ABSTRACT
In the recent decade, analysis of circulating tumor DNA (ctDNA) has improved cancer care by allowing for rapid detection of actionable molecular targets. A new generation of circulating DNA tests is now becoming available commercially. These tests are characterized by a superior limit of detection of 0.01% vaF or better, allowing for the detection of radiologically occult molecular residual disease (MRD). MRD tests have the potential to revolutionize neoadjuvant and adjuvant treatment. In addition, these tests can be used as tumor markers to assess disease response. We reviewed the current evidence for the use of high-sensitivity MRD assays with particular focus on the genitourinary tumors. Multiple studies have now been reported in urothelial, renal, and recently testicular carcinoma. We find that the sensitivity varies across tumor types in the adjuvant setting and may reach a high of 100% in urothelial cancer. Specificity in tumor-informed MRD appears to be preserved across tumor types (98%-100%). Several trials are now prospectively validating MRD testing in biomarker integral studies, mainly in urothelial carcinoma.
Subject(s)
Biomarkers, Tumor , Circulating Tumor DNA , Urogenital Neoplasms , Humans , Urogenital Neoplasms/genetics , Urogenital Neoplasms/diagnosis , Urogenital Neoplasms/blood , Urogenital Neoplasms/pathology , Circulating Tumor DNA/blood , Circulating Tumor DNA/genetics , Biomarkers, Tumor/genetics , Biomarkers, Tumor/blood , Neoplasm, Residual/diagnosis , Sensitivity and Specificity , MaleABSTRACT
Juxtaglomerular cell tumor (JGCT) is a rare neoplasm, part of the family of mesenchymal tumors of the kidney. Although the pathophysiological and clinical correlates of JGCT are well known, as these tumors are an important cause of early-onset arterial hypertension refractory to medical treatment, their molecular background is unknown, with only few small studies investigating their karyotype. Herein we describe a multi-institutional cohort of JGCTs diagnosed by experienced genitourinary pathologists, evaluating clinical presentation and outcome, morphologic diversity, and, importantly, the molecular features. Ten JGCTs were collected from 9 institutions, studied by immunohistochemistry, and submitted to whole exome sequencing. Our findings highlight the morphologic heterogeneity of JGCT, which can mimic several kidney tumor entities. Three cases showed concerning histologic features, but the patient course was unremarkable, which suggests that morphologic evaluation alone cannot reliably predict the clinical behavior. Gain-of-function variants in RAS GTPases were detected in JGCTs, with no evidence of additional recurrent genomic alterations. In conclusion, we present the largest series of JGCT characterized by whole exome sequencing, highlighting the putative role of the MAPK-RAS pathway.
Subject(s)
Exome Sequencing , Juxtaglomerular Apparatus , Kidney Neoplasms , Humans , Male , Female , Kidney Neoplasms/genetics , Kidney Neoplasms/pathology , Adult , Juxtaglomerular Apparatus/pathology , Middle Aged , Young Adult , ras Proteins/genetics , Biomarkers, Tumor/genetics , Biomarkers, Tumor/analysis , Mutation , MAP Kinase Signaling System/genetics , MAP Kinase Signaling System/physiology , AdolescentABSTRACT
OBJECTIVE: To analyse surgical, functional, and mid-term oncological outcomes of robot-assisted nephroureterectomy (RANU) in a contemporary large multi-institutional setting. PATIENTS AND METHODS: Data were retrieved from the ROBotic surgery for Upper tract Urothelial cancer STtudy (ROBUUST) 2.0 database, an international, multicentre registry encompassing data of patients with upper urinary tract urothelial carcinoma undergoing curative surgery between 2015 and 2022. The analysis included all consecutive patients undergoing RANU except those with missing data in predictors. Detailed surgical, pathological, and postoperative functional data were recorded and analysed. Oncological time-to-event outcomes were: recurrence-free survival (RFS), metastasis-free survival (MFS), cancer-specific survival (CSS), and overall survival (OS). Survival analysis was performed using the Kaplan-Meier method, with a 3-year cut-off. A multivariable Cox proportional hazard model was built to evaluate predictors of each oncological outcome. RESULTS: A total of 1118 patients underwent RANU during the study period. The postoperative complications rate was 14.1%; the positive surgical margin rate was 4.7%. A postoperative median (interquartile range) estimated glomerular filtration rate decrease of -13.1 (-27.5 to 0) mL/min/1.73 m2 from baseline was observed. The 3-year RFS was 59% and the 3-year MFS was 76%, with a 3-year OS and CSS of 76% and 88%, respectively. Significant predictors of worse oncological outcomes were bladder-cuff excision, high-grade tumour, pathological T stage ≥3, and nodal involvement. CONCLUSIONS: The present study contributes to the growing body of evidence supporting the increasing adoption of RANU. The procedure consistently offers low surgical morbidity and can provide favourable mid-term oncological outcomes, mirroring those of open NU, even in non-organ-confined disease.
ABSTRACT
PURPOSE: Diagnostic ureteroscopy (dURS) is optional in the assessment of patients with upper tract urothelial carcinoma (UTUC) and provides the possibility of obtaining histology. METHODS: To evaluate endoscopic biopsy techniques and outcomes, we assessed data from patients from the CROES-UTUC registry. The registry includes multicenter prospective collected data on diagnosis and management of patients suspected having UTUC. RESULTS: We assessed 2380 patients from 101 centers. dURS with biopsy was performed in 31.6% of patients. The quality of samples was sufficient for diagnosis in 83.5% of cases. There was no significant association between biopsy techniques and quality (p = 0.458). High-grade biopsy accurately predicted high-grade disease in 95.7% and high-risk stage disease in 86%. In ureteroscopic low-grade tumours, the prediction of subsequent low-grade disease was 66.9% and low-risk stage Ta-disease 35.8%. Ureteroscopic staging correctly predicted non-invasive Ta-disease and ≥ T1 disease in 48.9% and 47.9% of patients, respectively. Cytology outcomes did not provide additional value in predicting tumour grade. CONCLUSION: Biopsy results adequately predict high-grade and high-risk disease, but approximately one-third of patients are under-staged. Two-thirds of patients with low-grade URS-biopsy have high-risk stage disease, highlighting the need for improved diagnostics to better assess patient risk and guide treatment decisions. CLINICAL TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov (ClinicalTrials.gov NCT02281188; https://clinicaltrials.gov/ct2/show/NCT02281188 ).
Subject(s)
Carcinoma, Transitional Cell , Kidney Neoplasms , Ureteral Neoplasms , Urinary Bladder Neoplasms , Humans , Carcinoma, Transitional Cell/diagnosis , Carcinoma, Transitional Cell/pathology , Ureteral Neoplasms/diagnosis , Ureteral Neoplasms/pathology , Prospective Studies , Ureteroscopy/methods , Biopsy , Kidney Neoplasms/diagnosis , Kidney Neoplasms/pathologyABSTRACT
PURPOSE: To assess the impact of neoadjuvant and adjuvant chemotherapy on survival outcomes, within a large multicenter cohort of Upper tract urothelial carcinoma patients treated with Nephroureterectomy. METHODS: A multicenter retrospective analysis utilizing the Robotic surgery for Upper Tract Urothelial Cancer Study registry was performed. Baseline, preoperative, perioperative, and pathologic variables of three groups of patients receiving surgery only, neoadjuvant or adjuvant chemotherapy were compared. Categorical and continuous variables among the three subgroups were compared with Chi square and ANOVA tests. The impact of perioperative chemotherapy on survival outcomes was assessed with the Kaplan Meier method. Univariable and multivariable Cox regression analyses were performed to identify predictors of survival. RESULTS: Overall, 1,994 patients were included. Overall and Clavien grade ≥3 complications rates were comparable among the three subgroups (p = 0.65 and p = 0.92). At Kaplan Meier analysis, neoadjuvant chemotherapy significantly improved cancer-specific survival (p = 0.03) and overall survival (p = 0.03) probabilities of patients with cT ≥ 3 tumors and of those with positive cN (p = 0.03 and p = 0.02). On multivariable analysis, neoadjuvant chemotherapy was independently associated with an improvement of cancer-specific survival in cT ≥ 3 patients (HR 0.44; p = 0.04), and of both cancer-specific survival (HR 0.50; p = 0.03) and overall survival (HR 0.53; p = 0.02) probabilities in positive cN patients. CONCLUSIONS: This large multicenter retrospective analysis suggests significant survival benefit in Upper tract urothelial carcinoma patients with either locally advanced or clinically positive nodes disease receiving neoadjuvant chemotherapy. These findings can be regarded as "hypothesis generating", stimulating future trials focusing on such advanced stages.
Subject(s)
Carcinoma, Transitional Cell , Kidney Neoplasms , Neoadjuvant Therapy , Nephroureterectomy , Registries , Ureteral Neoplasms , Humans , Male , Female , Retrospective Studies , Carcinoma, Transitional Cell/surgery , Carcinoma, Transitional Cell/drug therapy , Carcinoma, Transitional Cell/pathology , Aged , Ureteral Neoplasms/drug therapy , Ureteral Neoplasms/surgery , Ureteral Neoplasms/mortality , Ureteral Neoplasms/pathology , Kidney Neoplasms/surgery , Kidney Neoplasms/drug therapy , Kidney Neoplasms/pathology , Kidney Neoplasms/therapy , Chemotherapy, Adjuvant , Middle Aged , Lymphatic Metastasis , Survival Rate , Neoplasm StagingABSTRACT
PURPOSE OF REVIEW: This review aims to highlight the integration of artificial intelligence-powered radiomics in urologic oncology, focusing on the diagnostic and prognostic advancements in the realm of managing prostate, kidney, and bladder cancers. RECENT FINDINGS: As artificial intelligence continues to shape the medical imaging landscape, its integration into the field of urologic oncology has led to impressive results. For prostate cancer diagnostics, machine learning has shown promise in refining clinically-significant lesion detection, with some success in deciphering ambiguous lesions on multiparametric MRI. For kidney cancer, radiomics has emerged as a valuable tool for better distinguishing between benign and malignant renal masses and predicting tumor behavior from CT or MRI scans. Meanwhile, in the arena of bladder cancer, there is a burgeoning emphasis on prediction of muscle invasive cancer and forecasting disease trajectory. However, many studies showing promise in these areas face challenges due to limited sample sizes and the need for broader external validation. SUMMARY: Radiomics integrated with artificial intelligence offers a pioneering approach to urologic oncology, ushering in an era of enhanced diagnostic precision and reduced invasiveness, guiding patient-tailored treatment plans. Researchers must embrace broader, multicentered endeavors to harness the full potential of this field.
Subject(s)
Kidney Neoplasms , Muscle Neoplasms , Urinary Bladder Neoplasms , Urologic Neoplasms , Urology , Male , Humans , Artificial Intelligence , Urologic Neoplasms/diagnostic imaging , Urinary Bladder Neoplasms/diagnostic imaging , Kidney Neoplasms/diagnostic imagingABSTRACT
OPINION STATEMENT: Localized high-risk (HR) prostate cancer (PCa) is a heterogenous disease state with a wide range of presentations and outcomes. Historically, non-surgical management with radiotherapy and androgen deprivation therapy was the treatment option of choice. However, surgical resection with radical prostatectomy (RP) and pelvic lymph node dissection (PLND) is increasingly utilized as a primary treatment modality for patients with HRPCa. Recent studies have demonstrated that surgery is an equivalent treatment option in select patients with the potential to avoid the side effects from androgen deprivation therapy and radiotherapy combined. Advances in imaging techniques and biomarkers have also improved staging and patient selection for surgical resection. Advances in robotic surgical technology grant surgeons various techniques to perform RP, even in patients with HR disease, which can reduce the morbidity of the procedure without sacrificing oncologic outcomes. Clinical trials are not only being performed to assess the safety and oncologic outcomes of these surgical techniques, but to also evaluate the role of surgical resection as a part of a multimodal treatment plan. Further research is needed to determine the ideal role of surgery to potentially provide a more personalized and tailored treatment plan for patients with localized HR PCa.
Subject(s)
Prostatic Neoplasms , Male , Humans , Prostatic Neoplasms/surgery , Prostatic Neoplasms/pathology , Androgen Antagonists/therapeutic use , Androgens , Lymph Node Excision/methods , Combined Modality Therapy , Prostatectomy/methodsABSTRACT
BACKGROUND: Long noncoding RNAs (lncRNAs) are RNA molecules with over 200 nucleotides that do not code for proteins, but are known to be widely expressed and have key roles in gene regulation and cellular functions. They are also found to be involved in the onset and development of various cancers, including prostate cancer (PCa). Since PCa are commonly driven by androgen regulated signaling, mainly stimulated pathways, identification and determining the influence of lncRNAs in androgen response is useful and necessary. LncRNAs regulated by the androgen receptor (AR) can serve as potential biomarkers for PCa. In the present study, gene expression data analysis were performed to distinguish lncRNAs related to the androgen response pathway. METHODS AND RESULTS: We used publicly available RNA-sequencing and ChIP-seq data to identify lncRNAs that are associated with the androgen response pathway. Using Universal Correlation Coefficient (UCC) and Pearson Correlation Coefficient (PCC) analyses, we found 15 lncRNAs that have (a) highly correlated expression with androgen response genes in PCa and are (b) differentially expressed in the setting of treatment with an androgen agonist as well as antagonist compared to controls. Using publicly available ChIP-seq data, we investigated the role of androgen/AR axis in regulating expression of these lncRNAs. We observed AR binding in the promoter regions of 5 lncRNAs (MIR99AHG, DUBR, DRAIC, PVT1, and COLCA1), showing the direct influence of AR on their expression and highlighting their association with the androgen response pathway. CONCLUSION: By utilizing publicly available multiomics data and by employing in silico methods, we identified five candidate lncRNAs that are involved in the androgen response pathway. These lncRNAs should be investigated as potential biomarkers for PCa.
Subject(s)
Prostatic Neoplasms , RNA, Long Noncoding , Male , Humans , Androgens , RNA, Long Noncoding/genetics , Cell Line, Tumor , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/genetics , Prostatic Neoplasms/metabolism , Receptors, Androgen/genetics , Receptors, Androgen/metabolism , Gene Expression Regulation , Gene Expression Regulation, NeoplasticABSTRACT
OBJECTIVES: To develop and validate a prostate cancer (PCa) risk calculator (RC) incorporating multiparametric magnetic resonance imaging (mpMRI) and to compare its performance with that of the Prostate Biopsy Collaborative Group (PBCG) RC. PATIENTS AND METHODS: Men without a PCa diagnosis receiving mpMRI before biopsy in the Prospective Loyola University mpMRI (PLUM) Prostate Biopsy Cohort (2015-2020) were included. Data from a separate institution were used for external validation. The primary outcome was diagnosis of no cancer, grade group (GG)1 PCa, and clinically significant (cs)PCa (≥GG2). Binary logistic regression was used to explore standard clinical and mpMRI variables (prostate volume, Prostate Imaging-Reporting Data System [PI-RADS] version 2.0 lesions) with the final PLUM RC, based on a multinomial logistic regression model. Receiver-operating characteristic curve, calibration curves, and decision-curve analysis were evaluated in the training and validation cohorts. RESULTS: A total of 1010 patients were included for development (N = 674 training [47.8% PCa, 30.9% csPCa], N = 336 internal validation) and 371 for external validation. The PLUM RC outperformed the PBCG RC in the training (area under the curve [AUC] 85.9% vs 66.0%; P < 0.001), internal validation (AUC 88.2% vs 67.8%; P < 0.001) and external validation (AUC 83.9% vs 69.4%; P < 0.001) cohorts for csPCa detection. The PBCG RC was prone to overprediction while the PLUM RC was well calibrated. At a threshold probability of 15%, the PLUM RC vs the PBCG RC could avoid 13.8 vs 2.7 biopsies per 100 patients without missing any csPCa. At a cost level of missing 7.5% of csPCa, the PLUM RC could have avoided 41.0% (566/1381) of biopsies compared to 19.1% (264/1381) for the PBCG RC. The PLUM RC compared favourably with the Stanford Prostate Cancer Calculator (SPCC; AUC 84.1% vs 81.1%; P = 0.002) and the MRI-European Randomized Study of Screening for Prostate Cancer (ERSPC) RC (AUC 84.5% vs 82.6%; P = 0.05). CONCLUSIONS: The mpMRI-based PLUM RC significantly outperformed the PBCG RC and compared favourably with other mpMRI-based RCs. A large proportion of biopsies could be avoided using the PLUM RC in shared decision making while maintaining optimal detection of csPCa.
Subject(s)
Multiparametric Magnetic Resonance Imaging , Prostatic Neoplasms , Prunus domestica , Male , Humans , Magnetic Resonance Imaging/methods , Multiparametric Magnetic Resonance Imaging/methods , Prostate/diagnostic imaging , Prostate/pathology , Prostatic Neoplasms/pathology , Prospective Studies , Universities , Biopsy , Prostate-Specific AntigenABSTRACT
PURPOSE OF REVIEW: Our understanding of patterns of prostate cancer recurrence after primary treatment of localized disease has significantly evolved since the development of positron emission tomography (PET) agents targeting prostate cancer. Previously, most biochemical recurrences were not associated with imaging correlates when restaging with computed tomography (CT), magnetic resonance imaging (MRI), or bone scintigraphy and, hence, were typically assumed to represent occult metastases. A rising prostate specific antigen (PSA) after previous local therapy prompting a PET scan showing uptake limited to regional lymph nodes is an increasingly common clinical scenario as advanced prostate cancer imaging becomes more widely utilized. The optimal management strategy for patients who have lymph node recurrent prostate cancer is both unclear and evolving, particularly in terms of local and regionally directed therapies. Stereotactic body radiation therapy (SBRT) utilizes ablative radiation doses with steep gradients to achieve local tumor control while sparing nearby normal tissues. SBRT is an attractive therapeutic modality due to its efficacy, favorable toxicity profile, and flexibility to administer elective doses to areas of potential occult involvement. The purpose of this review is to briefly describe how SBRT is being implemented in the era of PSMA PET for the management of solely lymph node recurrent prostate cancer. RECENT FINDINGS: SBRT has been shown to effectively control individual lymph node tumor deposits within the pelvis and retroperitoneum for prostate cancer and is well-tolerated with a favorable toxicity profile. However, a major limitation thus far has been the lack of prospective trials supporting the use of SBRT for oligometastatic nodal recurrent prostate cancer. As further trials are conducted, its exact role in the treatment paradigm of recurrent prostate cancer will be better established. Although PET-guided SBRT appears feasible and potentially beneficial, there is still considerable uncertainty about the use of elective nodal radiotherapy (ENRT) in patients with nodal recurrent oligometastatic prostate cancer. PSMA PET has undoubtedly advanced imaging of recurrent prostate cancer, revealing anatomic correlates for disease recurrence that previously went undetected. At the same time, SBRT continues to be explored in prostate cancer with feasibility, a favorable risk profile, and satisfactory oncologic outcomes. However, much of the existing literature comes from the pre-PSMA PET era and integration of this novel imaging approach has led to greater focus on new and ongoing clinical trials to rigorously evaluate this approach and compare to other established treatment modalities utilized for oligometastatic, nodal recurrence of prostate cancer.
Subject(s)
Prostatic Neoplasms , Radiosurgery , Male , Humans , Positron Emission Tomography Computed Tomography/methods , Neoplasm Recurrence, Local/diagnostic imaging , Neoplasm Recurrence, Local/radiotherapy , Neoplasm Recurrence, Local/pathology , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/radiotherapy , Prostatic Neoplasms/pathology , Positron-Emission Tomography , Lymph Nodes/diagnostic imaging , Lymph Nodes/pathology , Salvage TherapyABSTRACT
OBJECTIVES: The COVID-19 pandemic has significantly affected the 2021 match application cycle as in person sub-internships and interviews have been halted. Given the abrupt change, we aimed to characterize the utilization of social media and virtual open house platforms by integrated vascular surgery residency programs for outreach and networking during the pandemic for the 2021 cycle. METHODS: A list of accredited integrated vascular surgery residency programs was compiled using the Electronic Residency Application Service (ERAS) website provided by the Academic Medical Colleges (AMC). The social media platforms Twitter, Instagram, and Facebook were queried for accounts associated with the training programs or their associated institutional vascular surgery divisions. Each discovered account was surveyed for date of creation as well as posts outlining virtual interactive events such as open houses, meet-and-greets, and virtual sub-internship opportunities. Slopes of the curves representing total account numbers and account numbers on each platform were compared from pre-COVID to current day using linear regression and t-statistics. RESULTS: There were 64 integrated vascular surgery residency programs participating in the 2021 match cycle. 70.3% (N = 45) of programs had a social media presence on at least one of the three platforms. 54.7% (N = 35) of programs had an associated Twitter account. 43.9% (N = 28) of programs had an associated Instagram account. Six (9.4%) programs were found on Facebook. The number of social media accounts significantly increased from March 2020 (37 vs 69, p < .001) to March 2021. CONCLUSIONS: Vascular surgery residency programs have significantly increased use of social media platforms over a 12-month period beginning in March 2020, indicating adaptation to the restrictions prompted by the pandemic.
Subject(s)
COVID-19 , Internship and Residency , Social Media , Humans , COVID-19/epidemiology , Pandemics , Linear ModelsABSTRACT
PHENOMENON: The 2020-2021 residency application cycle was subject to major alterations following the COVID-19 global pandemic. This study determined the online presence of US-based residency training programs during this time period. APPROACH: An official list of accredited US residency programs for 24 medical specialties was obtained through the Electronic Residency Application Service Programs' online presence and was evaluated for website ownership in addition to Twitter, Instagram, and Facebook account ownership. Date of social media account foundation and virtual opportunities offered were recorded. Doximity Residency Navigator for 2020-2021 was used to determine program rank, and programs were stratified by location using Association of American Medical Colleges regions. Program rank and geographic location were used to determine potential trends in online presence. This study was performed during the residency application cycle from September 2, 2020, to November 29, 2020, during which applications were submitted and the interview cycle began. FINDINGS: Fifty-seven percent of the 4,562 programs had a presence on social media. One-third of all accounts were created after March 1, 2020, and most (58%) were residency program-associated. A total of 1,315 programs offered virtual open houses through Twitter (829), Instagram (792), and Facebook (295). First-quartile programs had significantly more social media accounts per program on average (1.8) than those in subsequent quartiles, and Western region programs had significantly more accounts per program on average (1.3) than the Central (1.0), Northeastern (1.0), and Southern (1.1) regions. INSIGHTS: US residency programs created social media accounts and online opportunities for applicants following March 1, 2020. Online interactions may serve as substitutes at a time when in-person interaction is not possible. Future studies may examine the influence and impact of virtual interactions.Supplemental data for this article is available online at https://doi.org/10.1080/10401334.2022.2047050.
Subject(s)
COVID-19 , Internship and Residency , Medicine , Social Media , HumansABSTRACT
BACKGROUND: Most Prostate Imaging-Reporting and Data System (PI-RADS) 3 lesions do not contain clinically significant prostate cancer (CSPCa; grade group ≥2). This study was aimed at identifying clinical and magnetic resonance imaging (MRI)-derived risk fac- tors that predict CSPCa in men with PI-RADS 3 lesions. METHODS: This study analyzed the detection of CSPCa in men who underwent MRI-targeted biopsy for PI-RADS 3 lesions. Multivariable logistic regression models with goodness-of-fit testing were used to identify variables associated with CSPCa. Receiver operating curves and decision curve analyses were used to estimate the clinical utility of a predictive model. RESULTS: Of the 1784 men reviewed, 1537 were included in the training cohort, and 247 were included in the validation cohort. The 309 men with CSPCa (17.3%) were older, had a higher prostate-specific antigen (PSA) density, and had a greater likelihood of an anteriorly located lesion than men without CSPCa (p < .01). Multivariable analysis revealed that PSA density (odds ratio [OR], 1.36; 95% confidence interval [CI], 1.05-1.85; p < .01), age (OR, 1.05; 95% CI, 1.02-1.07; p < .01), and a biopsy-naive status (OR, 1.83; 95% CI, 1.38-2.44) were independently associated with CSPCa. A prior negative biopsy was negatively associated (OR, 0.35; 95% CI, 0.24-0.50; p < .01). The application of the model to the validation cohort resulted in an area under the curve of 0.78. A predicted risk threshold of 12% could have prevented 25% of biopsies while detecting almost 95% of CSPCas with a sensitivity of 94% and a specificity of 34%. CONCLUSIONS: For PI-RADS 3 lesions, an elevated PSA density, older age, and a biopsy-naive status were associated with CSPCa, whereas a prior negative biopsy was negatively associated. A predictive model could prevent PI-RADS 3 biopsies while missing few CSPCas. LAY SUMMARY: Among men with an equivocal lesion (Prostate Imaging-Reporting and Data System 3) on multiparametric magnetic resonance imaging (mpMRI), those who are older, those who have a higher prostate-specific antigen density, and those who have never had a biopsy before are at higher risk for having clinically significant prostate cancer (CSPCa) on subsequent biopsy. However, men with at least one negative biopsy have a lower risk of CSPCa. A new predictive model can greatly reduce the need to biopsy equivocal lesions noted on mpMRI while missing only a few cases of CSPCa.
Subject(s)
Prostatic Neoplasms , Biopsy , Humans , Magnetic Resonance Imaging , Male , Prostate-Specific Antigen , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/diagnostic imaging , Retrospective Studies , Risk FactorsABSTRACT
PURPOSE: Multiparametric magnetic resonance imaging (mpMRI)-ultrasound (US) fusion-guided biopsy may improve prostate cancer (PCa) detection and reduce grade misclassification. We compared PCa detection rates on systematic, magnetic resonance imaging-targeted, and combined biopsy with evaluation of important subgroups. MATERIALS AND METHODS: Men with clinical suspicion of harboring PCa from 2 institutions with visible Prostate Imaging-Reporting and Data System (PI-RADSTMv2) lesions receiving mpMRI-US fusion-guided prostate biopsy were included (2015-2020). Detection of PCa was categorized by grade group (GG). Clinically-significant PCa (csPCa) was defined as ≥GG2. Patients were stratified by biopsy setting and PI-RADS. RESULTS: Of 1,236 patients (647 biopsy-naïve) included, 626 (50.6%) harbored PCa and 412 (33.3%) had csPCa on combined biopsy. Detection of csPCa was 27.9% vs 23.3% (+4.6%) and GG1 PCa was 11.3% vs 17.8% (-6.5%) for targeted vs systematic cores. Benefit in csPCa detection was higher in the prior negative than biopsy-naïve setting (+7.8% [p <0.0001] vs +1.7% [p=0.3]) while reduction in GG1 PCa detection remained similar (-5.6% [p=0.0002] vs -7.3% [p=0.0001]). Targeted biopsy showed increased csPCa detection for PI-RADS 5, decrease in GG1 for PI-RADS 3, and both for PI-RADS 4 relative to systematic biopsy. Combined biopsy detected more csPCa (+10.0%) and slightly fewer GG1 PCa (-0.5%) compared to systematic alone. Upgrading to ≥GG2 by targeted biopsy occurred in 9.8% with no cancer and 23.6% with GG1 on systematic biopsy. CONCLUSIONS: Combined biopsy doubled the benefit of targeted biopsy alone in detection of csPCa without increasing GG1 PCa diagnoses relative to systematic biopsy. Utility of targeted biopsy was higher in the prior negative biopsy cohort, but advantages of combined biopsy were maintained regardless of biopsy history.
Subject(s)
Image-Guided Biopsy/methods , Magnetic Resonance Imaging/methods , Prostate/pathology , Prostatic Neoplasms/pathology , Ultrasonography, Interventional/methods , Aged , Humans , Male , Middle Aged , Retrospective StudiesABSTRACT
PURPOSE: Perioperative pelvic floor muscle training can hasten recovery of bladder control and reduce severity of urinary incontinence following radical prostatectomy. Nevertheless, most men undergoing prostatectomy do not receive this training. The purpose of this trial was to test the effectiveness of interactive mobile telehealth (mHealth) to deliver an evidence-based perioperative behavioral training program for post-prostatectomy incontinence. MATERIALS AND METHODS: This was a 3-site, 2-arm, randomized trial (2014-2019). Men with prostate cancer scheduled to undergo radical prostatectomy were randomized to a perioperative behavioral program (education, pelvic floor muscle training, progressive exercises, bladder control techniques) or a general prostate cancer education control condition, both delivered by mHealth for 1-4 weeks preoperatively and 8 weeks postoperatively. The primary outcome was time to continence following surgery measured by the ICIQ (International Consultation on Incontinence Questionnaire) Short-Form. Secondary outcomes measured at 6, 9 and 12 months included Urinary Incontinence Subscale of Expanded Prostate Cancer Index Composite; pad use; International Prostate Symptom Score QoL Question and Global Perception of Improvement. RESULTS: A total of 245 men (ages 42-78 years; mean=61.7) were randomized. Survival analysis using the Kaplan-Meier estimate showed no statistically significant between-group differences in time to continence. Analyses at 6 months indicated no statistically significant between-group differences in ICIQ scores (mean=7.1 vs 7.0, p=0.7) or other secondary outcomes. CONCLUSIONS: mHealth delivery of a perioperative program to reduce post-prostatectomy incontinence was not more effective than an mHealth education program. More research is needed to assess whether perioperative mHealth programs can be a helpful addition to standard prostate cancer care.
Subject(s)
Prostatic Neoplasms , Telemedicine , Urinary Incontinence , Adult , Aged , Exercise Therapy/methods , Humans , Male , Middle Aged , Pelvic Floor , Prostatectomy/adverse effects , Prostatectomy/methods , Prostatic Neoplasms/surgery , Quality of Life , Treatment Outcome , Urinary Incontinence/diagnosis , Urinary Incontinence/etiology , Urinary Incontinence/prevention & controlABSTRACT
INTRODUCTION: General surgery residency training programs adapted to the COVID-19 pandemic by going online instead of in-person, through virtual interviews, social media engagement, and virtual open houses. The impact of these virtual interactions is unknown. We sought to understand their effectiveness as per residency program directors and assistant program directors. MATERIALS AND METHODS: An institutional review board approval was obtained to conduct this anonymous survey. A Qualtrics XM survey containing multiple-choice and short-answer questions was distributed to 590 residency program and assistant program directors through the Association of Program Directors in Surgery (APDS) listserv on July 6, July 13, and July 20. RESULTS: We observed a response rate of approximately 11% across the 590 surgeons contacted. Nearly all (90%) respondents offered virtual preinterview interactions, primarily virtual open houses, virtual facility tours, and virtual question and answer (Q&A) sessions with residents and faculty; 48% of respondents were unsure of the utility of virtual interactions and the majority (54%) felt that virtual interaction limits a program's ability to evaluate applicants. Virtual Q&As were ranked to be the most effective interaction (7.6/10); 80% of respondents felt that visiting rotations were "somewhat important" to "very important," the two highest options available. In addition, 74% felt that applicants missed out on fully experiencing the program by forgoing these rotations. Most respondents (78%) noted that evaluation of applicants' preinterview did not change as a result of virtual interactions. Nearly half (48%) of the respondents offered more interview days due to the virtual format. A fifth (21%) of respondents stated that virtual interactions resulted in a change in the rank position of an applicant. Respondents ranked Twitter and Instagram higher in applicant engagement than Facebook. Factors that impacted interview or rank order list the most were late/absent step two CK scores (33%) and a lack of away rotations (31%), both being limitations largely due to the pandemic. With respect to future application cycles, most (71%) raised concerns regarding disparities between applicants applying in-person and virtually if both or either are offered. CONCLUSIONS: Our study suggests that program directors and associate program directors have reservations about the use of virtual interactions with applicants. Interestingly, these data suggest that visiting subinternships are useful for programs in evaluating applicants. This may encourage students to pursue rotations at other institutions at the expense of already-limited resources. It remains unclear whether virtual interactions will be used in the future, but respondents largely agreed that the virtual means of interacting with and disseminating information to the applicants of the 2020-2021 general surgery Match were a success.
Subject(s)
COVID-19 , Internship and Residency , COVID-19/epidemiology , Humans , Pandemics/prevention & control , Surveys and QuestionnairesABSTRACT
INTRODUCTION: Prostate cancer is a common neoplasm but conventional imaging methods such as CT and bone scan are often insensitive. A new class of PET agents have emerged to diagnose and manage prostate cancer. METHODS: The relevant literature on PET imaging agents for prostate cancer was reviewed. RESULTS: This review shows a broad range of PET imaging agents, the most successful of which is prostate specific membrane antigen (PSMA) PET. Other agents either lack the sensitivity or specificity of PSMA PET. CONCLUSION: Among the available PET agents for prostate cancer, PSMA PET has emerged as the leader. It is likely to have great impact on the diagnosis, staging and management of prostate cancer patients.
Subject(s)
Positron-Emission Tomography/methods , Prostatic Neoplasms/diagnostic imaging , Humans , MaleABSTRACT
OBJECTIVES: For men with intermediate prostate-specific antigen (PSA) levels (4-10 ng/mL), urine-based biomarkers and multiparametric magnetic resonance imaging (MRI) are increasingly used as reflex tests before prostate biopsy. We assessed the cost effectiveness of these reflex tests in the United States. METHODS: We used an existing microsimulation model of prostate cancer (PCa) progression and survival to predict lifetime outcomes for a hypothetical cohort of 55-year-old men with intermediate PSA levels. Urine-based biomarkers-PCa antigen (PCA3), TMPRSS2:ERG gene fusion (T2:ERG), and the MyProstateScore (MPS) for any PCa and for high-grade (Gleason score ≥7) PCa (MPShg)-were generated using biomarker data from 1112 men presenting for biopsy at 10 United States institutions. MRI results were based on published sensitivity and specificity for high-grade PCa. Costs and utilities were sourced from literature and Medicare reimbursement schedules. Outcome measures included life years, quality-adjusted life years (QALYs), and lifetime medical costs per patient. Incremental cost-effectiveness ratios were empirically calculated on the basis of simulated life histories under different reflex testing strategies. RESULTS: Biopsying all men provided the most life years and QALYs, followed by reflex testing using MPShg, MPS, MRI, T2:ERG, PCA3, and biopsying no men (QALY range across strategies 15.98-16.09). Accounting for costs, MRI and MPShg were dominated by other strategies. PCA3, T2:ERG, and MPS were likely to be the most cost-effective strategy at willingness-to-pay thresholds of $100 000/QALY, $125 000/QALY, and $150 000/QALY, respectively. CONCLUSIONS: Using PCA3, T2:ERG, or MPS as reflex tests has greater economic value than MRI, biopsying all men, or biopsying no men with intermediate PSA levels.
Subject(s)
Biomarkers/urine , Computer Simulation , Cost-Benefit Analysis , Early Detection of Cancer/economics , Magnetic Resonance Imaging , Prostate-Specific Antigen/analysis , Aged , Antigens, Neoplasm/genetics , Humans , Male , Medicare/economics , Middle Aged , Oncogene Proteins, Fusion/genetics , Prostatic Neoplasms/prevention & control , Quality-Adjusted Life Years , Sensitivity and Specificity , United StatesABSTRACT
This article reviews the essential role of imaging in clinical staging and restaging of renal cell carcinoma (RCC). To completely characterize and stage an indeterminate renal mass, renal CT or MRI without and with IV contrast administration is recommended. The critical items for initial clinical staging of an indeterminate renal mass or of a known RCC according to the TNM staging system are tumor size, renal sinus fat invasion, urinary collecting system invasion, perinephric fat invasion, venous invasion, adrenal gland invasion, invasion of the perirenal (Gerota) fascia, invasion into other adjacent organs, the presence of enlarged or pathologic regional (retroperitoneal) lymph nodes, and the presence of distant metastatic disease. Larger tumor size is associated with higher stage disease and invasiveness, lymph node spread, and distant metastatic disease. Imaging practice guidelines for clinical staging of RCC, as well as the role of renal mass biopsy, are highlighted. Specific findings associated with response of advanced cancer to antiangiogenic therapy and immunotherapy are discussed, as well as limitations of changes in tumor size after targeted therapy. The accurate clinical staging and restaging of RCC using renal CT or MRI provides important prognostic information and helps guide the optimal management of patients with RCC.
Subject(s)
Carcinoma, Renal Cell/diagnostic imaging , Carcinoma, Renal Cell/pathology , Kidney Neoplasms/diagnostic imaging , Kidney Neoplasms/pathology , Magnetic Resonance Imaging/methods , Tomography, X-Ray Computed/methods , Humans , Kidney/diagnostic imaging , Kidney/pathology , Neoplasm StagingABSTRACT
BACKGROUND. Despite advances in prostate cancer treatment, rates of biochemical recurrence remain high, relating to lack of detection of small-volume metastatic disease using conventional imaging for initial staging. OBJECTIVE. The purpose of this study was to assess the potential use of 18F-fluciclovine PET/MRI for initial staging of high-risk prostate cancer and evaluating response to androgen deprivation therapy (ADT). METHODS. This prospective clinical trial enrolled 14 men with newly diagnosed high-risk prostate cancer and negative or equivocal conventional staging imaging for metastatic disease between January 2018 and February 2019. All patients underwent pretreatment 18F-fluciclovine PET/MRI including multiparametric prostate MRI; 12 underwent 18F-fluciclovine PET/MRI after surgery or between ADT and radiotherapy. Confidence in identification of the primary intraprostatic lesion and nodal metastases was independently rated on a 0-3 Likert scale by three readers with nuclear medicine experience for 18F-fluciclovine PET/MRI and three readers with abdominal imaging experience for MRI alone. Findings scored as 2 or 3 by at least two readers of a given modality were considered positive. A single reader measured SUVmean, SUVmax, and volume of the MRI-defined intraprostatic lesion and SUVmax of suspicious lymph nodes on PET before and after initiation of ADT. Changes in SUV were analyzed using nonparametric Wilcox-on signed-rank tests. RESULTS. The biopsy-proven lesion in the prostate gland was accurately identified in all 14 patients on both MRI and 18F-fluciclovine PET/MRI. Suspected nodal metastases were detected in three patients on MRI and seven patients on 18F-fluciclovine PET/MRI. After ADT, all patients showed decreased activity within the intraprostatic lesion and/or all suspicious lymph nodes. The primary lesion SUVmean was 4.5 ± 1.1 (range, 2.7-6.5) before treatment and 2.4 ± 1.1 (range, 0.0-3.6) after initiation of ADT (p = .008). For suspicious lymph nodes, the pretreatment SUVmax was 5.5 ± 3.7 (range, 2.8-12.7) and the post-treatment SUVmax was 2.8 ± 1.4 (range, 1.4-5.5) (p = .03). CONCLUSION.18F-labeled fluciclovine PET/MRI shows potential utility in initial staging of high-risk prostate cancer and in evaluating response to ADT. CLINICAL IMPACT. Given the FDA approval and widespread availability of 18F-fluciclovine, the findings could have an impact in the immediate future in guiding initial management of patients with prostate cancer. TRIAL REGISTRATION. ClinicalTrials.gov NCT03264456.