Earliest known hominin activity in the Philippines by 709 thousand years ago.

Over 60 years ago, stone tools and remains of megafauna were discovered on the Southeast Asian islands of Flores, Sulawesi and Luzon, and a Middle Pleistocene colonization by Homo erectus was initially proposed to have occurred on these islands1-4. However, until the discovery of Homo floresiensis in 2003, claims of the presence of archaic hominins on Wallacean islands were hypothetical owing to the absence of in situ fossils and/or stone artefacts that were excavated from well-documented stratigraphic contexts, or because secure numerical dating methods of these sites were lacking. As a consequence, these claims were generally treated with scepticism 5 . Here we describe the results of recent excavations at Kalinga in the Cagayan Valley of northern Luzon in the Philippines that have yielded 57 stone tools associated with an almost-complete disarticulated skeleton of Rhinoceros philippinensis, which shows clear signs of butchery, together with other fossil fauna remains attributed to stegodon, Philippine brown deer, freshwater turtle and monitor lizard. All finds originate from a clay-rich bone bed that was dated to between 777 and 631 thousand years ago using electron-spin resonance methods that were applied to tooth enamel and fluvial quartz. This evidence pushes back the proven period of colonization 6 of the Philippines by hundreds of thousands of years, and furthermore suggests that early overseas dispersal in Island South East Asia by premodern hominins took place several times during the Early and Middle Pleistocene stages1-4. The Philippines therefore may have had a central role in southward movements into Wallacea, not only of Pleistocene megafauna 7 , but also of archaic hominins.

Benefit of dynamic contrast-enhanced (DCE) imaging for prostate cancer detection depending on readers experience in prostate MRI.

AIM: To investigate the relevance of dynamic contrast enhanced imaging (DCE) within multiparametric magnetic resonance imaging (mpMRI) for the detection of clinically significant prostate cancer (csPC) depending on reader experience. MATERIALS AND METHODS: Consecutive patients with 3 T mpMRI and subsequent combined MRI/ultrasound fusion-guided targeted and systematic biopsy from January to September 2019 were included. All mpMRI examinations were read separately by two less experienced (R1; <500 prostate MRI) and two expert radiologists (R2; >5,000 prostate MRI) in consensus and blinded re-read as biparametric MRI (bpMRI). The primary endpoint was the performance comparison of mpMRI versus bpMRI of R1 and R2. RESULTS: Fifty-three of 124 patients had csPC (43%). The PI-RADS agreement of bpMRI and mpMRI was fair for R1 (κ = 0.373) and moderate for R2 (κ = 0.508). R1 assessed 11 csPC with PI-RADS ≤3 (20.8%) on mpMRI and 12 (22.6%) on bpMRI (R2: 1 [1.9%] and 6 [11.3%], respectively). Sensitivity for csPC of mpMRI was 79.3% (NPV 79.3%) for R1 and 98.1% (NPV 97.5%) for R2 (bpMRI: 77.4% [NVP 75.5%] and 86.8% [NPV 84.4%], respectively). Specificity of mpMRI for csPC was 59.2% for R1 and 54.9% for R2 (bpMRI: 52.1% and 53.5%, respectively). Overall accuracy of mpMRI was 79.8% for R1 compared to bpMRI 66.9% (p=0.017; R2: 87.1% and 81.5%; p=0.230). CONCLUSION: Prostate MRI benefits from reader experience. Less experienced readers missed a relevant proportion of csPC with mpMRI and even more with bpMRI. The overall performance of expert readers was comparable for mpMRI and bpMRI but DCE enabled detection of some further ISUP 2 PC.

Clinical characteristics, treatment patterns and relapse in patients with clinical stage IS testicular cancer.

PURPOSE: Clinical stage I (CSI) testicular germ cell tumors (TGCT) represents disease confined to the testis without metastasis and CSIS is defined as persistently elevated tumor markers (TM) after orchiectomy, indicating subclinical metastatic disease. This study aims at assessing clinical characteristics and oncological outcome in CSIS. METHODS: Data from five tertiary referring centers in Germany were screened. We defined correct classification of CSIS according to EAU guidelines. TM levels, treatment and relapse-free survival were assessed and differences between predefined groups (chemotherapy, correct/incorrect CSIS) were analyzed with Fisher's exact and Chi-square test. RESULTS: Out of 2616 TGCT patients, 43 (1.6%) were CSIS. Thereof, 27 were correctly classified (cCSIS, 1.03%) and 16 incorrectly classified (iCSIS). TMs that defined cCSIS were in 12 (44.4%), 10 (37%), 3 (11.1%) and 2 (7.4%) patients AFP, ß-HCG, AFP plus ß-HCG and LDH, respectively. In the cCSIS group, six patients were seminoma and 21 non-seminoma. Treatment consisted of active surveillance, carboplatin-mono AUC7 and BEP (bleomycin, etoposide and cisplatin). No difference between cCSIS and iCSIS with respect to applied chemotherapy was found (p = 0.830). 5-year relapse-free survival was 88.9% and three patients (11%) in the cCSIS group relapsed. All underwent salvage treatment (3xBEP) with no documented death. CONCLUSION: Around 1% of all TGCT were classified as cCSIS patients. Identification of cCSIS is of critical importance to avoid disease progression and relapses by adequate treatment. We report a high heterogeneity of treatment patterns, associated with excellent long-term survival irrespective of the initial treatment approach.

MRI grading for the prediction of prostate cancer aggressiveness.

OBJECTIVES: T o evaluate the value of multiparametric MRI (mpMRI) for the prediction of prostate cancer (PCA) aggressiveness. METHODS: In this single center cohort study, consecutive patients with histologically confirmed PCA were retrospectively enrolled. Four different ISUP grade groups (1, 2, 3, 4-5) were defined and fifty patients per group were included. Several clinical (age, PSA, PSAD, percentage of PCA infiltration) and mpMRI parameters (ADC value, signal increase on high b-value images, diameter, extraprostatic extension [EPE], cross-zonal growth) were evaluated and correlated within the four groups. Based on combined descriptors, MRI grading groups (mG1-mG3) were defined to predict PCA aggressiveness. RESULTS: In total, 200 patients (mean age 68 years, median PSA value 8.1 ng/ml) were analyzed. Between the four groups, statistically significant differences could be shown for age, PSA, PSAD, and for MRI parameters cross-zonal growth, high b-value signal increase, EPE, and ADC (p < 0.01). All examined parameters revealed a significant correlation with the histopathologic biopsy ISUP grade groups (p < 0.01), except PCA diameter (p = 0.09). A mixed linear model demonstrated the strongest prediction of the respective ISUP grade group for the MRI grading system (p < 0.01) compared to single parameters. CONCLUSIONS: MpMRI yields relevant pre-biopsy information about PCA aggressiveness. A combination of quantitative and qualitative parameters (MRI grading groups) provided the best prediction of the biopsy ISUP grade group and may improve clinical pathway and treatment planning, adding useful information beyond PI-RADS assessment category. Due to the high prevalence of higher grade PCA in patients within mG3, an early re-biopsy seems indicated in cases of negative or post-biopsy low-grade PCA. KEY POINTS: • MpMRI yields relevant pre-biopsy information about prostate cancer aggressiveness. • MRI grading in addition to PI-RADS classification seems to be helpful for a size independent early prediction of clinically significant PCA. • MRI grading groups may help urologists in clinical pathway and treatment planning, especially when to consider an early re-biopsy.

Multiparametric magnetic resonance imaging can exclude prostate cancer progression in patients on active surveillance: a retrospective cohort study.

OBJECTIVES: To assess the ability of multiparametric MRI (mp-MRI) of the prostate to exclude prostate cancer (PCa) progression during monitoring patients on active surveillance (AS). METHODS: One hundred forty-seven consecutive patients on AS with mp-MRI (T2WI, DWI, DCE-MRI) at 3T were initially enrolled. Fifty-five received follow-up mp-MRI after a minimum interval of 12 months and subsequent targeted MR/US fusion-guided biopsy (FUS-GB) plus concurrent systematic transrectal ultrasound-guided (TRUS-GB) biopsy as reference standard. Primary endpoint was the negative predictive value (NPV) of the follow-up mp-MRI to exclude histopathologic tumor progression using PRECISE recommendations. Secondary endpoints were the positive predictive value (PPV), sensitivity, specificity, Gleason score (GS) upgrades, and comparison of biopsy method. RESULTS: Of 55 patients, 29 (53%) had a GS upgrade on re-biopsy. All 29 patients showed a tumor progression on follow-up mp-MRI. Fifteen of 55 patients (27%) displayed signs of tumor progression, but had stable GS on re-biopsy. None of the 11 patients (20%) without signs of progression on follow-up mp-MRI had a GS upgrade on re-biopsy. The NPV was 100%, PPV was 66%, sensitivity was 100%, and specificity 42%. FUS-GB resulted in GS upgrade significantly more often (n = 28; 51%) compared with TRUS-GB (n = 12; 22%; p < 0.001). CONCLUSIONS: (Follow-up) Mp-MRI can reliably exclude PCa progression in patients on AS. Standard serial re-biopsies might be waived if follow-up mp-MRIs are stable. Over 60% of patients with signs of tumor progression on mp-MRI during AS had a GS upgrade on re-biopsy. Targeted re-biopsies should be performed if cancer progression or higher-grade PCa is suspected on mp-MRI. KEY POINTS: • None of the patients with unsuspicious mp-MRI had a GS upgrade in re-biopsy and mp-MRI might replace serial biopsies in these cases • More than 60% of patients with mp-MRI signs of tumor progression had subsequent Gleason score (GS) upgrades • Targeted re-biopsies should be performed in case of higher GS cancer suspicion on mp-MRI.

Comparison of analgesic techniques in MRI-guided in-bore prostate biopsy.

OBJECTIVES: To evaluate different analgesic techniques in MRI-guided in-bore prostate biopsy (IB-GB) regarding the influence on patient procedural experience of pain. METHODS: Two hundred fifty-two consecutive patients who had received an IB-GB either with intrarectal instillation of 2% lidocaine gel (n = 126, group A) or with periprostatic nerve block (PPNB) with 2% mepivacaine (n = 126, group B) were retrospectively included in this study. Pain scores were measured on a visual analog scale, the operating room time (ORT) was recorded for each biopsy and correlations between the parameters were analysed. RESULTS: Pain scores for IB-GB were slightly lower in group B compared with group A (2.0 ± 1.9; 2.4 ± 1.7; p = 0.02). In group A, significantly more targeted biopsy cores were acquired (group B: 5.2 ± 1.1; group A: 5.6 ± 0.8; p < 0.01). ORT was comparable and not significantly different in both groups. There was only a weak correlation between pain scores and ORT in group B (rS = 0.22; p = 0.01), but no correlation between pain scores and the number of biopsy cores or the prostate volume. CONCLUSIONS: Pain levels are generally low for MRI-guided in-bore biopsy using either PPNB or intrarectal instillation of lidocaine gel. A statistically significant, slightly lower pain score was documented for PPNB and might be preferred when the focus is analgesia. On the other hand, due to the minor difference and easier administration, intrarectal gel instillation seems to be a reasonable practice for standard analgesia for MRI-guided in-bore biopsy. KEY POINTS: • Pain levels were low for MRI-guided in-bore biopsy using either PPNB or intrarectal instillation of lidocaine gel as analgesic method. • PPNB prior to IB-GB resulted in a slightly lower pain score but required a higher effort. • Intrarectal gel anaesthesia seems to be a reasonable practice for standard analgesia for IB-GB in an outpatient setting.

Hyoscine butylbromide significantly decreases motion artefacts and allows better delineation of anatomic structures in mp-MRI of the prostate.

OBJECTIVES: To prospectively evaluate the effect of hyoscine butylbromide (HBB) on visualisation of anatomical details and motion-related artefacts in mp-MRI of the prostate at 3.0 Tesla. METHODS: One hundred and three consecutive patients (65 ± 10 years) were included in this trial, powered to demonstrate an improvement of image quality after HBB administration, assessed on a 5-point scale by two blinded readers. All patients received high-spatial resolution axial T2-weighted TSE sequences at 3.0 T without spasmolytic agent, repeated after application of 40 mg HBB and followed by routine mp-MRI. Secondary endpoints were (1) susceptibility to side effects, (2) dependence of spasmolytic effect on patients´ weight, and (3) prostate volume. RESULTS: In 68% of patients, HBB significantly improved the anatomic score (mean 3.4 ± 0.9 before and 4.4 ± 0.7 after HBB for both readers, p = <0.001). In 67%, HBB significantly enhanced the artefact score (mean 3.2 ± 1 before and 4.2 ± 0.8 after HBB for reader 1, p = <0.001; 3.2 ± 1 and 4.1 ± 0.8 for reader 2, p = <0.001). Subgroup analysis revealed no statistically significant difference between patients with different bodyweight or prostate volume. Inter-reader agreement was excellent (k = 0.95-0.98). CONCLUSIONS: Hyoscine butylbromide significantly improves image quality and reduces motion-related artefacts in mp-MRI of the prostate independent of bodyweight or prostate volume. No side effects were reported. KEY POINTS: • Hyoscine butylbromide (HBB) improved image quality in over 2/3 of patients. • Severe artefacts were reduced after HBB in more than 20%. • The number of non-diagnostic MRI was reduced to <1% after HBB. • HBB effect was independent of bodyweight and prostate volume. • No side effects of HBB were reported in this study population.

Residual tumor resection (RTR).

Residual tumor resection in patients with advanced testicular tumor plays a vital role in the multimodal treatment. Treatment indications for residual tumor resection have changed over the last two decades. While patients with advanced seminoma after chemotherapy or radiotherapy rarely need surgery, it is mandatory for most non-seminomatous tumor patients to undergo post-chemotherapy tumor resection. Due to adjunctive surgical procedures, the operation is surgically demanding and should be performed only in specialized high-volume referral centers. Additional surgical procedures such as nephrectomy, partial colectomy or vascular interventions including caval and aortic resection with grafting might be required. Consequently, several complications can be seen in the peri- and postoperative course. We aim to describe indications for residual tumor resection, operative technique, including adjunctive surgeries and the most common peri- and postoperative complications.

Targeted MRI-guided prostate biopsy: are two biopsy cores per MRI-lesion required?

PURPOSE: This study evaluates the feasibility of performing less than two core biopsies per MRI-lesion when performing targeted MR-guided in-bore prostate biopsy. METHODS: Retrospectively evaluated were 1545 biopsy cores of 774 intraprostatic lesions (two cores per lesion) in 290 patients (66 ± 7.8 years; median PSA 8.2 ng/ml) regarding prostate cancer (PCa) detection, Gleason score, and tumor infiltration of the first (FBC) compared to the second biopsy core (SBC). Biopsies were acquired under in-bore MR-guidance. RESULTS: For the biopsy cores, 491 were PCa positive, 239 of 774 (31 %) were FBC and 252 of 771 (33 %) were SBC (p = 0.4). Patient PCa detection rate based on the FBC vs. SBC were 46 % vs. 48 % (p = 0.6). For clinically significant PCa (Gleason score ≥4 + 3 = 7) the detection rate was 18 % for both, FBC and SBC (p = 0.9). Six hundred and eighty-seven SBC (89 %) showed no histologic difference. On the lesion level, 40 SBC detected PCa with negative FBC (7.5 %). Twenty SBC showed a Gleason upgrade from 3 + 3 = 6 to ≥3 + 4 = 7 (2.6 %) and 4 to ≥4 + 3 = 7 (0.5 %). CONCLUSION: The benefit of a second targeted biopsy core per suspicious MRI-lesion is likely minor, especially regarding PCa detection rate and significant Gleason upgrading. Therefore, a further reduction of biopsy cores is reasonable when performing a targeted MR-guided in-bore prostate biopsy. KEY POINTS: • Higher PI-RADS overall score (IV-V) correlated well with PCa detection rate • In more than 80 % SBC was concordant regarding overall PCa detection • In almost 90 % there was no Gleason upgrading by the SBC • Only 2/54 (3.7 %) csPCa was missed when the SBC was omitted • For IB-GB a further reduction of biopsy cores is reasonable.

In multiple situational light settings, visual observation for skin colour assessment is comparable with colorimeter measurement.

BACKGROUND: Finding inexpensive and reliable techniques for assessing skin colour is important, given that it is related to several adverse human health outcomes. Visual observation is considered a subjective approach assessment and, even when made by trained assessor, concern has been raised about the need for controlled lighting in the study venue. The aim of this study is to determine whether visual skin colour assessments correlate with objective skin colour measurements in study venues with different lighting types and configurations. METHODS: Two trained investigators, with confirmed visual acuity, visually classified the inner, upper arm skin colour of 556 adults using Munsell(®) colour classifications converted to Individual Typology Angle (°ITA) values based on published data. Skin colour at the same anatomic site was also measured using a colorimeter. Each participant was assessed in one of 10 different buildings, each with a different study day. Munsell(®) -derived °ITA values were compared to colorimeter °ITA values for the full sample and by building/day. RESULTS: We found a strong positive, monotonic correlation between Munsell(®) derived °ITA values and colorimeter °ITA values for all participants (Spearman ρ = 0.8585, P < 0.001). Similar relationships were found when Munsell(®) and colorimeter °ITA values were compared for participants assessed in the same building for all 10 buildings (Spearman ρ values ranged from 0.797 to 0.934, all correlations were statistically significant at P < 0.001). CONCLUSION: It is possible to visually assess individual skin colour in multiple situational lighting settings and retrieve results that are comparable with objective measurements of skin colour. This was true for individuals of varying population groups and skin pigmentation.

MRI characteristics and oncological follow-up of patients with ISUP grade group 4 or 5 prostate cancer.

OBJECTIVES: To analyze multiparametric MRI (mpMRI) characteristics of patients with International Society of Urological Pathology (ISUP) grade group (GG) 4 or 5 prostate cancer (PC) and to correlate MRI parameters with the occurrence of biochemical recurrence (BCR) after radical prostatectomy (RPE). METHODS: In this single-center cohort study consecutive patients with mpMRI and ISUP GG 4 or 5 PC were retrospectively analyzed. Clinical, MR-guided biopsy, and diagnostic mpMRI parameter were assessed. A subcohort of patients with RPE and follow-up was analyzed separately. A univariate and multivariate analyses were performed to determine parameters that are associated to patients with BCR after RPE. RESULTS: 145 patients (mean age 70y, median PSA 10.9 ng/ml) were analyzed. 99% had a PI-RADS classification of 4 or 5, 48% revealed MRI T3 stage, and median diameter of the MRI index lesion (IL) was 15 mm. IL showed a median ADC value of 668 ×10-6 mm2/s and exhibited contrast enhancement in 94% of the cases. For patients with follow-up after RPE (n = 82; mean follow-up time 68 ± 27 m), MRI parameters were significantly different for contact length of the IL to the pseudocapsule (LCC), MRI T3 stage, and IL localization (p < 0.05). Higher PSAD and MRI T3 stage were independent parameters for the risk of BCR when incorporating clinical, biopsy, and MRI parameters. CONCLUSION: ISUP GG 4 or 5 PC has distinctive characteristics on mpMRI and were detected on MRI in all cases. In addition, higher PSAD and MRI T3 stage were significant predictors for BCR after RPE.

MRI in-bore biopsy following MRI/US fusion-guided biopsy in patients with persistent suspicion of clinically significant prostate cancer.

PURPOSE: Patients with suspicion of clinically significant prostate cancer (csPC) on multiparametric prostate MRI (mpMRI) but negative or inconclusive MRI/US fusion-guided biopsy (FB) can be challenging in clinical practice. To assess the utility of MRI in-bore biopsy (IB) in patients with discordant imaging and histopathological findings after FB. METHODS: Consecutive patients with Prostate Imaging Reporting and Data System (PI-RADS) category 4 or 5 on mpMRI at 3T after FB without histologically confirmed csPC who underwent IB between 01/2014 and 05/2022, were retrospectively included. The primary objective was to assess the detection rate of csPC. Secondary objectives were to analyze clinical parameters, MRI parameters, and lesion localization. RESULTS: In the final cohort of 51 patients, the IB resulted in an overall detection rate of 71% for PC and 47% for csPC. Furthermore, in 55% of cases with initial low-grade PC, the Gleason score was upgraded after IB. CsPC was often detected apical and/or anterior. The detection rate for PC was 58% in PI-RADS category 4 and 94% in PI-RADS category 5 (csPC 39% and 61%, respectively). Patients with csPC had statistically significant smaller prostate volumes, a higher PI-RADS category, a higher prostate-specific antigen density (PSAD), and were older. CONCLUSIONS: For a relevant proportion of patients with PI-RADS category 4 or 5 and negative or inconclusive findings on previous FB, but with persistent suspicion of csPC, a subsequent IB verified the presence of csPC. Therefore, IB can be a backup in cases of uncertainty.

Maintaining success, reducing treatment burden, focusing on survivorship: highlights from the third European consensus conference on diagnosis and treatment of germ-cell cancer.

In November 2011, the Third European Consensus Conference on Diagnosis and Treatment of Germ-Cell Cancer (GCC) was held in Berlin, Germany. This third conference followed similar meetings in 2003 (Essen, Germany) and 2006 (Amsterdam, The Netherlands) [Schmoll H-J, Souchon R, Krege S et al. European consensus on diagnosis and treatment of germ-cell cancer: a report of the European Germ-Cell Cancer Consensus Group (EGCCCG). Ann Oncol 2004; 15: 1377-1399; Krege S, Beyer J, Souchon R et al. European consensus conference on diagnosis and treatment of germ-cell cancer: a report of the second meeting of the European Germ-Cell Cancer Consensus group (EGCCCG): part I. Eur Urol 2008; 53: 478-496; Krege S, Beyer J, Souchon R et al. European consensus conference on diagnosis and treatment of germ-cell cancer: a report of the second meeting of the European Germ-Cell Cancer Consensus group (EGCCCG): part II. Eur Urol 2008; 53: 497-513]. A panel of 56 of 60 invited GCC experts from all across Europe discussed all aspects on diagnosis and treatment of GCC, with a particular focus on acute and late toxic effects as well as on survivorship issues. The panel consisted of oncologists, urologic surgeons, radiooncologists, pathologists and basic scientists, who are all actively involved in care of GCC patients. Panelists were chosen based on the publication activity in recent years. Before the meeting, panelists were asked to review the literature published since 2006 in 20 major areas concerning all aspects of diagnosis, treatment and follow-up of GCC patients, and to prepare an updated version of the previous recommendations to be discussed at the conference. In addition, ∼50 E-vote questions were drafted and presented at the conference to address the most controversial areas for a poll of expert opinions. Here, we present the main recommendations and controversies of this meeting. The votes of the panelists are added as online supplements.

Holmium laser ablation of the prostate (HoLAP): intermediate-term results of 144 patients.

PURPOSE: To retrospectively analyse the intermediate-term outcome of holmium laser ablation of the prostate (HoLAP) of up to 4 years postoperatively in one of the largest series and to define the selection criteria for patients who benefit from potentially lower complications associated with HoLAP. METHODS: Between June 2006 and November 2010, 144 patients with benign prostatic obstruction were treated at two centres with standardised HoLAP (2.0 J/50 Hz or 3.2 J/25 Hz with Versapulse(®) 80-100 W laser Lumenis(®)). Median follow-up was 21 months (range, 1-54). International prostate symptom score and quality of life (IPSS-QoL), PSA, prostate volume, maximal flow rate (Qmax), postvoiding residual volume (Vres) were evaluated pre- and postoperatively. All complications were graded according to CTCAE (v4.03). RESULTS: Mean patient age was 70.1 ± 7.7 years (range, 46-90). With a preoperative median prostate volume of 40 ml (range, 10-130), the median operation time was 50 min (range, 9-138). We observed a median catheterisation time of 1 day (range, 0-12) and hospitalisation time of 2 days (range, 1-16). IPSS-QoL, Qmax and Vres were significantly improved after 3 months, and all parameters remained unchanged after 12, 24 and 36 months. The rate of re-operation was significantly lower in patients with prostate volume <40 ml, compared to patients with prostates ≥ 40 ml (9.1 vs. 25 %, p = 0.04). CONCLUSIONS: HoLAP is a safe and effective procedure for the treatment of prostates <40 ml. Patients benefit from HoLAP because of a low bleeding rate and short hospital stay. Due to high recurrence rates, HoLAP should be avoided in prostates >40 ml.

Inter-reader agreement of the ESUR score for prostate MRI using in-bore MRI-guided biopsies as the reference standard.

OBJECTIVES: The recent European Society of Urogenital Radiology (ESUR) guidelines for evaluation and reporting of prostate multiparametric magnetic resonance imaging (mp-MRI) include the Prostate Imaging Reporting and Data System (PI-RADS). The aim of this study was to investigate the inter-reader agreement of this scoring system. METHODS: One hundred and sixty-four lesions in 67 consecutive patients with elevated prostate-specific antigen and previously negative trans-rectal ultrasound (TRUS)-guided biopsy were scored retrospectively by three blinded readers using PI-RADS. Mp-MRI was performed at 3 T using T2-weighted, diffusion-weighted and dynamic contrast-enhanced imagings (T2WI, DWI, DCE-MRI). Histology of all lesions was obtained by in-bore MRI-guided biopsy. Cohen's kappa statistics were calculated for all readers. RESULTS: Inter-reader agreement for all lesions was good to moderate (T2WI, κ = 0.55; DWI, κ = 0.64; DCE-MRI, κ = 0.65). For tumour lesions it was good (T2WI, κ = 0.66; DWI, κ = 0.80; DCE-MRI, κ = 0.63) and for benign lesions moderate to good (T2WI, κ = 0.46; DWI, κ = 0.52; DCE-MRI, κ = 0.67). Using an overall PI-RADS score with a threshold of ≥10, we achieved a sensitivity of 85.7 %, and negative predictive value of 90.1 % for biopsied lesions. CONCLUSION: PI-RADS score shows good to moderate inter-reader agreement and enables standardised evaluation of prostate mp-MRI, with high sensitivity and negative predictive value. KEY POINTS: • The European Society of Urogenital Radiology recently published guidelines for prostate MRI. • We have evaluated inter-reader agreement of ESUR scoring for multiparametric prostate MRI. • PI-RADS shows good to moderate inter-reader agreement and is clinically applicable. • PI-RADS achieves in our series high sensitivity and negative predictive value for biopsied lesions. • PI-RADS can be used as standardised scoring system in prostate cancer detection.

[The importance of pathology in the German prostate cancer study PREFERE]. / Die Bedeutung der Pathologie in der deutschen Prostatakrebsstudie PREFERE.

Prostate cancer is the most common carcinoma of elderly males and holds the third place in the ranking of cancer-specific mortality. However, total mortality rate of 3 % is low and half of the patients die from other diseases, which is for the most part due to significantly improved diagnostic methods and the increasing use of prostate-specific antigen (PSA) screening. This has led to a stage migration towards early tumor stages that are prognostically heterogeneous and require differentiated treatment. The German and European guidelines recommend four therapy options (i.e. radical prostatectomy, percutaneous irradiation, permanent seed implantation and active surveillance) for localized prostate cancer and from contemporary study data it is unclear which therapy is most beneficial. This will be the subject of the PREFERE trial, a prospective randomized multicentre trial which plans to recruit 7,600 patients and to observe them over a period of up to 17 years. The histopathological diagnosis of the primary biopsy plays a crucial role in the inclusion criteria, as this article outlines in detail.

PSMA-1007 Uptake in Ganglia of the Sympathetic Trunk and Its Intra-individual Reproducibility.

AIM/PURPOSE: 18F-labeled PSMA ligands offer various advantages as PET tracers over 68Ga-labeled PSMA counterparts. Especially, an improved spatial resolution leads to improved detection rates of smaller prostate cancer (PCa) lesions. However, physiological PSMA uptake of ganglia of the sympathetic trunk can be quickly misinterpreted as possible PSMA-positive lymph node metastases. The aim of this retrospective study is to investigate [18F]PSMA-1007 uptake and its intra-individual reproducibility in ganglia of the sympathetic trunk. METHODS: We retrospectively included 28 consecutive patients (median age 69 ± 9 with a range of 49-90) with biochemical recurrence of PCa who underwent [18F]PSMA-1007 PET/CT scan and, accordingly, a follow-up examination between August 2018 and August 2021. Cervical, coeliac, and sacral ganglia were identified on the iterative PET reconstructions and correlated with CT component. Tracer uptake of ganglia was determined by measuring SUVmax and SUVmean values. Anatomical position of the ganglia in relation to adjacent vertebral bodies were noted. Statistical analyses were conducted using two-way repeated measures ANOVA and descriptive statistics. RESULTS: The highest [18F]PSMA-1007 uptake was found in coeliac ganglia followed by cervical and sacral ganglia. The SUVmax in coeliac ganglia was 3.13 ± 0.85 (follow-up scan 3.11 ± 0.93), in cervical ganglia 2.73 ± 0.69 (follow-up scan 2.67 ± 0.74), and in sacral ganglia 1.67 ± 0.50 (follow-up scan 1.64 ± 0.52). The SUVmean in coeliac ganglia was 2.28 ± 0.64 (follow-up scan 2.28 ± 0.66), in cervical ganglia 1.62 ± 0.43 (follow-up scan 1.61 ± 0.43) and in sacral ganglia 1.15 ± 0.33 (follow-up scan 1.12 ± 0.34). In a given ganglion station, there was no statistically significant difference of SUVmax or SUVmean values between baseline and follow-up scans. CONCLUSIONS: The first systematically described physiological [18F]PSMA-1007 uptake in ganglia of the sympathetic trunk showed a low variability of SUVmax or SUVmean and a good intra-individual reproducibility of [18F]PSMA-1007 uptake in follow-up scans. These findings might improve and guide the differentiation of ganglia from possible malignant lesions.

Improved diffusion-weighted imaging of the prostate: Comparison of readout-segmented and zoomed single-shot imaging.

OBJECTIVES: Diffusion weighted imaging (DWI) is the most important sequence for detection and grading prostate cancer (PCa), but it is considerably prone to artifacts. New approaches like zoomed single-shot imaging (z-EPI) with advanced image processing or multi-shot readout segmentation (rs-EPI) try to improve DWI quality. This study evaluates objective and subjective image quality (IQ) of rs-EPI and z-EPI with and without advanced processing. MATERIALS AND METHODS: Fifty-six consecutive patients (67 ± 8 years; median PSA 8.3 ng/ml) with mp-MRI performed at 3 Tesla between February and October 2019 and subsequently verified PCa by targeted plus systematic MRI/US-fusion biopsy were included in this retrospective single center cohort study. Rs-EPI and z-EPI were prospectively acquired in every patient. Signal intensities (SI) of PCa and benign tissue in ADC, b1000, and calculated high b-value images were analyzed. Endpoints were signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), PCa contrast intensity (CI), and subjective IQ on a 5-point scale evaluated by three blinded readers. Wilcoxon signed rank test, Friedman test and Cohen's kappa coefficient was calculated. RESULTS: SNR, CNR, and PCa CI of z-EPI with and without advanced processing was superior to rs-EPI (p < 0.01), whereas no significant differences were observed between z-EPI with and without advanced processing. Subjective IQ was significantly higher for z-EPI with advanced processing compared rs-EPI for ADC, b1000, and calculated high b-values (p < 0.01). Compared to z-EPI without advanced processing, z-EPI with advanced processing was superior for ADC and calculated high b-values (p < 0.01), but no significant differences were shown for b1000 images. CONCLUSIONS: Z-EPI with and without advanced processing was superior to rs-EPI regarding objective imaging parameters and z-EPI with advanced processing was superior to rs-EPI regarding subjective imaging parameters for the detection of PCa.

Multiparametric MRI characteristics of prostatitis and atrophy in the peripheral zone in men without prostate cancer.

PURPOSE: To analyse multiparametric magnetic resonance imaging (mpMRI) characteristics and appearance of histopathologically proven non-cancerous intraprostatic findings focussing on quantity of prostatitis and atrophy in the peripheral zone. METHOD: In this retrospective analysis consecutive patients with mpMRI followed by MRI/TRUS-fusion biopsy comprising targeted (TB) and systematic biopsy (SB) cores without prostate cancer (PC) at histopathology were included. Subgroup analysis was performed in younger men (≤50 years). The proportions of prostatitis and atrophy were quantified for each biopsy core based on histopathology. MRI findings in the peripheral zone (PZ) and index lesions (IL, most suspicious/representative lesion) were characterized regarding changes in T2w, ADC value, and enhancement of dynamic contrast enhancement (DCE) and correlated with quantity of prostatitis and atrophy. RESULTS: Seventy-two patients were analysed. The median baseline characteristics were PSA 5.4 ng/ml (4.0-7.9), PI-RADS classification 3 (2-4), prostate volume 43 ml (33-57), and PSA density 0.13 ng/ml2 (0.10-0.19). Prostatitis was found in 44 % (n = 32) and atrophy in 65 % (n = 47) of cases. The quantity of atrophy demonstrated a significant correlation to T2w changes, ADC increase and DCE enhancement (p = 0.05, p = 0.05, p = 0.01), whereas quantity of prostatitis did not show any significant correlation to the MRI changes (p = 0.68, p = 0.58, p = 0.95). Quantity of prostatitis and atrophy increased with PI-RADS classification. Younger men had lower PSA (4.4 vs. 7.8 ml/ng; p < 0.001), smaller prostate volume (40 vs. 59 ml; p = 0.001), and lower PI-RADS classification (2-3 vs. 3-4; p = 0.005) and prostatitis and atrophy were less frequently observed (p ≤ 0.01, p = 0.03). CONCLUSIONS: Quantity of atrophy and prostatitis had different influence on MRI characteristics and increased within higher PI-RADS classification. Younger men had diffuse hypointense changes at T2w images, but less quantity of prostatitis and atrophy.

Gemcitabine and Cisplatin Versus Methotrexate, Vinblastine, Doxorubicin, and Cisplatin in Advanced or Metastatic Bladder Cancer: Results of a Large, Randomized, Multinational, Multicenter, Phase III Study.

PURPOSE: Gemcitabine plus cisplatin (GC) and methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) were compared in patients with locally advanced or metastatic transitional-cell carcinoma (TCC) of the urothelium. PATIENTS AND METHODS: Patients with stage IV TCC and no prior systemic chemotherapy were randomized to GC (gemcitabine 1,000 mg/m2 days 1, 8, and 15; cisplatin 70 mg/m2 day 2) or standard MVAC every 28 days for a maximum of six cycles. RESULTS: Four hundred five patients were randomized (GC, n = 203; MVAC, n = 202). The groups were well-balanced with respect to prognostic factors. Overall survival was similar on both arms (hazards ratio [HR], 1.04; 95% confidence interval [CI], 0.82 to 1.32; P = .75), as were time to progressive disease (HR, 1.05; 95% CI, 0.85 to 1.30), time to treatment failure (HR, 0.89; 95% CI, 0.72 to 1.10), and response rate (GC, 49%; MVAC, 46%). More GC patients completed six cycles of therapy, with fewer dose adjustments. The toxic death rate was 1% on the GC arm and 3% on the MVAC arm. More GC than MVAC patients had grade 3/4 anemia (27% v 18%, respectively) and thrombocytopenia (57% v 21%, respectively). On both arms, the RBC transfusion rate was 13 of 100 cycles and grade 3/4 hemorrhage or hematuria was 2%; the platelet transfusion rate was four patients per 100 cycles and two patients per 100 cycles on GC and MVAC, respectively. More MVAC patients, compared with GC patients, had grade 3/4 neutropenia (82% v 71%, respectively), neutropenic fever (14% v 2%, respectively), neutropenic sepsis (12% v 1%, respectively), and grade 3/4 mucositis (22% v 1%, respectively) and alopecia (55% v 11%, respectively). Quality of life was maintained during treatment on both arms; however, more patients on GC fared better regarding weight, performance status, and fatigue. CONCLUSION: GC provides a similar survival advantage to MVAC with a better safety profile and tolerability. This better-risk benefit ratio should change the standard of care for patients with locally advanced and metastatic TCC from MVAC to GC.