Splenic 18F-FDG uptake on baseline PET/CT is associated with oncological outcomes and tumor immune state in uterine cervical cancer.

OBJECTIVE: The spleen represents an important contributor to tumor immune escape, but the relevance of increased splenic metabolic activity remains to be fully elucidated. METHODS: We retrospectively measured the spleen-to-liver standard uptake value (SLR) on 18F-FDG PET/CT examinations of 92 consecutive patients with FIGO stage IB1 to IVA cervical cancer and integrated the results with survival, response to treatment, tumor immune infiltrate, and baseline characteristics. RESULTS: SLRmax > 0.92 (p = .026) and SLRmean > 0.94 (p = .005) were significantly associated with decreased DFS in univariable analysis. Multivariable models were built using best subset selection; ΔSLRmax and either SLRmax or SLRmean were consistently selected, strongly reinforcing the association between SLR variables and DFS in relation to potential confounders (all models p ≤ .002). Independent associations were found for SLRmax using multivariable Cox regression models for DFS (all p ≤ .003). Further, uni- and multivariable analyses demonstrated the negative impact of higher SLR values on pathological complete response. A statistically significant higher proportion of patients with high SLRmax had a dense infiltrate of CD20+ (p = .036) and CD68+ (p = .015) immune cells, as well as PD-L1+ tumor cells (p = .019) as compared to those with low SLRmax. Finally, high SLRmax status was neither associated with systemic inflammatory markers (except for an increased white blood cell count; p = .038), nor with clinically overt infection. CONCLUSION: This hypothesis-generating study provides the first evidence that increased splenic metabolic activity is a negative prognostic and predictive biomarker in locally advanced cervical cancer. In addition, it might help to discriminate immunologically 'hot' from 'cold' cervical tumors.

Imaging modalities in synchronous oligometastatic prostate cancer.

PURPOSE: Along with a number of other malignancies, the term "oligometastatic" prostate cancer has recently emerged. It represents an attempt to define a subtype of cancer with a limited metastatic load that might perform more favorably than a distinctly disseminated disease, or even one that may be managed in a potentially curative way. Since there is currently a knowledge gap of what imaging modalities should be utilized to classify patients as having this type of tumor, we aimed to shed light on the role of conventional and marker-based imaging in the setting of synchronous oligometastatic prostate cancer as well as summarize the available evidence for its clinical application. METHODS: A literature search on December 15th 2017 was conducted using the Pubmed database. RESULTS: Functional imaging techniques like 68Ga PSMA. 68Ga PSMA PET-CT has currently been shown the best detection rates for the assessment of nodal, bone and visceral metastases, especially for smaller lesions at low PSA levels. CONCLUSIONS: Functional imaging helps detect low-burden disease metastatic patients. However, these imaging modalities are not available in every center and thus clinicians may be prone to prescribe systemic treatment rather than referring patients for cytoreductive treatments. We hope that the ongoing prospective trials will help guide clinicians in making a more personalized management of synchronous metastatic patients.

Detection of Clinically Significant Prostate Cancer: Short Dual-Pulse Sequence versus Standard Multiparametric MR Imaging-A Multireader Study.

Purpose To compare the diagnostic performance of a short dual-pulse sequence magnetic resonance (MR) imaging protocol versus a standard six-pulse sequence multiparametric MR imaging protocol for detection of clinically significant prostate cancer. Materials and Methods This HIPAA-compliant study was approved by the regional ethics committee. Between July 2013 and March 2015, 63 patients from a prospectively accrued study population who underwent MR imaging of the prostate including transverse T1-weighted; transverse, coronal, and sagittal T2-weighted; diffusion-weighted; and dynamic contrast material-enhanced MR imaging with a 3-T imager at a single institution were included in this retrospective study. The short MR imaging protocol image set consisted of transverse T2-weighted and diffusion-weighted images only. The standard MR imaging protocol image set contained images from all six pulse sequences. Three expert readers from different institutions assessed the likelihood of prostate cancer on a five-point scale. Diagnostic performance on a quadrant basis was assessed by using areas under the receiver operating characteristic curves, and differences were evaluated by using 83.8% confidence intervals. Intra- and interreader agreement was assessed by using the intraclass correlation coefficient. Transperineal template saturation biopsy served as the standard of reference. Results At histopathologic evaluation, 84 of 252 (33%) quadrants were positive for cancer in 38 of 63 (60%) men. There was no significant difference in detection of tumors larger than or equal to 0.5 mL for any of the readers of the short MR imaging protocol, with areas under the curve in the range of 0.74-0.81 (83.8% confidence interval [CI]: 0.64, 0.89), and for readers of the standard MR imaging protocol, areas under the curve were 0.71-0.77 (83.8% CI: 0.62, 0.86). Ranges for sensitivity were 0.76-0.95 (95% CI: 0.53, 0.99) and 0.76-0.86 (95% CI: 0.53, 0.97) and those for specificity were 0.84-0.90 (95% CI: 0.79, 0.94) and 0.82-0.90 (95% CI: 0.77, 0.94) for the short and standard MR protocols, respectively. Ranges for interreader agreement were 0.48-0.60 (83.8% CI: 0.41, 0.66) and 0.49-0.63 (83.8% CI: 0.42, 0.68) for the short and standard MR imaging protocols. Conclusion For the detection of clinically significant prostate cancer, no difference was found in the diagnostic performance of the short MR imaging protocol consisting of only transverse T2-weighted and diffusion-weighted imaging pulse sequences compared with that of a standard multiparametric MR imaging protocol. © RSNA, 2017 Online supplemental material is available for this article.

Multiparametric magnetic resonance imaging characteristics of normal, benign and malignant conditions in the prostate.

OBJECTIVES: To identify the multiparametric magnetic resonance imaging (mpMRI) characteristics of normal, benign and malignant conditions in the prostate. METHODS: Fifty-six histopathological whole-mount radical prostatectomy specimens from ten randomly selected patients with prostate cancer (PC) were matched with corresponding transverse mpMRI slices. The mpMRI was performed prior to biopsy and consisted of T2-weighted imaging (T2-WI), diffusion-weighted imaging (DWI), dynamic contrast-enhanced imaging (DCE) and magnetic resonance spectroscopic imaging (MRSI). RESULTS: In each prostate specimen, a wide range of histopathological conditions were observed. They showed consistent but overlapping characteristics on mpMRI. Normal glands in the transition zone showed lower signal intensity (SI) on T2-WI, lower ADC values and lower citrate peaks on MRSI as compared to the peripheral zone (PZ) due to sparser glandular elements and more prominent collagenous fibres. In the PZ, normal glands were iso-intense on T2-WI, while high SI areas represented cystic atrophy. Mimickers of well-differentiated PC on mpMRI were inflammation, adenosis, HG-PIN and post-atrophic hyperplasia. CONCLUSION: Each prostate is a unique mix of normal, benign and/or malignant areas that vary in extent and distribution resulting in very heterogeneous characteristics on mpMRI. Understanding the main concepts of this mpMRI-histopathological correlation may increase the diagnostic confidence in reporting mpMRI. KEYPOINTS: • In each prostate specimen a wide range of histopathological conditions was observed. • Interpretation of mpMRI may be difficult because benign conditions may mimic PC. • High signal intensity areas in the PZ on T2-WI represented cystic atrophy. • The TZ showed sparser glands and more collagenous fibres than the PZ.

Preferences in the management of high-risk prostate cancer among urologists in Europe: results of a web-based survey.

OBJECTIVE: To explore preferences in the management of patients with newly diagnosed high-risk prostate cancer (PCa) among urologists in Europe through a web-based survey. MATERIALS AND METHODS: A web-based survey was conducted between 15 August and 15 September 2013 by members of the Prostate Cancer Working Group of the Young Academic Urologists Working Party of the European Association of Urology (EAU). A specific, 29-item multiple-choice questionnaire covering the whole spectrum of diagnosis, staging and treatment of high-risk PCa was e-mailed to all urologists included in the mailing list of EAU members. Europe was divided into four geographical regions: Central-Eastern Europe (CEE), Northern Europe (NE), Southern Europe (SE) and Western Europe (WE). Descriptive statistics were used. Differences among sample segments were obtained from a z-test compared with the total sample. RESULTS: Of the 12,850 invited EAU members, 585 urologists practising in Europe completed the survey. High-risk PCa was defined as serum PSA ≥20 ng/mL or clinical stage ≥ T3 or biopsy Gleason score ≥ 8 by 67% of responders, without significant geographical variations. The preferred single-imaging examinations for staging were bone scan (74%, 81% in WE and 70% in SE; P = 0.02 for both), magnetic resonance imaging (53%, 72% in WE and 40% in SE; P = 0.02 and P = 0.01, respectively) and computed tomography (45%, 60% in SE and 23% in WE; P = 0.01 for both). Pre-treatment predictive tools were routinely used by 62% of the urologists, without significant geographical variations. The preferred treatment was radical prostatectomy as the initial step of a multiple-treatment approach (60%, 40% in NE and 70% in CEE; P = 0.02 and P < 0.01, respectively), followed by external beam radiation therapy with androgen deprivation therapy (29%, 45% in NE and 20% in CEE; P = 0.01 and P = 0.02, respectively), and radical prostatectomy as monotherapy (4%, 7% in WE; P = 0.04). When surgery was performed, the open retropubic approach was the most popular (58%, 74% in CEE, 37% in NE; P < 0.01 for both). Pelvic lymph node dissection was performed by 96% of urologists, equally split between a standard and extended template. There was no consensus on the definition of disease recurrence after primary treatment, and much heterogeneity in the administration of adjuvant and salvage treatments. CONCLUSION: With the limitation of a low response rate, the present study is the first survey evaluating preferences in the management of high-risk PCa among urologists in Europe. Although the definition of high-risk PCa was fairly uniform, wide variations in patterns of primary and adjuvant/salvage treatments were observed. These differences might translate into variations in quality of care with a possible impact on ultimate oncological outcome.

Performance of MRI for Detection of ≥pT1b Disease in Local Staging of Endometrial Cancer.

Magnetic resonance imaging (MRI) can be used for the preoperative local staging of endometrial cancer (EC). The presence of ≥pT1b disease (i.e., tumor invasion in ≥50% of the myometrium, into the cervical stroma or spread outside the uterus) has important prognostic value and implications for the decision to perform lymphadenectomy. The purpose of this study was to assess the performance of MRI for the detection of ≥pT1b disease and to evaluate whether tumor size measured via MRI was predictive for ≥pT1b disease, independent of imaging signs of deep invasion. MRI T-staging and tumor diameter and volume were correlated with histopathology of the hysterectomy specimen in 126 patients. MRI had a sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 70.0%, 83.3%, 79.2%, 75.3% and 77.0%, respectively, for the detection of ≥pT1b disease. A tumor diameter of ≥40 mm and volume of ≥20 mL measured via MRI were predictive for ≥pT1b disease at rates of 78.3% and 87.1%, respectively. An EC size of at least 5 mm upon MRI was predictive for ≥pT1b disease in more than 50% of cases. Our results support the use of MRI in the preoperative staging of EC and suggest including size criteria in EC staging guidelines.

A Systematic Review on the Role of Imaging in Early Recurrent Prostate Cancer.

CONTEXT: In patients treated for prostate cancer, a rising serum prostate-specific antigen (PSA) level is a first sign of relapse, but imaging is needed to determine the localization of the recurrence, which may be local, in lymph nodes, and/or metastatic. With the increasing success rate of earlier salvage therapy, the diagnosis has become pertinent when the recurrent PSA level is still very low. OBJECTIVE: To systematically review the literature on the role of the existing imaging techniques in patients with early recurrent prostate cancer. EVIDENCE ACQUISITION: A systematic literature search across the MEDLINE and EMBASE databases was conducted in February 2018, searching for original studies reporting on imaging in a (sub)group of patients with recurrent PSA levels not higher than 5ng/ml. This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. The methodological quality of the studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. EVIDENCE SYNTHESIS: A total of 98 studies were included in this systematic review, reporting on the role of transrectal ultrasonography (TRUS), computed tomography (CT), bone scintigraphy (BS), single-photon emission CT, multiparametric magnetic resonance imaging (mpMRI), whole-body MRI (wbMRI), and positron emission tomography (PET)-CT/MRI using 18F fluoro-deoxy-glucose, 11C choline, 18F (fluoro)(methyl)choline, 11C acetate, 18F FACBC (fluciclovine) and prostate-specific membrane antigen (PSMA)-based tracers. CT and BS were not sufficiently sensitive in the early recurrence setting. For the detection of local recurrence, TRUS or mpMRI can be used; however, at the lowest PSA levels, few data were available, only after radical prostatectomy, showing a wide range of positivity. TRUS or mpMRI need to be combined with (PET)-CT to assess distant disease, but new techniques such as wbMRI, PET-MRI, or PET-CT allow for an all-in-one approach. At recurrent PSA levels <0.5ng/ml, detection rates up to 31.3% were reported using 11C choline PET-CT and up to 65.0% using 68Ga PSMA-11 PET-CT. At recurrent PSA levels <0.2ng/ml, detection rates of 68Ga PSMA-11 PET-CT ranged from 11.3% to as high as 58.3%. CONCLUSIONS: Detection rates of different imaging techniques depend on the PSA level at the time of imaging. Recent advanced imaging techniques may detect the localization of the recurrence, even when the PSA levels are still very low. PATIENT SUMMARY: In patients treated for prostate cancer, a rising serum prostate-specific antigen (PSA) level is a sign of recurrence of the disease. Advanced imaging techniques may demonstrate the localization of the recurrence, even when the PSA levels are still very low.

Focal therapy in localised prostate cancer: Real-world urological perspective explored in a cross-sectional European survey.

INTRODUCTION: The urological community's opinion over focal therapy (FT) for prostate cancer (PCa) has never been assessed. Our aim was to investigate the current opinion on FT in the European urological community. METHODS: A 25-item questionnaire was devised according to the Cherries checklist and distributed through SurveyMonkey using a web link from November 2016 to October 2017. After a pilot validation (n = 40 urologists), the survey was sent through EAU and 9 other national European urological societies mailing list. Twitter was also used. RESULTS: We received 484 replies from 51 countries. Almost half (44.8%, n = 217) stated FT would represent a step forward, and 52.0% (n = 252) would suggest FT to a patient. Almost three-quarters (70.8%, n = 343) agreed FT will become a standard option after improvements in patient selection (n = 66) or when its effectiveness will be proven (n = 78), or both (n = 199). Most frequently used definition of FT was treatment of all significant (life-threatening) cancer foci whilst leaving untreated the rest of the gland (39.3%, n = 190). FT use was considered as an alternative to whole-gland treatments by 29.7% (n = 144), and to AS by 25.0% (n = 121). On multivariate analysis, FT availability and publications were associated with a positive opinion on FT. Conversely, attending International congresses, treating high PCa volumes and high percentages of high-risk PCa was associated with a negative opinion. CONCLUSIONS: FT is considered as an attractive option for PCa treatment by the European urological community sampled by our survey. FT availability positively influences these thoughts. The present survey suggests whilst some early adopters already embraced FT, the relative majority of the urological community is prone to embrace FT in the near future, once current areas of debate are solved.

Role of multiparametric magnetic resonance imaging in early detection of prostate cancer.

UNLABELLED: Most prostate cancers (PC) are currently found on the basis of an elevated PSA, although this biomarker has only moderate accuracy. Histological confirmation is traditionally obtained by random transrectal ultrasound guided biopsy, but this approach may underestimate PC. It is generally accepted that a clinically significant PC requires treatment, but in case of an non-significant PC, deferment of treatment and inclusion in an active surveillance program is a valid option. The implementation of multiparametric magnetic resonance imaging (mpMRI) into a screening program may reduce the risk of overdetection of non-significant PC and improve the early detection of clinically significant PC. A mpMRI consists of T2-weighted images supplemented with diffusion-weighted imaging, dynamic contrast enhanced imaging, and/or magnetic resonance spectroscopic imaging and is preferably performed and reported according to the uniform quality standards of the Prostate Imaging Reporting and Data System (PIRADS). International guidelines currently recommend mpMRI in patients with persistently rising PSA and previous negative biopsies, but mpMRI may also be used before first biopsy to improve the biopsy yield by targeting suspicious lesions or to assist in the selection of low-risk patients in whom consideration could be given for surveillance. TEACHING POINTS: • MpMRI may be used to detect or exclude significant prostate cancer. • MpMRI can guide targeted rebiopsy in patients with previous negative biopsies. • In patients with negative mpMRI consideration could be given for surveillance. • MpMRI may add valuable information for the optimal treatment selection.

Systematic ultrasound-guided saturation and template biopsy of the prostate: indications and advantages of extended sampling.

OBJECTIVES: Prostate biopsy (PB) is the gold standard for the diagnosis of prostate cancer (PCa). However, the optimal number of biopsy cores remains debatable. We sought to compare contemporary standard (10-12 cores) vs. saturation (=18 cores) schemes on initial as well as repeat PB. METHODS: A non-systematic review of the literature was performed from 2000 through 2013. Studies of highest evidence (randomized controlled trials, prospective non-randomized studies, and retrospective reports of high quality) comparing standard vs saturation schemes on initial and repeat PB were evaluated. Outcome measures were overall PCa detection rate, detection rate of insignificant PCa, and procedure-associated morbidity. RESULTS: On initial PB, there is growing evidence that a saturation scheme is associated with a higher PCa detection rate compared to a standard one in men with lower PSA levels (<10 ng/ml), larger prostates (>40 cc), or lower PSA density values (<0.25 ng/ml/cc). However, these cut-offs are not uniform and differ among studies. Detection rates of insignificant PCa do not differ in a significant fashion between standard and saturation biopsies. On repeat PB, PCa detection rate is likewise higher with saturation protocols. Estimates of insignificant PCa vary widely due to differing definitions of insignificant disease. However, the rates of insignificant PCa appear to be comparable for the schemes in patients with only one prior negative biopsy, while saturation biopsy seems to detect more cases of insignificant PCa compared to standard biopsy in men with two or more prior negative biopsies. Very extensive sampling is associated with a high rate of acute urinary retention, whereas other severe adverse events, such as sepsis, appear not to occur more frequently with saturation schemes. DISCUSSION: Current evidence suggests that saturation schemes are associated with a higher PCa detection rate compared to standard ones on initial PB in men with lower PSA levels or larger prostates, and on repeat PB. Since most data are derived from retrospective studies, other endpoints such as detection rate of insignificant disease - especially on repeat PB - show broad variations throughout the literature and must, thus, be interpreted with caution. Future prospective controlled trials should be conducted to compare extended templates with newer techniques, such as image-guided sampling, in order to optimize PCa diagnostic strategy.