PSMA-RLT in Patients with Metastatic Hormone-Sensitive Prostate Cancer : A Retrospective Study

Background: Prostate-specific membrane antigen (PSMA)-directed radioligand therapy (RLT) is a novel treatment for patients with castration-resistant prostate cancer (CRPC). Given the mode of action, patients in an earlier disease stage, such as hormone-sensitive prostate cancer (HSPC), are also likely to benefit from [177Lu]Lu-PSMA- (177Lu-PSMA) or [225Ac]Ac-PSMA-radioligand treatment (225Ac-PSMA). In this retrospective study, we analyzed the safety and efficacy of PSMARLT in early-stage and hormone-sensitive metastatic prostate cancer patients. Methods: A retrospective study was performed in patients who received 177Lu-PSMA and/or 225Ac-PSMA with early-stage metastatic prostate cancer. The primary outcome parameter evaluated in this study was the progression-free survival (PFS) after PSMA-RLT and toxicity according to the Common Terminology Criteria for Adverse Events. Secondary outcome parameters were prostate-specific antigen (PSA) response and the date of onset of CRPC state. Results: In total, 20 patients were included of which 18 patients received 177Lu-PSMA radioligand and two patients received tandem treatment with both 177Lu-PSMA and 225Ac-PSMA radioligands. Patients received a median of 2 treatment cycles (range 1–6) and a median activity of 6.2 GBq 177Lu-PSMA per cycle (interquartile range (IQR) 5.2–7.4 GBq). PSMA-RLT was overall well-tolerated. The most common grade 1–2 side effects were xerostomia (n = 6) and fatigue (n = 8), which were only temporarily reported. One patient that received 225Ac-PSMA developed grade 3–4 bone marrow toxicity. The median PFS was 12 months (95% confidence interval (CI), 4.09–19.9 months). Seventeen (85%) patients had a ≥50% PSA response following PSMA-RLT. One patient developed CRPC 9 months following PSMA-RLT. Conclusions: In this small cohort study, PSMA-RLT appeared safe and showed encouraging efficacy for (metastasized) early-stage and hormone-sensitive prostate cancer patients. Prospective studies are awaited and should include long-term follow-up

How can robot-assisted surgery provide value for money?

Objectives To develop an interactive tool that estimates what potential benefits are needed for the robot to provide value for money when compared with endoscopic or open surgical interventions.Design A generic online interactive tool was developed to analyze the (health) effects needed to compensate for the additional costs of using a surgical robotic system from a healthcare perspective. The application of the tool is illustrated with a hypothetical new surgical robotic platform. A synthesis of evidence from different sources was used combined with interviews with surgeons.Setting Flexible tool that can be adapted to flexible settings.Participants Any hospital patient group for which robotic, endoscopic or open surgical procedures may be considered as appropriate treatment alternatives (eg, urology, gynecology, and so on).Intervention Robotically assisted surgical interventions.Comparator Endoscopic or open surgical interventions.Main outcome measures Thresholds of how much (health) effect is needed for robot-assisted surgery to provide value for money and to become cost-effective.Results The utilization rate of the surgical robotic system and a reduction in complications appeared to be important aspects in determining the value for money. To become cost-effective, it was deemed important for new surgical robotic systems to have added clinical benefit and become less costly than the current system.Conclusions This paper and its assisting interactive tool can be used by clinicians, researchers, and policymakers to gain insight in the benefit needed to provide value for money when using a (new) surgical robotic system or, when the effects are known or can be estimated, to assess the value for money for a specific indication. For robotic surgery to provide most value for money, we recommend assessing for each indication whether the necessary effects seem achievable

The Effects of Multidisciplinary Team Meetings on Clinical Practice for Colorectal, Lung, Prostate and Breast Cancer: A Systematic Review

Objective: The aim of our systematic review is to identify the effects of multidisciplinary team meetings (MDTM) for lung, breast, colorectal and prostate cancer. Methods: Our systematic review, performed following PRISMA guidelines, included studies examining the impact of MDTMs on treatment decisions, patient and process outcomes. Electronic databases PUBMED, EMBASE, Cochrane Library and Web of Science were searched for articles published between 2000 and 2020. Risk of bias and level of evidence were assessed using the ROBINS-I tool and GRADE scale. Results: 41 of 13,246 articles were selected, evaluating colorectal (21), lung (10), prostate (6) and breast (4) cancer. Results showed that management plans were changed in 1.6–58% of cases after MDTMs. Studies reported a significant impact of MDTMs on surgery type, and a reduction of overall performed surgery after MDTM. Results also suggest that CT and MRI imaging significantly increased after MDTM implementation. Survival rate increased significantly with MDTM discussions according to twelve studies, yet three studies did not show significant differences. Conclusions: Despite heterogeneous data, MDTMs showed a significant impact on management plans, process outcomes and patient outcomes. To further explore the impact of MDTMs on the quality of healthcare, high-quality research is needed

Quantitative microbubble enhanced transrectal ultrasound as a tool for monitoring hormonal treatment of prostate carcinoma

BACKGROUND: We quantified changes in prostate carcinoma vascularity treated with anti-androgens using color Doppler and power transrectal ultrasound in combination with microbubble contrast agent Levovist. METHODS: Thirty-six men with prostate carcinoma were studied at baseline and at intervals during treatment. At each attendance, Levovist((R)) (10 ml, 300 mg/ml) was given as an iv bolus. Using quantitative analysis, we calculated the pre-enhancement scores, arrival time, time to peak, peak value, and area under the time-enhancement curve (AUC). These were compared to pre-treatment values and serial PSA measurements. RESULTS: The pre-enhancement, peak value, and AUC each showed a marked response with reductions within one week. The average AUC declined to 68% +/- 9% (mean +/- standard error) by week 1, 56% +/- 9% by week 3, and 20% +/- 4% by week 6. A strong correlation with changes in the mean PSA (r = 0.95, P < 0.001) was also measured. In four patients, Doppler indices did not fall with PSA: two patients with the most marked discrepancy relapsed at 6 months. CONCLUSION: The vascular enhancement declined with therapy, similar to PSA. Microbubble enhanced ultrasound can show early response to treatmen

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

PSMA-RLT in Patients with Metastatic Hormone-Sensitive Prostate Cancer: A Retrospective Study

Background: Prostate-specific membrane antigen (PSMA)-directed radioligand therapy (RLT) is a novel treatment for patients with castration-resistant prostate cancer (CRPC). Given the mode of action, patients in an earlier disease stage, such as hormone-sensitive prostate cancer (HSPC), are also likely to benefit from [177Lu]Lu-PSMA- (177Lu-PSMA) or [225Ac]Ac-PSMA-radioligand treatment (225Ac-PSMA). In this retrospective study, we analyzed the safety and efficacy of PSMA-RLT in early-stage and hormone-sensitive metastatic prostate cancer patients. Methods: A retrospective study was performed in patients who received 177Lu-PSMA and/or 225Ac-PSMA with early-stage metastatic prostate cancer. The primary outcome parameter evaluated in this study was the progression-free survival (PFS) after PSMA-RLT and toxicity according to the Common Terminology Criteria for Adverse Events. Secondary outcome parameters were prostate-specific antigen (PSA) response and the date of onset of CRPC state. Results: In total, 20 patients were included of which 18 patients received 177Lu-PSMA radioligand and two patients received tandem treatment with both 177Lu-PSMA and 225Ac-PSMA radioligands. Patients received a median of 2 treatment cycles (range 1&ndash;6) and a median activity of 6.2 GBq 177Lu-PSMA per cycle (interquartile range (IQR) 5.2&ndash;7.4 GBq). PSMA-RLT was overall well-tolerated. The most common grade 1&ndash;2 side effects were xerostomia (n = 6) and fatigue (n = 8), which were only temporarily reported. One patient that received 225Ac-PSMA developed grade 3&ndash;4 bone marrow toxicity. The median PFS was 12 months (95% confidence interval (CI), 4.09&ndash;19.9 months). Seventeen (85%) patients had a &ge;50% PSA response following PSMA-RLT. One patient developed CRPC 9 months following PSMA-RLT. Conclusions: In this small cohort study, PSMA-RLT appeared safe and showed encouraging efficacy for (metastasized) early-stage and hormone-sensitive prostate cancer patients. Prospective studies are awaited and should include long-term follow-up

Clinical use of the SelectMDx urinary-biomarker test with or without mpMRI in prostate cancer diagnosis : a prospective, multicenter study in biopsy-naive men

Background Risk stratification in men with suspicion of prostate cancer (PCa) requires reliable diagnostic tests, not only to identify high-grade PCa, also to minimize the overdetection of low-grade PCa, and reduction of "unnecessary" prostate MRIs and biopsies. This study aimed to evaluate the SelectMDx test to detect high-grade PCa in biopsy-naive men. Subsequently, to assess combinations of SelectMDx test and multi-parametric (mp) MRI and its potential impact on patient selection for prostate biopsy. Methods This prospective multicenter diagnostic study included 599 biopsy-naive patients with prostate-specific antigen level >= 3 ng/ml. All patients underwent a SelectMDx test and mpMRI before systematic transrectal ultrasound-guided biopsy (TRUSGB). Patients with a suspicious mpMRI also had an in-bore MR-guided biopsy (MRGB). Histopathologic outcome of TRUSGB and MRGB was used as reference standard. High-grade PCa was defined as ISUP Grade Group (GG) >= 2. The primary outcome was the detection rates of low- and high-grade PCa and number of biopsies avoided in four strategies, i.e., (1) SelectMDx test-only, (2) mpMRI-only, (3) SelectMDx test followed by mpMRI when SelectMDx test was positive (conditional strategy), and (4) SelectMDx test and mpMRI in all (joint strategy). A positive SelectMDx test outcome was a risk score of >=-2.8. Decision curve analysis (DCA) was performed to assess clinical utility. Results Prevalence of high-grade PCa was 31% (183/599). Thirty-eight percent (227/599) of patients had negative SelectMDx test in whom biopsy could be avoided. Low-grade PCa was not detected in 35% (48/138) with missing 10% (18/183) high-grade PCa. Yet, mpMRI-only could avoid 49% of biopsies, not detecting 4.9% (9/183) of high-grade PCa. The conditional strategy reduces the number of mpMRIs by 38% (227/599), avoiding biopsy in 60% (357/599) and missing 13% (24/183) high-grade PCa. Low-grade PCa was not detected in 58% (80/138). DCA showed the highest net benefit for the mpMRI-only strategy, followed by the conditional strategy at-risk thresholds >10%. Conclusions SelectMDx test as a risk stratification tool for biopsy-naive men avoids unnecessary biopsies in 38%, minimizes low-grade PCa detection, and misses only 10% high-grade PCa. Yet, using mpMRI in all patients had the highest net benefit, avoiding biopsy in 49% and missing 4.9% of high-risk PCa. However, if mpMRI availability is limited or expensive, using mpMRI-only in SelectMDx test positive patients is a good alternative strategy

Lutetium-177-PSMA-617 in low-volume hormone-sensitive metastatic prostate cancer: A prospective pilot study

Purpose: [177Lu]Lu-PSMA-617 radioligand therapy (177Lu-PSMA) is a novel treatment for metastatic castration-resistant prostate cancer (mCRPC), which could also be applied to patients with metastatic hormone-sensitive prostate cancer (mHSPC) with PSMA expression. In this prospective study (NCT03828838), we analyzed toxicity, radiation doses, and treatment effect of 177Lu-PSMA in pateints with low-volume mHSPC. Patients and Methods: Ten progressive patients with mHSPC following local treatment, with a maximum of ten metastatic lesions on [68Ga]Ga-PSMA-11 PET/diagnostic-CT imaging (PSMA-PET) and serum PSA doubling time <6 months received two cycles of 177Lu-PSMA. Whole-body single-photon emission CT/CT (SPECT/CT) and blood dosimetry was performed to calculate doses to the tumors and organs at risk (OAR). Adverse events (AE), laboratory values (monitoring response and toxicity), and quality of life were monitored until week 24 after cycle 2, the end of study (EOS). All patients underwent PSMA-PET at screening, 8 weeks after cycle 1, 12 weeks after cycle 2, and at EOS. Results: All patients received two cycles of 177Lu-PSMA without complications. No treatment-related grade III–IV adverse events were observed. According to dosimetry, none of the OAR reached threshold doses for radiation-related toxicity. Moreover, all target lesions received a higher radiation dose than the OAR. All 10 patients showed altered PSA kinetics, postponed androgen deprivation therapy, and maintained good quality of life. Half of the patients showed a PSA response of more than 50%. One patient had a complete response on PSMA-PET imaging until EOS and two others had only minimal residual disease. Conclusions: 177Lu-PSMA appeared to be a feasible and safe treatment modality in patients with low-volume mHSPC

Cohort profile – the Renal cell cancer: Lifestyle, prognosis and quality of life (ReLife) study in the Netherlands

Purpose The Renal cell cancer: Lifestyle, prognosis and quality of life (ReLife) study is set up to obtain insight into the association of patient and tumour characteristics, lifestyle habits and circulating biomarkers with body composition features in patients with localised renal cell cancer (RCC). Further, it aims to assess the association of body composition features, lifestyle habits and circulating biomarkers with clinical outcomes, including health-related quality of life.Participants The ReLife study is a multicentre prospective cohort study involving 368 patients with newly diagnosed stages I–III RCC recruited from January 2018 to June 2021 from 18 hospitals in the Netherlands. At 3 months, 1 year and 2 years after treatment, participants fill out a general questionnaire and questionnaires about their lifestyle habits (eg, diet, physical activity, smoking and alcohol consumption), medical history and health-related quality of life. At all three time points, patients wear an accelerometer and have blood samples taken. CT scans for body composition analysis are being collected. Permission is asked for collection of tumour samples. Information about disease characteristics, treatment of the primary tumour and clinical outcomes is being collected from medical records by the Netherlands Cancer Registry.Findings to date A total of 836 invited patients were eligible and 368 patients were willing to participate and were included (response rate 44%). The mean age of patients was 62.5±9.0 years and 70% was male. The majority had stage I (65%) disease and were treated with radical nephrectomy (57%). Data collection at 3 months and 1 years after treatment have been finalised.Future plans Data collection at 2 years after treatment is expected to be finalised in June 2023 and longitudinal clinical data will continue to be collected. Results of studies based on this cohort are important to develop personalised evidence-based lifestyle advice for patients with localised RCC to enable them to get more control over their disease course