Data on the detection of clinically significant prostate cancer by magnetic resonance imaging (MRI)-guided targeted and systematic biopsy.

This is a data article from the original publication "Reasons for missing clinically significant prostate cancer by targeted magnetic resonance imaging/ultrasound fusion-guided biopsy" [1]. From January 2014 to April 2019 a sample collective of 785 patients with 3T multiparametric magnetic resonance imaging (mp-MRI) of the prostate and subsequent combined systematic biopsy (SB) and magnetic resonance imaging/ultrasound (US) fusion-guided biopsy (TB) was retrospectively analyzed. Prostate cancer (PCa) detection by TB and/or additional SB was analyzed.

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.

Reasons for missing clinically significant prostate cancer by targeted magnetic resonance imaging/ultrasound fusion-guided biopsy.

OBJECTIVES: This study evaluates cases with clinically significant prostate cancer (csPCa) missed by targeted biopsy (TB) and analyzes the diagnostic impact of an additional systematic biopsy (SB) in a large patient collective. METHODS: Consecutive patients with a 3 T multiparametric prostate MRI (mpMRI) and a subsequent MRI/US fusion-guided TB plus 12-core US-guided SB from 01/2014 to 04/2019 were included in this study. Primary study endpoint was the analysis of cases with a csPCa missed by TB and detected by SB. Secondary study objectives were the PCa detection and the correlation with clinical and MRI parameters. RESULTS: In total 785 patients met the inclusion criteria. 342 patients had a csPCa (median PSAD 0.29 ng/mL/cm3). In 42 patients (13 %), a csPCa was detected only by SB. In 36 of these cases, the localization of the positive SB cores matched with the cancer suspicious region described on mpMRI (mCSR). Cases with a csPCA missed by TB showed either an insufficient MRI segmentation (prostate boundary correlation) (31 %) and/or insufficient lesion registration (lesion transfer, tracking, and/or matching) (48 %), a missed small lesion (14 %), or a failed center of a large lesion (10 %). Median PSAD of patients with non-significant PCa detected by SB was 0.15 ng/mL/cm3. CONCLUSIONS: Main reasons for missing a csPCa by TB were insufficient prostate segmentation or imprecise lesion registration within MRI/US fusion-guided biopsy. Consequently, verification of MRI quality, exact mCSR assessment, and advanced biopsy experience may improve accuracy. Altogether, an additional SB adds limited clinical benefit in men with PSAD ≤ 0.15 ng/mL/cm3.

PSMA PET/CT vs. CT alone in newly diagnosed biochemical recurrence of prostate cancer after radical prostatectomy: Comparison of detection rates and therapeutic implications.

OBJECTIVES: To compare prostate specific membrane antigen (PSMA) Positron Emission Tomography/Computed Tomography (PET/CT) and computed tomography (CT) alone for the detection of biochemical recurrence of prostate cancer (PCa) and effect on treatment. METHODS: This retrospective study included 59 patients with recently recorded biochemical recurrence of PCa (mean PSA 1.96 ± 1.64 ng/mL) after radical prostatectomy. Patients received PET/CT with either 68Ga-PSMA-11 (n = 36) or 18F-PSMA-1007 (n = 23). PET/CT and CT images were evaluated separately in regard to PCa lesion count, type, and localisation by two physicians. Histopathology, follow-up imaging and PSA levels after salvage irradiation served as reference standard. A McNemar test was used to compare detection rates. Changes in therapeutic approaches based on staging differences between CT alone and PET/CT were assessed in a virtual multidisciplinary tumour board. RESULTS: There were 142 lesions in 50 of 59 patients. PSMA PET/CT detected 141 lesions (99.3 %) in 50 patients (84.7 %), while CT detected 72 lesions (50.7 %) in 29 patients (49.2 %). A significantly higher detection rate of PSMA PET/CT was observed on a lesion-based analysis (p < 0.0001) and on a patient based analysis (p < 0.0001). Herein, both 68Ga- and 18F-PSMA PET/CT performed significantly better than CT alone (p < 0.0001, respectively). In 9 patients (15.3 %) no relapse was detectable by either modality. All lesions detected by CT were also detected by PSMA PET/CT. In 38 patients PSMA PET/CT detected more lesions than CT alone, altering the treatment approach in 22 of these patients. CONCLUSION: PSMA PET/CT is superior to CT alone in detecting biochemical recurrence in PCa patients after radical prostatectomy and offered additional therapeutic options in a substantial number of patients.

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.

Analysis of PI-RADS 4 cases: Management recommendations for negatively biopsied patients.

PURPOSE: To evaluate if subgroups of patients assigned to MRI category PI-RADS 4 regarding clinical and MRI imaging aspects have distinct risks of prostate cancer (PCa) to facilitate adequate clinical management of this population, especially after negative targeted biopsy. METHODS: This prospective, IRB approved single center cross-sectional study includes 931 consecutive patients after mp-MRI at 3 T for PCa detection. 193 patients with PI-RADS assessment category 4 received subsequent combined targeted MRI/US fusion-guided and systematic 12-core TRUS-guided biopsy as reference standard and were finally analyzed. The primary endpoint was PCa detection of PI-RADS 4 with MRI subgroup analyses. Secondary endpoints were analyses of clinical data, location of PCa, and detection of targeted biopsy cores. RESULTS: PCa was detected in 119 of 193 patients (62%) including clinically significant PCa (csPCa; Gleason score ≥3 + 4 = 7) in 92 patients (48%). MRI subgroup analysis revealed 95% PCa (73% csPCa) in unambiguous PI-RADS 4 index lesions without additional, interfering signs of prostatitis in the peripheral zone or overlaying signs of severe stromal hyperplasia in the transition zone according to PI-RADS v2. Transition zone confined PI-RADS-4-lesions with overlaying signs of stromal hyperplasia showed PCa only in 11% (4% csPCa). Targeted biopsy cores missed the csPCa index lesion in 7% of the patients. PSA density (PSAD) was significantly higher in PCa patients. CONCLUSIONS: Small csPCa can reliably be detected with mp-MRI by experienced readers, but can be missed by targeted MR/US fusion biopsy alone. Targeted re-biopsy of unambiguous (peripheral) PI-RADS-4-lesions is recommended; whereas transition zone confined PI-RADS-4-lesions with overlaying signs of stromal hyperplasia might be followed-up by re-MRI primarily.

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.

Predictive power of the ESUR scoring system for prostate cancer diagnosis verified with targeted MR-guided in-bore biopsy.

PURPOSE: This study evaluates the diagnostic value of the ESUR scoring system (PI-RADS) regarding prostate cancer detection using MR-guided in-bore biopsies (IB-GB) as the reference standard. METHODS: 566 lesions in 235 consecutive patients (65.7 ± 7.9 years, PSA 9.9 ± 8.5 ng/ml) with a multiparametric (mp)-MRI (T2WI, DWI, DCE) of the prostate at 3T were scored using the PI-RADS scoring system. PI-RADS single (PSsingle), summed (PSsum), and overall (PSoverall) scores were determined. All lesions were histologically verified by IB-GB. RESULTS: Lesions with a PSsum below 9 contained no prostate cancer (PCa) with Gleason score (GS) ≥ 4+3=7. A PSsum of 13-15 (PSoverall V) resulted in 87.8% (n=108) in PCa and in 42.3% (n=52) in GS ≥ 4+3=7. Transition zone (TZ) lesions with a PSsum of 13-15 (PSoverall V) resulted in 76.3% (n=36) in PCa and in 26.3% (n=10) in GS ≥ 4+3=7, whereas for peripheral zone (PZ) lesions cancer detection rate at this score was 92.9% (n=79) and 49.4% (n=42) for GS ≥ 4+3=7. Using a threshold of PSsum ≥ 10, sensitivity was 86.0%, and negative predictive value (NPV) was 86.2%. For higher grade PCa sensitivity was 98.6%, and NPV was 99.5%. CONCLUSION: A PSsum below 9 excluded a higher grade PCa, whereas lesions with a PSsum ≥ 13 (PSoverall V) represented in 88% PCa, and in 42% higher grade PCa. The PSsum or PSoverall demonstrated a better diagnostic value for PZ lesions with higher detection rates for higher grade PCa compared to TZ lesions.

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.

Human neutrophil immunodeficiency syndrome is associated with an inhibitory Rac2 mutation.

A 5-week-old male infant presented with severe bacterial infections and poor wound healing, suggesting a neutrophil defect. Neutrophils from this patient exhibited decreased chemotaxis, polarization, azurophilic granule secretion, and superoxide anion (O(2)(-)) production but had normal expression and up-regulation of CD11b. Rac2, which constitutes >96% of the Rac in neutrophils, is a member of the Rho family of GTPases that regulates the actin cytoskeleton and O(2)(-) production. Western blot analysis of lysates from patient neutrophils demonstrated decreased levels of Rac2 protein. Addition of recombinant Rac to extracts of the patient neutrophils reconstituted O(2)(-) production in an in vitro assay system. Molecular analysis identified a point mutation in one allele of the Rac2 gene resulting in the substitution of Asp57 by an Asn (Rac2(D57N)). Asp57 is invariant in all defined GTP-binding proteins. Rac2(D57N) binds GDP but not GTP and inhibits oxidase activation and O(2)(-) production in vitro. These data represent the description of an inhibitory mutation in a member of the Rho family of GTPases associated with a human immunodeficiency syndrome.

Disparities in the respiratory burst between human and rat neutrophils.

The importance of reactive oxygen species (ROS) in neutrophil (PMN)-mediated injury to host tissues has been strongly implicated in a number of animal models. Peculiarities of the laboratory rat PMN, including an apparent paucity of superoxide release, prompted us to examine disparities in the respiratory burst between human and rat PMNs. Using isolated PMNs, we examined oxygen consumption, superoxide release, nitrate/nitrite release, and dihydrorhodamine (DHR) oxidation in response to an array of soluble stimuli. Our findings confirm that intact rat PMNs release little superoxide in comparison to human PMNs when primed and activated by soluble stimuli. For example, PMA-activated human PMNs released superoxide at 10.1 +/- 2.7 times the rate of rat PMNs (P < 0.01). However, measurements of oxygen consumption, cell-associated oxidant production (by DHR oxidation) and release of superoxide from electroporated cells suggests that rat PMNs generate oxidants at rates equivalent to human PMNs but preferentially release them in an intracellular compartment. Implications for the study of PMN-mediated oxidant injury in animal models are discussed.

In vivo treatment with granulocyte colony-stimulating factor results in divergent effects on neutrophil functions measured in vitro.

We have studied the effects of granulocyte colony-stimulating factor (G-CSF) administration to normal individuals on a variety of functional and biochemical neutrophil characteristics that relate to host defense. G-CSF adversely affected neutrophil (polymorphonuclear leukocyte [PMN]) chemotaxis. While this could be partially explained by reduced assembly of neutrophil F-actin, we also recognized an elevated cytosolic calcium mobilization and a normal upregulation of neutrophil CD11b. G-CSF resulted in reduced PMN killing of Staphylococcus aureus with a 10:1 (bacteria:neutrophil) ratio and normal killing with a 1:1 ratio. In association with this, we demonstrated divergent effects on the respiratory burst of intact cells and divergent effects on the content of marker proteins for neutrophil granules. While G-CSF may have resulted in increased content of cytochrome b558 in the cell membrane, it did not alter the amounts of cytosolic oxidase components. After therapy, there was normal content of the azurophilic granule marker, myeloperoxidase, decreased content of the specific granule marker, lactoferrin, and normal content of lysozyme (found in both granules classes). Finally, G-CSF therapy markedly reduced the apoptotic rate of the isolated neutrophil. Therefore, considering disparate functional and biochemical activities, the real benefit of G-CSF therapy may lie in enhanced number and survival of neutrophils.

Receptor-mediated calcium entry is required for maximal effects of platelet activating factor primed responses in human neutrophils.

The effect of receptor mediated calcium entry (RMCE) on platelet activating factor (PAF) stimulated human neutrophils (PMNs) was investigated using SKF 96365, a selective inhibitor of RMCE. Changes in cytosolic calcium concentration were determined by the fluorometric dye indo-1, AM, superoxide generation by cytochrome c reduction, and CD11b surface expression by flow cytometry. SKF 96365 pre-treatment diminished the cytosolic calcium rise in PAF primed PMNs. SKF 96365 treatment significantly (p < 0.05) decreased superoxide generation in PAF primed PMNs, but did not affect activation of the PMN oxidase by fMLP or PMA. Chelation of extracellular calcium by EGTA, intracellular calcium by BAPTA, AM, and RMCE blockade by SKF 96365 all statistically inhibited the PAF induced increase in surface expression of CD11b (p < 0.05); moreover, SKF 96365 inhibited to a greater extent than EGTA or BAPTA, AM treatment. These results suggest that RMCE is required for maximal effects of PAF on PMN function.

Interleukin-4 is chemotactic for mouse macrophages.

An important component of the cell-mediated immune response often is the migration of macrophages to the site of immune activity. Although much evidence suggests that macrophage migration is regulated by antigen-specific T cells, the influence of T cell-derived cytokines on macrophage chemotaxis has not been well studied. Here we present evidence that interleukin-4 (IL-4), a cytokine derived from T helper 2 (Th 2) cells, is chemotactic for mouse peritoneal macrophages. In an in vitro chemotaxis assay using Boyden chambers, recombinant IL-4 was chemotactic for mouse peritoneal exudate macrophages. This response was inhibited in a dose-dependent manner by the anti-IL-4 antibody, 11B11. As shown here and previously, interleukin-2 (IL-2) and interferon-gamma (IFN-gamma), cytokines derived from T helper 1 cells, are not chemotactic for mouse macrophages.