Concomitant Carcinoma in situ in Cystectomy Specimens Is Not Associated with Clinical Outcomes after Surgery

Objective: The aim of this study was to externally validate the prognostic value of concomitant urothelial carcinoma in situ (CIS) in radical cystectomy (RC) specimens using a large international cohort of bladder cancer patients. Methods: The records of 3,973 patients treated with RC and bilateral lymphadenectomy for urothelial carcinoma of the bladder (UCB) at nine centers worldwide were reviewed. Surgical specimens were evaluated by a genitourinary pathologist at each center. Uni- and multivariable Cox regression models addressed time to recurrence and cancer-specific mortality after RC. Results: 1,741 (43.8%) patients had concomitant CIS in their RC specimens. Concomitant CIS was more common in organ-confined UCB and was associated with lymphovascular invasion (p < 0.001). Concomitant CIS was not associated with either disease recurrence or cancer-specific death regardless of pathologic stage. The presence of concomitant CIS did not improve the predictive accuracy of standard predictors for either disease recurrence or cancer-specific death in any of the subgroups. Conclusions: We could not confirm the prognostic value of concomitant CIS in RC specimens. This, together with the discrepancy between pathologists in determining the presence of concomitant CIS at the morphologic level, limits the clinical utility of concomitant CIS in RC specimens for clinical decision-making. Copyright (C) 2011 S. Karger AG, Base

External validation of the preoperative Karakiewicz nomogram in a large multicentre series of patients with renal cell carcinoma

To perform a formal external validation of the preoperative Karakiewicz nomogram (KN) for the prediction of cancer-specific survival (CSS) using a large series of surgically treated patients diagnosed with organ-confined or metastatic renal cell carcinoma (RCC).Patient population originated from a series of retrospectively gathered cases that underwent radical or partial nephrectomy between years 1995 and 2007 for suspicion of kidney cancer. The original Cox coefficients were used to generate the predicted risk of CSS at 1, 2, 5, and 10 years following surgery and compared to the observed risk of CSS in the current population. External validation was quantified using measures of predictive accuracy, defined as model discrimination and calibration.A total of 3,374 patients were identified. Relative to the original development cohort, the current sample population had a larger proportion of patients with localized (40.0 vs. 26.3 \%, P < 0.001) and non-metastatic (92.2 vs. 88.1 \%, P = 0.03) disease at presentation. Model discrimination for the prediction of CSS was 87.8 \% (95 \% CI, 84.4-91.4) at 1 year, 87.0 \% (95 \% CI, 84.4-89.5) at 2 years, 84.7 \% (95 \% CI, 82.3-87.1) at 5 years, and 85.9 \% (95 \% CI, 83.2-88.6) at 10 years. The relationship between predicted and observed CSS risk was adequate in the calibration plot.The use of the KN for the prediction of CSS in patients diagnosed with renal cell carcinoma was validated in the current study. In consequence, this tool may be recommended for routine clinical counseling in patients with various stages of RCC in the preoperative setting

National trends in hospital-acquired preventable adverse events after major cancer surgery in the USA

Objectives: While multiple studies have demonstrated variations in the quality of cancer care in the USA, payers are increasingly assessing structure-level and process-level measures to promote quality improvement. Hospital-acquired adverse events are one such measure and we examine their national trends after major cancer surgery. Design: Retrospective, cross-sectional analysis of a weighted-national estimate from the Nationwide Inpatient Sample (NIS) undergoing major oncological procedures (colectomy, cystectomy, oesophagectomy, gastrectomy, hysterectomy, lung resection, pancreatectomy and prostatectomy). The Agency for Healthcare Research and Quality Patient Safety Indicators (PSIs) were utilised to identify trends in hospital-acquired adverse events. Setting: Secondary and tertiary care, US hospitals in NIS Participants: A weighted-national estimate of 2 508 917 patients (>18 years, 1999–2009) from NIS. Primary outcome measures Hospital-acquired adverse events. Results: 324 852 patients experienced ≥1-PSI event (12.9%). Patients with ≥1-PSI experienced higher rates of in-hospital mortality (OR 19.38, 95% CI 18.44 to 20.37), prolonged length of stay (OR 4.43, 95% CI 4.31 to 4.54) and excessive hospital-charges (OR 5.21, 95% CI 5.10 to 5.32). Patients treated at lower volume hospitals experienced both higher PSI events and failure-to-rescue rates. While a steady increase in the frequency of PSI events after major cancer surgery has occurred over the last 10 years (estimated annual % change (EAPC): 3.5%, p<0.001), a concomitant decrease in failure-to-rescue rates (EAPC −3.01%) and overall mortality (EAPC −2.30%) was noted (all p<0.001). Conclusions: Over the past decade, there has been a substantial increase in the national frequency of potentially avoidable adverse events after major cancer surgery, with a detrimental effect on numerous outcome-level measures. However, there was a concomitant reduction in failure-to-rescue rates and overall mortality rates. Policy changes to improve the increasing burden of specific adverse events, such as postoperative sepsis, pressure ulcers and respiratory failure, are required

Systemic therapy for metastatic renal cell carcinoma in the first-line setting : a systematic review and network meta-analysis

Purpose: Management of metastatic renal cell cancer (mRCC) has undergone a paradigm shift with immune-checkpoint inhibitors (ICI) in the first-line setting. However, direct comparative data are inadequate to inform treatment decisions. Therefore, we aimed to assess first-line therapy for mRCC and indirectly compare the efficacy and safety of currently available treatments. Materials and methods: Multiple databases were searched for articles published before June 2020. Studies that compared overall and/or progression-free survival (OS/PFS) and/or adverse events (AEs) in mRCC patients were considered eligible. Results: Six studies matched our eligibility criteria. For OS, pembrolizumab plus axitinib [hazard ratio (HR) 0.85, 95% credible interval (CrI) 0.73–0.98] and nivolumab plus ipilimumab (HR 0.86, 95% CrI 0.75–0.99) were significantly more effective than sunitinib, and pembrolizumab plus axitinib was probably the best option based on analysis of the treatment ranking. For PFS, pembrolizumab plus axitinib (HR 0.86, 95% CrI 0.76–0.97) and avelumab plus axitinib (HR 0.85, 95% CrI 0.74–0.98) were statistically superior to sunitinib, and avelumab plus axitinib was likely to be the preferred option based on analysis of the treatment ranking, closely followed by pembrolizumab plus axitinib. Nivolumab plus ipilimumab had significantly lower rates of serious AEs than sunitinib. Conclusion: Pembrolizumab plus axitinib seemed to be the most efficacious first-line agents, while nivolumab plus ipilimumab had the most favorable efficacy–tolerability equilibrium. These findings may facilitate individualized treatment strategies and inform future direct comparative trials in an expanding treatment options without direct comparison between approved drugs

PSA, stage, grade and prostate cancer specific mortality in Asian American patients relative to Caucasians according to the United States Census Bureau race definitions

Background: The United States Census Bureau recommends distinguishing between “Asians” vs. “Native Hawaiians or Other Pacific Islanders” (NHOPI). We tested for prognostic differences according to this stratification in patients with prostate cancer (PCa) of all stages. Methods: Descriptive statistics, time-trend analyses, Kaplan–Meier plots and multivariate Cox regression models were used to test for differences at diagnosis, as well as for cancer specific mortality (CSM) according to the Census Bureau’s definition in either non-metastatic or metastatic patients vs. 1:4 propensity score (PS)-matched Caucasian controls, identified within the Surveillance, Epidemiology and End Results database (2004–2016). Results: Of all 380,705 PCa patients, NHOPI accounted for 1877 (0.5%) vs. 23,343 (6.1%) remaining Asians vs. 93.4% Caucasians. NHOPI invariably harbored worse PCa characteristics at diagnosis. The rates of PSA ≥ 20&nbsp;ng/ml, Gleason ≥ 8, T3/T4, N1- and M1 stages were highest for NHOPI, followed by Asians, followed by Caucasians (PSA ≥ 20: 18.4 vs. 14.8 vs. 10.2%, Gleason ≥ 8: 24.9 vs. 22.1, vs. 15.9%, T3/T4: 5.5 vs. 4.2 vs. 3.5%, N1: 4.4 vs. 2.8, vs. 2.7%, M1: 8.3 vs. 4.9 vs. 3.9%). Despite the worst PCa characteristics at diagnosis, NHOPI did not exhibit worse CSM than Caucasians. Moreover, despite worse PCa characteristics, Asians exhibited more favorable CSM than Caucasians in comparisons that focussed on non-metastatic and on metastatic patients. Conclusions: Our observations corroborate the validity of the distinction between NHOPI and Asian patients according to the Census Bureau’s recommendation, since these two groups show differences in PSA, grade and stage characteristics at diagnosis in addition to exhibiting differences in CSM even after PS matching and multivariate adjustment

Small renal masses with tumor size 0 to 2 cm : A SEER-based study and validation of NCCN guidelines

Background: The NCCN Clinical Practice Guidelines in Oncology for Kidney Cancer recommend active surveillance as an option for initial management of T1a 0- to 2-cm renal lesions, in addition to partial nephrectomy, radical nephrectomy, and focal ablation. However, contemporary data regarding the distribution of patient and renal cell carcinoma characteristics within this special patient group are scarce. Methods: Within the SEER database (2002-2016), 13,364 patients with T1aNanyMany 0- to 2-cm renal lesions treated with nephrectomy were identified. Data were tabulated according to histologic subtype, Fuhrman grade (FG1-2 vs FG3-4), age category, and sex. In addition, rates of synchronous metastases were quantified. Results: Overall, clear-cell (69.3%), papillary (21.4%), chromophobe (6.9%), multilocular cystic (2.0%), sarcomatoid dedifferentiation (0.2%), and collecting-duct histologic subtypes (0.2%) were identified. Advanced age was associated with a lower rate of FG1-2 clear cell histologic subtype (70.8%-50.3%) but higher rates of FG1-2 papillary (11.1%-23.9%) and chromophobe histologic subtypes (6.2%-8.5%). Overall, 14.5% individuals harbored FG3-4 clear cell (9.8%) or FG3-4 papillary histologic subtypes (4.8%), and both were more prevalent in men. FG3-4 clearcell and FG3-4 papillary histologic subtypes increased with age,more so in women than in men. The overall rate of synchronous metastases was 0.4% and ranged from 0 in the multilocular cystic subtype to 0.9% in the FG3-4 papillary histologic subtype, respectively, except for 13.8%in the sarcomatoid dedifferentiation histologic subtype. Conclusions: Most T1a 0- to 2-cm renal cell carcinoma represents the low-grade clear-cell or low-grade papillary histologic subtype, with an FG3-4 minority. Even in patients with the FG3-4 histologic subtype, rates of synchronous metastases are virtually zero

ПОБОЧНЫЕ ЭФФЕКТЫ СОРАФЕНИБА, СУНИТИНИБА И ТЕМСИРОЛИМУСА И ИХ ЛЕЧЕНИЕ У БОЛЬНЫХ МЕТАСТАТИЧЕСКИМ ПОЧЕЧНО-КЛЕТОЧНЫМ РАКОМ

Objective: to provide a systematic review of the adverse reactions of sorafenib, sunitinib, and temsirolimus and to outline actions for their prevention and correction.Materials and methods. To provide a description of the main methods to decrease the toxicity of these drugs, the authors made a systemat- ic review of their adverse reactions, by using the publications available in the PubMed database, monographs on the medicines, and instruc- tions for their medical use. Results. The frequency of their adverse reactions varied from &lt; 1 to 72%. Grades III—IV side effects are noted more rarely; their incidence is &lt; 1 to 13% for sorafenib, &lt; 1 to 16% for sunitinib, and 1 to 20% for temsirolimus. Sinitinib causes most grades III—IV adverse reactions and sofafenib does the least. However, close comparative studies of the safety of these kinase inhibitors are still lacking. Virtually all side effects can be effectively prevented and treated.  Conclusion. The prevention, timely recognition, and treatment of the adverse reactions of these agents are of great importance, which allows avoidance of the unneeded dosage reduction that may result in worse therapeutic efficiency.   Цель исследования — представить систематический обзор побочных эффектов сорафениба, сунитиниба и темсиролимуса, а также в общих чертах описать меры по их предупреждению и коррекции. Материалы и методы. Для того чтобы представить описание основных методов, направленных на снижение токсичности этих препаратов, нами проведен систематический обзор побочных эффектов на основе публикаций в базе данных PubMed, монографий по лекарственным препаратам и инструкций по их медицинскому применению.Результаты. Частота развития побочных эффектов варьирует от &lt; 1 до 72%. Побочные эффекты III—IV степени отмечаются реже, частота их возникновения от &lt; 1 до 13% для сорафениба, от &lt; 1 до 16% — для сунитиниба и от 1 до 20% — для темсиролимуса. Сунитиниб вызывает наибольшее количество побочных эффектов III—IV степени, а сорафениб — наименьшее. Однако все еще отсутствуют тщательные сравнительные клинические исследования безопасности этих ингибиторов киназ. Практически все побочные эффекты можно эффективно предупреждать и лечить.Заключение. Большое значение имеют профилактика, своевременное распознавание и лечение побочных эффектов этих препаратов, что позволяет избежать ненужного снижения дозы, грозящего ослаблением эффективности лечения.