Thromboprophylaxis during neoadjuvant chemotherapy for bladder cancer reduces thromboembolism and bleeding.

OBJECTIVES: To assess the risk of venous thromboembolic events (VTEs) and bleeding with or without thromboprophylaxis during neoadjuvant chemotherapy in bladder cancer patients scheduled for radical cystectomy. MATERIALS AND METHODS: We conducted a retrospective cohort study in 4886 patients with non-metastatic bladder cancer undergoing cystectomy across 28 centres in 13 countries between 1990 and 2021. Inverse probability weighting analyses were performed to estimate the effect of thromboprophylaxis on VTE and bleeding. RESULTS: In 147 patients (3%) VTEs were recorded within the first year. These occurred a median (interquartile range [IQR]) of 127 (82-198) days after bladder cancer diagnosis. Bleeding events occurred in 131 patients (3%) within the first year. These occurred a median (IQR) of 101 (83-171) days after cancer diagnosis. In inverse probability weighting analyses, compared to patients without thromboprophylaxis during chemotherapy, patients with thromboprophylaxis had not only a lower risk of VTE (hazard ratio [HR] 0.32, 95% confidence interval [CI] 0.12-0.81; P = 0.016) but also a lower bleeding risk (HR 0.03, 95% CI 0.09-0.12; P <0.0001). The retrospective nature of the study was its main limitation. CONCLUSIONS: In this retrospective analysis, the benefit of thromboprophylaxis during neoadjuvant chemotherapy before cystectomy is in line with data from randomised trials in other malignancies. Our data suggest thromboprophylaxis is protective against VTEs and should be the standard of care during neoadjuvant chemotherapy.

Why Do Men Reject Adjuvant Radiotherapy following Radical Prostatectomy? A Systematic Survey.

INTRODUCTION: The aim of this study was to investigate non-adherence rates to adjuvant radiotherapy (aRT) after radical prostatectomy (RP) and to obtain patient reported reasons for rejecting aRT despite recommendation by a multidisciplinary team discussion (MTD). METHODS: In a retrospective monocentric analysis, we identified 1,197 prostate cancer patients who underwent RP between 2014 and 2022 at our institution, of which 735 received a postoperative MTD recommendation. Patients with a recommendation for aRT underwent a structured phone interview with predefined standardised qualitative and quantitative questions and were stratified into "adherent" (aRT performed) and "non-adherent" groups (aRT not performed). RESULTS: Of 55 patients receiving a recommendation for aRT (7.5% of all RP patients), 24 (44%) were non-adherent. Baseline tumour characteristics were comparable among the groups. "Fear of radiation damage" was the most common reason for rejection, followed by "lack of information," "feeling that the treating physician does not support the recommendation" and "the impression that aRT is not associated with improved oncological outcome." Salvage radiotherapy was performed in 25% of non-adherent patients. CONCLUSION: High rates of non-adherence to aRT after RP were observed, and reasons for this phenomenon are most likely multifactorial. Multidisciplinary and individualized patient counselling might be a key for increasing adherence rates.

Unilateral Pelvic Lymph Node Dissection in Prostate Cancer Patients Diagnosed in the Era of Magnetic Resonance Imaging-targeted Biopsy: A Study That Challenges the Dogma.

PURPOSE: Bilateral extended pelvic lymph node dissection at the time of radical prostatectomy is the current standard of care if pelvic lymph node dissection is indicated; often, however, pelvic lymph node dissection is performed in pN0 disease. With the more accurate staging achieved with magnetic resonance imaging-targeted biopsies for prostate cancer diagnosis, the indication for bilateral extended pelvic lymph node dissection may be revised. We aimed to assess the feasibility of unilateral extended pelvic lymph node dissection in the era of modern prostate cancer imaging. MATERIALS AND METHODS: We analyzed a multi-institutional data set of men with cN0 disease diagnosed by magnetic resonance imaging-targeted biopsy who underwent prostatectomy and bilateral extended pelvic lymph node dissection. The outcome of the study was lymph node invasion contralateral to the prostatic lobe with worse disease features, ie, dominant lobe. Logistic regression to predict lymph node invasion contralateral to the dominant lobe was generated and internally validated. RESULTS: Overall, data from 2,253 patients were considered. Lymph node invasion was documented in 302 (13%) patients; 83 (4%) patients had lymph node invasion contralateral to the dominant prostatic lobe. A model including prostate-specific antigen, maximum diameter of the index lesion, seminal vesicle invasion on magnetic resonance imaging, International Society of Urological Pathology grade in the nondominant side, and percentage of positive cores in the nondominant side achieved an area under the curve of 84% after internal validation. With a cutoff of contralateral lymph node invasion of 1%, 602 (27%) contralateral pelvic lymph node dissections would be omitted with only 1 (1.2%) lymph node invasion missed. CONCLUSIONS: Pelvic lymph node dissection could be omitted contralateral to the prostate lobe with worse disease features in selected patients. We propose a model that can help avoid contralateral pelvic lymph node dissection in almost one-third of cases.

Prognostic value of pretreatment inflammatory markers in localised prostate cancer before radical prostatectomy.

PURPOSE: There is growing evidence of an association between inflammatory processes and cancer development and progression. In different solid tumor entities, a pronounced inflammatory response is associated with worse oncological outcome. In this study, we aim to evaluate the prognostic role of clinically established pretreatment inflammatory markers in patients with localised prostate cancer (PCa) before radical prostatectomy (RP). METHODS: A total of 641 men met our inclusion criteria and were followed prospectively for a median of 2.85 years. Univariable logistic and Cox regression analysis were performed to analyse associations between preoperative inflammatory markers and tumor characteristics, and biochemical recurrence free survival (BRFS). RESULTS: Median age at RP was 64 years. Gleason Score (GS) 7a (263, 41%) was the most prevalent histology, whereas high-risk PCa (≥ GS 8) was present in 156 (24%) patients. Lympho-nodal metastasis and positive surgical margin (PSM) were detected in 69 (11%) and 180 (28%) patients, respectively. No statistically relevant association could be shown between pretreatment inflammatory markers with worse pathological features like higher tumor stage or grade, nodal positive disease or PSM (for all p > 0.05). Additionally, pretreatment inflammatory markers were not associated with a shorter BRFS (p > 0.05). Known risk factors (tumor grade, tumor stage, nodal positivity and positive surgical margins) were all associated with a shorter BRFS (for all p < 0.0001). CONCLUSION: In this large prospective cohort, preoperative inflammatory markers were not associated with worse outcome.

The role of primary retroperitoneal lymph node dissection in the treatment of stage II seminoma.

PURPOSE OF REVIEW: Stage II seminoma is responsive to chemo- or radiotherapy with a progression-free survival of 87-95% at 5 years but at the cost of short- and long-term toxicity. After evidence about these long-term morbidities emerged, four surgical cohorts investigating the role of retroperitoneal lymph node dissection (RPLND) as a treatment option for stage II disease were initiated. RECENT FINDINGS: Currently, two RPLND series have been published as a complete report, while data from other series have only been published as congress abstracts. In series without adjuvant chemotherapy, recurrence rates ranged from 13% to 30% after follow-ups of 21-32 months. In those receiving RPLND and adjuvant chemotherapy, the recurrence rate was 6% after a mean follow-up of 51 months. Across all trials, recurrent disease was treated with systemic chemotherapy (22/25), surgery (2/25), and radiotherapy (1/25). The rate of pN0 disease after RPLND varied between 4% and 19%. Postoperative complications were reported in 2-12%, while antegrade ejaculation was maintained in 88-95% of patients. Median length of stay ranged from 1 to 6 days. SUMMARY: In men with clinical stage II seminoma, RPLND is a safe and promising treatment option. Further research is needed to determine the risk of relapse and to personalize treatment options based on patient-specific risk factors.

An Algorithm to Personalize Nerve Sparing in Men with Unilateral High-Risk Prostate Cancer.

PURPOSE: Current guidelines do not provide strong recommendations on preservation of the neurovascular bundles during radical prostatectomy in case of high-risk (HR) prostate cancer and/or suspicious extraprostatic extension (EPE). We aimed to evaluate when, in case of unilateral HR disease, contralateral nerve sparing (NS) should be considered or not. MATERIALS AND METHODS: Within a multi-institutional data set we selected patients with unilateral HR prostate cancer, defined as unilateral EPE and/or seminal vesicle invasion (SVI) on multiparametric (mp) magnetic resonance imaging (MRI), or unilateral International Society of Urologic Pathologists (ISUP) 4-5 or prostate specific antigen ≥20 ng/ml. To evaluate when to perform NS based on the risk of contralateral EPE, we relied on chi-square automated interaction detection, a recursive machine-learning partitioning algorithm developed to identify risk groups, which was fit to predict the presence of EPE on final pathology, contralaterally to the prostate lobe with HR disease. RESULTS: A total of 705 patients were identified. Contralateral EPE was documented in 87 patients (12%). Chi-square automated interaction detection identified 3 groups, consisting of 1) absence of SVI on mpMRI and index lesion diameter ≤15 mm, 2) index lesion diameter ≤15 mm and contralateral ISUP 2-3 or index lesion diameter >15 mm and negative contralateral biopsy or ISUP 1, and 3) SVI on mpMRI or index lesion diameter >15 mm and contralateral biopsy ISUP 2-3. We named those groups as low, intermediate and high-risk, respectively, for contralateral EPE. The rate of EPE and positive surgical margins across the groups were 4.8%, 14% and 26%, and 5.6%, 13% and 18%, respectively. CONCLUSIONS: Our study challenges current guidelines by proving that wide bilateral excision in men with unilateral HR disease is not justified. Pending external validation, we propose performing NS and incremental NS in case of contralateral low and intermediate EPE risk, respectively.

Use of MS-GUIDE for identification of protein biomarkers for risk stratification of patients with prostate cancer.

BACKGROUND: Non-invasive liquid biopsies could complement current pathological nomograms for risk stratification of prostate cancer patients. Development and testing of potential liquid biopsy markers is time, resource, and cost-intensive. For most protein targets, no antibodies or ELISAs for efficient clinical cohort pre-evaluation are currently available. We reasoned that mass spectrometry-based prescreening would enable the cost-effective and rational preselection of candidates for subsequent clinical-grade ELISA development. METHODS: Using Mass Spectrometry-GUided Immunoassay DEvelopment (MS-GUIDE), we screened 48 literature-derived biomarker candidates for their potential utility in risk stratification scoring of prostate cancer patients. Parallel reaction monitoring was used to evaluate these 48 potential protein markers in a highly multiplexed fashion in a medium-sized patient cohort of 78 patients with ground-truth prostatectomy and clinical follow-up information. Clinical-grade ELISAs were then developed for two of these candidate proteins and used for significance testing in a larger, independent patient cohort of 263 patients. RESULTS: Machine learning-based analysis of the parallel reaction monitoring data of the liquid biopsies prequalified fibronectin and vitronectin as candidate biomarkers. We evaluated their predictive value for prostate cancer biochemical recurrence scoring in an independent validation cohort of 263 prostate cancer patients using clinical-grade ELISAs. The results of our prostate cancer risk stratification test were statistically significantly 10% better than results of the current gold standards PSA alone, PSA plus prostatectomy biopsy Gleason score, or the National Comprehensive Cancer Network score in prediction of recurrence. CONCLUSION: Using MS-GUIDE we identified fibronectin and vitronectin as candidate biomarkers for prostate cancer risk stratification.

Oncological and functional outcomes after testis-sparing surgery in patients with germ cell tumors: a systematic review of 285 cases.

INTRODUCTION AND OBJECTIVES: In several urogenital cancers, organ-preserving surgery represents the preferred treatment approach, but in patients with testicular germ cell tumors (tGCTs), radical orchiectomy represents the standard of care. This study aimed to summarize published case series assessing oncological and functional outcomes after testis-sparing surgery (TSS) in patients with tGCTs. MATERIALS AND METHODS: A systematic literature review and individual patient data meta-analysis were conducted of published cases with tGCT treated with TSS. RESULTS: Of 2,333 reports, we included 32 reports providing data on 285 patients, including 306 testicles treated with TSS. Adjacent germ cell neoplasia in situ (GCNIS) was described in 43%. Hypogonadism and infertility after TSS were diagnosed in 27% and 18%. In patients undergoing adjuvant testicular radiotherapy, hypogonadism was diagnosed in 40%. Patients treated with adjuvant testicular radiotherapy after TSS exhibited a significantly lower incidence of local recurrence (2% vs. 50%, p < 0.001). Distant metastases after TSS were observed in 2%. CONCLUSION: The current data questions the benefits of TSS in tGCT patients. If at all, TSS should only be offered to well-informed patients with a singular testicle, excellent compliance, a singular tumor less than 2 cm located at the lower pole of the testicle, and normal preoperative endocrine function. Unless patients plan to father a child within a short time frame, adjuvant testicular radiotherapy should be recommended after TSS. Radical orchiectomy remains the standard of care, but future studies may support the use of TSS in selected men.

Assessment of the Anastomosis after Radical Prostatectomy: A Review of Available Diagnostic Methods.

INTRODUCTION: After radical prostatectomy, many institutions perform cystography to exclude vesicourethral anastomotic leakage before removing a urethral catheter. We reviewed diagnostic methods to exclude leakage compared to the reference standard cystography. METHODS: We performed systematic literature review to summarize the published options and outcomes for assessment of vesicourethral anastomotic leakage after radical prostatectomy. RESULTS: Of 2,137 publications, 45 full-text manuscripts underwent full-text screening, of which 9 studies contributing 919 patients were included. Seven studies described ultrasound-guided assessment (four transrectal, two transabdominal, one transperineal). Two further studies described the use of computerized tomography. Ultrasound-guided assessment of the anastomosis after radical prostatectomy shows promising agreement with cystography. Computerized tomography-aided assessment of vesicourethral anastomosis detects more leakages; however, clinical consequences are not defined. CONCLUSION: Further studies are warranted to (1) identify men at risk of anastomotic leakage who should undergo assessment before trial without a catheter and (2) provide prospective comparisons of different ultrasound-guided approaches.

Radical Hemiscrotectomy and En Bloc Orchidectomy: Surgical Technique and Perioperative and Oncologic Outcomes of a Supra-Regional UK Referral Centre.

BACKGROUND AND PURPOSE: Hemiscrotectomy with en bloc orchidectomy represents a radical primary, completion, or salvage option in men with inguinoscrotal cancers. We describe our surgical technique and peri-operative and oncological outcomes. PATIENTS AND METHODS: Retrospective cohort study of 16 men treated at a supra-regional referral centre with open radical hemiscrotectomy with or without en bloc orchidectomy between 2010 and 2020. Peri-operative and survival outcomes were analysed. RESULTS: Radical hemiscrotectomy with or without en bloc orchidectomy was performed on 16 patients comprising 7 well-differentiated liposarcomas, 4 dedifferentiated liposarcomas, 2 leiomyosarcomas, 1 mesothelioma, 1 rhabdomyosarcoma and 1 mammary type myofibroblastoma. Primary hemiscrotectomy was performed in four, completion hemiscrotectomy in nine and salvage hemiscrotectomy in three. The median hospital stay was 2 days [interquartile range (IQR) 2-4]. Four patients (25%) had post-operative complications including wound infection or haematoma. During a median follow-up of 18 months (IQR 2-66), one patient (6%) died following a recurrence in the pelvis and retroperitoneum. DISCUSSION: and Conclusions If careful dissection is performed, radical hemiscrotectomy and en bloc orchidectomy is a radical but safe procedure with a short hospital stay. Haematoma and infection represent the main complications, and within limited follow-up most men showed no recurrence.

Diagnostic accuracy of ultrasonography, computed tomography, cystoscopy and cytology to detect urinary tract malignancies in patients with asymptomatic hematuria.

PURPOSE: To report the incidence of urinary tract malignancies (UTM) and to compare the diagnostic accuracy of cytology with cystoscopy, renal ultrasound (US) and computed tomography (CT) in patients with hematuria. METHODS: A retrospective analysis was conducted of patients who underwent cystoscopy, cytology, US and CT for hematuria between 2011 and 2017. Age, gender, BMI, smoking status, and results of further diagnostic interventions including transurethral resection of the bladder (TURB), ureterorenoscopy (URS), renal biopsy and imaging were extracted from medical charts. Logistic regression to identify risk factors for UTM was performed. Discriminatory accuracy of US, CT and cytology was assessed by 2 × 2 tables. RESULTS: Of 847 patients, 432 (51%) presented with non-visible hematuria (NVH) and 415 (49%) with visible hematuria (VH). Of all patients with NVH, seven (1.6%) had bladder cancer (BCA), three (< 1%) had renal cell cancer (RCC) and no single patient had upper tract urothelial cancer (UTUC). Of the patients with VH, 62 (14.9%) were diagnosed with BCA, 7 (1.6%) with RCC and 4 (< 1%) with UTUC. In multivariable analysis VH, higher age, smoking and lower BMI were associated with an increased risk for UTM. The specificity/negative predictive value of US for the detection of RCC or UTUC in patients with NVH and VH were 96%/100% and 95%/99%, respectively. CONCLUSION: Due to the low incidence of UTM, the necessity of further diagnostics should be questioned in patients with NVH. In contrast, patients with VH are at considerable risk for BCA, and cystoscopy and upper tract imaging is justified.

The prognostic significance of lactate dehydrogenase levels in seminoma patients with advanced disease: an analysis by the Global Germ Cell Tumor Collaborative Group (G3).

PURPOSE: The prognostic significance of lactate dehydrogenase (LDH) in patients with metastatic seminoma is not defined. We investigated the prognostic impact of LDH levels prior to first-line systemic treatment and other clinical characteristics in this subset of patients. METHODS: Files from two registry studies and one single-institution database were analyzed retrospectively. Uni- and multivariate analyses were conducted to identify patient characteristics associated with recurrence free survival (RFS), overall survival (OS), and complete response rate (CRR). RESULTS: The dataset included 351 metastatic seminoma patients with a median follow-up of 5.36 years. Five-year RFS, OS and CRR were 82%, 89% and 52%, respectively. Explorative analysis revealed a cut-off LDH level of < 2.5 upper limit of normal (ULN) (n = 228) vs. ≥ 2.5 ULN (n = 123) to be associated with a significant difference concerning OS associated with 5-years OS rates of 93% vs. 83% (p = 0.001) which was confirmed in multivariate analysis (HR 2.87; p = 0.004). Furthermore, the cut-off LDH < 2.5 ULN vs. ≥ 2.5 ULN correlated with RFS and CRR associated with a 5-years RFS rate and CRR of 76% vs. 86% (p = 0.012) and 32% vs. 59% (p ≤ 0.001), respectively. CONCLUSIONS: LDH levels correlate with treatment response and survival in metastatic seminoma patients and should be considered for their prognostic stratification.

Sertoli Cell Tumors of the Testes: Systematic Literature Review and Meta-Analysis of Outcomes in 435 Patients.

BACKGROUND: Sertoli cell tumors (SCTs) of the testes are rare, and the literature provides only weak evidence concerning their clinical course and management. The objective of this study was to summarize evidence on SCTs' clinical presentation, clinicopathological risk factors for malignancy, treatment options, and oncological outcomes. MATERIALS AND METHODS: Data sources included Medline, Embase, Scopus, the Cochrane Database of Systematic Reviews, and Web of Science. Published case reports, case series, and cohorts were included. Data on clinicopathological variables, treatment of local or metastatic disease, site of metastasis, or survival were extracted from each study considered in this paper, and associations between clinicopathological variables and metastatic disease were analyzed. Whenever feasible, data on individual patients were collected. RESULTS: Of the 435 patients included, only one (<1%) showed local recurrence after testis-sparing surgery (TSS). Three patients underwent adjuvant retroperitoneal lymphadenectomy. Fifty patients presented with metastases, located in the retroperitoneal lymph nodes (76%), lungs (36%), and bones (16%); median time to recurrence was 12 months. Risk factors for metastatic disease included age, tumor size, necrosis, tumor extension to the spermatic cord, angiolymphatic invasion, and mitotic index. Patients with metastases had a median life expectancy of 20 months. In six patients, metastasectomy resulted in complete remission. CONCLUSION: Our findings suggest that few local recurrences result after TSS, and no adjuvant therapy can be regarded as a standard of care. Several risk factors are predictive of metastatic disease. Surgery leads to remission in metastatic disease, whereas systemic treatment alone does not result in long-term remission. IMPLICATIONS FOR PRACTICE: Testicular Sertoli cell tumors usually present without metastatic disease and show low local recurrence rates after testis-sparing surgery; no adjuvant therapy option can be regarded as a standard of care. Patients with risk factors should undergo staging investigations. Those with metastatic disease have poor prognoses, and metastasectomy may be offered in selected cases.

Leydig-cell tumour of the testis: retrospective analysis of clinical and therapeutic features in 204 cases.

PURPOSE: Leydig-cell tumours (LCT) of the testis are poorly understood clinically. The aim of this report is to analyse the clinical characteristics of LCT in a large patient sample and to compare these findings with corresponding data of germ-cell tumours (GCT). METHODS: In a sample of 208 patients treated during 1995-2017 in 33 institutions, the following characteristics were registered: age, presenting symptoms, primary tumour size, testis-sparing surgery (TSS) or orchiectomy, malignancy, laterality, medical history, and outcome. Data analysis included descriptive statistical methods and logistic regression analysis. RESULTS: The ratio LCT:GCT is 1:23 (4.4%). The findings are as follows: median age 41 years, undescended testis 8%, bilateral LCTs 3%, malignant LCT 2.5%, contralateral GCT 2.5%, incidental detection 28%, scrotal symptoms 43%, infertility 18%, elevated estradiol levels 29%. TSS was performed in 56% with no local relapse. Of the patients with malignant LCT, one was cured through surgery. CONCLUSION: LCT is rare, with a relative frequency (relative to GCT) of 1:23. Malignancy is found in 2.5%. LCT and GCT share a number of clinical features, e.g. bilaterality, history of undescended testis, and presenting age. TSS is safe in benign LCT. Surgery is the treatment of choice in malignant LCT.

Treatment options and results of adjuvant treatment in nonmuscle-invasive bladder cancer (NMIBC) during the Bacillus Calmette-Guérin shortage.

PURPOSE OF REVIEW: Given the worldwide shortage of Bacillus Calmette-Guérin (BCG), we review the efficacy of alternative BCG application schedules, doses or strains and intravesical chemotherapy in patients with nonmuscle-invasive bladder cancer (NMIBC). RECENT FINDINGS: Modifying BCG schedules by reducing the dose is preferable to reducing the frequency of BCG that increases recurrence rates and should be avoided if possible. Changing the BCG substrain represents a reasonable option, as current evidence does not suggest different oncological outcomes with specific BCG substrains. Mitomycin C (MMC) alone is inferior to BCG with maintenance, but promising results have been demonstrated when used with chemohyperthermia and electromotive drug administration. Several other intravesical chemotherapies including Gemcitabine and Epirubicin should be used when both BCG and MMC are in short supply. SUMMARY: In case of BCG shortage, much will depend on the severity and length of the BCG shortage, but our review supports several solutions: First, we recommend contacting the local pharmacist or BCG supplier to consider alternative BCG strains or sterile splitting of BCG doses. In the complete absence of BCG, consideration should be given to MMC with chemohyperthermia or electromotive drug administration where available or other intravesical chemotherapy. High-risk patients should be considered for cystectomy.

CXCL12 expression is an adverse predictor for disease recurrence in patients with metastatic non-seminomatous testicular germ cell tumors.

BACKGROUND: To validate the utility of the chemokine ligand 12 (CXCL12) as prognostic marker in patients with localized and metastatic germ cell tumors (GCT). METHODS: CXCL12 expression was analyzed on a tissue microarray consisting of 750 tissue cores of different histological tumor components, Germ cell neoplasia in situ (GCNIS) and adjacent normal tissue of 263 testicular cancer patients using a semi-quantitative score. The association between CXCL12 expression and recurrence-free survival (RFS) as well as overall survival (OS) was assessed using Kaplan-Meier curves with log-rank tests. RESULTS: CXCL12 expression was absent in all seminomas but was found in 52 of 99 (52.5%) non-seminomas. Follow-up was available for 260 patients of which 36 (13.8%) recurred. In patients with stage 1 non-seminoma GCT, CXCL12 expression was not associated with higher risk of disease recurrence (p = 0.270). In contrast, post chemotherapy RFS of patients with metastatic non-seminoma and positive CXCL12 expression was significantly shorter compared to CXCL12 negative patients (p = 0.003). OS differences were not statistically different between patients with CXCL12 positive or negative tumors for either localized or metastatic disease. CONCLUSIONS: CXCL12 is almost exclusively expressed in non-seminoma. Pure seminoma, GCNIS and adjacent normal testicular tissue are CXCL12 negative. Our analysis suggests that patients with metastatic disease and a CXCL12-positive non-seminoma are at higher risk for disease recurrence after first-line chemotherapy and might thus be candidates for more intensive treatment and/or closer follow-up.

Current and potential future role of PSMA-PET in patients with castration-resistant prostate cancer.

PURPOSE: To review the current literature and discuss potential future roles of the novel positron emission tomography (PET) tracers targeting the prostate-specific membrane antigen (PSMA) in patients with castration-resistant prostate cancer (CRPC). METHODS: A literature search on February 19th 2018 was conducted using the Medline database and www.clinicaltrials.gov . Additionally, illustrative cases of CRPC patients from our own institution who were restaged and treated based on PSMA-PET scan results are provided. RESULTS: 11 Studies met the inclusion criteria. PSMA-PET detected more metastatic lesions compared to conventional bone scan. Several patients were up-staged from non-metastatic CRPC (nmCRPC) to metastatic CRPC (mCRPC). Currently, no clear consensus exists regarding treatment response assessment in PSMA-PET scans for mCRPC patients undergoing treatment. Also, the role of PSMA-PET as a gatekeeper for systemic therapy or radioligands is currently undefined. PSMA-guided metastasis-directed radiotherapy may not only alleviate local symptoms but has the potential to defer systemic treatment in patients with oligoprogressive CRPC. CONCLUSION: Compared to bone scan, PSMA-PET is more sensitive and specific to detect metastases but the therapeutic consequences of PSMA-PET results in the setting of CRPC remain unclear. Until future studies define the role of PSMA-PET in patients with CRPC, the current standard for imaging remains bone scan and computerized tomography.

Systemic inflammatory markers have independent prognostic value in patients with metastatic testicular germ cell tumours undergoing first-line chemotherapy.

BACKGROUND: The prognostic utility of systemic inflammatory markers has so far not been investigated in patients with metastatic testicular germ cell tumours (GCTs). METHODS: International Germ Cell Cancer Cooperative Group (IGCCCG) risk groups and blood-based systemic inflammatory markers (haemoglobin, leukocytes, platelets (P), neutrophils (N), lymphocytes (L), C-reactive protein (CRP) and albumin) of 146 patients undergoing first-line chemotherapy for GCT were retrieved. In addition, N to L ratio (NLR), P to L ratio and the systemic immune-inflammation index (SII=N × P/L) were calculated. The prognostic ability of these markers for overall survival (OS) were assessed using regression analyses and Kaplan-Meier curves with log-rank tests. RESULTS: In univariate Cox regression, low haemoglobin and albumin as well as high leukocytes, N, NLR, SII and CRP were associated with a shorter OS. In multivariable Cox regression analyses, high leukocyte (hazard ratio (HR) 1.274 (95% confidence interval (CI) 1.057-1.535); P=0.011) and N count (1.470 (1.092-1.980); P=0.011), higher NLR (84.5 (2.2-3193.4); P=0.017) and SII (12.15 (1.17-126.26); P=0.037) remained independent prognostic predictors for OS besides the IGCCCG risk groups. CONCLUSIONS: Systemic inflammatory markers might have prognostic utility for patients with metastatic GCT. The planned IGCCCG update could be an opportunity to test these markers in a larger data set.

Three-Dimensional Texture Analysis with Machine Learning Provides Incremental Predictive Information for Successful Shock Wave Lithotripsy in Patients with Kidney Stones.

PURPOSE: We sought to determine the predictive value of 3-dimensional texture analysis of computerized tomography images for successful shock wave lithotripsy in patients with kidney stones. MATERIALS AND METHODS: Patients with preoperative and postoperative computerized tomography, previously untreated kidney stones and a stone diameter of 5 to 20 mm were included in study. A total of 224, 3-dimensional texture analysis features of each kidney stone, including attenuation measured in HU and the clinical variables body mass index, initial stone size and skin to stone distance, were analyzed using 5 commonly used machine learning models. The data set was split in a ratio of 2/3 for model derivation and 1/3 for validation. Machine learning based predictions of shock wave lithotripsy success in the validation cohort were evaluated by calculating sensitivity, specificity and the AUC. RESULTS: For shock wave lithotripsy success the 3 clinical variables body mass index, initial stone size and skin to stone distance showed an AUC of 0.68, 0.58 and 0.63, respectively. No predictive value was found for HU. A random forest classifier using 3, 3-dimensional texture analysis features had an AUC of 0.79. By combining these 3 features with clinical variables discriminatory accuracy improved further with an AUC of 0.85 for 3-dimensional texture analysis features and skin to stone distance, an AUC of 0.8 for 3-dimensional texture analysis features and body mass index, and an AUC of 0.81 for 3-dimensional texture analysis and stone size. CONCLUSIONS: This preliminary study indicates that the clinical variables body mass index, initial stone size and skin to stone distance show limited value to predict shock wave lithotripsy success while stone HU values were not predictive. Select 3-dimensional texture analysis features identified by machine learning provided incremental accuracy to predict the success of shock wave lithotripsy.