RESUMO
Prostate specific antigen (PSA) has transformed the diagnosis and treatment of prostate cancer by enabling early detection at global scale. Due to expression in both benign and malignant cells, PSA-based prostate cancer screening using single cut-points yields imperfect diagnostic performance and has led to the detection and over-treatment of low-grade prostate cancer. Additional challenges in the interpretation of PSA include substantial inter and intrapersonal variation, differences with age and prostate volume, and selection of standardized PSA value cutoffs for clinical application. In response, refinements to PSA including risk and age-based thresholds, age and genetic adjustments, PSA density, percentage free PSA, and PSA velocity have been proposed and extensively studied. In this review, we focus on the clinical role of PSA as a screening biomarker with a particular emphasis on its test characteristics, clinically actionable thresholds, and strategies to refine its clinical interpretation.
RESUMO
OBJECTIVE: To investigate if use of the Crowd-Sourced Assessment of Technical Skills (CSATS) platform and video peer review with constructive feedback is associated with improvement in technical skill and patient outcomes for robotic-assisted laparoscopic prostatectomy (RALP). METHODS: Five fellowship-trained urologists voluntarily submitted RALP cases for CSATS Global Evaluative Assessment of Robotic Skills (GEARS) scoring and expert narrative review between April 15, 2022-April 30, 2023. Surgeon-selected and randomly selected cases were reviewed. Surgeons underwent local peer review of videos with constructive feedback. Change in GEARS scores and frequency of postoperative outcomes over the 12-month periods before and during the study were analyzed in logistic regression models. Bias was assessed with sensitivity analysis comparing surgeon-selected to randomly selected cases. RESULTS: GEARS scores for randomly selected vs surgeon-selected cases did not differ significantly. Overall GEARS score correlated positively with annual surgical RALP volume (r = 0.39, P = .003) and negatively with years in practice (r = -0.34, P = .01). After adjusting for confounders, there was no significant improvement in overall GEARS Score (0.01 ± 0.02/month, P = .48); but likelihood of sepsis (Odds Ratio 0.07, 95% CI 0.01-1.00, P = .05) and pelvic fluid collection (Odds Ratio 0.09, 95% CI 0.01-0.99, P = .049) were significantly decreased during the intervention period (n = 165) compared to the prior 12months (n = 144). No outcome increased in likelihood (P > .05). CONCLUSION: Integration of CSATS and local video peer review is associated with significant improvement in patient outcomes after RALP, despite no significant change in surgeons' GEARS scores. This is the first study demonstrating improvement in patient RALP outcomes after implementation of such a paradigm in practicing surgeons.
RESUMO
Non-small-cell lung cancer (NSCLC) with concurrent mutations in KRAS and the tumour suppressor LKB1 (KL NSCLC) is refractory to most therapies and has one of the worst predicted outcomes. Here we describe a KL-induced metabolic vulnerability associated with serine-glycine-one-carbon (SGOC) metabolism. Using RNA-seq and metabolomics data from human NSCLC, we uncovered that LKB1 loss enhanced SGOC metabolism via serine hydroxymethyltransferase (SHMT). LKB1 loss, in collaboration with KEAP1 loss, activated SHMT through inactivation of the salt-induced kinase (SIK)-NRF2 axis and satisfied the increased demand for one-carbon units necessary for antioxidant defence. Chemical and genetic SHMT suppression increased cellular sensitivity to oxidative stress and cell death. Further, the SHMT inhibitor enhanced the in vivo therapeutic efficacy of paclitaxel (first-line NSCLC therapy inducing oxidative stress) in KEAP1-mutant KL tumours. The data reveal how this highly aggressive molecular subtype of NSCLC fulfills their metabolic requirements and provides insight into therapeutic strategies.
Assuntos
Quinases Proteína-Quinases Ativadas por AMP , Antioxidantes , Carcinoma Pulmonar de Células não Pequenas , Glicina Hidroximetiltransferase , Proteína 1 Associada a ECH Semelhante a Kelch , Neoplasias Pulmonares , Mutação , Proteínas Serina-Treonina Quinases , Proteínas Proto-Oncogênicas p21(ras) , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Glicina Hidroximetiltransferase/genética , Glicina Hidroximetiltransferase/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Antioxidantes/metabolismo , Animais , Estresse Oxidativo , Camundongos , Linhagem Celular Tumoral , Fator 2 Relacionado a NF-E2/metabolismo , Fator 2 Relacionado a NF-E2/genéticaRESUMO
OBJECTIVE: A subset of patients are diagnosed with lethal prostate cancer (CaP) early in life before prostate-specific antigen (PSA) screening is typically initiated. To identify opportunities for improved detection, we evaluated patient sociodemographic factors associated with advanced vs. localized (CaP) diagnosis across the age spectrum. METHODS: We conducted a retrospective cohort study using the National Cancer Database, identifying patients diagnosed with CaP from 2004 to 2020. We compared characteristics of patients diagnosed at the advanced (cN1 or M1) versus localized (cT1-4N0M0) stage. Using multivariable logistic regression, we evaluated the associations among patient clinical and sociodemographic factors and advanced diagnosis, stratifying patients by age as ≤55 (before screening is recommended for most patients), 56 to 65, 66 to 75, and ≥76 years. RESULTS: We identified 977,722 patients who met the inclusion criteria. The mean age at diagnosis was 65.3 years and 50,663 (5.1%) had advanced disease. Overall, uninsured (ORâ¯=â¯3.20, 95% CI 3.03-3.78) and Medicaid-insured (OR 2.58, 95% CI 2.48-2.69) vs. privately insured status was associated with higher odds of diagnosis with advanced disease and this effect was more pronounced for younger patients. Among patients ≤55 years, uninsured (OR 4.14, 95% CI 3.69-4.65) and Medicaid-insured (OR 3.39, 95% CI 3.10-3.72) vs. privately insured patients were associated with higher odds of advanced cancer at diagnosis. Similarly, residence in the lowest vs. highest income quartile was associated with increased odds of advanced CaP in patients ≤55 years (OR 1.15, 95% CI 1.02-1.30). Black vs. White race was associated with increased odds of advanced CaP at diagnosis later in life (OR 1.17, 95% CI 1.09-1.25); however, race was not significantly associated with advanced stage CaP in those ≤55 years (Pâ¯=â¯0.635). CONCLUSIONS: Sociodemographic disparities in diagnosis at advanced stages of CaP were more pronounced in younger patients, particularly with respect to insurance status. These findings may support greater attention to differential use of early CaP screening based on patient health insurance.
Assuntos
Neoplasias da Próstata , Fatores Sociodemográficos , Masculino , Estados Unidos/epidemiologia , Humanos , Estudos Retrospectivos , Seguro Saúde , Neoplasias da Próstata/diagnóstico , Medicaid , Pessoas sem Cobertura de Seguro de Saúde , Cobertura do SeguroRESUMO
Background: extended pelvic lymph node dissection (ePLND) increases the detection rate of lymph node positive prostate cancer compared to a standard pelvic lymph node dissection (sPLND). However, improvement of patient outcomes remains questionable. Here we report and compare 3-year postoperative PSA recurrence rates between patients that underwent sPLND versus ePLND at the time of prostatectomy. Methods: 162 patients received a sPLND (which involvedremoval of periprostatic, external iliac, and obturator lymph nodes bilaterally), and 142 patients received an ePLND (which involved removal of periprostatic, external iliac, obturator, hypogastric, and common iliac nodes bilaterally). Decision to undergo ePLND versus sPLND at our institution was changed in 2016 based on the National Comprehensive Cancer Network guideline. The median follow-up time was 7 and 3 years for sPLND and ePLND patients, respectively. All node-positive patients were offered adjuvant radiotherapy. Kaplan-Meier analysis was carried out to assess the impact of a PLND on early postoperative PSA progression-free survival. Subgroup analyses were done for node-negative and node-positive patients, as well as Gleason score. Results: Gleason score and T stage were not significantly different between patients who received an ePLND and sPLND. The pN1 rate for ePLND and sPLND were 20% (28/142) and 6% (10/162), respectively. There was no difference in the use of adjuvant treatments in the pN0 patients. Significantly, more ePLND pN1 patients received adjuvant androgen deprivation therapy (25/28 vs. 5/10 P = 0.012) and radiation (27/28 vs. 4/10 P = 0.002). Yet, no difference in biochemical recurrence between ePLND and sPLND was observed (P = 0.44). This remained true in subgroup analyses of node-positive (P = 0.26), node-negative (P = 0.78), Gleason Score 6-7 (P = 0.51), and Gleason Score 8-10 (P = 0.77). Conclusions: PLND provided no additional therapeutic benefit, even though ePLND patients were significantly more likely to have node-positive disease and undergo adjuvant treatment, compared to a sPLND.
RESUMO
PURPOSE OF REVIEW: Metastatic prostate cancer remains universally lethal. Although de-novo metastatic prostate cancer was historically managed with systemic therapy alone, local therapies are increasingly utilized in the early treatment of the disease, particularly in patients with oligometastatic prostate cancer (OMPC). OMPC represents an intermediate stage between clinically localized and widespread metastatic disease. Diseases classified within this stage present an opportunity for localized targeting of the disease prior to progression to widespread metastases. The purpose of this review is to discuss the contemporary and emerging local therapies for the treatment of OMPC. RECENT FINDINGS: To date, there are three utilized forms of local therapy for OMPC: cryoablation, radiation therapy, and cytoreductive prostatectomy. Cryoablation can be utilized for the total ablation of the prostate and has shown promising results in patients with OMPC either in combination with ADT or with ADT and systemic chemotherapy. Radiation therapy along with ADT has demonstrated improvement in progression-free survival. The STAMPEDE Arm G, PEACE-1, and the HORRAD clinical trials have investigated radiation therapy for mPCa compared to standard of care versus systemic therapy with varying results. Cytoreductive radical prostatectomy (CRP) in conjunction with ADT has also been proposed in the management of OPMC with promising results from case-control and retrospective studies. Currently there are larger controlled trials investigating CRP for OPMC including the SIMCAP, LoMP, TRoMbone, SWOG 1802, IP2-ATLANTA, g-RAMPP, and FUSCC-OMPCa trials. Given the novel nature of local treatments for OPMC, treatment selection is still controversial and requires long-term follow-up and randomized clinical trials to aid patient and clinician decision making.
Assuntos
Neoplasias da Próstata , Masculino , Humanos , Estudos Retrospectivos , Neoplasias da Próstata/patologia , Próstata/patologia , Prostatectomia/métodos , Procedimentos Cirúrgicos de Citorredução , Antagonistas de Androgênios/uso terapêutico , Metástase Neoplásica/tratamento farmacológico , Metástase Neoplásica/patologiaRESUMO
PURPOSE: To summarize contemporary and emerging strategies for the diagnosis and management of metastatic hormone sensitive prostate cancer (mHSPC), focusing on diagnostic testing and therapeutics. METHODS: Literature review using PUBMED-Medline databases as well as clinicaltrials.gov to include reported or ongoing clinical trials on treatment for mHSPC. We prioritized the findings from phase III randomized clinical trials, systematic reviews, meta-analyses and clinical practice guidelines. RESULTS: There have been significant changes to the diagnosis and staging evaluation of mHSPC with the integration of increasingly accurate positron emission tomography (PET) imaging tracers that exceed the performance of conventional computerized tomography (CT) and bone scan. Germline multigene testing is recommended for the evaluation of patients newly diagnosed with mHSPC given the prevalence of actionable alterations that may create candidacy for specific therapies. Although androgen deprivation therapy (ADT) remains the backbone of treatment for mHSPC, approaches to first-line treatment include the integration of multiple agents including androgen receptor synthesis inhibitors (ARSI; abiraterone) Androgen Receptor antagonists (enzalutamide, darolutamide, apalautamide), and docetaxel chemotherapy. The combination of ADT, ARSI, and docetaxel chemotherapy has recently been evaluated in a randomized trial and was associated with significantly improved overall survival including in patients with a high burden of disease. The role of local treatment to the prostate with radiation has been evaluated in randomized trials with additional studies underway evaluating the role of cytoreductive radical prostatectomy. CONCLUSION: The staging and initial management of patients with mHSPC has undergone significant advances in the last decade with advancements in the diagnosis, treatment and sequencing of therapies.
Assuntos
Neoplasias da Próstata , Masculino , Humanos , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/genética , Neoplasias da Próstata/terapia , Docetaxel , Antagonistas de Androgênios/uso terapêutico , Resultado do Tratamento , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Hormônios/uso terapêuticoRESUMO
PURPOSE OF REVIEW: Approximately 15% of prostate cancer patients have lymph node metastases at the time of radical prostatectomy (RP). However, there is no universally accepted standard of care for these men. The options for treatment in this subset of patients range from observation to a combination of adjuvant androgen deprivation therapy (aADT) and radiation therapy (RT). RECENT FINDINGS: A recent systematic review showed that there was no clear choice out of the options above to treat these patients. Studies have shown that patients treated with adjuvant radiation therapy have lower all-cause mortality when compared to patients treated with salvage radiation therapy. In this review, we summarize treatment options for pathologic node-positive (pN1) patients and discuss the urgent need for robust clinical trials that includes observation as the control group to help establish a standard of care for treating patients with node-positive prostate cancer after RP.
Assuntos
Neoplasias da Próstata , Masculino , Humanos , Neoplasias da Próstata/cirurgia , Neoplasias da Próstata/patologia , Antagonistas de Androgênios/uso terapêutico , Prostatectomia , Antígeno Prostático EspecíficoRESUMO
Introduction and Objective: In 2018, the U.S. Food and Drug Administration approved the da Vinci single-port (SP) system, in which four instruments are still utilized, but enter through a single-site access trocar. Herein, we report the largest case series for SP robot-assisted radical prostatectomy (RARP) to date. Our primary aim is to analyze the perioperative and short-term outcomes of this procedure. Our secondary aim is an assessment of the learning curve with this new platform. Methods: A total of 157 patients underwent SP RARP by two surgeons who have completed >3000 multiport robotic surgeries collectively. Institutional Review Board-approved prospectively collected data were used. Basic demographic preoperative variables and perioperative outcomes were analyzed. Results: Median patient age and prostate-specific antigen was 63 years and 6.3 ng/mL before treatment (interquartile range [IQR] 4.7-8.2 ng/mL). Average prostate weight was 47 g. The median operating time was 195 minutes (IQR 165-221.25 minutes) with a median estimated blood loss of 100 mL (IQR 100-200 mL). Surgeon 1's operating time stabilized around case #56, and Surgeon 2 around case #26. Surgeon 2 used the transperitoneal approach for the first 7 cases. There were no intraoperative complications. There were six total postoperative complications (3.8%) and four (2.5%) were Clavien-Dindo scale ≥IIIa. One hundred ten patients went home same day, 45 stayed 1 night at the hospital, with only 2 patients requiring stay in the hospital for more than 1 night (70%, 29%, and 1% respectively). With the median follow-up period of 9 months, rates of biochemical recurrence, pad-free, and potency preservation were 8.3%, 82.5%, and 64.4%, respectively. Conclusions: This case series confirms the safety and efficacy of SP RARP with acceptable short-term outcomes. There is a significant learning curve for this new modality. Shorter hospital stay appears to be an early benefit of the SP platform.
Assuntos
Neoplasias da Próstata , Procedimentos Cirúrgicos Robóticos , Robótica , Humanos , Curva de Aprendizado , Masculino , Pessoa de Meia-Idade , Próstata/cirurgia , Antígeno Prostático Específico , Prostatectomia/métodos , Neoplasias da Próstata/cirurgia , Procedimentos Cirúrgicos Robóticos/métodos , Resultado do TratamentoRESUMO
To determine which method of radiotherapy proves more effective after prostatectomy: Adjuvant (ART) or early salvage (ESRT), we observed the pathologic and adverse risk factors of patients and their results from both treatments, looking specifically at biochemical-free survival rates, metastasis-free survival rates, and overall survival rates. Peer review articles containing their own data collected between 1986 and 2022 were reviewed. We reviewed 67 peer review articles and included 33 that met criteria. Studies focused on the adverse risk factors and the results of patients either before/after receiving adjuvant or early salvage/salvage radiotherapy were included in the analysis. Patient characteristics had an effect on what treatment a patient would receive; if a patient had more than one adverse risk factor such as a high Gleason score, prostate-specific antigen (PSA) level, T-stage, or positive margins, they would receive immediate radiation after prostatectomy, which would classify as ART. If the patient had no adverse risk factors after surgery, they would be placed in an observation period to follow their PSA and overall health, and only if necessary, undergo ESRT. Of the 33 studies, ART was proven to be only slightly more beneficial when relating to biochemical recurrence-free survival while ART and ESRT results were similar in metastasis-free survival and overall survival. ART and ESRT are overall comparable in their patient outcomes, despite their own unique pros and cons. The use of ESRT reduces overtreatment in men who may not experience biochemical recurrence. However, in those with very high-risk pathologic features, a multi-disciplinary approach should be utilized to best determine which mode of radiation therapy after surgery is recommended.
RESUMO
INTRODUCTION: Testicular germ cell tumors, particularly nonseminomatous germ cell tumors (NSGCT), comprise the most common solid malignancy in male children and younger adults. While these patients experience excellent survival outcomes, few studies have characterized their survival by age. Thus, we aimed to characterize the relative survival of NSGCT by age, stratifying patients by stage group. METHODS: Using the Surveillance Epidemiology and End Results (SEER) database, we divided patients with NSGCT into pediatric patients and adolescents (<19 years), young adults (19-30 years), and older adults (>30 years). Survival analysis, using Cox proportional hazards models and Kaplan Meier curves, described overall and cancer-specific survival (CSS) of each age category for Stage I-III NSGCT by stage group. RESULTS: A total of 14,786 patients met inclusion criteria and comprised the age groups <19 years (N=1,287), 19 to 30 years (N=7,729), and >30 years (N=5,770). Stage group distribution at presentation was similar between each group. Survival analysis demonstrated no differences in cancer-specific survival (CSS) among Stage I or II NSGCT. However, among Stage III tumors, multivariable models noted worse CSS in patients >30 years (HR=3.35 (95%CI: 1.45-7.73), P=0.005) and those 19-30 years (HR=2.28 (95%CI: 0.99-5.21), P=0.053) compared to pediatric and adolescent patients. CONCLUSIONS: Younger NSGCT patients experience excellent oncologic outcomes compared to their older counterparts. These survival differences by age group are largely driven by differential survival among Stage III neoplasms. Furthermore, our report lends additional evidence that age is an important prognostic factor in advanced NSGCT, including pediatric and adolescent patients.
Assuntos
Neoplasias Embrionárias de Células Germinativas , Neoplasias Testiculares , Adolescente , Adulto , Idoso , Criança , Humanos , Masculino , Estadiamento de Neoplasias , Neoplasias Embrionárias de Células Germinativas/patologia , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Análise de Sobrevida , Neoplasias Testiculares/patologia , Adulto JovemRESUMO
PURPOSE: Retroperitoneal lymph node dissection (RPLND) for men with clinical stage (CS) I or II testicular nonseminomatous germ cell tumor (NSGCT) has both staging and therapeutic implications. We aimed to investigate the impact of lymph node count (LNC) on outcome after primary RPLND for men with CS I or II NSGCT using a nationally representative data set. MATERIALS AND METHODS: A retrospective analysis of men who received a primary RPLND for CS I or II NSGCT was performed using the National Cancer Database. The Kaplan-Meier method was used to determine overall survival (OS) according to LNC. Logistic regression analyses were used to identify factors associated with LNC >20 and factors predictive of lymph node-positive (pN+) disease after primary RPLND. RESULTS: Of 1,376 men who comprised our analytical cohort, 50.1% and 49.9% had 1-20 lymph nodes (LNs) and >20 LNs removed, respectively. Five-year OS rates were 96.4% and 99.1% for men with 1-20 and >20 LNs resected, respectively (p=0.004). A higher proportion of men with >20 LNs removed were treated at academic centers, had private insurance, presented with higher AJCC (American Joint Committee on Cancer) CS and were more likely to have pN+ disease, compared to those with 1-20 LNs removed. Factors significantly associated with pN+ disease after RPLND include higher AJCC CS and LNC (per 10-count increase). CONCLUSIONS: Higher LNC after primary RPLND significantly increases the likelihood of identifying pN+ disease and is associated with improved OS. Our data support the therapeutic implications of a thoroughly performed RPLND in the primary setting.
Assuntos
Neoplasias Embrionárias de Células Germinativas , Neoplasias Testiculares , Humanos , Excisão de Linfonodo/métodos , Linfonodos/patologia , Linfonodos/cirurgia , Masculino , Estadiamento de Neoplasias , Neoplasias Embrionárias de Células Germinativas/patologia , Neoplasias Embrionárias de Células Germinativas/cirurgia , Espaço Retroperitoneal/patologia , Estudos Retrospectivos , Neoplasias Testiculares/patologia , Resultado do TratamentoRESUMO
INTRODUCTION: We sought to understand patient- and institution-level factors associated with use of locoregional therapy for newly diagnosed metastatic prostate cancer in the era before the availability of evidence supporting its efficacy. METHODS: We queried the National Cancer Database to identify patients diagnosed with metastatic prostate adenocarcinoma (stage M1) between 2004 and 2017. We assessed patient factors associated with definitive local therapy with radiotherapy or radical prostatectomy using multilevel logistic regression accounting for clustering within institutions. We further characterized trends in facility-level use and examined institutional factors associated with utilization. RESULTS: We identified 35,933 patients with M1 prostate cancer at 1,188 facilities. A total of 4,146 patients (11.5%) received local therapy for M1 disease (radiation therapy in 3,378 and radical prostatectomy in 768). Use of local treatment was concentrated among a smaller number of facilities: 50% of all local therapy was delivered at 161 facilities (14% of total). At the patient level, uninsured status (OR 0.62, 95% CI 0.49-0.79, p <0.01) and high comorbidity (Charlson-Deyo score, OR 0.39, 95% CI 0.26-0.6, p <0.01) were associated with lower odds of local therapy. High-utilizing facilities (top quartile) were more commonly community centers (OR 1.76, 95% CI 10.7-2.95, p <0.01) and differed by geographic region (South Atlantic vs West South Central region: OR 0.48, 95% CI 0.25-0.88, p=0.02). CONCLUSIONS: In the period before locoregional therapy was supported by clinical practice guidelines, locoregional therapy use varied significantly at the facility level and was driven by a smaller number of high-utilizing facilities. These findings can contextualize expected increase in the use of local therapy for metastatic prostate cancer.
RESUMO
PURPOSE: The American Urological Association (AUA) Annual Meeting serves as the premier platform for presenting unpublished research in urology. Among selected abstracts, podium presentations represent the most impactful submissions. While podium presentations receive a large audience through conference attendance and social media posts, it is unclear how often they manifest as publications in peer-reviewed journals. MATERIALS AND METHODS: Podium presentations from the 2017 AUA Annual Meeting were reviewed. Abstracts were assessed for publication between January 1, 2015 and May 31, 2020 allowing for a 3-year window of publication and accounting for publications prior to the submission deadline. Abstract authors were individually searched with key terms being added sequentially until <30 results were generated in PubMed®. Abstracts were deemed published if at least 1 author and 1 conclusion matched a manuscript. Publication rate, time to publication, and 2019 journal impact factor were collected. Statistical analysis was performed by linear and logistic regression. RESULTS: Of 872 podium presentations, 453 (51.9%) were published within 3 years. Median time from submission to publication was 12.5 months (IQR: 7.5-20.5). The number of articles published at 1, 2 and 3 years from submission was 203, 368 and 430, respectively. The median journal impact factor of publications was 3.2 (IQR: 2.0-5.8). Oncology studies (OR=1.21 [95% CI: 0.91-1.60], p=0.186) had similar rates of publication compared to non-oncology studies. CONCLUSIONS: While AUA podium presentations disseminate valuable data, approximately half were not published in peer-reviewed journals within 3 years. Therefore, care must be taken when promoting findings or adopting new practices based on these presentations alone.
Assuntos
Congressos como Assunto , Editoração/estatística & dados numéricos , Sociedades Médicas , Urologia , Humanos , Fatores de Tempo , Estados UnidosRESUMO
PURPOSE: Salvage radical prostatectomy is rare due to the risk of postoperative complications. We compare salvage Retzius-sparing robotic assisted radical prostatectomy (SRS-RARP) with salvage standard robotic assisted radical prostatectomy (SS-RARP). MATERIALS AND METHODS: A total of 72 patients across 9 centers were identified (40 SRS-RARP vs 32 SS-RARP). Demographics, perioperative data, and pathological and functional outcomes were compared using Student's t-test and ANOVA. Cox proportional hazard models and Kaplan-Meier curves were constructed to assess risk of incontinence and time to continence. Linear regression models were constructed to investigate postoperative pad use and console time. RESULTS: Median followup was 23 vs 36 months for SRS-RARP vs SS-RARP. Console time and estimated blood loss favored SRS-RARP. There were no differences in complication rates or oncologic outcomes. SRS-RARP had improved continence (78.4% vs 43.8%, p <0.001 for 0-1 pad, 54.1% vs 6.3%, p <0.001 for 0 pad), lower pads per day (0.57 vs 2.03, p <0.001), and earlier return to continence (median 47 vs 180 days, p=0.008). SRS-RARP was associated with decreased incontinence defined as >0-1 pad (HR 0.28, 95% CI 0.10-0.79, p=0.016), although not when defined as >0 pad (HR 0.56, 95% CI 0.31-1.01, p=0.053). On adjusted analysis SRS-RARP was associated with decreased pads per day. Lymph node dissection and primary treatment with stereotactic body radiation therapy were associated with longer console time. CONCLUSIONS: SRS-RARP is a feasible salvage option with significantly improved urinary function outcomes. This may warrant increased utilization of SRS-RARP to manage men who fail nonsurgical primary treatment for prostate cancer.
Assuntos
Tratamentos com Preservação do Órgão/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Prostatectomia/efeitos adversos , Neoplasias da Próstata/cirurgia , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Terapia de Salvação/efeitos adversos , Incontinência Urinária/epidemiologia , Idoso , Estudos de Viabilidade , Humanos , Tampões Absorventes para a Incontinência Urinária/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Tratamentos com Preservação do Órgão/métodos , Tratamentos com Preservação do Órgão/estatística & dados numéricos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/terapia , Próstata/patologia , Próstata/cirurgia , Prostatectomia/métodos , Prostatectomia/estatística & dados numéricos , Estudos Retrospectivos , Medição de Risco/estatística & dados numéricos , Procedimentos Cirúrgicos Robóticos/estatística & dados numéricos , Terapia de Salvação/métodos , Terapia de Salvação/estatística & dados numéricos , Fatores de Tempo , Resultado do Tratamento , Incontinência Urinária/etiologia , Incontinência Urinária/terapiaRESUMO
The bladder cancer (BCa) microenvironment comprises heterogeneous tumor cell populations, the surrounding stroma and the extracellular matrix (ECM). Collagen, the scaffold of the tumor microenvironment, regulates ECM remodeling to promote tumor infiltration, angiogenesis, invasion and migration. The present study examined how collagen type VIα (COL6A) 1 and 2 function during BCa pathogenesis and progression, with the aim of facilitating the development of precision therapeutics, risk stratification and molecular diagnosis. COL6A1 and COL6A2 mRNA expression in nonmuscle invasive BCa (NMIBC) and MIBC tissue samples was measured using reverse transcriptionquantitative PCR. In addition, the tumorsuppressive effects of COL6A1 and COL6A2 in human BCa EJ cells (MGHU1) were assessed. Compared with normal controls, COL6A1 and COL6A2 mRNA expression was downregulated in both NMIBC and MIBC tissue samples (P<0.05, respectively). COL6A1 and COL6A2 effectively inhibited the proliferation of human BCa EJ cells (MGHU1) and induced cell cycle arrest at the G1 phase. Additionally, COL6A1 and COL6A2 served roles in MAPK and AKT signaling by increasing p38 MAPK phosphorylation and decreasing AKT phosphorylation. Finally, COL6A1 and COL6A2 inhibited wound healing and invasion by suppressing the activity of matrix metalloproteinase (MMP)2 and MMP9. In conclusion, COL6A1 and COL6A2 may act as classical collagens by forming a physical barrier to inhibit BCa tumor growth and invasion.
Assuntos
Colágeno Tipo VI/genética , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Colágeno Tipo VI/metabolismo , Pontos de Checagem da Fase G1 do Ciclo Celular , Regulação Neoplásica da Expressão Gênica , Humanos , Pessoa de Meia-Idade , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Neoplasias da Bexiga Urinária/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
INTRODUCTION AND OBJECTIVE: Administrative databases (AD) provide investigators with nationally representative study populations to answer research questions using large sample sizes. We aimed to quantify the trends and incidence of AD use in published manuscripts in urologic oncology. We examined 6 commonly used databases: National Cancer Database, surveillance, epidemiology, and end results database (SEER), SEER-Medicare, Nationwide Inpatient Sample, National Surgical Quality Improvement Program, and Premier Healthcare Database. METHODS: A literature review, powered by PubMed and DistillerSR, aggregated manuscripts that used the aforementioned databases to study a genitourinary malignancy between July 1, 2000 through June 30, 2019. Included publications were categorized by database used, corresponding author department affiliation, organ, journal, year, and contribution - defined as temporal treatment trends, outcomes and survival, comparative effectiveness research, or cost-effectiveness. RESULTS: There were 2,265 publications across 302 journals that met the inclusion criteria. Between 2000 and 2019 the compound annual growth rate of these publications was 18.7%. SEER use grew at a rate of 14.6% annually. National Cancer Database use grew 28.2% annually. Prostate cancer comprised the majority of publications (51.3%), followed by kidney (23.1%) and bladder (22.5%) cancer. Journals publishing these manuscripts had a median impact factor of 3.28 (IQRâ¯=â¯1.84-5.74) in 2019. Urologists published 52.5% of AD manuscripts over the study period. CONCLUSIONS: Our results show substantial growth in the use of ADs for the study of urologic oncology. Given the broad use of ADs, investigators and specialty societies should advocate for continued improvement in the data captured by them.
Assuntos
Bases de Dados Factuais/estatística & dados numéricos , Bases de Dados Factuais/tendências , Publicações Periódicas como Assunto/estatística & dados numéricos , Publicações/tendências , Melhoria de Qualidade , Neoplasias Urológicas/diagnóstico , Neoplasias Urológicas/terapia , Humanos , Projetos de PesquisaRESUMO
OBJECTIVE: To evaluate the addition of software-assisted fusion magnetic resonance imaging (MRI) targeted biopsy to systematic biopsy and determine clinical and imaging factors associated with improved prostate cancer (PCa) detection. METHODS: We analyzed 454 patients who had prostate MRI and underwent combined systematic and software-assisted fusion MRI-targeted biopsy at 2 academic centers between July 2015 and December 2017. For our analysis, we compared the Gleason grade group of cores obtained systematically to cores obtained using MRI-targeting. Using multivariable analysis, we examined clinical and imaging factors associated with higher grade group disease in MRI-targeted cores. RESULTS: Software assisted fusion MRI-targeted biopsy detected higher grade group disease in 18.3% of patients. Factors associated with higher grade group disease in MRI-targeted cores included anterior MRI lesion location (odds ratio [OR] 3.15, P< 0.01) and multiple lesions on MRI (OR 2.47, Pâ¯=â¯0.01). Increasing prostate volume per cubic centimeter was noted to be negatively associated (OR 0.98, Pâ¯=â¯0.02). Notably, factors not found to be associated with improved detection included PIRADS classification 5 compared to 3 (OR 2.47, Pâ¯=â¯0.08), PIRADS classification 4 compared to 3 (OR 1.37, Pâ¯=â¯0.50), previous negative biopsy (OR 1.48, Pâ¯=â¯0.29), inclusion on an active surveillance protocol (OR 1.36, Pâ¯=â¯0.48), transitional zone lesion location (OR 0.72, Pâ¯=â¯0.45), and institution at which biopsy was performed (OR 1.81, Pâ¯=â¯0.16). CONCLUSION: Adding software-assisted fusion MRI-targeting to systematic prostate biopsy offers benefit for men with an anterior and multiple MRI lesions. In absence of these factors, systematic biopsy alone or with cognitive fusion may be considered.
Assuntos
Biópsia Guiada por Imagem , Imageamento por Ressonância Magnética , Próstata/patologia , Neoplasias da Próstata/patologia , Idoso , Humanos , Biópsia Guiada por Imagem/métodos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , SoftwareRESUMO
PURPOSE: During COVID-19, many operating rooms were reserved exclusively for emergent cases. As a result, many elective surgeries for renal cell carcinoma (RCC) were deferred, with an unknown impact on outcomes. Since surveillance is commonplace for small renal masses, we focused on larger, organ-confined RCCs. Our primary endpoint was pT3a upstaging and our secondary endpoint was overall survival. MATERIALS AND METHODS: We retrospectively abstracted cT1b-T2bN0M0 RCC patients from the National Cancer Database, stratifying them by clinical stage and time from diagnosis to surgery. We selected only those patients who underwent surgery. Patients were grouped by having surgery within 1 month, 1-3 months, or >3 months after diagnosis. Logistic regression models measured pT3a upstaging risk. Kaplan Meier curves and Cox proportional hazards models assessed overall survival. RESULTS: A total of 29,746 patients underwent partial or radical nephrectomy. Delaying surgery >3 months after diagnosis did not confer pT3a upstaging risk among cT1b (ORâ¯=â¯0.90; 95% CI: 0.77-1.05, Pâ¯=â¯0.170), cT2a (ORâ¯=â¯0.90; 95% CI: 0.69-1.19, Pâ¯=â¯0.454), or cT2b (ORâ¯=â¯0.96; 95% CI: 0.62-1.51, Pâ¯=â¯0.873). In all clinical stage strata, nonclear cell RCCs were significantly less likely to be upstaged (P <0.001). A sensitivity analysis, performed for delays of <1, 1-3, 3-6, and >6 months, also showed no increase in upstaging risk. CONCLUSION: Delaying surgery up to, and even beyond, 3 months does not significantly increase risk of tumor progression in clinically localized RCC. However, if deciding to delay surgery due to COVID-19, tumor histology, growth kinetics, patient comorbidities, and hospital capacity/resources, should be considered.