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OBJECTIVE: To quantify the oncological risks of bladder-sparing therapy (BST) in patients with Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle-invasive bladder cancer (NMIBC) compared to upfront radical cystectomy (RC). PATIENTS AND METHODS: Pre-specified data elements were collected from retrospective cohorts of patients with BCG-unresponsive NMIBC from 10 international sites. After Institutional Review Board approval, patients were included if they had BCG-unresponsive NMIBC meeting United States Food and Drug Administration criteria. Oncological outcomes were collected following upfront RC or BST. BST regimens included re-resection or surveillance only, repeat BCG, intravesical chemotherapy, systemic immunotherapy, and clinical trials. RESULTS: Among 578 patients, 28% underwent upfront RC and 72% received BST. The median (interquartile range) follow-up was 50 (20-69) months. There were no statistically significant differences in metastasis-free survival, cancer-specific survival, or overall survival between treatment groups. In the BST group, high-grade recurrence rates were 37% and 52% at 12 and 24 months and progression to MIBC was observed in 7% and 13% at 12 and 24 months, respectively. RC was performed in 31.7% in the BST group and nodal disease was found in 13% compared with 4% in upfront RC (P = 0.030). CONCLUSION: In a selected cohort of patients, initial BST offers comparable survival outcomes to upfront RC in the intermediate term. Rates of recurrence and progression increase over time especially in patients treated with additional lines of BST.
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BACKGROUND: Even though cytoreductive nephrectomy (CN) was once the standard of care for patients with advanced renal cell carcinoma (RCC), its role in treatment has not been well analyzed or defined in the era of immunotherapy (IO). MATERIALS AND METHODS: This study analyzed pathological outcomes in patients with advanced or metastatic RCC who received IO prior to CN. This was a multi-institutional, retrospective study of patients with advanced or metastatic RCC. Patients were required to receive IO monotherapy or combination therapy prior to radical or partial CN. The primary endpoint assessed surgical pathologic outcomes, including American Joint Committee on Cancer (AJCC) staging and frequency of downstaging, at the time of surgery. Pathologic outcomes were correlated to clinical variables using a Wald-chi squared test from Cox regression in a multi-variable analysis. Secondary outcomes included objective response rate (ORR) defined by response evaluation criteria in solid tumors (RECIST) version 1.1 and progression-free survival (PFS), which were estimated using the Kaplan-Meier method with reported 95% CIs. RESULTS: Fifty-two patients from 9 sites were included. Most patients were male (65%), 81% had clear cell histology, 11% had sarcomatoid differentiation. Overall, 44% of patients experienced pathologic downstaging, and 13% had a complete pathologic response. The ORR immediately prior to nephrectomy was stable disease in 29% of patients, partial response in 63%, progressive disease in 4%, and 4% unknown. Median follow-up for the entire cohort was 25.3 months and median PFS was 3.5 years (95% CI, 2.1-4.9). CONCLUSIONS: IO-based interventions prior to CN in patients with advanced or metastatic RCC demonstrates efficacy, with a small fraction of patients showing a complete response. Additional prospective studies are warranted to investigate the role of CN in the modern IO-era.
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PURPOSE: We studied whether adding percent free PSA to total PSA improves prediction of clinically significant prostate cancer and fatal prostate cancer. MATERIALS AND METHODS: A total of 6,727 men within the intervention arm of PLCO (Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial) had baseline percent free PSA. Of this cohort, 475 had clinically significant prostate cancer and 98 had fatal prostate cancer. Cumulative incidence and Cox analyses were conducted to evaluate the association between percent free PSA/PSA and clinically significant prostate cancer/fatal prostate cancer. Harrell's C index evaluated predictive ability. Kaplan-Meier analysis assessed survival. RESULTS: Median follow-up was 19.7 years, median baseline PSA was 1.19 ng/mL, median percent free PSA was 18%. Cumulative incidence of fatal prostate cancer for men with baseline PSA ≥2 ng/mL and percent free PSA ≤10 was 3.2% and 6.1% at 15 and 25 years, respectively, compared to 0.03% and 1.1% for men with percent free PSA >25%. In younger men (55-64 years) with baseline PSA 2-10 ng/mL, C index improved from 0.56 to 0.60 for clinically significant prostate cancer and from 0.53 to 0.64 for fatal prostate cancer with addition of percent free PSA. In older men (65-74 years), C index improved for clinically significant prostate cancer from 0.60 to 0.66, with no improvement in fatal prostate cancer. Adjusting for age, digital rectal exam, family history of prostate cancer, and total PSA, percent free PSA was associated with clinically significant prostate cancer (HR 1.05, P < .001) per 1% decrease. Percent free PSA improved prediction of clinically significant prostate cancer and fatal prostate cancer for all race groups. CONCLUSIONS: In a large U.S. screening trial, the addition of percent free PSA to total PSA in men with baseline PSA ≥2 ng/mL improved prediction of clinically significant prostate cancer and fatal prostate cancer. Free PSA should be used to risk-stratify screening and decrease unnecessary prostate biopsies.
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Antígeno Prostático Específico , Neoplasias de la Próstata , Masculino , Humanos , Anciano , Tamizaje Masivo , Detección Precoz del Cáncer , Neoplasias de la Próstata/patología , Próstata/patologíaRESUMEN
OBJECTIVE: Utilization of partial nephrectomy (PN) for T2 renal mass is controversial due to concerns regarding burden of morbidity, though most cited data are from open PN (OPN). We compared surgical quality and functional outcomes of RPN and OPN for clinical T2a renal masses (cT2aRM). METHODS: Retrospective analysis of 150 consecutive patients [RPN 59/OPN 91] who underwent PN from July 2008 to June 2016. Main outcome was achievement of Trifecta [negative surgical margin, no major urologic complications, and ≥90% preservation of estimated glomerular filtration rate (eGFR)]. Multivariable analysis was performed to identify factors of Trifecta attainment. RESULTS: Mean tumor size (RPN 7.9 vs. OPN 8.4 cm, p = 0.139) and median RENAL score (p = 0.361) were similar. No difference was noted for positive margins (RPN 3.4% vs. OPN 1.1%, p = 0.561), ΔeGFR (RPN - 6.2 vs. OPN - 7.8, p = 0.543), and ≥ 90% eGFR recovery (RPN 54.1% vs. OPN 47.2%, p = 0.504). RPN had lower blood loss (p = 0.015), hospital stay (p = 0.013), and Clavien ≥ 3 complications (RPN 5.1% vs. OPN 16.5%, p = 0.041). Trifecta rate was significantly higher in RPN (47.5% vs. 34.0%, p = 0.041). Multivariable analysis demonstrated decreasing RENAL score (OR 1.11, p < 0.001), RPN (OR 1.2, p = 0.013), and decreasing EBL (OR 1.02, p = 0.016) to be associated with Trifecta attainment. CONCLUSIONS: RPN provided similar functional and oncologic precision to OPN, while being associated with improvements in major complications, the latter of which was reflected in a higher rate of Trifecta achievement for RPN. RPN may be considered to be a first-line option for select patients with cT2aRM when feasible and safe.
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Neoplasias Renales/cirugía , Nefrectomía/métodos , Procedimientos Quirúrgicos Robotizados , Anciano , Femenino , Tasa de Filtración Glomerular , Humanos , Riñón/fisiología , Neoplasias Renales/patología , Masculino , Márgenes de Escisión , Persona de Mediana Edad , Estadificación de Neoplasias , Complicaciones Posoperatorias/epidemiología , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
PURPOSE: To compare renal function and survival outcomes in patients with baseline chronic kidney disease (CKD) stage 2 undergoing partial (PN) or radical nephrectomy (RN), as nephron-sparing surgery is considered to be elective in this group. METHODS: Retrospective analysis of patients with CKD stage 2 and T1/T2 renal mass undergoing PN or RN from 2001 to 2015. Patients were stratified into substage CKD 2a or CKD 2b and analyzed between types of surgery. Primary outcome was overall survival (OS), eGFR < 45 at last follow-up was the secondary outcome. Multivariable analysis (MVA) was conducted for predictors of eGFR < 45 and OS. Kaplan-Meier analyses were conducted for freedom from eGFR < 45 and OS. RESULTS: 1213 patients analyzed (CKD 2a 609/CKD 2b 604) on MVA, RN (OR 3.68, p = 0.001) and CKD 2b (OR 3.3, p = 0.002) were independently associated with development of eGFR < 45 at last follow-up and RN (OR 3.76, p = 0.005) and eGFR < 45 (OR 2.51, p = 0.029) were associated with decreased OS. Kaplan-Meier analyses revealed that patients with CKD 2a/PN had the highest 5-year freedom from eGFR < 45 (94.3%) compared to CKD 2a/RN patients (91.5%), CKD2b/PN patients (87.6%) and CKD 2b/RN patients 82.0% (p < 0.001). Kaplan-Meier analyses for OS demonstrated that patients with CKD 2a/PN had significantly greater 5-year OS (97.6%) compared to CKD 2a/RN patients (95.2%), CKD 2b/PN patients (93.2%), and CKD 2b/RN patients (92.4%, p = 0.043). CONCLUSIONS: Patients with baseline CKD stage 2, particularly CKD 2b and undergoing RN, are at increased risk of GFR < 45, which was associated with decreased OS. In patients with CKD 2b, a nephron-sparing strategy is indicated and should be prioritized when feasible.
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Procedimientos Quirúrgicos Electivos , Nefrectomía/métodos , Insuficiencia Renal Crónica/mortalidad , Insuficiencia Renal Crónica/cirugía , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recuperación de la Función , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
Because of their importance in maintaining protein homeostasis, molecular chaperones, including heat-shock protein 90 (Hsp90), represent attractive drug targets. Although a number of Hsp90 inhibitors are in preclinical/clinical development, none strongly differentiate between constitutively expressed Hsp90ß and stress-induced Hsp90α, the two cytosolic paralogs of this molecular chaperone. Thus, the importance of inhibiting one or the other paralog in different disease states remains unknown. We show that the natural product, gambogic acid (GBA), binds selectively to a site in the middle domain of Hsp90ß, identifying GBA as an Hsp90ß-specific Hsp90 inhibitor. Furthermore, using computational and medicinal chemistry, we identified a GBA analog, referred to as DAP-19, which binds potently and selectively to Hsp90ß. Because of its unprecedented selectivity for Hsp90ß among all Hsp90 paralogs, GBA thus provides a new chemical tool to study the unique biological role of this abundantly expressed molecular chaperone in health and disease.
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Proteínas HSP90 de Choque Térmico/antagonistas & inhibidores , Proteínas HSP90 de Choque Térmico/química , Xantonas/farmacología , Simulación por Computador , Células HEK293 , Humanos , Mutagénesis Sitio-Dirigida , Dominios Proteicos , Isoformas de Proteínas , Xantonas/metabolismoRESUMEN
Systemic therapy strategies in the setting of localized and locally advanced renal cell carcinoma have continued to evolve in two directions: (i) as adjuvant therapy (to reduce the risk of recurrence or progression in high-risk localized groups); or (ii) as neoadjuvant therapy as a strategy to render primary renal tumors amenable to planned surgical resection in settings where radical resection or nephron-sparing surgery was not thought to be safe or feasible. In the realm of adjuvant therapy, the results of adjuvant therapy phase III randomized clinical trials have been mixed and contradictory; nevertheless, the findings of the landmark Sunitinib Treatment of Renal Adjuvant Cancer study have led to approval of sunitinib as an adjuvant agent in the USA. In the realm of neoadjuvant therapy, presurgical tumor reduction has been shown in a number of phase II studies utilizing targeted molecular agents and in a recently published small randomized double-blind placebo-controlled study, and an expanding body of literature suggests benefit in select patients. Thus, large randomized clinical trial data are not present to support this approach, and guidelines for use of presurgical therapy have not been promulgated. The advent of immunomodulation through checkpoint inhibition represents an exciting horizon for adjuvant and neoadjuvant strategies. The present article reviews the current status and future prospects of adjuvant and neoadjuvant therapy in localized and locally advanced renal cell carcinoma.
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Antineoplásicos/uso terapéutico , Carcinoma de Células Renales/terapia , Neoplasias Renales/terapia , Sunitinib/uso terapéutico , Carcinoma de Células Renales/patología , Quimioterapia Adyuvante , Humanos , Neoplasias Renales/patología , Terapia Neoadyuvante , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: We compared renal functional outcomes of robotic (RPN) and open partial nephrectomy (OPN) in patients with chronic kidney disease (CKD), a definite indication for nephron-sparing surgery. METHODS: A multicenter retrospective analysis of OPN and RPN in patients with baseline ≥ CKD Stage III [estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2] was performed. Primary outcome was change in eGFR (ΔeGFR, mL/min/1.73 m2) between preoperative and last follow-up with respect to RENAL nephrometry score group [simple (4-6), intermediate (7-9), complex (10-12)]. Secondary outcomes included eGFR decline > 50%. RESULTS: 728 patients (426 OPN, 302 RPN, mean follow-up 33.3 months) were analyzed. Similar RENAL score distribution (p = 0.148) was noted between groups. RPN had lower median estimated blood loss (p < 0.001), and hospital stay (3 vs. 5 days, p < 0.001). Median ischemia time (OPN 23.7 vs. RPN 21.5 min, p = 0.089), positive margin (p = 0.256), transfusion (p = 0.166), and 30-day complications (p = 0.208) were similar. For OPN vs. RPN, mean ΔeGFR demonstrated no significant difference for simple (0.5 vs. 0.3, p = 0.328), intermediate (2.1 vs. 2.1, p = 0.384), and complex (4.9 vs. 6.1, p = 0.108). Cox regression analysis demonstrated that decreasing preoperative eGFR (OR 1.10, p = 0.001) and complex RENAL score (OR 5.61, p = 0.03) were independent predictors for eGFR decline > 50%. Kaplan-Meier analysis demonstrated 5-year freedom from eGFR decline > 50% of 88.6% for OPN and 88.3% for RPN (p = 0.724). CONCLUSIONS: RPN and OPN demonstrated similar renal functional outcomes when stratified by tumor complexity group. Increasing tumor age and tumor complexity were primary drivers associated with functional decline. RPN provides similar renal functional outcomes to OPN in appropriately selected patients.
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Neoplasias Renales/cirugía , Nefrectomía/métodos , Insuficiencia Renal Crónica , Procedimientos Quirúrgicos Robotizados , Anciano , Femenino , Tasa de Filtración Glomerular , Humanos , Neoplasias Renales/complicaciones , Masculino , Insuficiencia Renal Crónica/complicaciones , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Stereotactic magnetic resonance (MR)-guided adaptive radiotherapy (SMART) for renal cell carcinoma may result in more precise treatment delivery through the capabilities for improved image quality, daily adaptive planning, and accounting for respiratory motion during treatment with real-time MR tracking. In this study, we aimed to characterize the safety and feasibility of SMART for localized kidney cancer. Twenty patients with localized kidney cancer (ten treated in a prospective phase 1 trial and ten in the supplemental cohort) were treated to 40 Gy in five fractions on a 0.35 T MR-guided linear accelerator with daily adaptive planning and a cine MR-guided inspiratory breath hold technique. The median follow-up time was 17 mo (interquartile range: 13-20 months). A single patient developed local failure at 30 mo. No grade ≥3 adverse events were reported. The mean decrease in estimated glomerular filtration rate was -1.8 ml/min/1.73 m2 (95% confidence interval or CI [-6.6 to 3.1 ml/min/1.73 m2]), and the mean decrease in tumor diameter was -0.20 cm (95% CI [-0.6 to 0.2 cm]) at the last follow-up. Anterior location and overlap of the 25 or 28 Gy isodose line with gastrointestinal organs at risk were predictive of the benefit from online adaptive planning. Kidney SMART is feasible and, at the early time point evaluated in this study, was well tolerated with minimal decline in renal function. More studies are warranted to further evaluate the safety and efficacy of this technique. PATIENT SUMMARY: For patients with localized renal cell carcinoma who are not surgical candidates, stereotactic magnetic resonance--guided adaptive radiotherapy is a feasible and safe noninvasive treatment option that results in minimal impact on kidney function.
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Carcinoma de Células Renales , Neoplasias Renales , Radiocirugia , Humanos , Carcinoma de Células Renales/radioterapia , Planificación de la Radioterapia Asistida por Computador/métodos , Estudios Prospectivos , Radiocirugia/métodos , Neoplasias Renales/radioterapia , Riñón , Espectroscopía de Resonancia MagnéticaRESUMEN
Renal cell carcinoma (RCC) has historically been considered resistant to radiotherapy. However, advances in the field of radiation oncology have led to safe delivery of higher radiation doses through the use of stereotactic body radiotherapy (SBRT) that have shown significant activity against RCC. SBRT has now been shown to be a highly effective modality for management of localized RCC for nonsurgical candidates. Increasing evidence also points to a role for SBRT in the management of oligometastatic RCC as a means for not only providing palliation but prolonging time to progression and potentially improving survival.
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Carcinoma de Células Renales , Neoplasias Renales , Radiocirugia , Humanos , Carcinoma de Células Renales/patología , Neoplasias Renales/patologíaRESUMEN
Purpose: To better understand whether the marital status impacts 90-day postoperative outcomes following kidney cancer surgery. Methods: We performed a retrospective cohort study of adult patients undergoing elective partial or radical nephrectomy to manage kidney masses from 2003 to 2017 using the Premier Hospital Database, a national hospital discharge dataset. Multinomial logistic regression models controlling for a wide range of clinicodemographic, surgical, and hospital characteristics were used to assess an association between marital status and postoperative complications. The primary outcome was 90-day complications, including minor complications (Clavien grades 1-2), non-fatal major complications (Clavien grades 3-4), and mortality (Clavien grade 5). Secondary outcomes included patient disposition and readmission rates. Results: The study cohort comprised 106,752 patients, of which 61,188 (57.32%) were married. The overall incidence of minor complications, major complications, and death was 24.04%, 6.00%, and 0.71%, respectively. Marriage was associated with a significantly lower incidence of minor (RR 0.97; 95% CI: 0.94-0.99) complications following open or radical nephrectomy and major complications (RR 0.89; 95% CI: 0.84-0.95) for all surgical types and approaches. There was no association between marital status and mortality (RR 0.94; 95% CI: 0.81-1.10). Conclusion: Marriage is associated with a significant reduction in major complications following kidney cancer surgery, likely because it is associated with greater social support, which is beneficial in the postoperative phase of care. Marital status and social support may play a role in the preoperative decision-making process and counseling for patients considering kidney cancer surgery.
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Segmental ureterectomy (SU) is an alternative to radical nephroureterectomy (RNU) in the treatment of upper-tract urothelial carcinoma (UTUC) of the ureter. SU generally preserves renal function, at the expense of less intensive cancer control. We aim to assess whether SU is associated with inferior survival compared to RNU. Using the National Cancer Database (NCDB), we identified patients diagnosed with localized UTUC of the ureter between 2004-2015. We used a propensity-score-overlap-weighted (PSOW) multivariable survival model to compare survival following SU vs. RNU. PSOW-adjusted Kaplan-Meier curves were generated and we performed a non-inferiority test of overall survival. A population of 13,061 individuals with UTUC of the ureter receiving either SU or RNU was identified; of these, 9016 underwent RNU and 4045 SU. Factors associated with decreased likelihood of receiving SU were female gender (OR, 0.81; 95% CI, 0.75-0.88; p < 0.001), advanced clinical T stage (cT4) (OR, 0.51; 95% CI, 0.30-0.88; p = 0.015), and high-grade tumor (OR, 0.76; 95% CI, 0.67-0.86; p < 0.001). Age greater than 79 years was associated with increased probability of undergoing SU (OR, 1.18; 95% CI, 1.00-1.38; p = 0.047). There was no statistically significant difference in OS between SU and RNU (HR, 0.98; 95% CI, 0.93-1.04; p = 0.538). SU was not inferior to RNU in PSOW-adjusted Cox regression analysis (p < 0.001 for non-inferiority). In weighted cohorts of individuals with UTUC of the ureter, the use of SU was not associated with inferior survival compared to RNU. Urologists should continue to utilize SU in appropriately selected patients.
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Radical cystectomy (RC) is an integral part of the management of patients with advanced-stage bladder cancer. This major oncologic operation is prone to complications resulting in morbidity and mortality. We analyzed the critical steps of open RC, performed an evidence-based review of these steps, and discussed our experience and approach. We conducted a literature review of the open RC technique, identified the critical steps that consistently appeared across different sources, and organized these steps into a framework. PubMed was queried with the critical steps as keywords for relevant articles published from 1 January 2013 to 1 August 2023. We utilized this query to conduct a systematic review of the literature using the outcomes of overall survival and 90-day complication rate. We developed the "Summary for the 10 Critical Operative Steps of Radical Cystectomy", a concise guide to the approach to open RC. When available, an evidence-based analysis of each critical step was performed. We also included additional components of cystectomy optimization such as pre-habilitation in the preoperative phase, standard versus extended lymphadenectomy, the vaginal-sparing approach to female radical cystectomy, patient-reported outcomes following urinary diversion, the use of a mesh for stoma formation, and the use of the ERAS protocol for postoperative care. An evidence-based assessment of RC may help provide valuable information to optimize surgical techniques and patient outcomes.
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INTRODUCTION: Retroperitoneal lymph node dissection (RPLND) is the standard of care for testicular cancer in various disease settings. Deep vein thrombosis (DVT) complications have been reported to occur in <1% of primary RPLND cases and up to 3% of postchemotherapy (PC-RPLND) cases. While prophylactic anticoagulation (AC) has been well-documented to reduce DVT rates in patients undergoing surgery in general, the benefit of prophylactic AC in RPLND has not been assessed. In this retrospective cohort study, we seek to address this unmet need by evaluating the rates and associated risk factors of DVT and pulmonary embolism (PE) with a national and institutional database, assess the changing patterns in DVT prophylaxis with postoperative AC following RPLND, and quantify the potential benefit of prophylactic AC in patients who have undergone RPLND using a risk-stratified approach. METHODS: The National Surgical Quality Improvement Program (NSQIP) database was queried for patients who underwent RPLND during the 10-year period from 2011 to 2021. An institutional database was queried for all patients undergoing RPLND from 2013 to 2022. Patient characteristics and operative outcomes were compared between the NSQIP and the institutional database. The institutional database was stratified by prior oncologic treatment (i.e., primary RPLND vs. PC-RPLND) and outcomes were compared. Postoperative AC rate was determined and trended by year. The use of postoperative AC and PE events were stratified by clinical stage. The absolute risk reduction (ARR) of AC prophylaxis on PE events and the number needed to treat (NNT) with AC prophylaxis to prevent a single PE event was determined. RESULTS: In total, the NSQIP database query resulted in 779 patients and our institutional database query resulted in 188 patients. The rate of DVT and PE was 1.2% and 0.5% vs. 2.1% and 1.6% in the NSQIP and institutional cohort, respectively. The rate of postoperative AC following RPLND in patients from the institutional database increased from 5% in 2013 to 43% in 2022 (Pâ¯=â¯0.01). There were no statistically significant differences in complication rates, including bleeding events, chyle leaks, or hospital readmissions amongst patients who were prescribed AC at discharge and those who were not. No stage I patients developed PEs and no stage I patients were prescribed AC. The ARR for AC prophylaxis for development of PE was found to be 0.023 for the clinical stage II and stage III cohorts. The NNT to prevent a single PE with AC was 44 and 43 for the stage II and stage III cohorts, respectively. CONCLUSIONS: AC appears beneficial with minimal risk of harm after RPLND, especially in patients with higher risk of developing DVT/PE, highlighting the safety and efficacy of this regimen. There was a significant increase in the rate of AC prophylaxis at discharge amongst patients undergoing RPLND in the institutional database from 2013 to 2022. A risk-stratified protocol of postoperative AC following RPLND appears reasonable, and further prospective trials are warranted to formally confirm this recommendation.
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Neoplasias de Células Germinales y Embrionarias , Neoplasias Testiculares , Masculino , Humanos , Estudios Retrospectivos , Neoplasias Testiculares/patología , Espacio Retroperitoneal/patología , Escisión del Ganglio Linfático/efectos adversos , Escisión del Ganglio Linfático/métodos , Neoplasias de Células Germinales y Embrionarias/cirugía , Anticoagulantes/uso terapéutico , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/cirugíaRESUMEN
PURPOSE: Bacillus Calmette-Guerin (BCG) is the standard of care for high-risk nonmuscle invasive bladder cancer (NMIBC), but half of patients develop disease recurrence. Intravesical regimens for BCG unresponsive NMIBC are limited. We report the safety, efficacy, and differential response of sequential gemcitabine/docetaxel (gem/doce) depending on BCG failure classification. METHODS: Multi-institutional retrospective analysis of patients treated with induction intravesical gem/doce (≥5/6 instillations) for recurrent high-risk NMIBC after BCG therapy from May 2018 to December 2021. Maintenance therapy was provided to those without high-grade (HG) recurrence on surveillance cystoscopy. Kaplan-Meier curves and Cox regression analyses were utilized to assess survival and risk factors for disease recurrence. RESULTS: Our cohort included 102 patients with BCG-unresponsive NMIBC. Median age was 72 years and median follow-up was 18 months. Six-, 12-, and 24-month high-grade recurrence-free survival was 78%, 65%, and 49%, respectively. Twenty patients underwent radical cystectomy (median 15.5 months from induction). Six patients progressed to muscle invasive disease. Fifty-seven percent of patients experienced mild/moderate adverse effects (AE), but only 6.9% experienced a delay in treatment schedule. Most common AE were urinary frequency/urgency (41%) and dysuria (21%). Patients with BCG refractory disease were more likely to develop HG recurrence when compared to patients with BCG relapsing disease (HR 2.14; 95% CI 1.02-4.49). CONCLUSIONS: In patients with recurrence after BCG therapy, sequential intravesical gem/doce is an effective and well-tolerated alternative to early cystectomy. Patients with BCG relapsing disease are more likely to respond to additional intravesical gem/doce. Further investigation with a prospective trial is imperative.
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Neoplasias Vesicales sin Invasión Muscular , Neoplasias de la Vejiga Urinaria , Humanos , Anciano , Gemcitabina , Docetaxel/uso terapéutico , Vacuna BCG/uso terapéutico , Estudios Retrospectivos , Estudios Prospectivos , Recurrencia Local de Neoplasia/tratamiento farmacológicoRESUMEN
BACKGROUND: To evaluate effect and outcomes of combination primary immunotherapy (IO) and nephrectomy for advanced renal cell carcinoma (RCC). METHODS: We conducted a multicenter, retrospective analysis of patients with advanced/metastatic RCC who received IO followed by nephrectomy. Primary outcome was Bifecta (negative surgical margins and no 30-day surgical complications). Secondary outcomes included progression-free survival (PFS) following surgery, reduction in tumor/thrombus size, RENAL score, and clinical/pathologic downstaging. Cox regression multivariable analysis was conducted for predictors of Bifecta and PFS. Kaplan-Meier analysis assessed PFS, comparing Bifecta and non-Bifecta groups. RESULTS: A total of 56 patients were analyzed (median age 63 years; median follow-up 22.5 months). A total of 40 (71.4%) patients were intermediate IMDC risk. Patients were treated with immunotherapy for median duration of 8.1 months. Immunotherapy resulted in reductions in tumor size (P < .001), thrombus size (P = .02), and RENAL score (P < .001); 38 (67.9%) patients were clinically downstaged on imaging (P < .001) and 25 (44.6%) patients were pathologically downstaged following surgery (P < .001). Bifecta was achieved in 38 (67.9%) patients. Predictors for bifecta achievement included decreasing tumor size (HR 1.08, P = .043) and pathological downstaging (HR 2.13, P = .047). Bifecta (HR 5.65, P = .009), pathologic downstaging (HR 5.15, P = .02), and increasing reduction in tumor size (HR 1.2, P = .007) were associated with improved PFS. Bifecta patients demonstrated improved 2-year PFS (84% vs. 71%, P = .019). CONCLUSIONS: Primary immunotherapy reduced tumor/thrombus size and complexity. Pathologically downstaged patients were more likely to achieve bifecta, and these patients displayed improved 2-year PFS. Our study supports further inquiry in the use of CRN following primary immunotherapy for advanced renal cancer.
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Carcinoma de Células Renales , Neoplasias Renales , Trombosis , Humanos , Persona de Mediana Edad , Carcinoma de Células Renales/cirugía , Estudios Retrospectivos , Neoplasias Renales/cirugía , Nefrectomía/métodos , Trombosis/cirugía , InmunoterapiaRESUMEN
BACKGROUND: The impact of positive surgical margins (PSM) on outcomes in partial nephrectomy (PN) is controversial. We investigated impact of PSM for patients undergoing PN on overall survival (OS) in different stages of renal cell carcinoma (RCC). METHODS: Retrospective analysis of patients from the US National Cancer Database who underwent PN for cT1a-cT2b N0M0 RCC between 2004-13. Patients were stratified by pathological stage (pT1a, pT1b, pT2a, pT2b, and pT3a [upstaged]) and analyzed by margin status. Cox Regression multivariable analysis (MVA) was performed to investigate associations of PSM and covariates on all-cause mortality (ACM). Kaplan-Meier analysis (KMA) of OS was performed for PSM versus negative margin (NSM) by pathological stage. Sub-analysis of Charlson Comorbidity Index 0 (CCI=0) subgroup was conducted to reduce bias from comorbidities. RESULTS: We analyzed 42,113 PN (pT1a: 33,341 [79.2%]; pT1a, pT1b: 6689 [15.9%]; pT2a: 757 [1.8%]; pT2b: 165 [0.4%]; and pT3a: upstaged 1161 [2.8%]). PSM occurred in 6.7% (2823) (pT1a: 6.5%, pT1b: 6.3%, pT2a: 5.9%, pT2b: 6.1%, pT3a: 14.1%, P<0.001). On MVA, PSM was associated with 31% increase in ACM (HR 1.31, P<0.001), which persisted in CCI=0 sub-analysis (HR: 1.25, P<0.001). KMA revealed negative impact of PSM vs. NSM on 5-year OS: pT1 (87.3% vs. 90.9%, P<0.001), pT2 (86.7% vs. 82.5%, P=0.48), and upstaged pT3a (69% vs. 84.2%, P<0.001). CONCLUSIONS: PSM after PN was independently associated with across-the-board decrement in OS, which worsened in pT3a disease and persisted in sub-analysis of patients with CCI=0. PSM should prompt more aggressive surveillance or definitive resection strategies.
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Carcinoma de Células Renales/mortalidad , Carcinoma de Células Renales/cirugía , Neoplasias Renales/mortalidad , Neoplasias Renales/cirugía , Márgenes de Escisión , Nefrectomía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Renales/patología , Bases de Datos Factuales , Femenino , Humanos , Neoplasias Renales/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Nefrectomía/métodos , Nefrectomía/mortalidad , Análisis de Regresión , Estudios Retrospectivos , Análisis de Supervivencia , Resultado del Tratamiento , Estados Unidos/epidemiología , Adulto JovenRESUMEN
BACKGROUND: Use of partial nephrectomy (PN) in T3 renal cell carcinoma (RCC) is controversial. OBJECTIVE: To evaluate quality outcomes of robot-assisted PN (RAPN) for clinical T3a renal masses (cT3aRM). DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective multicenter analysis of patients with cT3aN0M0 RCC who underwent RAPN. INTERVENTION: RAPN. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was a trifecta composite outcome of negative surgical margins, warm ischemia time (WIT) ≤25 min, and no perioperative complications. The optimal outcome was defined as achieving this trifecta and ≥90% preservation of the estimated glomerular filtration rate (eGFR) and no stage upgrading of chronic kidney disease. Multivariable analysis (MVA) identified risk factors associated with lack of the optimal outcome. Kaplan-Meier analysis was conducted for survival outcomes. RESULTS AND LIMITATIONS: Analysis was conducted for 157 patients (median follow-up 26 mo). The median tumor size was 7.0 cm (interquartile range [IQR] 5.0-7.8) and the median RENAL score was 9 (IQR 8-10). Median estimated blood loss (EBL) was 242 ml (IQR 121-354) and the median WIT was 19 min (IQR 15-25). A total of 150 patients (95.5%) had negative margins. Complications were noted in 25 patients (15.9%), with 4.5% having Clavien grade 3-5 complications. The median change in eGFR was 7 ml/min/1.72 m2, with ≥90% eGFR preservation in 55.4%. The trifecta outcome was achieved for 64.3% and the optimal outcome for 37.6% of the patients. MVA revealed that greater age (odds ratio [OR] 1.06; p = 0.002), increasing RENAL score (OR 1.30; p = 0.035), and EBL >300 ml (OR 5.96, p = 0.006) were predictive of failure to achieve optimal outcome. The 5-yr recurrence-free survival, cancer-specific survival, and overall survival, were 82.1%, 93.3%, and 91.3%, respectively. Limitations include the retrospective design. CONCLUSIONS: RAPN for select cT3a renal masses is feasible and safe, with acceptable quality outcomes. Further investigation is requisite to delineate the role of RAPN in cT3a RCC. PATIENT SUMMARY: Robot-assisted partial nephrectomy in patients with stage 3a kidney cancer provided acceptable survival, functional, and morbidity outcomes in the hands of experienced surgeons, and may be considered as an option when clinically indicated.
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Carcinoma de Células Renales , Neoplasias Renales , Robótica , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/cirugía , Humanos , Neoplasias Renales/patología , Márgenes de Escisión , Nefrectomía/métodos , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: The efficacy of partial nephrectomy (PN) in setting of pT3a pathologic-upstaged renal cell carcinoma (RCC) is controversial. We compared oncologic and functional outcomes of radical nephrectomy (RN) and PN in patients with upstaged pT3a RCC. PATIENTS AND METHODS: This was a multicenter retrospective analysis of patients with cT1-2N0M0 RCC upstaged to pT3a postoperatively. The primary outcome was recurrence-free survival, with secondary outcomes of overall survival and de novo estimated glomular filtration rate (eGFR) < 60. Multivariable analysis was performed to identify predictive factors for oncologic outcomes. Kaplan-Meier analyses (KMA) were obtained to elucidate survival outcomes. RESULTS: A total of 929 patients had pT3a upstaging (686 [72.6%] RN; 243 [25.7%] PN; mean follow-up, 48 months). Tumor size was similar (RN 7.7 cm vs. PN 7.3 cm; P = .083). PN had decreased ΔeGFR (6.1 vs. RN 19.4 mL/min/1.73m2; P < .001) and de novo eGFR < 60 (9.5% vs. 21%; P = .008). Multivariable analysis for recurrence showed increasing RENAL score (hazard ratio [HR], 3.8; P < .001), clinical T stage (HR, 1.8; P < .001), positive margin (HR, 1.57; P = .009), and high grade (HR, 1.21; P = .01) to be independent predictors, whereas surgery was not (P = .076). KMA revealed 5-year recurrence-free survival for cT1-upstaged PN, cT1-upstaged RN, cT2-upstaged PN, and cT2-upstaged RN of 79%, 74%, 70%, and 51%, respectively (P < .001). KMA revealed 5-year overall survival for cT1-upstaged PN, cT1-upstaged RN, cT2-upstaged PN, and cT2-upstaged RN of 64%, 65.2%, 56.4%, and 55.2%, respectively (P = .059). CONCLUSIONS: In pathologically upstaged pT3a RCC, PN did not adversely affect risk of recurrence and provided functional benefit. Surgical decision-making in patients at risk for T3a upstaging should be individualized and driven by tumor as well as functional risks.
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Carcinoma de Células Renales , Neoplasias Renales , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/cirugía , Humanos , Neoplasias Renales/patología , Neoplasias Renales/cirugía , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Nefrectomía , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Aim and Background: To investigate the association of serum uric acid (SUA) levels along with statin use in Renal Cell Carcinoma (RCC), as statins may be associated with improved outcomes in RCC and SUA elevation is associated with increased risk of chronic kidney disease (CKD). Methods: Retrospective study of patients undergoing surgery for RCC with preoperative/postoperative SUA levels between 8/2005-8/2018. Analysis was carried out between patients with increased postoperative SUA vs. patients with decreased/stable postoperative SUA. Kaplan-Meier analysis (KMA) calculated overall survival (OS) and recurrence free survival (RFS). Multivariable analysis (MVA) was performed to identify factors associated with increased SUA levels and all-cause mortality. The prognostic significance of variables for OS and RFS was analyzed by cox regression analysis. Results: Decreased/stable SUA levels were noted in 675 (74.6%) and increased SUA levels were noted in 230 (25.4%). A higher proportion of patients with decreased/stable SUA levels took statins (27.9% vs. 18.3%, p = 0.0039). KMA demonstrated improved 5- and 10-year OS (89% vs. 47% and 65% vs. 9%, p < 0.001) and RFS (94% vs. 45% and 93% vs. 34%, p < 0.001), favoring patients with decreased/stable SUA levels. MVA revealed that statin use (Odds ratio (OR) 0.106, p < 0.001), dyslipidemia (OR 2.661, p = 0.004), stage III and IV disease compared to stage I (OR 1.887, p = 0.015 and 10.779, p < 0.001, respectively), and postoperative de novo CKD stage III (OR 5.952, p < 0.001) were predictors for increased postoperative SUA levels. MVA for all-cause mortality showed that increasing BMI (OR 1.085, p = 0.002), increasing ASA score (OR 1.578, p = 0.014), increased SUA levels (OR 4.698, p < 0.001), stage IV disease compared to stage I (OR 7.702, p < 0.001), radical nephrectomy (RN) compared to partial nephrectomy (PN) (OR 1.620, p = 0.019), and de novo CKD stage III (OR 7.068, p < 0.001) were significant factors. Cox proportional hazard analysis for OS revealed that increasing age (HR 1.017, p = 0.004), increasing BMI (Hazard Ratio (HR) 1.099, p < 0.001), increasing SUA (HR 4.708, p < 0.001), stage III and IV compared to stage I (HR 1.537, p = 0.013 and 3.299, p < 0.001), RN vs. PN (HR 1.497, p = 0.029), and de novo CKD stage III (HR 1.684, p < 0.001) were significant factors. Cox proportional hazard analysis for RFS demonstrated that increasing ASA score (HR 1.239, p < 0.001, increasing SUA (HR 9.782, p < 0.001), and stage II, III, and IV disease compared to stage I (HR 2.497, p < 0.001 and 3.195, p < 0.001 and 6.911, p < 0.001) were significant factors. Conclusions: Increasing SUA was associated with poorer outcomes. Decreased SUA levels were associated with statin intake and lower stage disease as well as lack of progression to CKD and anemia. Further investigation is requisite.