Urban relatives ameliorate survival disparities for genitourinary cancer in rural patients.

INTRODUCTION: Patients living in rural areas have worse cancer-specific outcomes. This study examines the effect of family-based social capital on genitourinary cancer survival. We hypothesized that rural patients with urban relatives have improved survival relative to rural patients without urban family. METHODS: We examined rural and urban based Utah individuals diagnosed with genitourinary cancers between 1968 and 2018. Familial networks were determined using the Utah Population Database. Patients and relatives were classified as rural or urban based on 2010 rural-urban commuting area codes. Overall survival was analyzed using Cox proportional hazards models. RESULTS: We identified 24,746 patients with genitourinary cancer with a median follow-up of 8.72 years. Rural cancer patients without an urban relative had the worst outcomes with cancer-specific survival hazard ratios (HRs) at 5 and 10 years of 1.33 (95% CI 1.10-1.62) and 1.46 (95% CI 1.24-1.73), respectively relative to urban patients. Rural patients with urban first-degree relatives had improved survival with 5- and 10-year survival HRs of 1.21 (95% CI 1.06-1.40) and 1.16 (95% CI 1.03-1.31), respectively. CONCLUSIONS: Our findings suggest rural patients who have been diagnosed with a genitourinary cancer have improved survival when having relatives in urban centers relative to rural patients without urban relatives. Further research is needed to better understand the mechanisms through which having an urban family member contributes to improved cancer outcomes for rural patients. Better characterization of this affect may help inform policies to reduce urban-rural cancer disparities.

Metastatic Sites in Rare Genitourinary Malignancies and Primary Cancer Sites in Genitourinary Organ Metastases: A Secondary Analysis Using the Japanese Pathological Autopsy Registry Database.

Background: The epidemiology of metastases from rare genitourinary cancer and metastases to genitourinary organs from other primary neoplasms remains poorly understood. Objective: To investigate the epidemiology of rare genitourinary metastases from rare genitourinary organ-type cancer and to genitourinary organs using data from a large national autopsy registry in Japan. Design setting and participants: A secondary analysis of the data reported in the Annual of the Pathological Autopsy Cases in Japan and the Japanese Mortality Database from 1993 to 2020 was performed. Outcome measurements and statistical analysis: Via a retrospective epidemiologic analysis, we evaluated the frequency (probability of occurrence [number per person]) and proportion (percentage) of metastases from upper urinary tract, adrenal, testicular, urethral, and penile cancers. Moreover, the sites of primary tumors metastasizing to genitourinary organs were examined. Results and limitations: In Japan, the mortality rate of upper urinary tract cancer is increasing rapidly. In the integrated database with 365 099 autopsies and 835 959 metastatic organs, the major metastatic sites (range of frequency ratios) of rare genitourinary organ-type cancers were the lungs (0.38-0.47), liver (0.21-0.56), bone (0.16-0.33), adrenal gland (0.10-0.20), peritoneum (0.0-0.16), and kidneys (0.07-0.22). The major primary sites (range of proportions) of genitourinary organ metastases were the respiratory tract (5.6-34.0%), stomach (4.7-27.0%), hematologic site (0.9-24.9%), lymphoid (2.4-22.2%), bladder (0.8-20.0%), prostate (0.7-14.1%), rectal (2.0-11.7%), and pancreas (2.6-11.0%). The cancers with a high likelihood of genitourinary metastasis were respiratory and stomach cancers. However, the study lacked individual-level information, and there might be a concomitant selection bias in this autopsy study. Conclusions: This large-scale autopsy database analysis identified the epidemiology of metastasis from rare genitourinary organ-type cancer and the origins of metastasis to genitourinary organs. Patient summary: This study provides valuable metastatic epidemiologic data and clinical information that are fundamental to the mechanisms of genitourinary metastasis.

Interactive training workshop to improve prostate mpMRI knowledge: results from the ESOR Nicholas Gourtsoyiannis teaching fellowship.

PURPOSE: Prostate MRI is established for the investigation of patients presenting with suspected early prostate cancer. Outcomes are dependent on both image quality and interpretation. This study assessed the impact of an educational intervention on participants' theoretical knowledge of the technique. METHODS: Eighty-one clinicians from two centers with varying experience in prostate MRI participated. Baseline knowledge was assessed with 10 written and image-based multiple-choice questions (MCQs) prior to a course including didactic lectures and hands-on interactive workshops on prostate MRI interpretation. Post-course, participants completed a second 10-question MCQ test, matched by format, themes, and difficulty, to assess for any improvement in knowledge and performance. Results were assessed using the Wilcoxon rank sum test, and the Wilcoxon signed-rank test for paired data. RESULTS: Thirty-nine participants, including 25/49 (51.0%) and 14/32 (43.8%) at each center completed both assessments, with their results used for subsequent evaluation. Overall, there was a significant improvement from pre- (4.92 ± 2.41) to post-course scores (6.77 ± 1.46), p < 0.001 and at both Copenhagen (5.92 ± 2.25 to 7.36 ± 1.25) and Toronto (3.14 ± 1.51 to 5.71 ± 1.20); p = 0.005 and p = 0.002, respectively. Participants with no prostate MRI experience showed the greatest improvement (3.77 ± 1.97 to 6.18 ± 1.5, p < 0.001), followed by intermediate level (< 500 MRIs reported) experience (6.18 ± 1.99 to 7.46 ± 1.13, p = 0.058), then advanced (> 500 MRIs reported) experience (6.83 ± 2.48 to 7.67 ± 0.82, p = 0.339). CONCLUSIONS: A dedicated prostate MRI teaching course combining didactic lectures and hands-on workshops significantly improved short-term theoretical knowledge of the technique for clinicians with differing levels of experience. CRITICAL RELEVANCE STATEMENT: A dedicated teaching course significantly improved theoretical knowledge of the technique particularly for clinicians with less reporting experience and a lower baseline knowledge. The multiple-choice questions format mapped improved performance and may be considered as part of future MRI certification initiatives. KEY POINTS: • Prostate MRI knowledge is important for image interpretation and optimizing acquisition sequences. • A dedicated teaching course significantly improved theoretical knowledge of the technique. • Improved performance was more apparent in clinicians with less reporting experience and a lower baseline knowledge.

Can Only the Shape Feature in Radiomics Help Machine Learning Show That Bladder Cancer Has Invaded Muscles?

OBJECTIVES: The presence of muscle invasion is an important factor in establishing a treatment strategy for bladder cancer (BCa). The aim of this study is to reveal the diagnostic performance of radiomic shape features in predicting muscle-invasive BCa. METHODS: In this study, 60 patients with histologically proven BCa who underwent a preoperative MRI were retrospectively recruited. The whole tumor volume was segmented on apparent diffusion coefficient (ADC) maps and T2W images. Afterward, the shape features of the volume of interest were extracted using PyRadiomics. Machine learning classification was performed using statistically different shape features in MATLAB® (The MathWorks, Inc., Natick, Massachusetts, United States). RESULTS: The findings revealed that 27 bladder cancer patients had muscle invasion, while 33 had superficial bladder cancer (53 men and seven women; mean age: 62±14). Surface area, volume, and relevant features were significantly greater in the invasive group than in the non-invasive group based on the ADC maps (P<0.05). Superficial bladder cancer had a more spherical form compared to invasive bladder cancer (P=0.05) with both imaging modalities. Flatness and elongation did not differ significantly between groups with either modality (P>0.05). Logistic regression had the highest accuracy of 83.3% (sensitivity 82.8%, specificity 84%) in assessing invasion based on the shape features of ADC maps, while K-nearest neighbors had the highest accuracy of 78.2% (sensitivity 79.1%, specificity 69.4%) in assessing invasion based on T2W images. CONCLUSIONS: Shape features can be helpful in predicting muscle invasion in bladder cancer using machine learning methods.

Final Results of a Phase I Trial of WST-11 (TOOKAD Soluble) Vascular-targeted Photodynamic Therapy for Upper Tract Urothelial Carcinoma.

PURPOSE: Vascular-targeted photodynamic therapy with the intravascular photosensitizing agent padeliporfin (WST-11/TOOKAD-Soluble) has demonstrated therapeutic efficacy as an ablative treatment for localized cancer with potential adaptation for endoscopic management of upper tract urothelial carcinoma. This Phase I trial (NCT03617003) evaluated the safety of vascular-targeted photodynamic therapy with WST-11 in upper tract urothelial carcinoma. MATERIALS AND METHODS: Nineteen patients underwent up to 2 endoscopic vascular-targeted photodynamic therapy treatments, with follow-up for up to 6 months. Patients who had residual or recurrent upper tract urothelial carcinoma (any grade/size) failing prior endoscopic treatment or unable or unwilling to undergo surgical resection were eligible for inclusion. The primary endpoint was to identify the maximally tolerated dose of laser light fluence. A dose escalation model was employed, with increasing light fluence (100-200 mW/cm) using a modified continual reassessment method. The secondary endpoint was treatment efficacy, defined by absence of visible tumor and negative urine cytology 30 days posttreatment. RESULTS: Fourteen (74%) patients received the maximally tolerated dose of 200 mW/cm, 2 (11%) of whom experienced a dose-limiting toxicity. The initial 30-day treatment response rate was 94% (50% complete, 44% partial). Eight patients underwent a second treatment, with a final observed 68% complete response rate. Leading toxicities were flank pain (79%) and hematuria (84%), which were transient. No ureteral strictures associated with treatment were identified during follow-up. CONCLUSIONS: Vascular-targeted photodynamic therapy with WST-11 has an acceptable safety profile with strong potential as an effective, kidney-sparing endoscopic management option for upper tract urothelial carcinoma. The recently initiated multicenter Phase 3 ENLIGHTED trial (NCT04620239) is expected to provide further evidence on this therapy.

Promoting the use of the PI-QUAL score for prostate MRI quality: results from the ESOR Nicholas Gourtsoyiannis teaching fellowship.

OBJECTIVES: The Prostate Imaging Quality (PI-QUAL) score is a new metric to evaluate the diagnostic quality of multiparametric magnetic resonance imaging (MRI) of the prostate. This study assesses the impact of an intervention, namely a prostate MRI quality training lecture, on the participant's ability to apply PI-QUAL. METHODS: Sixteen participants (radiologists, urologists, physicists, and computer scientists) of varying experience in reviewing diagnostic prostate MRI all assessed the image quality of ten examinations from different vendors and machines. Then, they attended a dedicated lecture followed by a hands-on workshop on MRI quality assessment using the PI-QUAL score. Five scans assessed by the participants were evaluated in the workshop using the PI-QUAL score for teaching purposes. After the course, the same participants evaluated the image quality of a new set of ten scans applying the PI-QUAL score. Results were assessed using receiver operating characteristic analysis. The reference standard was the PI-QUAL score assessed by one of the developers of PI-QUAL. RESULTS: There was a significant improvement in average area under the curve for the evaluation of image quality from baseline (0.59 [95 % confidence intervals: 0.50-0.66]) to post-teaching (0.96 [0.92-0.98]), an improvement of 0.37 [0.21-0.41] (p < 0.001). CONCLUSIONS: A teaching course (dedicated lecture + hands-on workshop) on PI-QUAL significantly improved the application of this scoring system to assess the quality of prostate MRI examinations. KEY POINTS: • A significant improvement in the application of PI-QUAL for the assessment of prostate MR image quality was observed after an educational intervention. • Appropriate training on image quality can be delivered to those involved in the acquisition and interpretation of prostate MRI. • Further investigation will be needed to understand the impact on improving the acquisition of high-quality diagnostic prostate MR examinations.

Clinical molecular diagnosis of breast and female reproductive system tumors / 中华检验医学杂志

The gynecological tumours such as Breast cancer or female reproductive system tumors are a serious threat to female health. With the development of molecular diagnosis, the genomic changes of gynecological tumours have been revealed continuously, and the diagnosis and treatment modes of tumors have gradually changed. The detection of molecular targets which potentially participated in the transformation or progress of disease has become an important section of the management of female reproductive tumors, and accurate identification of molecular targets of tumors plays an important role in disease diagnosis, monitoring of metastasis, prediction of recurrence and treatment. This review briefly discusses the risk assessment, molecular typing, targeted therapy, toxic and side effects, and prognosis evaluation of breast and female reproductive system tumors by molecular diagnosis.

Spermatic cord anastomosing hemangioma mimicking a malignant inguinal tumor: A case report and literature review.

Background: Anastomosing hemangioma (AH) is a rare vascular tumor and occurs in various organs. It is difficult to distinguish AH from malignant tumors even through multimodal imaging examination. AH located in the inguinal region is even rare. We present the diagnosis and treatment of a patient with spermatic cord AH in detail and conduct a literature review. Case Report: An 84-year-old Chinese man had swelling pain in his right scrotum. A hard and fixed mass was palpable in the right inguinal region. Preoperative radiological examination considered it a neurogenic or vascular tumor. Malignant soft tissue sarcoma could not be excluded. He underwent radical inguinal right orchiectomy under intraspinal anesthesia. The diagnosis of spermatic cord AH was confirmed by pathological examination. The patient recovered uneventfully and remained disease-free during an 18-month follow-up. Conclusion: Spermatic cord AH is quite rare and could be misdiagnosed as a malignant tumor. Pathological evidence might be necessary. The optimal choice of treatment should be determined through a comprehensive assessment of both tumor and patient factors.

Promoting the use of the PRECISE score for prostate MRI during active surveillance: results from the ESOR Nicholas Gourtsoyiannis teaching fellowship.

OBJECTIVES: The PRECISE criteria for serial multiparametric magnetic resonance imaging (MRI) of the prostate during active surveillance recommend the use of a dedicated scoring system (PRECISE score) to assess the likelihood of clinically significant radiological change. This pilot study assesses the effect of an interactive teaching course on prostate MRI during active surveillance in assessing radiological change in serial imaging. METHODS: Eleven radiology fellows and registrars with different experience in prostate MRI reading participated in a dedicated teaching course where they initially evaluated radiological change (based on their previous training in prostate MRI reading) independently in fifteen patients on active surveillance (baseline and follow-up scan), and then attended a lecture on the PRECISE score. The initial scans were reviewed for teaching purposes and afterwards the participants re-assessed the degree of radiological change in a new set of images (from fifteen different patients) applying the PRECISE score. Receiver operating characteristic analysis was performed. Confirmatory biopsies and PRECISE scores given in consensus by two radiologists (involved in the original draft of the PRECISE score) were the reference standard. RESULTS: There was a significant improvement in the average area under the curve (AUC) for the assessment of radiological change from baseline (AUC: 0.60 [Confidence Intervals: 0.51-0.69] to post-teaching (AUC: 0.77 [0.70-0.84]). This was an improvement of 0.17 [0.016-0.28] (p = 0.004). CONCLUSIONS: A dedicated teaching course on the use of the PRECISE score improves the accuracy in the assessment of radiological change in serial MRI of the prostate.

Case report and literature review: Primary leiomyosarcoma of the penis.

Background: Leiomyosarcoma (LMS) is a malignant spindle-cell mesenchymal tumor originating from the smooth muscle cells, which mostly affects soft tissues and abdominopelvic organs over extremities. Primary LMS of the penis is a relatively uncommon mesenchymal tissue disease and a poorly understood condition. Case Report: A 69-year-old man presented with a growing, painless mass protruding from the penis. The irregularly lobulated lump was roughly 3 cm × 2.5 cm, with a smooth surface, tough texture, distinct boundary, and no tenderness. It was determined to be a penile tumor during the preoperative radiological evaluation. The patient underwent resection of the penile mass, followed by extended resection in the second operation. The diagnosis of LMS was verified by pathological examination. During a 20-month follow-up, the patient made a smooth recovery and remained disease-free. Conclusion: An immunohistochemical examination is essential for rendering this rare diagnosis. Radical excision of tumor lesions with negative cut margins is guaranteed to be the best treatment for primary penile LMS. Close follow-up should be provided due to the high rate of local recurrence.

Mesenchymal stromal/stem cell-derived exosomes and genitourinary cancers: A mini review.

Mesenchymal stromal/stem cell- (MSC-) derived exosomes are gaining popularity for their involvement in tissue repair and repressing various tumors through extensive patterns. Nevertheless, the impact of extracellular vesicles produced by stem cells on tumor formation and progression is controversial and seems to depend on several factors. The utilization of MSCs' various capabilities in urogenital neoplasms is widely regarded as a potential future therapeutic as well. These genitourinary neoplasms include prostatic neoplasms, ovarian neoplasms, cervical neoplasms, endometrial neoplasms, bladder neoplasms, and renal cell neoplasms. The present study has concentrated on the most recent information on genitourinary neoplasms employing MSCs derived exosomes' many capabilities, such as delivering effective RNAs, extensive tissue compatibility, and specificity with tumor identification without inherent limitations of cell therapy.

Inter-reader agreement of the PI-QUAL score for prostate MRI quality in the NeuroSAFE PROOF trial.

OBJECTIVES: The Prostate Imaging Quality (PI-QUAL) score assesses the quality of multiparametric MRI (mpMRI). A score of 1 means all sequences are below the minimum standard of diagnostic quality, 3 implies that the scan is of sufficient diagnostic quality, and 5 means that all three sequences are of optimal diagnostic quality. We investigated the inter-reader reproducibility of the PI-QUAL score in patients enrolled in the NeuroSAFE PROOF trial. METHODS: We analysed the scans of 103 patients on different MR systems and vendors from 12 different hospitals. Two dedicated radiologists highly experienced in prostate mpMRI independently assessed the PI-QUAL score for each scan. Interobserver agreement was assessed using Cohen's kappa with standard quadratic weighting (κw) and percent agreement. RESULTS: The agreement for each single PI-QUAL score was strong (κw = 0.85 and percent agreement = 84%). A similar agreement (κw = 0.82 and percent agreement = 84%) was observed when the scans were clustered into three groups (PI-QUAL 1-2 vs PI-QUAL 3 vs PI-QUAL 4-5). The agreement in terms of diagnostic quality for each single sequence was highest for T2-weighted imaging (92/103 scans; 89%), followed by dynamic contrast-enhanced sequences (91/103; 88%) and diffusion-weighted imaging (80/103; 78%). CONCLUSION: We observed strong reproducibility in the assessment of PI-QUAL between two radiologists with high expertise in prostate mpMRI. At present, PI-QUAL offers clinicians the only available tool for evaluating and reporting the quality of prostate mpMRI in a systematic manner but further refinements of this scoring system are warranted. KEY POINTS: • Inter-reader agreement for each single Prostate Imaging Quality (PI-QUAL) score (i.e., PI-QUAL 1 to PI-QUAL 5) was strong, with weighted kappa = 0.85 (95% confidence intervals: 0.51 - 1) and percent agreement = 84%. • Interobserver agreement was strong when the scans were clustered into three groups according to the ability (or not) to rule in and to rule out clinically significant prostate cancer (i.e., PI-QUAL 1-2 vs PI-QUAL 3 vs PI-QUAL 4-5), with weighted kappa = 0.82 (95% confidence intervals: 0.68 - 0.96) and percent agreement = 84%. • T2-weighted acquisitions were the most compliant with the Prostate Imaging Reporting and Data System (PI-RADS) v. 2.0 technical recommendations and were the sequences of highest diagnostic quality for both readers in 95/103 (92%) scans, followed by dynamic contrast enhanced acquisition with 81/103 (79%) scans and lastly by diffusion-weighted imaging with 79/103 (77%) scans.

Oral microbiota in the oral-genitourinary axis: identifying periodontitis as a potential risk of genitourinary cancers.

Periodontitis has been proposed as a novel risk factor of genitourinary cancers: although periodontitis and genitourinary cancers are two totally distinct types of disorders, epidemiological and clinical studies, have established associations between them. Dysbiosis of oral microbiota has already been established as a major factor contributing to periodontitis. Recent emerging epidemiological evidence and the detection of oral microbiota in genitourinary organs indicate the presence of an oral-genitourinary axis and oral microbiota may be involved in the pathogenesis of genitourinary cancers. Therefore, oral microbiota provides the bridge between periodontitis and genitourinary cancers. We have carried out this narrative review which summarizes epidemiological studies exploring the association between periodontitis and genitourinary cancers. We have also highlighted the current evidence demonstrating the capacity of oral microbiota to regulate almost all hallmarks of cancer, and proposed the potential mechanisms of oral microbiota in the development of genitourinary cancers.

[Osteoclast-Like giant cell bladder carcinoma: Case report]. / Carcinoma de vejiga de células gigantes parecidas a osteoclasto: reporte de caso.

BACKGROUND: Osteoclast-like giant cell bladder carcinomas are an extremely unusual and aggressive histological subtype of urothelial carcinomas. Only 30 cases are reported in the international literature. CLINICAL CASE: A 79-year-old male patient attended our Urology department for a six-month history of macroscopic hematuria. As part of its diagnostic protocol, a CT scan of the abdomen and pelvis with elimination phase was performed, finding a 12-mm filling defect at the level of the posterior wall of the bladder; subsequently, a cystoscopy was performed confirming the presence of a 1.5 cm bladder tumor, which was completely resected. Pathology analysis with hematoxylin and eosin staining revealed a composition of mononuclear cells and osteoclast-like giant cells; immunohistochemistry was positive for epithelial markers CK AE-1 / AE-3, EMA, P53 and CD68. CONCLUSIONS: These tumors are extremely unusual and aggressive. The only diagnostic method is through immunohistochemistry where the presence of epithelial markers for urothelium in neoplastic cells is confirmed. Radical surgical treatment is recommended and to date there is no proven effective adjuvant treatment. Its median overall survival is 15 months.

INTRODUCCIÓN: los carcinomas de vejiga de células gigantes parecidas a osteoclasto son un subtipo histológico extremadamente inusual y agresivo de los carcinomas uroteliales. Solamente se encuentran reportados 30 casos en la literatura internacional. CASO CLÍNICO: un paciente masculino de 79 años acudió a valoración a nuestro departamento de Urología por un cuadro de hematuria macroscópica de seis meses de evolución. Como parte de su protocolo diagnóstico se realizó una TC de abdomen y pelvis con fase de eliminación, encontrando un defecto de llenado de 12 mm a nivel de la pared posterior de la vejiga; posteriormente se realizó una cistoscopia confirmando la presencia de un tumor vesical de 1.5 cm, el cuál fue resecado en su totalidad. El análisis por Patología con tinción de hematoxilina y eosina reveló una composición por células mononucleares y células gigantes parecidas a osteoclasto; la inmunohistoquímica fue positiva para marcadores epiteliales CK AE-1/AE-3, EMA, P53 y CD68. CONCLUSIONES: estos tumores son extremadamente inusuales y agresivos. El único método diagnóstico es a través de inmunohistoquímica en donde se confirme la presencia de marcadores epiteliales para urotelio en las células neoplásicas. Se recomienda un tratamiento quirúrgico radical y a la fecha no existe un tratamiento adyuvante efectivo demostrado. Su supervivencia media global es de 15 meses.

Which criteria can be used to predict benignity in solid renal lesions lower-equal to 2 cm?

PURPOSE: To evaluate magnetic resonance imaging (MRI) criteria of solid renal lesions lower-equal to 2 cm to differentiate benign and malignant tumors, using histopathology as gold standard. METHODS: Three radiologists independently evaluated objective and subjective MRI criteria of focal renal lesions. A total of 105 nodules of patients who had MRI and histopathological results in our institution were included. Subjective criteria evaluated were signal on T2-weighted imaging, presence of microscopic and macroscopic fat, hemosiderin, hemorrhage, central scar, segmented inversion enhancement and enhancement type; objective criteria were gender, ADC value, heterogeneity on T2-weighted imaging and proportion of enhancement in late post-contrast phases. Finally, the readers classified the lesions in probably benign or malignant. Interobserver agreement was evaluated by the Gwet method, and the quantitative variables by intraclass correlation coefficients. To adjust the predictive model, the logistic regression model was used considering the benignity variable as outcome. RESULTS: A total of 26 nodules (24.5%) were benign and 79 (75.2%) were malignant, with size ranging from 7 to 20 mm (median: 14 mm). The most frequent subtype was papillary renal cell carcinoma (RCC) (35.2%), followed by clear-cell RCC (24.8%) and oncocytoma (12.4%). The univariate and multivariate analysis showed, among all categories evaluated, that microscopic fat (p: 0.072), intermediate (p: 0.004) and hyper-enhancement (p: 0.031) and female sex (p: 0.0047) had the best outcome for benignity, within odds ratios of 4.29, 5.75, 4.07 and 2.86, respectively. CONCLUSION: In small solid renal lesions lower-equal to 2 cm, microscopic fat, moderate and hyper-enhancement and female sex were associated with benignity.

The Origin of Tumor DNA in Urine of Urogenital Cancer Patients: Local Shedding and Transrenal Excretion.

In urogenital cancers, urine as a liquid biopsy for non-invasive cancer detection holds great promise for future clinical application. Their anatomical position allows for the local shedding of tumor DNA, but recent data indicate that tumor DNA in urine might also result from transrenal excretion. This study aims to assess the origin of tumor-associated DNA in the urine of 5 bladder and 25 cervical cancer patients. Besides natural voided urine, paired urine samples were collected in which contact with the local tumor was circumvented to bypass local shedding. The latter concerned nephrostomy urine in bladder cancer patients, and catheter urine in cervical cancer patients. Methylation levels of GHSR, SST, and ZIC1 were determined using paired bladder tumor tissues and cervical scrapes as a reference. Urinary methylation levels were compared to natural voided urine of matched controls. To support methylation results, mutation analysis was performed in urine and tissue samples of bladder cancer patients. Increased methylation levels were not only found in natural voided urine from bladder and cervical cancer patients, but also in the corresponding nephrostomy and catheter urine. DNA mutations detected in bladder tumor tissues were also detectable in all paired natural voided urine as well as in a subset of nephrostomy urine. These results provide the first evidence that the suitability of urine as a liquid biopsy for urogenital cancers relies both on the local shedding of tumor cells and cell fragments, as well as the transrenal excretion of tumor DNA into the urine.

Natural history of prostate cancer on active surveillance: stratification by MRI using the PRECISE recommendations in a UK cohort.

OBJECTIVES: The PRECISE recommendations for magnetic resonance imaging (MRI) in patients on active surveillance (AS) for prostate cancer (PCa) include repeated measurement of each lesion, and attribution of a PRECISE radiological progression score for the likelihood of clinically significant change over time. We aimed to compare the PRECISE score with clinical progression in patients who are managed using an MRI-led AS protocol. METHODS: A total of 553 patients on AS for low- and intermediate-risk PCa (up to Gleason score 3 + 4) who had two or more MRI scans performed between December 2005 and January 2020 were included. Overall, 2161 scans were retrospectively re-reported by a dedicated radiologist to give a PI-RADS v2 score for each scan and assess the PRECISE score for each follow-up scan. Clinical progression was defined by histological progression to ≥ Gleason score 4 + 3 (Gleason Grade Group 3) and/or initiation of active treatment. Progression-free survival was assessed using Kaplan-Meier curves and log-rank test was used to assess differences between curves. RESULTS: Overall, 165/553 (30%) patients experienced the primary outcome of clinical progression (median follow-up, 74.5 months; interquartile ranges, 53-98). Of all patients, 313/553 (57%) did not show radiological progression on MRI (PRECISE 1-3), of which 296/313 (95%) had also no clinical progression. Of the remaining 240/553 patients (43%) with radiological progression on MRI (PRECISE 4-5), 146/240 (61%) experienced clinical progression (p < 0.0001). Patients with radiological progression on MRI (PRECISE 4-5) showed a trend to an increase in PSA density. CONCLUSIONS: Patients without radiological progression on MRI (PRECISE 1-3) during AS had a very low likelihood of clinical progression and many could avoid routine re-biopsy. KEY POINTS: • Patients without radiological progression on MRI (PRECISE 1-3) during AS had a very low likelihood of clinical progression and many could avoid routine re-biopsy. • Clinical progression was almost always detectable in patients with radiological progression on MRI (PRECISE 4-5) during AS. • Patients with radiological progression on MRI (PRECISE 4-5) during AS showed a trend to an increase in PSA density.