1H-NMR-based urine metabolomics of prostate cancer and benign prostatic hyperplasia.

Background: Prostate cancer (PCa) and benign prostatic hyperplasia (BPH) are prevalent conditions affecting a significant portion of the male population, particularly with advancing age. Traditional diagnostic methods, such as digital rectal examination (DRE) and prostate-specific antigen (PSA) tests, have limitations in specificity and sensitivity, leading to potential overdiagnosis and unnecessary biopsies. Significance: This study explores the effectiveness of 1H NMR urine metabolomics in distinguishing PCa from BPH and in differentiating various PCa grades, presenting a non-invasive diagnostic alternative with the potential to enhance early detection and patient-specific treatment strategies. Results: The study demonstrated the capability of 1H NMR urine metabolomics in detecting distinct metabolic profiles between PCa and BPH, as well as among different Gleason grade groups. Notably, this method surpassed the PSA test in distinguishing PCa from BPH. Untargeted metabolomics analysis also revealed several metabolites with varying relative concentrations between PCa and BPH cases, suggesting potential biomarkers for these conditions.

Differences in Gut Microbiota Profiles and Microbiota Steroid Hormone Biosynthesis in Men with and Without Prostate Cancer.

Background: Although prostate cancer (PCa) is the most common cancer in men in Western countries, there is significant variability in geographical incidence. This might result from genetic factors, discrepancies in screening policies, or differences in lifestyle. Gut microbiota has recently been associated with cancer progression, but its role in PCa is unclear. Objective: Characterization of the gut microbiota and its functions associated with PCa. Design setting and participants: In a prospective multicenter clinical trial (NCT02241122), the gut microbiota profiles of 181 men with a clinical suspicion of PCa were assessed utilizing 16S rRNA sequencing. Outcome measurements and statistical analysis: Sequences were assigned to operational taxonomic units, differential abundance analysis, and α- and ß-diversities, and predictive functional analyses were performed. Plasma steroid hormone levels corresponding to the predicted microbiota steroid hormone biosynthesis profiles were investigated. Results and limitations: Of 364 patients, 181 were analyzed, 60% of whom were diagnosed with PCa. Microbiota composition and diversity were significantly different in PCa, partially affected by Prevotella 9, the most abundant genus of the cohort, and significantly higher in PCa patients. Predictive functional analyses revealed higher 5-α-reductase, copper absorption, and retinol metabolism in the PCa-associated microbiome. Plasma testosterone was associated negatively with the predicted microbial 5-α-reductase level. Conclusions: Gut microbiota of the PCa patients differed significantly compared with benign individuals. Microbial 5-α-reductase, copper absorption, and retinol metabolism are potential mechanisms of action. These findings support the observed association of lifestyle, geography, and PCa incidence. Patient summary: In this report, we found that several microbes and potential functions of the gut microbiota are altered in prostate cancer compared with benign cases. These findings suggest that gut microbiota could be the link between environmental factors and prostate cancer.

Diagnostic Performance and Safety of Positron Emission Tomography with 18F-rhPSMA-7.3 in Patients with Newly Diagnosed Unfavourable Intermediate- to Very-high-risk Prostate Cancer: Results from a Phase 3, Prospective, Multicentre Study (LIGHTHOUSE).

BACKGROUND: Radiohybrid (rh) 18F-rhPSMA-7.3 is a novel high-affinity prostate-specific membrane antigen (PSMA)-targeting radiopharmaceutical for prostate cancer (PCa) imaging. OBJECTIVE: To evaluate the diagnostic performance and safety of 18F-rhPSMA-7.3 in newly diagnosed PCa patients planned for prostatectomy. DESIGN, SETTING, AND PARTICIPANTS: Data on 18F-rhPSMA-7.3 were reported from the phase 3 prospective, multicentre LIGHTHOUSE study (NCT04186819). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Patients underwent positron emission tomography/computed tomography (PET/CT) 50-70 min after an injection of 296 MBq 18F-rhPSMA-7.3. Images were interpreted locally and by three blinded independent readers. The coprimary endpoints were patient-level sensitivity and specificity for the detection of pelvic lymph node (PLN) metastases, validated using histopathology at PLN dissection. Prespecified statistical thresholds (lower bounds of 95% confidence interval [CI]) were set at 22.5% for sensitivity and 82.5% for specificity. RESULTS AND LIMITATIONS: Of 372 patients screened, 352 had evaluable 18F-rhPSMA-7.3-PET/CT and 296 (99 [33%] with unfavourable intermediate-risk [UIR] and 197 [67%] with high-/very-high-risk [VHR] PCa) subsequently underwent surgery. As per the independent reads, 23-37 (7.8-13%) patients had 18F-rhPSMA-7.3-positive PLN. Seventy (24%) patients had one or more positive PLNs on histopathology. The sensitivity for PLN detection was 30% (95% CI, 19.6-42.1%) for reader 1, 27% (95% CI, 17.2-39.1%) for reader 2, and 23% (95% CI, 13.7-34.4%) for reader 3, not meeting the prespecified threshold. Specificity was 93% (95% CI, 88.8-95.9%), 94% (95% CI, 89.8-96.6%), and 97% (95% CI, 93.7-98.7%), respectively, exceeding the threshold for all readers. Specificity was high (≥92%) across both risk stratifications. Sensitivity was higher among high-risk/VHR (24-33%) than among UIR (16-21%) patients. Extrapelvic (M1) lesions were reported for 56-98/352 (16-28%) patients who underwent 18F-rhPSMA-7.3-PET/CT irrespective of surgery. Verification of these (predominantly by conventional imaging) gave a verified detection rate of 9.9-14% (positive predictive value, 51-63%). No serious adverse events were observed. CONCLUSIONS: Across all risk stratifications, 18F-rhPSMA-7.3-PET/CT had high specificity, meeting the specificity endpoint. The sensitivity endpoint was not met, although higher sensitivity was noted among high-risk/VHR than among UIR patients. Overall, 18F-rhPSMA-7.3-PET/CT was well tolerated, and identified N1 and M1 disease prior to surgery in newly diagnosed PCa patients. PATIENT SUMMARY: In order to select the most appropriate treatment for patients with prostate cancer, it is critical to diagnose the disease burden accurately at initial diagnosis. In this study, we investigated a new diagnostic imaging agent in a large population of men with primary prostate cancer. We found it to have an excellent safety profile and to provide clinically useful information regarding the presence of disease beyond the prostate.

Evolution of non-perfused volume after transurethral ultrasound ablation of prostate: A retrospective 12-month analysis.

Background: A detailed understanding of the non-perfused volume (NPV) evolution after prostate ablation therapy is lacking. The impact of different diseased prostate tissues on NPV evolution post-ablation is unknown. Purpose: To characterize the NPV evolution for three treatment groups undergoing heat-based prostate ablation therapy, including benign prostatic hyperplasia (BPH), primary prostate cancer (PCa), and radiorecurrent PCa. Materials and methods: Study design and data analysis were performed retrospectively. All patients received MRI-guided transurethral ultrasound ablation (TULSA). 21 BPH, 28 radiorecurrent PCa and 40 primary PCa patients were included. Using the T1-weighted contrast-enhanced MR image, the NPV was manually contoured by an experienced radiologist. All patients received an MRI immediately following the ablation. Follow-up included MRI at 3- and 12 months for BPH and radiorecurrent PCa patients and at 6- and 12 months for primary PCa patients. Results: A significant difference between BPH and radiorecurrent PCa patients was observed at three months (p < 0.0001, Wilcoxon rank sum test), with the median NPV decreasing by 77 % for BPH patients but increasing by 4 % for radiorecurrent PCa patients. At six months, the median NPV decreased by 97 % for primary PCa. Across all groups, although 40 % of patients had residual NPV at 12 months, it tended to be < 1 mL. Conclusion: The resolution of necrotic tissue after ablation was markedly slower for irradiated than treatment-naïve prostate tissue. These results may account for the increased toxicity observed after radiorecurrent salvage therapy. By 12 months, most necrotic prostate tissue had disappeared in every treatment group.

Nationwide analysis of survival after radical cystectomy for bladder cancer in Finland.

BACKGROUND: Population-based survival results after radical cystectomy (RC) are limited. Our objective was to report short and long-term survival results after RC for bladder cancer from Finland in a population-based setting. MATERIALS AND METHODS: The Finnish National Cystectomy Database containing retrospectively collected essential RC data covering the years 2005-2017 was combined with the survival data from the Finnish Cancer Registry. Kaplan-Meier plots were used to estimate survival and the survival graphs were illustrated according to the final pathological staging. Centers were divided according to operational volume, and the results were then compared using Pearsons's Chi-squared test. RESULTS: A total of 2047 patients were included in the study. 30-, and 90-day mortality was 1.3%, and 3.8%, respectively. The OS of the entire RC population at 5- and 10 years was 66% and 55%, and CSS was 74% and 72%, respectively. Center volume did not significantly associate with surgical mortality or long-term survival. The 5- and 10-year OS according to pT-category was 87% and 74% for pT0, 85% and 69% for pTa-pTis-pT1, 70% and 58% for pT2, 50% and 42% for pT3 and 41% and 30% for pT4. The corresponding 5- and 10-year CSS rates were 96% and 93% for pT0, 91% and 90% for pTa-pTis-pT1, 78% and 75% for pT2, 56% and 55% for pT3 and 47% and 44% for pT4. The 5- and 10-year OS rates in patients with no lymph node metastases (pN-) were 74% and 62%, and CSS 82% and 80%, respectively. If lymph nodes were positive (pN+), the corresponding OS rates were 44% and 34% and CSS 49% and 48%, respectively. CONCLUSION: RC survival results have improved in contemporary series and are associated with the pTNM-status. The nationwide results from Finland demonstrate outcome comparable to high volume single-center series.

Prostate cancer detection and segmentation on MRI using non-local mask R-CNN with histopathological ground truth.

BACKGROUND: Automatic detection and segmentation of intraprostatic lesions (ILs) on preoperative multiparametric-magnetic resonance images (mp-MRI) can improve clinical workflow efficiency and enhance the diagnostic accuracy of prostate cancer and is an essential step in dominant intraprostatic lesion boost. PURPOSE: The goal is to improve the detection and segmentation accuracy of 3D ILs in MRI by a proposed a deep learning (DL)-based algorithm with histopathological ground truth. METHODS: This retrospective study included 262 patients with in vivo prostate biparametric MRI (bp-MRI) scans and were divided into three cohorts based on their data analysis and annotation. Histopathological ground truth was established by using histopathology images as delineation reference standard on cohort 1, which consisted of 64 patients and was randomly split into 20 training, 12 validation, and 32 testing patients. Cohort 2 consisted of 158 patients with bp-MRI based lesion delineation, and was randomly split into 104 training, 15 validation, and 39 testing patients. Cohort 3 consisted of 40 unannotated patients, used in semi-supervised learning. We proposed a non-local Mask R-CNN and boosted its performance by applying different training techniques. The performance of non-local Mask R-CNN was compared with baseline Mask R-CNN, 3D U-Net and an experienced radiologist's delineation and was evaluated by detection rate, dice similarity coefficient (DSC), sensitivity, and Hausdorff Distance (HD). RESULTS: The independent testing set consists of 32 patients with histopathological ground truth. With the training technique maximizing detection rate, the non-local Mask R-CNN achieved 80.5% and 94.7% detection rate; 0.548 and 0.604 DSC; 5.72 and 6.36 95 HD (mm); 0.613 and 0.580 sensitivity for ILs of all Gleason Grade groups (GGGs) and clinically significant ILs (GGG > 2), which outperformed baseline Mask R-CNN and 3D U-Net. For clinically significant ILs, the model segmentation accuracy was significantly higher than that of the experienced radiologist involved in the study, who achieved 0.512 DSC (p = 0.04), 8.21 (p = 0.041) 95 HD (mm), and 0.398 (p = 0.001) sensitivity. CONCLUSION: The proposed DL model achieved state-of-art performance and has the potential to help improve radiotherapy treatment planning and noninvasive prostate cancer diagnosis.

Comparison of Bacillus Calmette-Guérin Maintenance Therapy with Monthly Instillations and the Southwest Oncology Group Protocol in the Treatment of Non-muscle-invasive Bladder Cancer.

BACKGROUND: Bacillus Calmette-Guérin (BCG) therapy using the Southwest Oncology Group (SWOG) maintenance protocol is the standard in non-muscle-invasive bladder cancer (NMIBC). Maintenance with monthly instillations is also widely used, but evidence comparing the two maintenance protocols is scarce. OBJECTIVE: To compare monthly and SWOG instillation schedules in maintenance BCG therapy. DESIGN, SETTING, AND PARTICIPANTS: We retrospectively identified patients with NMIBC treated with maintenance BCG according to either the monthly or the SWOG instillation regimen in two tertiary care centers in Finland between 2009 and 2019. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We compared discontinuation rates of the monthly and SWOG maintenance protocols due to toxicity, and recurrence and progression rates by protocols. Baseline characteristics were compared with the Wilcoxon rank sum test, chi-square test, and Fisher's exact test. The Kaplan-Meier method and Cox proportional hazards model were used to evaluate the discontinuation of BCG due to toxicity and oncological efficacy. RESULTS AND LIMITATIONS: We identified 723 patients, of whom 545 (75%) and 178 (25%) received maintenance according to the monthly and SWOG protocols, respectively. The median follow-up time was 66 (interquartile range: 45-99) mo. In the monthly and SWOG groups, 131 (24%) and 50 (28%) patients, respectively, discontinued BCG due to toxicity, with no difference in a univariate or multivariate analysis (hazard ratio 1.01, 95% confidence interval [CI]: 0.73-1.40, p = 0.940). The 5-yr recurrence-free survival rates in the monthly and SWOG groups were 65% (95% CI: 61-69%) and 71% (95% CI: 64-79%, p = 0.370), respectively. The 5-yr progression-free survival rates were 89% (95% CI: 86-92%) and 91% (95% CI: 86-96%, p = 0.240), respectively. CONCLUSIONS: Monthly maintenance is a comparable alternative to the SWOG protocol. PATIENT SUMMARY: In this study, we compared two schedules of intravesical bacillus Calmette-Guérin (BCG) treatment used in the treatment of non-muscle-invasive bladder cancer. We found that there were no significant differences between the two instillation schedules in terms of tolerability or efficacy.

Short- and long-term risks of photoselective laser vaporization of the prostate: a population-based comparison with transurethral resection of the prostate.

BACKGROUND: Transurethral resection of the prostate (TURP) is the standard surgical treatment for benign prostate enlargement (BPE). Photoselective vaporization of the prostate (PVP) is an alternative, but there is limited real-life evidence of PVP risks. OBJECTIVE: To compare short- and long-term risks of PVP to those of TURP in the treatment of BPE. MATERIALS AND METHODS: Consecutive patients who underwent elective PVP or TURP between 2006 and 2018 in 20 hospitals in Finland were retrospectively studied using a combination of national registries (n = 27,408; mean age 71 years). Short-term risks were postoperative mortality, major adverse cardiovascular events (MACE), and reoperations for bleeding. Long-term risks were reoperations for BPE or any urethral operations within 12 years. Differences between treatment groups were balanced by inverse probability of treatment weighting. Risks were analyzed using the Kaplan-Meier method and Cox regression. RESULTS: There were no differences in postoperative mortality or MACE between the study groups. Reoperations for bleeding were less frequent after PVP (0.9%, HR: 0.72, p = 0.042). Bleeding was more likely in patients with atrial fibrillation (number needed to treat [NNT] for PVP vs TURP: 61). Cumulative incidence for reoperation was higher after PVP (23.5%) than after TURP in long-term follow-up (17.8%; HR: 1.20, p < 0.0001, NNT: -31.7). CONCLUSIONS: PVP is associated with lower postoperative bleeding risk but higher long-term reoperation risk than TURP. Patients with high bleeding risk and a low likelihood of needing reoperation appear most suitable for laser vaporization.KEY MESSAGEPVP is associated with lower postoperative bleeding risk but higher long-term reoperation risk than TURP. PVP appears an attractive treatment option, especially for patients with high bleeding risk and a low likelihood of needing a reoperation.

Prognostic impact of variant histologies in urothelial bladder cancer treated with radical cystectomy.

OBJECTIVES: To evaluate variant histologies (VHs) for disease-specific survival (DSS) in patients with invasive urothelial bladder cancer (BCa) undergoing radical cystectomy (RC). MATERIALS AND METHODS: We analysed a multi-institutional cohort of 1082 patients treated with upfront RC for cT1-4aN0M0 urothelial BCa at eight centres. Univariable and multivariable Cox' regression analyses were used to assess the effect of different VHs on DSS in overall cohort and three stage-based analyses. The stages were defined as 'organ-confined' (≤pT2N0), 'locally advanced' (pT3-4N0) and 'node-positive' (pTanyN1-3). RESULTS: Overall, 784 patients (72.5%) had pure urothelial carcinoma (UC), while the remaining 298 (27.5%) harboured a VH. Squamous differentiation was the most common VH, observed in 166 patients (15.3%), followed by micropapillary (40 patients [3.7%]), sarcomatoid (29 patients [2.7%]), glandular (18 patients [1.7%]), lymphoepithelioma-like (14 patients [1.3%]), small-cell (13 patients [1.2%]), clear-cell (eight patients [0.7%]), nested (seven patients [0.6%]) and plasmacytoid VH (three patients [0.3%]). The median follow-up was 2.3 years. Overall, 534 (49.4%) disease-related deaths occurred. In uni- and multivariable analyses, plasmacytoid and small-cell VHs were associated with worse DSS in the overall cohort (both P = 0.04). In univariable analyses, sarcomatoid VH was significantly associated with worse DSS, while lymphoepithelioma-like VH had favourable DSS compared to pure UC. Clear-cell (P = 0.015) and small-cell (P = 0.011) VH were associated with worse DSS in the organ-confined and node-positive cohorts, respectively. CONCLUSIONS: More than 25% of patients harboured a VH at time of RC. Compared to pure UC, clear-cell, plasmacytoid, small-cell and sarcomatoid VHs were associated with worse DSS, while lymphoepithelioma-like VH was characterized by a DSS benefit. Accurate pathological diagnosis of VHs may ensure tailored counselling to identify patients who require more intensive management.

Deep learning prediction of non-perfused volume without contrast agents during prostate ablation therapy.

The non-perfused volume (NPV) is an important indicator of treatment success immediately after prostate ablation. However, visualization of the NPV first requires an injection of MRI contrast agents into the bloodstream, which has many downsides. Purpose of this study was to develop a deep learning model capable of predicting the NPV immediately after prostate ablation therapy without the need for MRI contrast agents. A modified 2D deep learning UNet model was developed to predict the post-treatment NPV. MRI imaging data from 95 patients who had previously undergone prostate ablation therapy for treatment of localized prostate cancer were used to train, validate, and test the model. Model inputs were T1/T2-weighted and thermometry MRI images, which were always acquired without any MRI contrast agents and prior to the final NPV image on treatment-day. Model output was the predicted NPV. Model accuracy was assessed using the Dice-Similarity Coefficient (DSC) by comparing the predicted to ground truth NPV. A radiologist also performed a qualitative assessment of NPV. Mean (std) DSC score for predicted NPV was 85% ± 8.1% compared to ground truth. Model performance was significantly better for slices with larger prostate radii (> 24 mm) and for whole-gland rather than partial ablation slices. The predicted NPV was indistinguishable from ground truth for 31% of images. Feasibility of predicting NPV using a UNet model without MRI contrast agents was clearly established. If developed further, this could improve patient treatment outcomes and could obviate the need for contrast agents altogether. Trial Registration Numbers Three studies were used to populate the data: NCT02766543, NCT03814252 and NCT03350529. Supplementary Information: The online version contains supplementary material available at 10.1007/s13534-022-00250-y.

Safety and efficacy of MRI-guided transurethral ultrasound ablation for radiorecurrent prostate cancer in the presence of gold fiducial markers.

BACKGROUND: Safety and efficacy of ultrasound prostate ablation for radiorecurrent prostate cancer (PCa) in the presence of gold fiducial markers has not been previously reported. PURPOSE: To evaluate safety, functional, and early-stage oncological outcomes for patients with gold fiducial markers undergoing salvage magnetic resonance imaging (MRI)-guided transurethral ultrasound ablation (sTULSA) for radiorecurrent PCa. MATERIAL AND METHODS: Data were acquired from an ethics-approved, single-center phase-1 study. Eight patients with 18 total gold fiducial markers inside the planned treatment volume were identified. MRI controls were performed at three and 12 months, followed by PSMA-PET-CT imaging and biopsies at 12 months. A control cohort of 13 patients who underwent sTULSA without markers were also identified for safety profile comparison. Adverse events were reported using the Clavien-Dindo classification, and questionnaires including EPIC-26, IPSS, and IIEF-5 were collected. RESULTS: Of 18 markers, 2 (11%) were directly responsible for poor ultrasound penetration. However, there were no local recurrences at 12 months. PSA, prostate volume, and non-perfused volume all decreased over time. At 12 months, 11/18 (61%) of fiducial markers had disappeared via sloughing. The adverse event profile was similar between both patient cohorts, and when controlled for ablation type, no statistical difference in functional outcomes between the two cohorts was observed. CONCLUSION: Patients with radiorecurrent PCa with intraprostatic gold fiducial markers can be successfully treated with TULSA. The early-stage efficacy of sTULSA for patients with intraprostatic gold markers is encouraging and the safety profile is unaffected by marker presence.

Clinical presentation of bacille Calmette-Guérin (BCG) infections after BCG instillation therapy.

OBJECTIVES: To investigate the timing of the clinical presentation of various types of bacille Calmette-Guérin (BCG) infections in a Finnish population of patients with bladder cancer treated with BCG instillation therapy. PATIENTS AND METHODS: We identified patients with a history of post-instillation BCG infection from 1996 to 2016 using the Finnish Cancer Registry and the Finnish National Infectious Diseases Registry. We categorised infections as systemic if the infection was found in the non-urogenital system and genitourinary (GU) if the infection affected the urogenital tract. We calculated the time interval between the last BCG instillation and the presentation of the infection. The infection was considered late if the time interval was ≥1 year. RESULTS: A total of 100 patients with BCG infection were identified during the study period. In all, 39 (39%) infections presented as systemic and 61 (61%) were in the GU tract. The majority of the systemic infections presented rapidly after the last instillation, while five (13%) presented after a latency of ≥1 year. The presentation of GU infections was more heterogeneous, with 12 (20%) presenting as late infections. CONCLUSION: This study confirms the concept of early and late infection types, especially among systemic infections. However, late infections appeared to be rarer than previously described. Urologists should be aware of the possibility of late BCG infection if patients develop symptoms even several years after the BCG regimen.

Flare on [18F]PSMA-1007 PET/CT after short-term androgen deprivation therapy and its correlation to FDG uptake: possible marker of tumor aggressiveness in treatment-naïve metastatic prostate cancer patients.

PURPOSE: Short-term androgen deprivation therapy (ADT) is known to increase heterogeneously prostate-specific membrane antigen (PSMA) expression. This phenomenon might indicate the potential of cancer lesions to respond to ADT. In this prospective study, we evaluated the flare on [18F]PSMA-1007 PET/CT after ADT in metastatic prostate cancer (PCa). Given that aggressive PCa tends to display FDG uptake, we particularly investigated whether the changes in PSMA uptake might correlate with glucose metabolism. METHODS: Twenty-five men with newly diagnosed treatment-naïve metastatic PCa were enrolled in this prospective registered clinical trial. All the patients underwent [18F]PSMA-1007 PET/CT immediately before and 3-4 weeks after ADT initiation (degarelix). Before ADT, [18F]FDG PET/CT was also performed. Standardized uptake values (SUV)max of primary and metastatic lesions were calculated in all PET scans. Serum PSA and testosterone blood samples were collected before the two PSMA PET scans. The changes in PSMA uptake after ADT were represented as ΔSUVmax. RESULTS: All the patients reached castration levels of testosterone at the time of the second [18F]PSMA-1007 PET/CT. Overall, 57 prostate, 314 lymph nodes (LN), and 406 bone lesions were analyzed. After ADT, 104 (26%) bone, 33 (11%) LN, and 6 (11%) prostate lesions showed an increase (≥ 20%) in PSMA uptake, with a median ΔSUVmax of + 50%, + 60%, and + 45%, respectively. Among the lesions detected at the baseline [18F]PSMA-1007 PET/CT, 63% bone and 46% LN were FDG-positive. In these metastases, a negative correlation was observed between the PSMA ΔSUVmax and FDG SUVmax (p < 0.0001). Moreover, a negative correlation between the ΔSUVmax and the decrease in serum PSA after ADT was noted (p < 0.0001). CONCLUSIONS: A heterogeneous increase in PSMA uptake after ADT was detected, most evidently in bone metastases. We observed a negative correlation between the PSMA flare and the intensity of glucose uptake as well as the decrease of serum PSA, suggesting that lesions presenting with such flare might potentially be less aggressive. TRIAL REGISTRATION: NCT03876912, registered 15 March 2019.

Evolving imaging methods of prostate cancer and the emergence of magnetic resonance imaging guided ablation techniques.

Established therapies for prostate cancer (PCa), surgery and radiotherapy, treat the entire gland regardless of the location of the cancerous lesion within the prostate. Although effective, these methods include a significant risk of worsening genitourinary outcomes. Targeted image-guided cancer therapy has gained acceptance through improved PCa detection, localization, and characterization by magnetic resonance imaging (MRI). Minimally-invasive ablative techniques aim to achieve comparable oncological outcomes to radical treatment while preserving genitourinary function. Transurethral ultrasound ablation (TULSA) and next-generation transrectal high-intensity focused ultrasound (HIFU) utilize MRI guidance to thermally ablate prostate tissue under real-time MRI monitoring and active temperature feedback control. Previous trials performed by our group and others, including a large multicenter study in men with localized favorable-risk disease, have demonstrated that TULSA provides effective prostate ablation with a favorable safety profile and low impact on quality of life. Recently, MRI-guided HIFU focal therapy was also shown as a safe and effective treatment of intermediate-risk PCa. Here we review the current literature on ablative techniques in the treatment of localized PCa with a focus on TULSA and HIFU methods.

Detection of prostate cancer bone metastases with fast whole-body 99mTc-HMDP SPECT/CT using a general-purpose CZT system.

BACKGROUND: We evaluated the effects of acquisition time, energy window width, and matrix size on the image quality, quantitation, and diagnostic performance of whole-body 99mTc-HMDP SPECT/CT in the primary metastasis staging of prostate cancer. METHODS: Thirty prostate cancer patients underwent 99mTc-HMDP SPECT/CT from the top of the head to the mid-thigh using a Discovery NM/CT 670 CZT system with list-mode acquisition, 50-min acquisition time, 15% energy window width, and 128 × 128 matrix size. The acquired list-mode data were resampled to produce data sets with shorter acquisition times of 41, 38, 32, 26, 20, and 16 min, narrower energy windows of 10, 8, 6, and 4%, and a larger matrix size of 256 × 256. Images were qualitatively evaluated by three experienced nuclear medicine physicians and quantitatively evaluated by noise, lesion contrast and SUV measurements. Diagnostic performance was evaluated from the readings of two experienced nuclear medicine physicians in terms of patient-, region-, and lesion-level sensitivity and specificity. RESULTS: The originally acquired images had the best qualitative image quality and lowest noise. However, the acquisition time could be reduced to 38 min, the energy window narrowed to 8%, and the matrix size increased to 256 × 256 with still acceptable qualitative image quality. Lesion contrast and SUVs were not affected by changes in acquisition parameters. Acquisition time reduction had no effect on the diagnostic performance, as sensitivity, specificity, accuracy, and area under the receiver-operating characteristic curve were not significantly different between the 50-min and reduced acquisition time images. The average patient-level sensitivities of the two readers were 88, 92, 100, and 96% for the 50-, 32-, 26-, and 16-min images, respectively, and the corresponding specificities were 78, 84, 84, and 78%. The average region-level sensitivities of the two readers were 55, 58, 59, and 56% for the 50-, 32-, 26-, and 16-min images, respectively, and the corresponding specificities were 95, 98, 96, and 95%. The number of equivocal lesions tended to increase as the acquisition time decreased. CONCLUSION: Whole-body 99mTc-HMDP SPECT/CT can be acquired using a general-purpose CZT system in less than 20 min without any loss in diagnostic performance in metastasis staging of high-risk prostate cancer patients.

Periodic trends in geographical variation of prostate cancer incidence and mortality in Finland between 1985 and 2019.

BACKGROUND: Evaluation of regional variation of prostate cancer (PCa) incidence and PCa-specific mortality is essential in the assessment of equity in a national healthcare system. We evaluated PCa incidence and PCa-specific mortality between different municipalities and hospital districts in Finland over 1985-2019. MATERIAL AND METHODS: Men diagnosed with PCa in Finland from 1985 through 2019 were retrieved from Finnish Cancer Registry. Age-standardized PCa incidence and mortality rates were estimated by municipality and hospital district as well as municipality urbanization, education, and income level using hierarchical Bayesian modeling. Standard deviations (SD) of the regional rates were compared between periods from 1985-1989 to 2015-2019. RESULTS: We identified 123,185 men diagnosed with any stage PCa between 1985 and 2019. SD of PCa incidence rate (per 100,000 person-years) showed that the total variation of PCa incidence between different municipalities was substantial and varied over time: from 22.2 (95% CI, 17.1-27.8) in 1985-1989 to 56.5 (95% CI, 49.8-64.5) in 2000-2004. The SD of PCa mortality rate between all municipalities was from 9.0 (95% CI, 6.6-11.8) in 2005-2009 to 2.4 (95% CI, 0.9-4.8) in 2015-2019. There was a trend toward a lower PCa-specific mortality rate in municipalities with higher education level. DISCUSSION: Regional variation in the incidence rate of PCa became more evident after initiation of PSA testing in Finland, which indicates that early diagnostic practice (PSA testing) of PCa has been different in different parts of the country. Variation in the national PCa mortality rate was indeed recognizable, however, this variation diminished at the same time as the mortality rate declined in Finland. It seems that after the initiation period of PSA testing, PSA has equalized PCa mortality outcomes in Finland.

Predicting the Need for Biopsy to Detect Clinically Significant Prostate Cancer in Patients with a Magnetic Resonance Imaging-detected Prostate Imaging Reporting and Data System/Likert ≥3 Lesion: Development and Multinational External Validation of the Imperial Rapid Access to Prostate Imaging and Diagnosis Risk Score.

BACKGROUND: Although multiparametric magnetic resonance imaging (MRI) has high sensitivity, its lower specificity leads to a high prevalence of false-positive lesions requiring biopsy. OBJECTIVE: To develop and externally validate a scoring system for MRI-detected Prostate Imaging Reporting and Data System (PIRADS)/Likert ≥3 lesions containing clinically significant prostate cancer (csPCa). DESIGN, SETTING, AND PARTICIPANTS: The multicentre Rapid Access to Prostate Imaging and Diagnosis (RAPID) pathway included 1189 patients referred to urology due to elevated age-specific prostate-specific antigen (PSA) and/or abnormal digital rectal examination (DRE); April 27, 2017 to October 25, 2019. INTERVENTION: Visual-registration or image-fusion targeted and systematic transperineal biopsies for an MRI score of ≥4 or 3 + PSA density ≥0.12 ng/ml/ml. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Fourteen variables were used in multivariable logistic regression for Gleason ≥3 + 4 (primary) and Gleason ≥4 + 3, and PROMIS definition 1 (any ≥4 + 3 or ≥6 mm any grade; secondary). Nomograms were created and a decision curve analysis (DCA) was performed. Models with varying complexity were externally validated in 2374 patients from six international cohorts. RESULTS AND LIMITATIONS: The five-item Imperial RAPID risk score used age, PSA density, prior negative biopsy, prostate volume, and highest MRI score (corrected c-index for Gleason ≥3 + 4 of 0.82 and 0.80-0.86 externally). Incorporating family history, DRE, and Black ethnicity within the eight-item Imperial RAPID risk score provided similar outcomes. The DCA showed similar superiority of all models, with net benefit differences increasing in higher threshold probabilities. At 20%, 30%, and 40% of predicted Gleason ≥3 + 4 prostate cancer, the RAPID risk score was able to reduce, respectively, 11%, 21%, and 31% of biopsies against 1.8%, 6.2%, and 14% of missed csPCa (or 9.6%, 17%, and 26% of foregone biopsies, respectively). CONCLUSIONS: The Imperial RAPID risk score provides a standardised tool for the prediction of csPCa in patients with an MRI-detected PIRADS/Likert ≥3 lesion and can support the decision for prostate biopsy. PATIENT SUMMARY: In this multinational study, we developed a scoring system incorporating clinical and magnetic resonance imaging characteristics to predict which patients have prostate cancer requiring treatment and which patients can safely forego an invasive prostate biopsy. This model was validated in several other countries.

The Mount Sinai Prebiopsy Risk Calculator for Predicting any Prostate Cancer and Clinically Significant Prostate Cancer: Development of a Risk Predictive Tool and Validation with Advanced Neural Networking, Prostate Magnetic Resonance Imaging Outcome Database, and European Randomized Study of Screening for Prostate Cancer Risk Calculator.

Background: The European Association of Urology guidelines recommend the use of imaging, biomarkers, and risk calculators in men at risk of prostate cancer. Risk predictive calculators that combine multiparametric magnetic resonance imaging with prebiopsy variables aid as an individualized decision-making tool for patients at risk of prostate cancer, and advanced neural networking increases reliability of these tools. Objective: To develop a comprehensive risk predictive online web-based tool using magnetic resonance imaging (MRI) and clinical data, to predict the risk of any prostate cancer (PCa) and clinically significant PCa (csPCa) applicable to biopsy-naïve men, men with a prior negative biopsy, men with prior positive low-grade cancer, and men with negative MRI. Design setting and participants: Institutional review board-approved prospective data of 1902 men undergoing biopsy from October 2013 to September 2021 at Mount Sinai were collected. Outcome measurements and statistical analysis: Univariable and multivariable analyses were used to evaluate clinical variables such as age, race, digital rectal examination, family history, prostate-specific antigen (PSA), biopsy status, Prostate Imaging Reporting and Data System score, and prostate volume, which emerged as predictors for any PCa and csPCa. Binary logistic regression was performed to study the probability. Validation was performed with advanced neural networking (ANN), multi-institutional European cohort (Prostate MRI Outcome Database [PROMOD]), and European Randomized Study of Screening for Prostate Cancer Risk Calculator (ERSPC RC) 3/4. Results and limitations: Overall, 2363 biopsies had complete clinical information, with 57.98% any cancer and 31.40% csPCa. The prediction model was significantly associated with both any PCa and csPCa having an area under the curve (AUC) of 81.9% including clinical data. The AUC for external validation was calculated in PROMOD, ERSPC RC, and ANN for any PCa (0.82 vs 0.70 vs 0.90) and csPCa (0.82 vs 0.78 vs 0.92), respectively. This study is limited by its retrospective design and overestimation of csPCa in the PROMOD cohort. Conclusions: The Mount Sinai Prebiopsy Risk Calculator combines PSA, imaging and clinical data to predict the risk of any PCa and csPCa for all patient settings. With accurate validation results in a large European cohort, ERSPC RC, and ANN, it exhibits its efficiency and applicability in a more generalized population. This calculator is available online in the form of a free web-based tool that can aid clinicians in better patients counseling and treatment decision-making. Patient summary: We developed the Mount Sinai Prebiopsy Risk Calculator (MSP-RC) to assess the likelihood of any prostate cancer and clinically significant disease based on a combination of clinical and imaging characteristics. MSP-RC is applicable to all patient settings and accessible online.

Mortality after surgery for benign prostate hyperplasia: a nationwide cohort study.

PURPOSE: To investigate postoperative mortality rates and risk factors for mortality after surgical treatment of benign prostate hyperplasia (BPH). METHODS: All patients who underwent partial prostate excision/resection from 2004 to 2014 in Finland were retrospectively assessed for eligibility using a nationwide registry. Procedures were classified as transurethral resection of the prostate (TURP), laser vaporization of the prostate (laser), and open prostatectomy. Univariable and multivariable regression were used to analyze the association of age, Charlson comorbidity index (CCI), operation type, annual center operation volume, study era, atrial fibrillation, and prostate cancer diagnosis with 90 days postoperative mortality. RESULTS: Among the 39,320 patients, TURP was the most common operation type for lower urinary tract symptoms in all age groups. The overall 90 days postoperative mortality was 1.10%. Excess mortality in the 90 days postoperative period was less than 0.5% in all age groups. Postoperative mortality after laser operations was 0.59% and 1.16% after TURP (p = 0.035). Older age, CCI score, and atrial fibrillation were identified as risk factors for postoperative mortality. Prostate cancer diagnosis and the center's annual operation volume were not significantly associated with mortality. The most common underlying causes of death were malignancy (35.5%) and cardiac disease (30.9%). CONCLUSION: Elective urologic procedures for BPH are generally considered safe, but mortality increases with age. Laser operations may be associated with lower mortality rates than the gold standard TURP. Thus, operative risks and benefits must be carefully considered on a case-by-case basis. Further studies comparing operation types are needed.

Increased Expression and Altered Cellular Localization of Fibroblast Growth Factor Receptor-Like 1 (FGFRL1) Are Associated with Prostate Cancer Progression.

Fibroblast growth factor receptors (FGFRs) 1-4 are involved in prostate cancer (PCa) regulation, but the role of FGFR-like 1 (FGFRL1) in PCa is unclear. FGFRL1 expression was studied by qRT-PCR and immunohistochemistry of patient tissue microarrays (TMAs) and correlated with clinical patient data. The effects of FGFRL1 knockdown (KD) in PC3M were studied in in vitro culture models and in mouse xenograft tumors. Our results showed that FGFRL1 was significantly upregulated in PCa. The level of membranous FGFRL1 was negatively associated with high Gleason scores (GSs) and Ki67, while increased cytoplasmic and nuclear FGFRL1 showed a positive correlation. Cox regression analysis indicated that nuclear FGFRL1 was an independent prognostic marker for biochemical recurrence after radical prostatectomy. Functional studies indicated that FGFRL1-KD in PC3M cells increases FGFR signaling, whereas FGFRL1 overexpression attenuates it, supporting decoy receptor actions of membrane-localized FGFRL1. In accordance with clinical data, FGFRL1-KD markedly suppressed PC3M xenograft growth. Transcriptomics of FGFRL1-KD cells and xenografts revealed major changes in genes regulating differentiation, ECM turnover, and tumor-stromal interactions associated with decreased growth in FGFRL1-KD xenografts. Our results suggest that FGFRL1 upregulation and altered cellular compartmentalization contribute to PCa progression. The nuclear FGFRL1 could serve as a prognostic marker for PCa patients.