Despite the rapid elaboration of multiple, novel systemic agents introduced for metastatic renal cell carcinoma (mRCC) in recent years, a durable complete response remains elusive with systemic ...therapy alone. Definitive treatment of the metastatic deposit remains the sole potentially curative option and is a cornerstone of mRCC therapy, offering potential for both local control and palliation of tumor‐related symptoms. In this review, the evidence supporting the definitive treatment of mRCC is examined and summarized, including the use of surgical metastasectomy, thermal ablation, radiotherapy, and other minimally invasive options. Multimodal approaches, including the combination of metastasectomy with novel systemic agents, are discussed. Finally, the authors review considerations for patient selection for this type of therapy and summarize available risk‐stratification tools that may help guide shared decision making.
Despite the abundance of novel systemic treatments now approved for the treatment of metastatic renal cell carcinoma, a complete response is rarely obtained. Locally directed therapy, including surgical metastasectomy or other ablative techniques resulting in the absence of identifiable disease, does result in a durable response. Herein, the data supporting surgical and nonsurgical management of metastatic renal cell carcinoma for both local tumor control and symptom palliation are reviewed.
Background The decision as to whether a patient can tolerate surgery is often subjective and can misjudge a patient's true physiologic state. The concept of frailty is an important assessment tool in ...the geriatric medical population, but has only recently gained attention in surgical patients. Frailty potentially represents a measureable phenotype, which, if quantified with a standardized protocol, could reliably estimate the risk of adverse surgical outcomes. Study Design Frailty was prospectively evaluated in the clinic setting in patients consenting for major general, oncologic, and urologic procedures. Evaluation included an established assessment tool (Hopkins Frailty Score), self-administered questionnaires, clinical assessment of performance status, and biochemical measures. Primary outcome was 30-day postoperative complications. Results There were189 patients evaluated: 117 from urology, 52 from surgical oncology, and 20 from general surgery clinics. Mean age was 62 years, 59.8% were male, and 71.4% were Caucasian. Patients who scored intermediately frail or frail on the Hopkins Frailty Score were more likely to experience postoperative complications (odds ratio OR 2.07, 95% CI 1.05 to 4.08, p = 0.036). Of all other preoperative assessment tools, only higher hemoglobin (p = 0.033) had a significant association and was protective for 30-day complications. Conclusions The aggregate score of patients as “intermediately frail or frail” on the Hopkins Frailty Score was predictive of a patient experiencing a postoperative complication. This preoperative assessment tool may prove beneficial when weighing the risks and benefits of surgery, allowing objective data to guide surgical decision-making and patient counseling.
Purpose More than 50,000 Americans were diagnosed with kidney and renal pelvis cancer in 2010. The National Program of Cancer Registries and SEER (Surveillance, Epidemiology and End Results) combined ...data include cancer incidences from the entire United States. Our study presents updated incidence data, evaluates trends and adds geographic distribution to the literature. Materials and Methods We examined invasive, microscopically confirmed kidney and renal pelvis cancers diagnosed from 2001 to 2010 that met United States Cancer Statistics reporting criteria for each year, excluding cases diagnosed by autopsy or death certificate. Histology codes classified cases as renal cell carcinoma. Rates and trends were estimated using SEER∗ Stat. Results A total of 342,501 renal cell carcinoma cases were diagnosed. The renal cell carcinoma incidence rate increased from 10.6/100,000 individuals in 2001 to 12.4/100,000 in 2010 and increased with age until ages 70 to 74 years. The incidence rate in men was almost double that in women. The annual percent change was higher in women than in men, in those 20 to 24 years old and in grade III tumors. Conclusions The annual percent change incidence increased from 2001 to 2010. Asian/Pacific Islanders and 20 to 24-year-old individuals had the highest annual percent change. While some increase resulted from localized disease, the highest annual percent change was in grade III tumors, indicating more aggressive disease. Continued monitoring of trends and epidemiological study are warranted to determine risk factors.
Currently, there is a large and growing body of evidence to support the impact of physical health and activity on cancer outcomes. Mental and physical components of self‐reported quality‐of‐life ...metrics have been shown to predict all‐cause mortality in patients with renal cell carcinoma. However, an inherent drawback of such metrics could be misunderstandings of quality‐of‐life domains and inaccurate responses in some settings.
Chronic inflammation is considered a major risk factor for cancer formation. Inflammation within the tumor environment plays a role in its response to therapy, growth, and prognosis. Cancer ...associated inflammation is known to occur in the tumor microenvironment and in the systemic circulation, and is correlated with disease progression and prognosis in many cancers. Blood cells such as neutrophils, lymphocytes, platelets, and circulating proteins such as C-reactive protein, and interleukins, such as IL-6, have been associated with inflammatory responses, which contribute to tumorigenesis. Cancer has found ways to evade the immune response; a pathway that can attenuate the innate immune response is via blocking immune checkpoints. Development of monoclonal antibodies against inhibitory immune checkpoints such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) have given rise to immunotherapy, which has shown remarkable responses in anti-tumor activity resulting in several U.S. Federal and Drug Administration (FDA)-approved checkpoint inhibitors. Various inflammatory markers and their prognostic and predictive implications in malignancies treated with immunotherapy will be discussed in this review.
The standard of care for locoregional renal cell carcinoma is surgery, but many patients experience recurrence. The objective of the current study was to determine if adjuvant atezolizumab (vs ...placebo) delayed recurrence in patients with an increased risk of recurrence after resection.
IMmotion010 is a randomised, double-blind, multicentre, phase 3 trial conducted in 215 centres in 28 countries. Eligible patients were patients aged 18 years or older with renal cell carcinoma with a clear cell or sarcomatoid component and increased risk of recurrence. After nephrectomy with or without metastasectomy, patients were randomly assigned (1:1) to receive atezolizumab (1200 mg) or placebo (both intravenous) once every 3 weeks for 16 cycles or 1 year. Randomisation was done with an interactive voice-web response system. Stratification factors were disease stage (T2 or T3a vs T3b-c or T4 or N+ vs M1 no evidence of disease), geographical region (north America excluding Mexico vs rest of the world), and PD-L1 status on tumour-infiltrating immune cells (<1% vs ≥1% expression). The primary endpoint was investigator-assessed disease-free survival in the intention-to-treat population, defined as all patients who were randomised, regardless of whether study treatment was received. The safety-evaluable population included all patients randomly assigned to treatment who received any amount of study drug (ie, atezolizumab or placebo), regardless of whether a full or partial dose was received. This trial is registered with ClinicalTrials.gov, NCT03024996, and is closed to further accrual.
Between Jan 3, 2017, and Feb 15, 2019, 778 patients were enrolled; 390 (50%) were assigned to the atezolizumab group and 388 (50%) to the placebo group. At data cutoff (May 3, 2022), the median follow-up duration was 44·7 months (IQR 39·1-51·0). Median investigator-assessed disease-free survival was 57·2 months (95% CI 44·6 to not evaluable) with atezolizumab and 49·5 months (47·4 to not evaluable) with placebo (hazard ratio 0·93, 95% CI 0·75-1·15, p=0·50). The most common grade 3-4 adverse events were hypertension (seven 2% patients who received atezolizumab vs 15 4% patients who received placebo), hyperglycaemia (ten 3% vs six 2%), and diarrhoea (two 1% vs seven 2%). 69 (18%) patients who received atezolizumab and 46 (12%) patients who received placebo had a serious adverse event. There were no treatment-related deaths.
Atezolizumab as adjuvant therapy after resection for patients with renal cell carcinoma with increased risk of recurrence showed no evidence of improved clinical outcomes versus placebo. These study results do not support adjuvant atezolizumab for treatment of renal cell carcinoma.
F Hoffmann-La Roche and Genentech, a member of the Roche group.
Tumour-infiltrating lymphocytes are associated with a survival benefit in several tumour types and with the response to immunotherapy
. However, the reason some tumours have high CD8 T cell ...infiltration while others do not remains unclear. Here we investigate the requirements for maintaining a CD8 T cell response against human cancer. We find that CD8 T cells within tumours consist of distinct populations of terminally differentiated and stem-like cells. On proliferation, stem-like CD8 T cells give rise to more terminally differentiated, effector-molecule-expressing daughter cells. For many T cells to infiltrate the tumour, it is critical that this effector differentiation process occur. In addition, we show that these stem-like T cells reside in dense antigen-presenting-cell niches within the tumour, and that tumours that fail to form these structures are not extensively infiltrated by T cells. Patients with progressive disease lack these immune niches, suggesting that niche breakdown may be a key mechanism of immune escape.
Recent development is reviewed in biomarkers of inflammation and immune activation in risk stratification of bladder cancer (BC).
PubMed, Wiley Online Library, and Science Direct databases were ...reviewed in November 2019 for relevant studies limited to those published in English from 2008 to 2019. Articles were included if they contained references to BC, urological cancers, inflammation, immune activation, disease risk, disease progression, genomics, proteomics, and biomarkers.
Inflammatory biomarkers show promise in prognostication in BC, including neutrophil-to-lymphocyte ratio, C-reactive protein, selected cytokines and stress proteins. Most of the current evidence, however, stems from retrospective studies. None of these biomarkers are sufficient by themselves to be used for prognostication. Using a panel of different biomarkers, alongside clinical and pathological data, seems to improve risk stratification. More robust data is necessary, however, before these biomarkers will be suitable for use in routine practice.
Biomarkers of inflammation and immune system activation can assist in risk stratification of BC. Currently most of these biomarkers lack robust external validity. In the future these biomarkers likely will have an important role in augmenting the conventional clinical and pathological predictors of outcomes in BC.
Background Frailty is an objective method of quantifying a patient’s fitness for surgery. Its clinical use is limited by the time needed to complete, as well as a lack of evidence-based interventions ...to improve outcomes in identified frail patients. The purpose of this study was to critically analyze the components of the Fried Frailty Criteria, among other preoperative variables, to create a simplified risk assessment amenable to a busy clinical setting, while maintaining prognostic ability for surgical outcomes. Study Design We performed a prospective evaluation of patients that included the 5-component Fried Frailty Criteria, traditional surgical risk assessments, biochemical laboratory values, and clinical and demographic data. Thirty-day postoperative outcomes were the outcomes of interest. Results There were 351 consecutive patients undergoing major intra-abdominal operations enrolled. Analysis demonstrated that shrinking and grip strength alone hold the same prognostic information as the full 5-component Fried Frailty Criteria for 30-day morbidity and mortality. The addition of American Society of Anesthesia (ASA) score and serum hemoglobin creates a composite risk score, which facilitates easy classification of patients into discrete low (ref), intermediate (odds ratio OR 1.974, 95% CI 1.006 to 3.877, p = 0.048), and high (OR 4.889, 95% CI 2.220 to 10.769, p < 0.001) risk categories, with a corresponding stepwise increase in risk for 30-day postoperative complications. Internal validation by bootstrapping confirmed the results. Conclusions This study demonstrated that 2 components of the Fried Frailty Criteria, shrinking and grip strength, hold the same predictive value as the full frailty assessment. When combined with American Society of Anesthesiologists score and serum hemoglobin, they form a straightforward, simple risk classification system with robust prognostic information.
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