Urine-derived bladder cancer organoids (urinoids) as a tool for cancer longitudinal response monitoring and therapy adaptation.

BACKGROUND: Bladder cancer is one of the most common cancer types worldwide. Generally, research relies on invasive sampling strategies. METHODS: Here, we generate bladder cancer organoids directly from urine (urinoids). In this project, we establish 12 urinoid lines from 22 patients with non-muscle and muscle-invasive bladder tumours, with an efficiency of 55%. RESULTS: The histopathological features of the urinoids accurately resemble those of the original bladder tumours. Genetically, there is a high concordance of single nucleotide polymorphisms (92.56%) and insertions & deletions (91.54%) between urinoids and original tumours from patient 4. Furthermore, these urinoids show sensitivity to bladder cancer drugs, similar to their tissue-derived organoid counterparts. Genetic analysis of longitudinally generated tumoroids and urinoids from one patient receiving systemic immunotherapy, identify alterations that may guide the choice for second-line therapy. Successful treatment adaptation was subsequently demonstrated in the urinoid setting. CONCLUSION: Therefore, urinoids can advance precision medicine in bladder cancer as a non-invasive platform for tumour pathogenesis, longitudinal drug-response monitoring, and therapy adaptation.

Deep learning based correction of RF field induced inhomogeneities for T2w prostate imaging at 7 T.

At ultrahigh field strengths images of the body are hampered by B1 -field inhomogeneities. These present themselves as inhomogeneous signal intensity and contrast, which is regarded as a "bias field" to the ideal image. Current bias field correction methods, such as the N4 algorithm, assume a low frequency bias field, which is not sufficiently valid for T2w images at 7 T. In this work we propose a deep learning based bias field correction method to address this issue for T2w prostate images at 7 T. By combining simulated B1 -field distributions of a multi-transmit setup at 7 T with T2w prostate images at 1.5 T, we generated artificial 7 T images for which the homogeneous counterpart was available. Using these paired data, we trained a neural network to correct the bias field. We predicted either a homogeneous image (t-Image neural network) or the bias field (t-Biasf neural network). In addition, we experimented with the single-channel images of the receive array and the corresponding sum of magnitudes of this array as the input image. Testing was carried out on four datasets: the test split of the synthetic training dataset, volunteer and patient images at 7 T, and patient images at 3 T. For the test split, the performance was evaluated using the structural similarity index measure, Wasserstein distance, and root mean squared error. For all other test data, the features Homogeneity and Energy derived from the gray level co-occurrence matrix (GLCM) were used to quantify the improvement. For each test dataset, the proposed method was compared with the current gold standard: the N4 algorithm. Additionally, a questionnaire was filled out by two clinical experts to assess the homogeneity and contrast preservation of the 7 T datasets. All four proposed neural networks were able to substantially reduce the B1 -field induced inhomogeneities in T2w 7 T prostate images. By visual inspection, the images clearly look more homogeneous, which is confirmed by the increase in Homogeneity and Energy in the GLCM, and the questionnaire scores from two clinical experts. Occasionally, changes in contrast within the prostate were observed, although much less for the t-Biasf network than for the t-Image network. Further, results on the 3 T dataset demonstrate that the proposed learning based approach is on par with the N4 algorithm. The results demonstrate that the trained networks were capable of reducing the B1 -field induced inhomogeneities for prostate imaging at 7 T. The quantitative evaluation showed that all proposed learning based correction techniques outperformed the N4 algorithm. Of the investigated methods, the single-channel t-Biasf neural network proves most reliable for bias field correction.

Feasibility of clinical studies of chemical exchange saturation transfer magnetic resonance imaging of prostate cancer at 7 T.

Chemical exchange saturation transfer (CEST) has been explored for differentiation between tumour and benign tissue in prostate cancer (PCa) patients. With ultrahigh field strengths such as 7-T, the increase of spectral resolution and sensitivity could allow for selective detection of amide proton transfer (APT) at 3.5 ppm and a group of compounds that resonate at 2 ppm (i.e., [poly]amines and/or creatine). The potential of 7-T multipool CEST analysis of the prostate and the detection of PCa was studied in patients with proven localised PCa who were scheduled to undergo robot-assisted radical prostatectomy (RARP). Twelve patients were prospectively included (mean age 68.0 years, mean serum prostate-specific antigen 7.8ng/mL). A total of 24 lesions larger than 2 mm were analysed. Used were 7-T T2-weighted (T2W) imaging and 48 spectral CEST points. Patients received 1.5-T/3-T prostate magnetic resonance imaging and galium-68-prostate-specific membrane antigen-positron emission tomography/computerised tomography to determine the location of the single-slice CEST. Based on the histopathological results after RARP, three regions of interest were drawn on the T2W images from a known malignant zone and benign zone in the central and peripheral zones. These areas were transposed to the CEST data, from which the APT and 2-ppm CEST were calculated. The statistical significance of the CEST between the central zone, the peripheral zone, and tumour was calculated using a Kruskal-Wallis test. The z-spectra showed that APT and even a distinct pool that resonated at 2 ppm were detectable. This study showed a difference trend in the APT levels, but no difference in the 2-ppm levels when tested between the central zone, the peripheral zone, and tumour (H(2) = 4.8, p = 0.093 and H(2) = 0.86, p = 0.651, respectively). Thus, to conclude, we could most likely detect APT and amines and/or creatine levels noninvasively in prostate using the CEST effect. At group level, CEST showed a higher level of APT in the peripheral versus the central zone; however, no differences of APT and 2-ppm levels were observed in tumours.

Staging fluorodeoxyglucose positron emission tomography/computed tomography for muscle-invasive bladder cancer: a nationwide population-based study.

OBJECTIVE: To provide insight into the use and staging information on lymph-node involvement added by fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) in patients with muscle-invasive bladder cancer (MIBC), based on a nationwide population-based cohort study. PATIENTS AND METHODS: We analysed a nationwide cohort of patients with MIBC without signs of distant metastases, newly diagnosed in the Netherlands between November 2017 and October 2019. From this cohort, we selected patients who underwent pre-treatment staging with CT only or CT and FDG-PET/CT. The distribution of patients, disease characteristics, imaging findings, nodal status (clinical nodal stage cN0 vs cN+) and treatment were described for each imaging modality group (CT only vs CT and FDG-PET/CT). RESULTS: We identified 2731 patients with MIBC: 1888 (69.1%) underwent CT only; 606 (22.2%) underwent CT and FDG-PET/CT, 237 (8.6%) underwent no CT. Of the patients who underwent CT only, 200/1888 (10.6%) were staged as cN+, vs 217/606 (35.8%) who underwent CT and FDG-PET/CT. Stratified analysis showed that this difference was found in patients with clinical tumour stage (cT)2 as well as cT3/4 MIBC. Of patients who underwent both imaging modalities and were staged with CT as cN0, 109/498 (21.9%) were upstaged to cN+ based on FDG-PET/CT. Radical cystectomy (RC) was the most common treatment within both imaging groups. Preoperative chemotherapy was more frequently applied in cN+ disease and in FDG-PET/CT-staged patients. Concordance of pathological N stage after upfront RC was higher among patients staged as cN+ with CT and FDG-PET/CT (50.0% pN+) than those staged as cN+ with only CT (39.3%). CONCLUSION: Patients with MIBC who underwent pre-treatment staging with FDG-PET/CT were more often staged as lymph node positive, regardless of cT stage. In patients with MIBC who underwent CT and FDG-PET/CT, FDG-PET/CT led to clinical nodal upstaging in approximately one-fifth. Additional imaging findings may influence subsequent treatment strategies.

Low adherence to recommended use of neoadjuvant chemotherapy for muscle-invasive bladder cancer.

PURPOSE: To evaluate guideline adherence and variation in the recommended use of neoadjuvant chemotherapy (NAC) and the effects of this variation on survival in patients with non-metastatic muscle-invasive bladder cancer (MIBC). PATIENTS AND METHODS: In this nationwide, Netherlands Cancer Registry-based study, we identified 1025 patients newly diagnosed with non-metastatic MIBC between November 2017 and November 2019 who underwent radical cystectomy. Patients with ECOG performance status 0-1 and creatinine clearance ≥ 50 mL/min/1.73 m2 were considered NAC-eligible. Interhospital variation was assessed using case-mix adjusted multilevel analysis. A Cox proportional hazards model was used to evaluate the association between hospital specific probability of using NAC and survival. All analyses were stratified by disease stage (cT2 versus cT3-4a). RESULTS: In total, of 809 NAC-eligible patients, only 34% (n = 277) received NAC. Guideline adherence for NAC in cT2 was 26% versus 55% in cT3-4a disease. Interhospital variation was 7-57% and 31-62%, respectively. A higher hospital specific probability of NAC might be associated with a better survival, but results were not statistically significant (HRcT2 = 0.59, 95% CI 0.33-1.05 and HRcT3-4a = 0.71, 95% CI 0.25-2.04). CONCLUSION: Guideline adherence regarding NAC use is low and interhospital variation is large, especially for patients with cT2-disease. Although not significant, our data suggest that survival of patients diagnosed in hospitals more inclined to give NAC might be better. Further research is warranted to elucidate the underlying mechanism. As literature clearly shows the potential survival benefit of NAC in patients with cT3-4a disease, better guideline adherence might be pursued.

From Surviving Cancer to Getting on With Life: Adult Testicular Germ Cell Tumor Survivors' Perspectives on Transition From Follow-Up Care to Long-Term Survivorship.

With an increasing incidence and a high cure rate, a growing number of testicular germ cell tumor (TGCT) survivors require specialized follow-up care. However, knowledge of these patients' needs is lacking, leaving TGCT survivors with unmet care needs at risk of symptom burden when transitioning to long-term survivorship. This grounded theory study aimed to understand the perspectives of TGCT survivors' transition from follow-up care to long-term survivorship. A total of 12 adult TGCT survivors in follow-up care or completion less than a year were in-depth semi-structured interviewed. Interviews were audiotaped and transcribed verbatim. Transcripts were analyzed by constant comparison, and the core category "Dealing with back-and-forth forces" emerged in the integrated concepts. Two comparative processes in dealing with those forces were identified: the process of Living beyond the sword of Damocles involved the transition from feeling threatened by cancer to overcoming those threats; the process of Getting on with one's life can be described as transitioning from a period where cancer overruled their lives to carrying on with everyday life. The processes toward long-term survivorship follow general characteristics; the transition itself is an individual journey that depends on (life) experiences. The constructed model can guide healthcare professionals and researchers involved in TGCT survivorship to understand TGCT survivors' individual and ensuing needs. When TGCT survivors receive individualized and tailored follow-up care, it can assist in preventing and reducing long-term and late effects on long-term survivorship.

Non-metastatic muscle-invasive bladder cancer: the role of age in receiving treatment with curative intent.

OBJECTIVES: To evaluate which patient and tumour characteristics are associated with remaining untreated in patients with potentially curable, non-metastatic muscle-invasive bladder cancer (MIBC), and to compare survival of untreated vs treated patients with similar characteristics. PATIENTS AND METHODS: For this cohort study, 15 047 patients diagnosed with cT2-T4aN0/xM0/x urothelial MIBC between 2005 and 2019 were identified in the Netherlands Cancer Registry. Factors associated with remaining untreated were identified using logistic regression analyses. Interhospital variation was assessed using multilevel analysis. Using a propensity score, the median overall survival (mOS) of untreated and treated patients was evaluated. Analyses were stratified by age (<75 vs ≥75 years). RESULTS: One-third of patients aged ≥75 years remained untreated; increasing age, worse performance status, worse renal function, cT4a stage and previous radiotherapy in the abdomen/pelvic area increased the odds of remaining untreated. One in 10 patients aged <75 years remained untreated; significant associations were only found for performance status, renal function and cT4a stage. Interhospital variation for remaining untreated was largest for patients aged ≥75 years, ranging from 37% to 69% (case-mix-adjusted). Irrespective of age, mOS was significantly worse for untreated patients: 6.4 months (95% confidence interval [CI] 5.1-7.3) vs 16.0 months (95% CI 13.5-19.1) for treated patients. CONCLUSION: On average, one in five patients with non-metastatic MIBC remained untreated. Untreated patients were generally older and had a more unfavourable prognostic profile. Untreated patients had significantly worse overall survival, regardless of age. Age alone should therefore not affect treatment decision-making. Considering the large interhospital variation, a proportion of untreated patients might be wrongfully denied life-prolonging treatment.

The first patient-reported outcomes from the Utrecht Prostate Cohort (UPC): the first platform facilitating 'trials within cohorts' (TwiCs) for the evaluation of interventions for prostate cancer.

PURPOSE: To describe the development and first outcomes of the Utrecht Prostate Cohort (UPC): the first 'trials within cohorts' (TwiCs) platform for prostate cancer (PCa). METHODS: All non-metastasized, histologically proven PCa patients who are planned to receive standard of care are eligible for inclusion in UPC. Patients provide informed consent for the collection of clinical and technical patient data, physician-reported outcomes, and patient-reported outcomes (PROs) up to 10 years post-treatment. Additionally, patients may provide broad consent for future randomization for experimental-intervention trials (TwiCs). Changes in PROs (EPIC-26 questionnaire domains) of the participants who received standard of care were analyzed using Wilcoxon signed-rank tests. RESULTS: In two years, 626 patients were enrolled, 503 (80.4%) of whom provided broad consent for future randomization. Among these, 293 (46.8%) patients underwent magnetic resonance-guided adaptive radiotherapy (MRgRT), 116 (18.5%) CT-guided external beam radiation therapy (EBRT), 109 (17.4%) robot-assisted radical prostatectomy (RARP), and 65 (10.4%) patients opted for active surveillance. Patients treated with MRgRT and CT-guided EBRT showed a transient but significant decline in urinary irritative/obstructive and bowel domain scores at 1-month follow-up. RARP patients showed a significant deterioration of urinary incontinence domain scores between baseline and all follow-up moments and significant improvement of urinary irritative/obstructive domain scores between baseline and 9- and 12-month follow-up. All radical treatment groups showed a significant decline in sexual domain scores during follow-up. Active surveillance patients showed no significant deterioration over time in all domains. CONCLUSION: The first results from the UPC study show distinct differences in PROs between treatment options for PCa. REGISTRATION NO: NCT04228211.

Mouse and human urothelial cancer organoids: A tool for bladder cancer research.

Bladder cancer is a common malignancy that has a relatively poor outcome. Lack of culture models for the bladder epithelium (urothelium) hampers the development of new therapeutics. Here we present a long-term culture system of the normal mouse urothelium and an efficient culture system of human bladder cancer cells. These so-called bladder (cancer) organoids consist of 3D structures of epithelial cells that recapitulate many aspects of the urothelium. Mouse bladder organoids can be cultured efficiently and genetically manipulated with ease, which was exemplified by creating genetic knockouts in the tumor suppressors Trp53 and Stag2. Human bladder cancer organoids can be derived efficiently from both resected tumors and biopsies and cultured and passaged for prolonged periods. We used this feature of human bladder organoids to create a living biobank consisting of bladder cancer organoids derived from 53 patients. Resulting organoids were characterized histologically and functionally. Organoid lines contained both basal and luminal bladder cancer subtypes based on immunohistochemistry and gene expression analysis. Common bladder cancer mutations like TP53 and FGFR3 were found in organoids in the biobank. Finally, we performed limited drug testing on organoids in the bladder cancer biobank.

Hospital volume is associated with postoperative mortality after radical cystectomy for treatment of bladder cancer.

OBJECTIVE: To contribute to the debate regarding the minimum volume of radical cystectomies (RCs) that a hospital should perform by evaluating the association between hospital volume (HV) and postoperative mortality. PATIENTS AND METHODS: Patients who underwent RC for bladder cancer between 1 January 2008 and 31 December 2018 were retrospectively identified from the Netherlands Cancer Registry. To create a calendar-year independent measure, the HV of RCs was calculated per patient by counting the RCs performed in the same hospital in the 12 months preceding surgery. The relationship of HV with 30- and 90-day mortality was assessed by logistic regression with a non-linear spline function for HV as a continuous variable, which was adjusted for age, tumour, node and metastasis (TNM) stage, and neoadjuvant treatment. RESULTS: The median (interquartile range; range) HV among the 9287 RC-treated patients was 19 (12-27; 1-75). Of all the included patients, 208 (2.2%) and 518 (5.6%) died within 30 and 90 days after RC, respectively. After adjustment for age, TNM stage and neoadjuvant therapy, postoperative mortality slightly increased between an HV of 0 and an HV of 25 RCs and steadily decreased from an HV of 30 onwards. The lowest risks of postoperative mortality were observed for the highest volumes. CONCLUSION: This paper, based on high-quality data from a large nationwide population-based cohort, suggests that increasing the RC volume criteria beyond 30 RCs annually could further decrease postoperative mortality. Based on these results, the volume criterion of 20 RCs annually, as recently recommended by the European Association of Urology Guideline Panel, might therefore be reconsidered.

Should patients with low-risk renal cell carcinoma be followed differently after nephron-sparing surgery vs radical nephrectomy?

OBJECTIVE: To investigate whether pT1 renal cell carcinoma (RCC) should be followed differently after partial (PN) or radical nephrectomy (RN) based on a retrospective analysis of a multicentre database (RECUR). SUBJECTS: A retrospective study was conducted in 3380 patients treated for nonmetastatic RCC between January 2006 and December 2011 across 15 centres from 10 countries, as part of the RECUR database project. For patients with pT1 clear-cell RCC, patterns of recurrence were compared between RN and PN according to recurrence site. Univariate and multivariate models were used to evaluate the association between surgical approach and recurrence-free survival (RFS) and cancer-specific mortality (CSM). RESULTS: From the database 1995 patients were identified as low-risk patients (pT1, pN0, pNx), of whom 1055 (52.9%) underwent PN. On multivariate analysis, features associated with worse RFS included tumour size (hazard ratio [HR] 1.32, 95% confidence interval [CI] 1.14-1.39; P < 0.001), nuclear grade (HR 2.31, 95% CI 1.73-3.08; P < 0.001), tumour necrosis (HR 1.5, 95% CI 1.03-2.3; P = 0.037), vascular invasion (HR 2.4, 95% CI 1.3-4.4; P = 0.005) and positive surgical margins (HR 4.4, 95% CI 2.3-8.5; P < 0.001). Kaplan-Meier analysis of CSM revealed that the survival of patients with recurrence after PN was significantly better than those with recurrence after RN (P = 0.02). While the above-mentioned risk factors were associated with prognosis, type of surgery alone was not an independent prognostic variable for RFS nor CSM. Limitations include the retrospective nature of the study. CONCLUSION: Our results showed that follow-up protocols should not rely solely on stage and type of primary surgery. An optimized regimen should also include validated risk factors rather than type of surgery alone to select the best imaging method and to avoid unnecessary imaging. A follow-up of more than 3 years should be considered in patients with pT1 tumours after RN. A novel follow-up strategy is proposed.

Additional surgical procedures and perioperative morbidity in post-chemotherapy retroperitoneal lymph node dissection for metastatic testicular cancer in two intermediate volume hospitals.

PURPOSE: To evaluate the perioperative morbidity of PC-RPLND in two intermediate volume centers and to identify predictors of high morbidity. METHODS: Retrospective analysis of 124 patients treated with open PC-RPLND at two tertiary referral centers between 2001 and 2018. Perioperative morbidity was determined by analyzing additional surgical procedures, intra-operative blood loss, and postoperative complications. RESULTS: An additional procedure was necessary for 33 patients (26.6%). The risk was higher in patients with IGCCCG intermediate/poor prognosis (OR 3.56; 95% CI 1.33-9.52) and residual tumor size > 5 cm (OR 3.53; 95% CI 1.39-8.93). Blood loss was higher in patients with IGCCCG intermediate/poor prognosis (ß = 0.177; p = 0.029), large residual tumor (ß = 0.570; p < 0.001), an additional intervention (ß = 0.342; p < 0.001) and teratoma on retroperitoneal histology (ß = - 0.19; p = 0.014). Thirty-one patients had a postoperative complication Clavien-Dindo Grade ≥ 2 (25.0%). Complication risk was highest in patients undergoing an additional intervention (OR 3.46; 95% CI 1.03-11.60; p = 0.044). CONCLUSIONS: The rate of additional interventions in our series is comparable to what has been reported in high-volume centers. IGCCCG intermediate/poor prognosis patients with high-volume disease and patients undergoing an additional surgical procedure can be classified as high-risk patients.

Clinical outcome of robot-assisted residual mass resection in metastatic nonseminomatous germ cell tumor.

PURPOSE: To evaluate the outcome of robot-assisted residual mass resection (RA-RMR) in nonseminomatous germ cell tumor (NSGCT) patients with residual tumor following chemotherapy. PATIENTS AND METHODS: Retrospective medical chart analysis of all patients with NSGCT undergoing RA-RMR at two tertiary referral centers between January 2007 and April 2019. Patients were considered for RA-RMR in case of a residual tumor between 10 and 50 mm at cross-sectional computed tomography (CT) imaging located ventrally or laterally from the aorta or vena cava, with normalized tumor markers following completion of chemotherapy, and no history of retroperitoneal surgery. RESULTS: A total of 45 patients were included in the analysis. The Royal Marsden stage before chemotherapy was IIA in 13 (28.9%), IIB in 16 (35.6%), IIC in 3 (6.7%) and IV in 13 patients (28.9%). The median residual tumor size was 1.9 cm (interquartile range [IQR] 1.4-2.8; range 1.0-5.0). Five procedures (11.1%) were converted to an open procedure due to a vascular injury (n = 2), technical difficulty (n = 2) or tumor debris leakage (n = 1). A postoperative adverse event occurred in two patients (4.4%). Histopathology showed teratoma, necrosis and viable cancer in 29 (64.4%), 14 (31.1%), and two patients (4.4%), respectively. After a median follow-up of 41 months (IQR 22-70), one patient (2.2%) relapsed in the retroperitoneum. The one- and 2-year recurrence-free survival rate was 98%. CONCLUSION: RA-RMR is an appropriate treatment option in selected patients, potentially providing excellent cure rates with minimal morbidity. Long-term outcome data are needed to further support this strategy and determine inclusion and exclusion criteria.

Influence of previous laparo-endoscopic inguinal hernia repair on performing radical prostatectomy: a nationwide survey among urological surgeons.

BACKGROUND: There is considerable demographic overlap of inguinal hernia patients and prostate cancer patients. Previous laparo-endoscopic inguinal hernia mesh repairs can complicate subsequent radical prostatectomies due to adhesions and distortion of anatomic planes. This study aims to assess the experience of urological surgeons on the safety and feasibility of performing radical prostatectomies after laparo-endoscopic inguinal hernia mesh repair. METHODS: For this cross-sectional study, an online 24 question survey was developed regarding the experience in performing a radical prostatectomy and pelvic lymph node dissection (PLND) with a prior preperitoneal inguinal hernia mesh repair. Between June 2016 and December 2017, the questionnaire was sent to all 68 urological surgeons performing radical prostatectomy in the Netherlands. RESULTS: The response rate of urological surgeons was 69% (n = 47). The majority (77%) of urological surgeons perform robot-assisted laparoscopic prostatectomies. A previous preperitoneal inguinal hernia repair was reported by 40% of urological surgeons in 10-30% of patients undergoing radical prostatectomy. Radical prostatectomy with prior preperitoneal inguinal hernia mesh repair is considered more difficult by 49%, predominantly because of (occasionally to always) experienced longer operating times (88.4%), increased blood loss (46.5%), difficult dissection of Retzius space (88.4%), nerve-sparing difficulties (32.6%), less adequate PLND (69.8%), and bladder- (16.3%) or peritoneal perforations (27.9%). Additionally, 11.6% had performed mesh explantation, 16.3% had aborted radical prostatectomies, and 35.7% experienced increased inguinal hernia recurrences after radical prostatectomies with prior preperitoneal inguinal hernia mesh repair. More experienced urological surgeons reported an increased difficulty for all outcomes. CONCLUSIONS: Laparo-endoscopic inguinal hernia mesh repair has a significant impact on performing a radical prostatectomy and PLND. Surgeons should postpone the inguinal hernia repair of patients in the workup for a radical prostatectomy, with the preferable option of performing the radical prostatectomy and inguinal hernia repair in the same procedure. Alternatively, a Lichtenstein repair can be performed.

Prospective Validation of Gallium-68 Prostate Specific Membrane Antigen-Positron Emission Tomography/Computerized Tomography for Primary Staging of Prostate Cancer.

PURPOSE: Prospective validation of 68Ga prostate specific membrane antigen positron emission tomography/computerized tomography is lacking in initial staging of prostate cancer. In this study we evaluated the diagnostic accuracy of 68Ga prostate specific membrane antigen positron emission tomography/computerized tomography for detecting lymph node metastasis in patients with intermediate-high risk prostate cancer. MATERIALS AND METHODS: Patients with newly diagnosed prostate cancer and negative bone scan findings at greater than 10% MSKCC (Memorial Sloan Kettering Cancer Center) risk for lymph node metastasis were prospectively included in study from October 2017 to October 2018. In candidates for extended pelvic lymph node dissection 68Ga prostate specific membrane antigen positron emission tomography/computerized tomography was performed prior to planned surgery. Scan results were evaluated in a second tumor board meeting to assess a potential change of management. Sensitivity, specificity, and positive and negative predictive value for detecting lymph node metastasis were calculated per patient and per resection template using histopathology as the reference. A positron emission tomography based change of management was also reported. RESULTS: A total of 103 patients were eligible for analysis and 97 extended pelvic lymph node dissections were performed. In 41 patients (42.3%) there was a total of 85 lymph node metastases. Positron emission tomography was positive in 17 patients, resulting in 41.5% patient based sensitivity (95% CI 26.7-57.8) for detecting lymph node metastasis. The patient based specificity rate was 90.9% (95% CI 79.3-96.6), and positive and negative predictive values were 77.3% (95% CI 54.2-91.3) and 67.6% (95% CI 55.6-77.7), respectively. A positron emission tomography based change of treatment was observed in 13 patients (12.6%). CONCLUSIONS: In patients with newly diagnosed prostate cancer at greater than 10% MSKCC risk for lymph node involvement 68Ga prostate specific membrane antigen positron emission tomography/computerized tomography detected lymph node metastasis with high specificity and moderate sensitivity. This led to a treatment change in 12.6% of patients.

Lymphovascular invasion and presence of embryonal carcinoma as risk factors for occult metastatic disease in clinical stage I nonseminomatous germ cell tumour: a systematic review and meta-analysis.

OBJECTIVE: To systematically review the literature on the prognostic value of lymphovascular invasion (LVI) and embryonal carcinoma (EC) for occult metastatic disease in clinical stage I nonseminomatous germ cell tumour (CS I NSGCT). MATERIALS AND METHODS: The PubMed, Embase (OVID) and SCOPUS databases were searched up to March 2019. Studies reporting on the association between LVI and/or EC and occult metastatic disease were considered for inclusion. The quality and risk of bias were evaluated by the Quality in Prognosis Studies tool. RESULTS: We screened 5287 abstracts and 207 full-text articles. We included 35 studies in the narrative synthesis and 24 studies in a meta-analysis. LVI showed the strongest effect. Pooled rates of occult metastasis were 47.5% and 16.9% for LVI-positive and LVI-negative patients, respectively (odds ratio [OR] 4.33, 95% confidence interval [CI] 3.55-5.30; P < 0.001). Pooled rates of occult metastasis were 33.2% for EC presence and 16.2% for EC absence (OR 2.49, 95% CI 1.64-3.77; P < 0.001). Pooled rates of occult metastasis were 40.0% for EC >50% and 20.0% for EC <50% (OR 2.62, 95% CI 1.93-3.56; P < 0.001). CONCLUSIONS: LVI is the strongest risk factor for relapse. The prognostic value of EC is high, but there is no common agreement on how to define this risk factor. Both EC presence and EC >50% have similar ORs for occult metastasis. This shows that the assessment of EC presence is sufficient for the classification of EC.

Sentinel node biopsy in clinical stage I testicular cancer enables early detection of occult metastatic disease.

OBJECTIVES: To report the long-term results of the sentinel node (SN) approach in patients with clinical stage I testicular tumours in our facility. PATIENTS AND METHODS: We conducted an analysis of 27 consecutive patients suspected of clinical stage I testicular germ cell tumour (TGCT) and treated with an SN procedure at our tertiary referral centre. SNs were identified using lymphoscintigraphy with or without single-photo-emission computed tomography with CT (SPECT/CT). Patients underwent laparoscopic retroperitoneal SN excision with inguinal orchiectomy. Patients with a tumour-positive SN underwent adjuvant treatment. Follow-up was conducted according to then-current guidelines. RESULTS: In two patients, no SNs were visualized on scintigraphy. In the remaining 25 patients, a median (range) of 3 (1-4) SNs per patient were removed. Two patients showed no malignancy on histopathological examination of the testis. Of the 23 patients diagnosed with TGCT (16 seminomas, seven non-seminomas), three (13.0%) had occult metastatic disease. All 23 patients were without evidence of disease at a median (range) follow-up of 63.9 (29.0-143.4) months. CONCLUSION: The SN procedure allows early identification of patients with occult metastatic disease in clinical stage I TGCT, enabling early treatment.

Neoadjuvant Chemotherapy for Muscle-Invasive Bladder Cancer: A Systematic Review and Two-Step Meta-Analysis.

BACKGROUND: Platinum-based neoadjuvant chemotherapy has been shown to improve survival outcomes in muscle-invasive bladder cancer patients. We performed a systematic review and meta-analysis to provide updated results of previous findings. We also summarized published data to compare clinical outcomes of methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) versus gemcitabine and cisplatin/carboplatin (GC) in the neoadjuvant setting. METHODS: A meta-analysis of 15 randomized clinical trials was performed to compare neoadjuvant chemotherapy plus local treatment with the same local treatment alone. Because no randomized trials have investigated MVAC versus GC in the neoadjuvant setting, a meta-analysis of 13 retrospective studies was performed to compare MVAC with GC. RESULTS: A total of 3,285 patients were included in 15 randomized clinical trials. There was a significant overall survival (OS) benefit associated with cisplatin-based neoadjuvant chemotherapy (hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.79-0.96). A total of 1,766 patients were included in 13 retrospective studies. There was no significant difference in pathological complete response between MVAC and GC. However, GC was associated with a significantly reduced overall survival (HR, 1.26; 95% CI, 1.01-1.57). After excluding carboplatin data, GC still seemed to be inferior to MVAC in OS (HR, 1.31; 95% CI, 0.99-1.74), but the difference was no longer statistically significant. CONCLUSION: These results support the use of cisplatin-based combination neoadjuvant chemotherapy in muscle-invasive bladder cancer. Although GC and MVAC had similar treatment response rates, the different survival outcome observed in this study requires further investigation. IMPLICATIONS FOR PRACTICE: Platinum-based neoadjuvant chemotherapy (NCT) has been shown to improve survival outcomes in muscle-invasive bladder cancer (MIBC) patients, but the optimal neoadjuvant regimen has not been established. Methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) and gemcitabine and cisplatin/carboplatin (GC) are two of the most commonly used chemotherapy regimens in modern oncology. In this two-step meta-analysis, an updated and more precise estimate of the survival benefit of cisplatin-based NCT in MIBC is provided. This study also demonstrated that MVAC might have superior overall survival compared with GC (with or without carboplatin data) in the neoadjuvant setting. The findings suggest that NCT should be standard care in MIBC, and MVAC could be the preferred neoadjuvant regimen.

Clinical Relevance of Incidental Prostatic Lesions on FDG-Positron Emission Tomography/Computerized Tomography-Should Patients Receive Further Evaluation?

PURPOSE: FDG ((18)F-fluoro-2-deoxy-D-glucose)-PET/CT (positron emission tomography)/(computerized tomography) is a widely used diagnostic tool for whole body imaging. Incidental prostatic uptake is often found on FDG-PET/CT. The objective of this study was to determine the clinical relevance of incidental prostatic uptake on FDG-PET/CT. MATERIALS AND METHODS: We analyzed 108 consecutive male patients with bladder cancer who underwent FDG-PET/CT and subsequently radical cystoprostatectomy between May 2009 and November 2014. PET/CT scans were blindly reviewed by a dedicated nuclear medicine physician for incidental prostatic FDG uptake. If present, the maximum standardized uptake value was determined. Subsequently incidental prostatic uptake was categorized as suspect, indeterminate or nonsuspect for prostate cancer. RESULTS: Incidental prostatic uptake was present in 43 of 108 patients (40%). Of these 43 patients 13 (30%) had occult prostate cancer in cystoprostatectomy specimens. Overall prostate cancer was found in 25 of 108 specimens (23%). If all incidental prostatic uptake was regarded as prostate cancer, the sensitivity and specificity of FDG-PET/CT for prostate cancer detection were 52% and 64%, respectively. Positive and negative predictive values were 30% and 82%, respectively. If only lesions labeled suspect or indeterminate were regarded as prostate cancer, sensitivity, specificity, and positive and negative predictive values were 32%, 76%, 29% and 79%, respectively. Categorizing indeterminate lesions as nonprostate cancer did not improve diagnostic accuracy. Gleason score did not correlate with maximum standardized uptake value or serum prostate specific antigen. CONCLUSIONS: Incidental prostatic uptake on FDG-PET/CT has a low positive predictive value for prostate cancer. An attempt to classify lesions as suspect or nonsuspect did not increase diagnostic accuracy. Based on these results physicians should be cautious about applying invasive diagnostic methods to detect prostate cancer in case of incidental prostatic uptake on FDG-PET/CT.