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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.
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Carcinoma de Células Transicionales , Fotoquimioterapia , Neoplasias Ureterales , Neoplasias de la Vejiga Urinaria , Humanos , Carcinoma de Células Transicionales/patología , Recurrencia Local de Neoplasia/tratamiento farmacológico , Fotoquimioterapia/métodos , Neoplasias Ureterales/patología , Ureteroscopía/métodos , Neoplasias de la Vejiga Urinaria/tratamiento farmacológicoRESUMEN
PURPOSE: Little is known regarding the prognostic implications of variant histology in upper tract urothelial carcinoma (UTUC). We sought to evaluate the impact of variant histology UTUC on patient survival outcomes at our institution. MATERIALS AND METHODS: We identified 705 patients who underwent nephroureterectomy for UTUC at our institution between January 1995 and December 2018. We tested the association between variant histology and cancer-specific survival (CSS) and overall survival (OS) using separate multivariable Cox models after adjusting for pathological stage. RESULTS: Forty-seven patients (6.7%) had variant histology, with prevalence increasing over time (p=0.003). Other demographic and surgical characteristics were similar between variant histology and pure urothelial carcinoma groups. While patients with variant histology were more likely to receive neoadjuvant chemotherapy (38% vs 15%, p <0.001), they were also more likely to have a higher pathological T stage (p <0.001). Variant histology was associated with significantly worse CSS (HR: 2.14; 95% CI 1.33, 3.44; p=0.002) and OS (HR: 1.74; 95% CI 1.15, 2.63; p=0.008). After adjusting for pathological T stage, variant histology was not significantly associated with CSS (HR: 1.17; 95% CI 0.72, 1.89; p=0.5) or OS (HR: 1.20; 95% CI 0.79, 1.84; p=0.4). CONCLUSIONS: Variant histology UTUC is associated with advanced stage and poor survival, and could serve as a useful biomarker for high-risk disease when pathological stage is unknown. However, the inferior CSS and OS with variant histology can be explained by the higher tumor stage on nephroureterectomy. Thus, finding variant histology on surgical pathology does not provide additional prognostic information beyond stage.
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Carcinoma de Células Transicionales , Neoplasias Ureterales , Neoplasias de la Vejiga Urinaria , Carcinoma de Células Transicionales/patología , Humanos , Nefroureterectomía , Pronóstico , Estudios Retrospectivos , Neoplasias Ureterales/patología , Neoplasias de la Vejiga Urinaria/cirugíaRESUMEN
OBJECTIVES: To evaluate three subtypes of continent-cutaneous urinary diversion (CCUD); Indiana pouch (IP), right colon pouch with appendico-umbilicostomy (AU), and right colon pouch with neo-appendico-umbilicostomy (NAU), by investigating diversion-specific complications and quality-of-life outcomes. MATERIALS AND METHODS: A retrospective review of an IRB-approved database was conducted for perioperative and outcome data. The EORTC QLQ-C30 questionnaire was used to assess quality of life; all responses were obtained > 6 months after diversion. RESULTS: Fifty-eight patients who underwent a CCUD at our institution from 2010 to 2016 (33 IP by two surgeons, 15 AU and ten NAU by third surgeon) were identified for this study. Higher age and Charlson Comorbidity Index (CCI) ≥ 3 were seen in the AU cohort when compared to the IP cohort (P = 0.02 and 0.02, respectively). NAU group were also older when compared to the IP group (P = 0.02). After a median follow-up of 21 months (range: 0.8-81.0), more high-grade diversion-related complications were reported for AU and NAU patients comparing to the IP group (P < 0.01 and P = 0.02, respectively). More stoma complications were also reported for the NAU cohort than the IP cohort (70% vs 30%, P = 0.03). In all groups, > 60% of stoma complications occurred at the skin or fascia level. In the 90-day postoperative period, a higher continence rate was reported for the IP cohort, and this difference was significant when compared to the NAU cohort (P = 0.04). Length of stay after surgery and revision rates were not significantly different. For all groups, the majority of patients reported little-to-no disturbance of daily functions and rated overall quality of life as good-to-excellent. CONCLUSION: Urinary diversion using the Indiana pouch and right colon pouch with appendico/neo-appendico-umbilicostomy are all associated with high rates of continence and patient satisfaction. When compared to IP, AU and NAU patients had higher rates of high-grade diversion-related complications and NAU patients had a higher stoma complications with lower 90-day continence rate.
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Apéndice/cirugía , Colon/cirugía , Estomía/efectos adversos , Complicaciones Posoperatorias/etiología , Calidad de Vida , Ombligo/cirugía , Neoplasias de la Vejiga Urinaria/cirugía , Reservorios Urinarios Continentes , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Derivación UrinariaRESUMEN
PURPOSE OF REVIEW: A review of the impact of several key patient characteristics on oncologic outcomes in bladder cancer (BC) summarized and analyzed in a narrative fashion. RECENT FINDINGS: The bulk of the published literature suggests that females and blacks have poorer cancer-specific outcomes. Both groups tend to present with worse disease, which may be driven by differences in access to timely and quality care. Attempts to assess the association between smoking status and history and BC outcomes have been hindered by the quality and heterogeneity of the data, although several studies have linked smoking with higher rates of recurrence and poorer survival. Being married, particularly in men, may improve survival after radical cystectomy (RC). Limited data suggests that socioeconomic and education levels may be associated with poorer survival; however, the data is limited. A growing body of investigation suggests that there are significant differences in oncologic outcomes in BC patients based on race, gender, smoking status, socioeconomic status, and others. Further focus and investigation is needed to validate these findings, investigate the root cause of these differences, and offer solutions to mitigate them.
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Disparidades en el Estado de Salud , Estado Civil , Recurrencia Local de Neoplasia , Factores Raciales , Fumar , Neoplasias de la Vejiga Urinaria/terapia , Escolaridad , Humanos , Renta , Recurrencia Local de Neoplasia/patología , Factores Sexuales , Tasa de Supervivencia , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
In this study, we sought to determine the effect of trainee (resident or fellow physician) involvement in male infertility surgical procedures on patient surgical outcomes and complications. The American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database was retrospectively reviewed for fertility surgical procedures from 2006 to 2012. The procedures included were as follows: epididymectomy, spermatocelectomy, varicocelectomy ± hernia repair, ejaculatory duct resection, vasovasostomy, vasoepididymostomy and 'unlisted procedure male genital system' (to capture sperm retrieval procedures). A variety of peri- and post-operative outcomes were examined. Trainee and nontrainee-involved groups were compared by Wilcoxon rank sum tests, followed by logistic regression, univariate and multivariate analyses. 924 cases were included: 309 with trainees and 615 without. The median post-graduate trainee year was 3 (range: 0-10). Patients in the trainee-involved cohort had higher rates of chronic obstructive pulmonary disease, steroid usage and black race. Mean operative time was 42.5% longer in trainee-involved cases, even after controlling for other covariates (76.2 vs. 49.5 min, p = .00). Hospital stay length was also longer in trainee-involved cases (0.41 vs. 0.35 days, p = .02). There were no differences in superficial infections (p = 1.00), deep wound infections (p = 1.00), urinary tract infections (p = .26), or reoperations (p = .23) with or without trainee involvement.
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Infertilidad Masculina , Internado y Residencia , Humanos , Infertilidad Masculina/etiología , Infertilidad Masculina/cirugía , Masculino , Tempo Operativo , Complicaciones Posoperatorias/epidemiología , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Over the course of several weeks following the first diagnosed case of COVID-19 in the U.S., the virus rapidly spread across our communities. It became evident that the pandemic was going to place a severe strain on all components of the U.S. healthcare system, and we needed to adapt our daily practices, training and education. In the present paper we discuss four pillars to face a pandemic: surgical and outpatients service, tele-medicine and tele-education. In the face of unprecedented risks in providing adequate health care to our patients during this current, evolving public health crisis of COVID-19, alternative patient management tools such as telemedicine services, allow clinicians to maintain necessary patient rapport with their healthcare provider when required. As a subspecialty, urology should take full advantage of telehealth and tele-education at this juncture. As tele-urology and tele-education can obviate the potential drawbacks of "social distancing" as it pertains to healthcare, the platform can also reduce the risk of COVID-19 spread, without compromising quality urological care and educational efforts. Telehealth can bring urologists and their patients together, perhaps closer than ever.
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Infecciones por Coronavirus/complicaciones , Coronavirus , Pandemias , Neumonía Viral/complicaciones , Urólogos , Urología/métodos , Betacoronavirus , COVID-19 , Infecciones por Coronavirus/epidemiología , Humanos , Neumonía Viral/epidemiología , SARS-CoV-2 , Estados UnidosRESUMEN
High-risk prostate cancer (PCa) is associated with higher rates of biochemical recurrence, clinical recurrence, metastasis, and PCa-specific death, compared to low-and intermediate-risk disease. Herein, we review the various definitions of high-risk PCa, describe the rationale for neoadjuvant therapy prior to radical prostatectomy, and summarize the contemporary data on neoadjuvant therapies. Since the 1990s, several randomized trials of neoadjuvant androgen deprivation therapy (ADT) have consistently demonstrated improved pathological parameters, specifically tumor downstaging and reduced extraprostatic extension, seminal vesicle invasion, and positive surgical margins without improvements in cancer-specific or overall survival. These studies, however, were not exclusive to high-risk patients and were limited by suboptimal follow-up periods. Newer studies of neoadjuvant ADT in high-risk PCa show promising pathological and oncological outcomes. Recent level 1 data suggests neoadjuvant chemohormonal therapy (CHT) may improve longer-term survival in high-risk PCa. Immunologic neoadjuvant trials are in their infancy, and further study is required. Neoadjuvant therapies may be promising additions to the multimodal therapeutic landscape of high-risk and locally advanced PCa in the near future.
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PURPOSE OF REVIEW: Bladder cancer is a deadly and common malignancy, with 24% of new cases presenting as T1 disease. High-grade T1 in particular represents a difficult entity to treat due to its clinical variability and known risks of recurrence, progression, and cancer-specific mortality. The differences in guidelines from major urologic organizations underscore this variability, and the past year has seen another BCG shortage, further complicating management. Advances have been made in the molecular and genomic characterization of high-grade T1, and new clinical trials are available to investigate alternative therapies. In this review, we summarize the variations in guidelines, alternatives to BCG, emerging molecular and genomic discoveries, and recent clinical trials. RECENT FINDINGS: Adherence to guidelines for non-muscle-invasive bladder cancer in the community among practicing urologists remains low, in part due to the variations in available guidelines. In the era of a BCG shortage, decreased dosing schedules and alternative intravesical options are increasingly being used. New biomarkers are being discovered to better risk-stratify patients, with future therapies aimed at targeting aggressive disease. HGT1 urothelial carcinoma remains a highly variable and aggressive disease, but we are making significant progress in better characterizing the clinical and molecular factors that influence recurrence and progression, to better guide management.
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Vacuna BCG/administración & dosificación , Carcinoma de Células Transicionales/terapia , Neoplasias de la Vejiga Urinaria/terapia , Administración Intravesical , Vacuna BCG/provisión & distribución , Biomarcadores/metabolismo , Carcinoma de Células Transicionales/genética , Carcinoma de Células Transicionales/metabolismo , Carcinoma de Células Transicionales/patología , Ensayos Clínicos como Asunto , Adhesión a Directriz , Humanos , Guías de Práctica Clínica como Asunto , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/metabolismo , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
BACKGROUND: Pelvic radiation is a known risk factor for the development and progression of erectile dysfunction. When medical therapy fails, the 3-piece inflatable penile prosthesis (IPP) can offer patients a definitive treatment option. Because of radiation-induced vascular changes and tissue fibrosis, a careful surgical approach is necessary to avoid intraoperative complications and attain successful outcomes. Despite its widespread use in prostate cancer treatment, there are no contemporary studies examining the effects that pelvic radiation can have on 3-piece IPP placement and device survival. AIM: To present technical considerations and contemporary outcomes of placing a 3-piece IPP for refractory erectile dysfunction in patients with a history of pelvic radiation. METHODS: We retrospectively reviewed 78 patients who underwent placement of a 3-piece IPP (AMS 700; Boston Scientific, Marlborough, MA, USA) after being treated with pelvic radiotherapy from 2003 through 2016. All patients had been treated with external beam and/or brachytherapy for treatment of prostate malignancy. An infrapubic approach was used in all patients, with reservoir placement in the space of Retzius or in the lateral retroperitoneal space. Patient demographics, perioperative data, and postoperative outcomes including prosthetic infection and mechanical failure were examined and statistical analysis was performed. OUTCOMES: Rates of device infection, revision surgery, and reservoir complications. RESULTS: No intraoperative complications were observed. After a mean follow-up of 49.0 months (6.6-116.8), 2 patients developed an infection of their prosthesis that required explantation. These patients underwent successful IPP removal and immediate reimplantation. 11 patients (14.1%) required revision surgery (pump replacement, n = 4; pump relocation, n = 2; cylinder replacement, n = 4; reservoir replacement owing to leak, n = 1). No reservoir-related complications such as herniation or erosion into adjacent structures were observed. CLINICAL IMPLICATIONS: The 3-piece IPP can be placed safely in a broad range of patients treated with pelvic radiotherapy. STRENGTHS AND LIMITATIONS: This study describes contemporary long-term outcomes of the IPP in patients treated with pelvic radiation and includes patients with prior pelvic surgery and artificial urinary sphincter, which are commonly encountered in practice. It is limited by its single-center experience and lacks a comparison group of patients. Objective patient satisfaction data were not available for inclusion. CONCLUSIONS: The 3-piece IPP can be placed successfully in patients with a history of pelvic radiation without a significant increase in infectious complications, reservoir erosion, or mechanical failure compared with the global literature. Loh-Doyle J, Patil MB, Nakhoda Z, et al. Three-Piece Inflatable Penile Prosthesis Placement Following Pelvic Radiation: Technical Considerations and Contemporary Outcomes. J Sex Med 2018;15:1049-1054.
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Disfunción Eréctil/etiología , Disfunción Eréctil/cirugía , Prótesis de Pene , Neoplasias de la Próstata/radioterapia , Adulto , Anciano , Anciano de 80 o más Años , Boston , Humanos , Masculino , Persona de Mediana Edad , Satisfacción del Paciente , Pelvis/efectos de la radiación , Infecciones Relacionadas con Prótesis/epidemiología , Estudios Retrospectivos , Factores Socioeconómicos , Esfínter Urinario Artificial/efectos adversosRESUMEN
5-Aza-2'-deoxycytidine (5azaC-dR) has been employed as an inhibitor of DNA methylation, a chemotherapeutic agent, a clastogen, a mutagen, an inducer of fragile sites and a carcinogen. However, its effects are difficult to quantify because it rapidly breaks down in aqueous solution to the stable compound 2'-deoxyriboguanylurea (GuaUre-dR). Here, we used a phosphoramidite that permits the introduction of GuaUre-dR at defined positions in synthetic oligodeoxynucleotides to demonstrate that it is a potent inhibitor of human DNA methyltransferase 1 (hDNMT1) and the bacterial DNA methyltransferase (M.EcoRII) and that it is a mutagen that can form productive base pairs with either Guanine or Cytosine. Pure GuaUre-dR was found to be an effective demethylating agent and was able to induce 5azaC-dR type fragile sites FRA1J and FRA9E in human cells. Moreover, we report that demethylation associated with C:G â G:C transversion and C:G â T:A transition mutations was observed in human cells exposed to pure GuaUre-dR. The data suggest that most of the effects attributed to 5azaC-dR are exhibited by its stable primary breakdown product.
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Sitios Frágiles del Cromosoma , Metilasas de Modificación del ADN/antagonistas & inhibidores , Desoxirribosa/análogos & derivados , Inhibidores Enzimáticos/toxicidad , Guanidinas/toxicidad , Mutágenos/toxicidad , Azacitidina/análogos & derivados , Azacitidina/toxicidad , Secuencia de Bases , Línea Celular Tumoral , ADN (Citosina-5-)-Metiltransferasa 1 , ADN (Citosina-5-)-Metiltransferasas/antagonistas & inhibidores , ADN-Citosina Metilasas/antagonistas & inhibidores , Decitabina , Desoxirribosa/química , Desoxirribosa/farmacología , Desoxirribosa/toxicidad , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Guanidinas/química , Guanidinas/farmacología , Humanos , Datos de Secuencia Molecular , Mutagénesis , Mutágenos/química , Oligodesoxirribonucleótidos/químicaRESUMEN
Introduction: Immunotherapy is revolutionizing the management of multiple cancer types. However, only a subset of patients responds to immunotherapy. One mechanism of resistance is the absence of immune infiltrates within the tumor. In situ vaccine with local means of tumor destruction that can induce immunogenic cell death have been shown to enhance tumor T cell infiltration and increase efficacy of immune checkpoint blockade. Methods: Here, we compare three different forms of localize tumor destruction therapies: radiation therapy (RT), vascular targeted photodynamic therapy (VTP) and cryoablation (Cryo), which are known to induce immunogenic cell death, with their ability to induce local and systemic immune responses in a mouse 4T1 breast cancer model. The effects of combining RT, VTP, Cryo with anti-PD1 was also assessed. Results: We observed that RT, VTP and Cryo significantly delayed tumor growth and extended overall survival. In addition, they also induced regression of non-treated distant tumors in a bilateral model suggesting a systemic immune response. Flow cytometry showed that VTP and Cryo are associated with a reduction in CD11b+ myeloid cells (granulocytes, monocytes, and macrophages) in tumor and periphery. An increase in CD8+ T cell infiltration into tumors was observed only in the RT group. VTP and Cryo were associated with an increase in CD4+ and CD8+ cells in the periphery. Conclusion: These data suggest that cell death induced by VTP and Cryo elicit similar immune responses that differ from local RT.
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INTRODUCTION: We evaluated surgical trends, perioperative management evolution, and oncologic outcomes in patients who underwent radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC) at a tertiary cancer center over a 24-year period. METHODS: Between 1995 and 2018, we evaluated 743 consecutive patients with UTUC who underwent RNU. Generalized additive models were used to estimate the associations between date of surgery and continuous outcomes using a linear model, dichotomous outcomes using a logit link, categorical outcomes using multinomial models, and 2- and 5-year survival outcomes using Cox proportional hazards models. RESULTS: Over the study period, preoperative diagnostic endoscopic biopsies increased from 10% to 66%, along with the proportion of patients who underwent RNU for high-grade disease from 55% to 91%. The rate of open RNU declined from 100% to 56% with a rise in minimally invasive approaches. Median lymph node yield increased with more retroperitoneal lymph node dissections performed. Neoadjuvant chemotherapy utilization increased with a contemporary utilization rate of 32%, coinciding with an increase in pT0 rate from 2% to 8%. Cancer-specific survival probabilities improved over the study period, while metastasis-free and overall survival remained stable. CONCLUSIONS: We found several changes in treatment patterns and outcomes for patients with UTUC over the past 2 decades. How individual alterations in management factors, such as patient selection, perioperative chemotherapy, lymphadenectomy, and salvage therapies, impact patient outcomes is challenging in the setting of multiple overlapping practice changes for this rare disease and warrants further investigation.
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Carcinoma de Células Transicionales , Neoplasias de la Vejiga Urinaria , Neoplasias Urológicas , Humanos , Nefroureterectomía , Carcinoma de Células Transicionales/cirugía , Neoplasias de la Vejiga Urinaria/cirugía , Neoplasias Urológicas/tratamiento farmacológico , Escisión del Ganglio LinfáticoRESUMEN
BACKGROUND: Immune checkpoint inhibitors (ICIs) are now a mainstay of metastatic renal cell carcinoma (RCC) management with five current Food and Drug Administration-approved regimens. However, data regarding nephrectomy outcomes following an ICI are limited. OBJECTIVE: To evaluate the safety and outcomes of nephrectomy following an ICI. DESIGN, SETTING, AND PARTICIPANTS: A retrospective review was performed of patients with primary locally advanced or metastatic RCC undergoing nephrectomy following an ICI in five US academic centers between January 2011 and September 2021. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Clinical data, perioperative outcomes, and 90-d complications/readmissions were recorded and evaluated by univariate and logistic regression models. Recurrence-free and overall survival probabilities were estimated by the Kaplan-Meier method. RESULTS AND LIMITATIONS: A total of 113 patients with a median (interquartile range) age of 63 (56-69) yr were included. The main ICI regimens were nivolumab ± ipilimumab (n = 85) and pembrolizumab ± axitinib (n = 24). Risk groups included 95% intermediate- and 5% poor-risk patients. Surgical procedures were 109 radical and four partial nephrectomies, including 60 open, 38 robotic, and 14 laparoscopic with five (10%) conversions. Two intraoperative complications were reported (bowel and pancreatic injury). The median operative time, estimated blood loss, and hospital stay were 3 h, 250 ml, and 3 d, respectively. A complete pathologic response (ypT0N0) was noted in six (5%) patients. The 90-d complication rate was 24%, with 12 (11%) patients requiring readmission. On a multivariable analysis, two or more risk factors (odds ratio [OR] 2.91, 95% confidence interval [CI]: 1.09, 7.42) and pathologic T stage ≥T3 (OR 4.21, 95% CI: 1.13-15.8) were independently associated with a higher 90-d complication rate. The 3-yr estimated overall survival and recurrence-free survival rates were 82% and 47%, respectively. Limitations include the retrospective nature and heterogeneous cohort in terms of clinicopathologic characteristics and ICI regimens received. CONCLUSIONS: Nephrectomy following ICI therapy is feasible and a potential consolidative therapy option in select patients. Further research in the neoadjuvant setting is also warranted. PATIENT SUMMARY: This study evaluates the outcomes of kidney surgery following immune checkpoint inhibitor therapy (mainly nivolumab and ipilimumab or pembrolizumab and axitinib) for patients with advanced kidney cancer. We utilized data from five academic centers across the USA and found that surgery in this setting did not have more complications or returns to the hospital than similar surgeries, indicating that it is a safe and feasible procedure at this time.
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Carcinoma de Células Renales , Neoplasias Renales , Humanos , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/cirugía , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/cirugía , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Nivolumab , Ipilimumab/efectos adversos , Axitinib , Estudios Retrospectivos , Nefrectomía/métodosRESUMEN
BACKGROUND: There is limited ability to accurately diagnose and clinically stage patients with upper tract urothelial carcinoma (UTUC). The most easily available and widely used urinary biomarker is urine cytology, which evaluates cellular material yet lacks sensitivity. We sought to assess the feasibility of performing next-generation sequencing (NGS) on urine cytology specimens from patients with UTUC and evaluate the genomic concordance with tissue from primary tumor. METHODS: In this retrospective study, we identified 48 patients with a diagnosis of UTUC treated at Memorial Sloan Kettering Cancer Center (MSK) between 2019 and 2022 who had banked or fresh urine samples. A convenience cohort of matching, previously sequenced tumor tissue was used when available. Urine specimens were processed and the residual material, including precipitated cell-free DNA, was sequenced using our tumor-naïve, targeted exome sequencing platform that evaluates 505 cancer-related genes (MSK-IMPACT). The primary outcome was at least 1 detectable mutation in urinary cytology specimens. The secondary outcome was concordance to matched tissue (using ANOVA or Chi-Square, as indicated). RESULTS: Genomic sequencing was successful for 45 (94%) of the 48 urinary cytology patient samples. The most common mutations identified were TERT (62.2%), KMT2D (46.7%), and FGFR3 (35.6%). All patients with negative urine cytology and low-grade tissue had successful cytology sequencing. Thirty-six of the 45 patients had matching tumor tissue available; concordance to matched tissue was 55% overall (131 of the total 238 oncogenic or likely oncogenic somatic mutations identified). However, in 94.4% (nâ¯=â¯34/36) of patients, the cytology had at least 1 shared mutation with tissue. Eleven (30.6%) patients had 100% concordance between cytology and tissue. CONCLUSIONS: Sequencing urinary specimens from selective UTUC cytology is feasible in nearly all patients with UTUC. Prospective studies are underway to investigate a clinical role for this promising technology.
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Carcinoma de Células Transicionales , Neoplasias de la Vejiga Urinaria , Humanos , Neoplasias de la Vejiga Urinaria/patología , Carcinoma de Células Transicionales/patología , Estudios Retrospectivos , Estudios Prospectivos , Estudios de Factibilidad , GenómicaRESUMEN
PURPOSE: Neoadjuvant chemotherapy (NAC) has proven survival benefits for patients with invasive urothelial carcinoma of the bladder, yet its role for upper tract urothelial carcinoma (UTUC) remains undefined. We conducted a multicenter, single-arm, phase II trial of NAC with gemcitabine and split-dose cisplatin (GC) for patients with high-risk UTUC before extirpative surgery to evaluate response, survival, and tolerability. METHODS: Eligible patients with defined criteria for high-risk localized UTUC received four cycles of split-dose GC before surgical resection and lymph node dissection. The primary study end point was rate of pathologic response (defined as < ypT2N0). Secondary end points included progression-free survival (PFS), overall survival (OS), and safety and tolerability. RESULTS: Among 57 patients evaluated, 36 (63%) demonstrated pathologic response (95% CI, 49 to 76). A complete pathologic response (ypT0N0) was noted in 11 patients (19%). Fifty-one patients (89%) tolerated at least three complete cycles of split-dose GC, 27 patients (47%) tolerated four complete cycles, and all patients proceeded to surgery. With a median follow up of 3.1 years, 2- and 5-year PFS rates were 89% (95% CI, 81 to 98) and 72% (95% CI, 59 to 87), while 2- and 5-year OS rates were 93% (95% CI, 86 to 100) and 79% (95% CI, 67 to 94), respectively. Pathologic complete and partial responses were associated with improved PFS and OS compared with nonresponders (≥ ypT2N any; 2-year PFS 100% and 95% v 76%, P < .001; 2-year OS 100% and 100% v 80%, P < .001). CONCLUSION: NAC with split-dose GC for high-risk UTUC is a well-tolerated, effective therapy demonstrating evidence of pathologic response that is associated with favorable survival outcomes. Given that these survival outcomes are superior to historical series, these data support the use of NAC as a standard of care for high-risk UTUC, and split-dose GC is a viable option for NAC.
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Carcinoma de Células Transicionales , Neoplasias de la Vejiga Urinaria , Humanos , Gemcitabina , Cisplatino , Carcinoma de Células Transicionales/tratamiento farmacológico , Carcinoma de Células Transicionales/cirugía , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Terapia NeoadyuvanteRESUMEN
INTRODUCTION: Oncologic implications of variant histology (VH) have been extensively studied in bladder cancer; however, further investigation is needed in upper tract urothelial carcinoma (UTUC). Our study aims to evaluate the impact of VH on oncological outcomes in UTUC patients treated with radical nephroureterectomy (RNU). METHODS: A retrospective analysis was performed on patients who underwent a robotic or laparoscopic RNU for UTUC using the ROBUUST database, a multi-institutional collaborative including 17 centers worldwide. Logistic regression was used to assess the effect of VH on urothelial recurrence (bladder, contralateral upper tract), metastasis, and survival following RNU. RESULTS: A total of 687 patients were included in this study. Median (IQR) age was 71 (64-78) years and 470 (68%) had organ confined disease. VH was present in 70 (10.2%) patients. In a median follow-up of 16 months, the incidence of urothelial recurrence, metastasis, and mortality was 26.8%, 15.3%, and 11.8%, respectively. VH was associated with increased risk of metastasis (HR 4.3, P <.0001) and death (HR 2.0, P =.046). In multivariable analysis, VH was noted to be an independent risk factor for metastasis (HR 1.8, P =.03) but not for urothelial recurrence (HR 0.99, P =.97) or death (HR 1.4, P =.2). CONCLUSION: Variant histology can be found in 10% of patients with UTUC and is an independent risk factor for metastasis following RNU. Overall survival rates and the risk of urothelial recurrence in the bladder or contralateral kidney are not affected by the presence of VH.
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Carcinoma de Células Transicionales , Neoplasias Ureterales , Neoplasias de la Vejiga Urinaria , Anciano , Humanos , Carcinoma de Células Transicionales/cirugía , Carcinoma de Células Transicionales/patología , Riñón/patología , Recurrencia Local de Neoplasia/patología , Nefroureterectomía/métodos , Estudios Retrospectivos , Neoplasias Ureterales/patología , Neoplasias de la Vejiga Urinaria/cirugíaRESUMEN
INTRODUCTION: As more centers develop robotic proficiency, progressing to a successful robot-assisted partial nephrectomy (RAPN) program depends on a number of factors. We describe our technique, results, and analysis of program setup for RAPN. MATERIALS AND METHODS: Between 2005 and 2011, 92 RAPNs were performed following maturation of a robotic prostatectomy program. Operating rooms and supply rooms were outfitted for efficient robotic throughput. Tilepro and intraoperative ultrasound were used for all cases. Training and experiential learning for surgeons, anesthesia and nursing staff was a high priority. An onsite robotic technician helped troubleshoot, prepare the room and staff prior to starting surgery, and provide assistance with different robotic models. RESULTS: Average operative time decreased over time from 235 min to 199 min (p = .03). Warm ischemia time decreased from 26 minutes to 23 minutes (p = .02) despite an increased complexity of tumors and operations on multiple tumors. Median estimated blood loss was 150 mL. Average length of hospital stay was 3 days (range 1-9). Average size of lesions was 2.7 cm (range 0.7-8.6). Final pathology demonstrated 71 (77%) malignant lesions and 21 (23%) benign lesions. CONCLUSIONS: The addition of a robot-assisted partial nephrectomy program to an institutional robotic program can be coordinated with several key steps. Outcomes from an operational, oncologic, and renal functional standpoint are acceptable. Despite increased complexity of tumors and treatment of multiple lesions, operative and warm ischemia times showed a decrease over time. An organizational model that involves the surgeons, anesthesia, nursing staff, and possibly a robotic technical specialist helps to overcome the learning curve.
Asunto(s)
Pérdida de Sangre Quirúrgica , Neoplasias Renales/cirugía , Laparoscopía/métodos , Nefrectomía/métodos , Robótica/métodos , Adulto , Anciano , Anciano de 80 o más Años , Volumen Sanguíneo , Femenino , Humanos , Neoplasias Renales/patología , Laparoscopía/educación , Laparoscopía/instrumentación , Curva de Aprendizaje , Tiempo de Internación , Masculino , Persona de Mediana Edad , Nefrectomía/educación , Nefrectomía/instrumentación , Robótica/educación , Factores de Tiempo , Isquemia TibiaRESUMEN
The purpose of the study is to evaluate the impact of a multimodal Enhanced Recovery After Surgery (ERAS) protocol on perioperative opioid consumption and hospital length of stay (LOS) after robotic-assisted radical prostatectomy (RARP). We compared the first 176 patients enrolled in the protocol (ERAS group) with the previous 176 patients (non-ERAS group) at a single quaternary institution from December 2017 to June 2019. The ERAS protocol included a multimodal opioid-sparing regimen utilizing acetaminophen, gabapentin, celecoxib, and liposomal bupivacaine. Demographic data, co-morbidities, post-operative pain scores, post-operative opiate consumption measured by morphine milligram equivalents (MME), operating time, and LOS were collected. The two groups were compared using chi-squared, Fisher exact, or Student t tests as appropriate. Multivariable logistic regression analysis was performed to identify predictors of prolonged LOS (> 1 day). The ERAS and non-ERAS groups were equivalent in terms of baseline characteristics and pathological data. The ERAS group had lower post-operative pain scores, post-operative opiate consumption (MME 15 vs. 46, p < 0.01), and LOS (1.2 vs. 1.7 days, p < 0.01) compared to the non-ERAS group. Only 22% in the ERAS cohort had a prolonged LOS compared to 39% of the non-ERAS group (p < 0.01). The ERAS protocol was a negative predictor of prolonged LOS on multivariable logistic regression analysis (odds ratio 0.39, 95% confidence interval 0.22-0.70, p < 0.01). A limitation of this study is its single-center retrospective design. The implementation of a multimodal opioid-sparing ERAS protocol was associated with improved pain control, reduced perioperative opioid usage, and shorter LOS after RARP.