically proven PCa patients who are planned to receive standard of care are eligible for inclusion in UPC. Patients provide informed consent for the collection of clinical and technical patient data, physician-reported outcomes, and patient-reported outcomes (PROs) up to 10 years post-treatment. Additionally, patients may provide broad consent for future randomization for experimental-intervention trials (TwiCs). Changes in PROs (EPIC-26 questionnaire domains) of the participants who received standard of care were analyzed using Wilcoxon signed-rank tests. RESULTS: In two years, 626 patients were enrolled, 503 (80.4%) of whom provided broad consent for future randomization. Among these, 293 (46.8%) patients underwent magnetic resonance-guided adaptive radiotherapy (MRgRT), 116 (18.5%) CT-guided external beam radiation therapy (EBRT), 109 (17.4%) robot-assisted radical prostatectomy (RARP), and 65 (10.4%) patients opted for active surveillance. Patients treated with MRgRT and CT-guided EBRT showed a transient but significant decline in urinary irritative/obstructive and bowel domain scores at 1-month follow-up. RARP patients showed a significant deterioration of urinary incontinence domain scores between baseline and all follow-up moments and significant improvement of urinary irritative/obstructive domain scores between baseline and 9- and 12-month follow-up. All radical treatment groups showed a significant decline in sexual domain scores during follow-up. Active surveillance patients showed no significant deterioration over time in all domains. CONCLUSION: The first results from the UPC study show distinct differences in PROs between treatment options for PCa. REGISTRATION NO: NCT04228211.

Optimization of Preoperative Lymph Node Staging in Patients with Muscle-Invasive Bladder Cancer Using Radiomics on Computed Tomography.

Approximately 25% of the patients with muscle-invasive bladder cancer (MIBC) who are clinically node negative have occult lymph node metastases at radical cystectomy (RC) and pelvic lymph node dissection. The aim of this study was to evaluate preoperative CT-based radiomics to differentiate between pN+ and pN0 disease in patients with clinical stage cT2-T4aN0-N1M0 MIBC. Patients with cT2-T4aN0-N1M0 MIBC, of whom preoperative CT scans and pathology reports were available, were included from the prospective, multicenter CirGuidance trial. After manual segmentation of the lymph nodes, 564 radiomics features were extracted. A combination of different machine-learning methods was used to develop various decision models to differentiate between patients with pN+ and pN0 disease. A total of 209 patients (159 pN0; 50 pN+) were included, with a total of 3153 segmented lymph nodes. None of the individual radiomics features showed significant differences between pN+ and pN0 disease, and none of the radiomics models performed substantially better than random guessing. Hence, CT-based radiomics does not contribute to differentiation between pN+ and pN0 disease in patients with cT2-T4aN0-N1M0 MIBC.

Hospital variation in treatment patterns and oncological outcomes for patients with muscle-invasive and metastatic bladder cancer in the Netherlands.

PURPOSE: Population-based studies on treatment patterns in oncology and corresponding clinical outcomes can help identify strategies towards optimal value for patients. This study was performed to describe the variation in treatment patterns and major oncological outcomes for muscle-invasive or metastatic bladder cancer (MIBC/mBC) patients in the Netherlands. METHODS: Patients diagnosed with cT2-4aN0-3M0-1 disease between 2008 and 2016 in seven large teaching hospitals in the Netherlands were included. Baseline characteristics, disease stage, intended and definitive treatment, and oncological outcomes were collected. Patients were categorized based on cTNM-stage: (1) cT2-4aN0M0, (2) cT2-4aN1-3M0 and (3) cT4b and/or M1. RESULTS: The total study population comprised 1853 patients, of which 1303 patients were diagnosed with cT2-4aN0M0 disease. Overall, curative treatment was intended in 81% (range 74-85%, P value = 0.132). Radical cystectomy (RC) and curative radiotherapy (RTx) ranged between hospitals from 42 to 66% and 13 to 27%, respectively (P value < 0.001). For 334 patients staged cT4b and/or M1, frequencies for palliative therapy and best supportive care (no anti-cancer therapy) ranged between hospitals from 20 to 54% and 44 to 71%, respectively (P value < 0.001). There was no association between hospital site and overall survival (OS) in a univariable and multivariable Cox regression for survival analysis (after adjusting for age and cT-stage), for all three cTNM-groups. Neoadjuvant or induction chemotherapy (NAIC) utilization rates before RC ranged from 8 to 38% (P value < 0.001). CONCLUSIONS: There is large inter-hospital variation in treatment intent in MIBC/mBC patients. This variation does not seem to translate to differences in overall survival rates. There is an ongoing trend of increased use of RC. Utilisation of NAIC is relatively low considering European guideline recommendations.

Development and External Validation of a Novel Nomogram to Predict Side-specific Extraprostatic Extension in Patients with Prostate Cancer Undergoing Radical Prostatectomy.

BACKGROUND: Prediction of side-specific extraprostatic extension (EPE) is crucial in selecting patients for nerve-sparing radical prostatectomy (RP). OBJECTIVE: To develop and externally validate nomograms including multiparametric magnetic resonance imaging (mpMRI) information to predict side-specific EPE. DESIGN, SETTING, AND PARTICIPANTS: A retrospective analysis of 1870 consecutive prostate cancer patients who underwent robot-assisted RP from 2014 to 2018 at three institutions. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Four multivariable logistic regression models were established, including combinations of patient-based and side-specific variables: prostate-specific antigen (PSA) density, highest ipsilateral International Society of Urological Pathology (ISUP) biopsy grade, ipsilateral percentage of positive cores on systematic biopsy, and side-specific clinical stage assessed by both digital rectal examination and mpMRI. Discrimination (area under the curve [AUC]), calibration, and net benefit of these models were assessed in the development cohort and two external validation cohorts. RESULTS AND LIMITATIONS: On external validation, AUCs of the four models ranged from 0.80 (95% confidence interval [CI] 0.68-0.88) to 0.83 (95% CI 0.72-0.90) in cohort 1 and from 0.77 (95% CI 0.62-0.87) to 0.78 (95% CI 0.64-0.88) in cohort 2. The three models including mpMRI staging information resulted in relatively higher AUCs compared with the model without mpMRI information. No major differences between the four models regarding net benefit were established. The model based on PSA density, ISUP grade, and mpMRI T stage was superior in terms of calibration. Using this model with a cut-off of 20%, 1980/2908 (68%) prostatic lobes without EPE would be found eligible for nerve sparing, whereas non-nerve sparing would be advised in 642/832 (77%) lobes with EPE. CONCLUSIONS: Our analysis resulted in a simple and robust nomogram for the prediction of side-specific EPE, which should be used to select patients for nerve-sparing RP. PATIENT SUMMARY: We developed a prediction model that can be used to assess accurately the likelihood of tumour extension outside the prostate. This tool can guide patient selection for safe nerve-sparing surgery.