Prognostic value of comorbidities in older patients with cancer: the ELCAPA cohort study.

BACKGROUND: In older patients, comorbidities competed with cancer for mortality risk. We assessed the prognostic value of comorbidities in older patients with cancer. PATIENTS AND METHODS: We analysed all patients >70 years of age with colorectal, breast, prostate, or lung cancer included in the prospective ELCAPA cohort. The Cumulative Illness Rating Scale-Geriatrics (CIRS-G) score was used to assess comorbidities. The primary endpoint was overall survival (OS) at 3, 12, and 36 months. The adjusted difference in the restricted mean survival time (RMST) was used to assess the strength of the relationship between comorbidities and survival. RESULTS: Of the 1551 patients included (median age 82 years; interquartile range 78-86 years), 502 (32%), 575 (38%), 283 (18%), and 191 (12%) had colorectal, breast, prostate, and lung cancer, respectively, and 50% had metastatic disease. Hypertension, kidney failure, and cognitive impairment were the most common comorbidities (67%, 38%, and 29% of the patients, respectively). A CIRS-G score >17, two or more severe comorbidities, more than seven comorbidities, heart failure, and cognitive impairment were independently associated with shorter OS. The greatest effect size was observed for CIRS-G >17 (versus CIRS-G <11): at 36 months, the adjusted differences in the RMST (95% confidence interval) were -6.0 months (-9.3 to -2.6 months) for colorectal cancer, -9.1 months (-13.2 to -4.9 months) for breast cancer, -8.3 months (-12.8 to -3.9 months) for prostate cancer, and -5.5 months (-9.9 to -1.1 months) for lung cancer (P < 0.05 for all). CONCLUSIONS: Comorbidities' type, number, and severity were independently associated with shorter OS. A 17-point cut-off over 56 for the total CIRS-G score could be considered in clinical practice.

[Mirror survey of patients with urge urinary incontinence and healthcare professionals]. / Enquête miroir auprès de patients et de professionnels de santé portant sur l'incontinence urinaire par urgenturie ou mixte.

BACKGROUND: This survey assessed how much of a taboo surrounds urge or mixed urinary incontinence (UI), through questions to affected patients and healthcare professionals using online questionnaires, with the objective to contrast the patients' perceptions with that of the doctors. METHODS: This quantitative study was preceded by a qualitative phase carried out with general practitioners, specialists, and UI patients. Following these phases, questionnaires were made available on the internet. They covered questions pertaining to perceptions of UI, degree of embarrassment and its consequences, patient-doctor relationship, and treatments. RESULTS: Overall, 310 UI patients of male or female gender participated in the study, as did 101 general practitioners, 50 urologists, and 30 gynecologists. The analysis revealed that 60% of patients felt embarrassment about UI, the condition representing for them a taboo topic similar to cancer. This taboo was shown to be seen further enhanced by doctors. UI was associated with a loss of self-esteem (51%) and restriction to daily life (44%). The patients' answers revealed that UI was only brought up by doctors in 6% of cases, whereas the patient was the first to bring it up in 55%, primarily with their general practitioner (80%). Thus, in 4 out of 10 cases, the issue was not addressed; 49% of patients stated they did not discuss their condition with their partner and 33% did not discuss it with anybody. CONCLUSION: UI is still a major taboo and we have a long way to go to change attitudes. LEVEL OF EVIDENCE: 3.

Immunotherapy in older patients with cancer.

Ageing implicates a remodeling of our immune system, which is a consequence of the physiological senescence of our cells and tissues coupled with environmental factors and chronic antigen exposure. An immune system that senesces includes more differentiated cells with accumulation of highly differentiated CD4 and CD8 T cells. The pool of naive T cells decreases with the exponential thymic involution induced by age. Differentiated T cells have similar, if not higher, functional capacities but scarce studies are looking at the impact of senescence among specific T cells. After a stimulation, other immune cells (monocytes, dendritic cells and NK) are functionally altered during ageing. It is as if the immune system was more efficient at the basal level, but less efficient after a stimulation in the old compared to young people, likely due to less reserve. Concerning the clinical impact, older people are more prone to certain pathogens and their clinical manifestations differ from the younger people. Severe flu and VZV reactivation are more frequent with an altered cellular response to vaccination. Vaccination failure can have detrimental consequences in people presenting frailty criteria. Old people frailty is majored by their comorbidities and diseases like cancer. Thus, chemotherapies are employed with circumspection in older patients. The use of anti-PD-1/PD-L1 immunotherapies is therefore attractive, because of less side effects with a better response compared to chemotherapy. Old persons inclusion is lacking in current studies and clinical trials. Some subgroups or pooled analyses confirm the gain in response without increased toxicities in older patients but their inclusion criteria differ from the real-life practice. Specific studies focusing on this population are needed because of the increasing cancer incidence with age and the overall ageing of the population.

[Evaluation of the elderly patient with cancer]. / Évaluation du patient âge présentant un cancer.

PURPOSE: To explain the notion of frailty, then to explain how crucial is the detection of frailty detection in the elderly patient, and, in cases of suspected frailty, how crucial is the need for geriatric assessment. To describe (i) how this assessment of the elderly cancer patient is performed, (ii) how the results of this geriatric assessment must drive the decision making, and (iii) the role of the geriatrician in the care pathway. METHOD: Bibliographic research from the Medline bibliographic database (NLM Pubmed tool) and Embase, as well as on the websites of scientific geriatric societies, from the National Cancer Institute using the following keywords: elderly, geriatrics, cancer, frailty, assessment, decision making. RESULTS: The goal of frailty detection is to optimize care, to maintain the independence and the survival of the patient. The prevalence of frailty increases with the age and the diagnosis of cancer. Detection of frailty in the elderly patient with cancer is performed using the G8 questionnaire recommended by the INCa. In case of anomaly or clinical justification, the patient receives a geriatric assessment, which is a multidimensional and multidisciplinary procedure. The clinician can call on the UCOG of the region in which he practices. The relevance of medical decisions will be based on the results of this geriatric assessment. The geriatrician plays a crucial role and will be involved throughout the care. CONCLUSION: The detection of frailty in the elderly patient with cancer is obligatory. Consecutive geriatric assessment can be performed by the UCOG of the region. The results of the geriatric assessment must serve as a basis for any therapeutic decision making and the preservation of the independence of the patient must remain the priority.

[Onco-urology of the aging patient: Epidemiological and biological aspects]. / Onco-urologie du sujet âgé : aspects épidemiologiques et biologiques.

PURPOSE: First, to present the epidemiological data of aging and of cancers and to describe the respectives expected evolutions. Second, to present biological and genetic data on aging and on the relationships between aging and oncogenesis. METHOD: Bibliographic search from the Medline bibliographic database (NLM Pubmed tool) and Embase, as well as from the web sites of geriatric scientific societies, the United Nations, the World Bank, the World Health Organization, the Institut National du Cancer and the Ligue Contre le Cancer from the following keywords: aging, elderly, cancer, epidemiology, biology, genetics. RESULTS: The entire world population is aging very significantly and very rapidly. In France, new cases of cancer are diagnosed in 62.4% of cases in patients over 65 and in 11.5% of cases in patients over 80 years. Cancer mortality occurs in 75.3% of cases in patients over 65 years of age and in 24.8% of cases in patients over 80 years of age. Cancer-specific mortality is consistently higher in patients older than 75 years compared to younger patients; this reflects, among other things, an age discrimination which is called agism. It has been established that cellular aging is marked by 9 major families of biological and genomic abnormalities. Biological aging and oncogenesis are intertwined with increasingly well established relationships. They are both the product of natural selection and they are found in all species with both renewal tissues and a distinction between germinal tissue and somatic tissue. CONCLUSION: Epidemiological data predict that oncology, including urological oncology, is becoming very predominantly geriatric oncology; it is critical and urgent that society be prepared for it and that every care-giver be prepared, that is, be specifically trained. Biological and genetic data argue for a great entanglement between aging and oncogenesis; research in each of these areas should be reconciled for mutual benefit.

[Geriatric specificities of prostate cancer]. / Spécificités gériatriques du cancer de la prostate.

PURPOSE: To describe the epidemiology of prostate cancer (PCa) and its natural history in the elderly patient. To propose adaptations of geriatric evaluation specific to PCa. Recall therapeutic options and the treatment options specific to elderly patients. METHOD: Bibliographic research from the Medline bibliographic database (NLM Pubmed tool) and Embase, as well as on the websites of scientific societies of geriatrics, from the National Cancer Institute using the following keywords: elderly, geriatrics, prostate cancer, diagnosis, treatment. RESULTS: The median age at diagnosis for PCa is 69 years old, making PCa the very type of cancer of the elderly. The specific mortality of the disease increases with age. This translates two of its characteristics. First, a diagnosis at higher grade and stage is more common in older patients than in younger patients. Secondly, use of curative therapeutic options is less common in elderly patients than in younger patients. SIOG recommends a specific geriatric assessment for patients with PCa, which may be useful, but the need for an initial detection of cognitive disorders is open to criticism. There is no therapeutic trial, if only prospective, dedicated to elderly patients with PCa. However, decision-making in the elderly patient with PCa must pursue two goals: first, the respect of the expectations specific to each patient and secondly, the search for the global clinical benefit; goals that should not be restricted to elderly patients. CONCLUSION: PCa in the elderly patient follow the current guidelines for diagnostic and for treatment. Compliance with these guidelines should eliminate both the late diagnosis and the under-treatment actually observed.

[Optimizing the management of bladder cancer in older patients]. / Optimisation de la prise en charge du cancer de la vessie chez les patients âgés.

AIM: To define and present potential improvements for the management of bladder cancer in older patients. METHOD: Bibliographical search was performed from the Medline bibliographic database (NLM Pubmed tool) and Embase focused on: bladder cancer, treatment, BCG, chemotherapy, cystectomy, and elderly. RESULTS: The oncological principles of medico-surgical management of bladder cancer do not differ according to age. On the other hand, the patient comorbidities have been likely to alter the tolerance of these treatments. At the NMIBC stages, no adaptation of the standard treatment has demonstrated any interest. At the MIBC stages, the prognosis was improved by geriatric multidisciplinary perioperative management. CONCLUSION: The indications and principles of surgical treatments must be identical regardless of the patient age. At the NMIBC stages, adjuvant therapy, including BCG therapy, should not be questioned because of the age of the patient. On the other hand, at the localized MIBC stages, neoadjuvant and adjuvant chemotherapy should not be considered as a standard and their indications assessed individually after geriatric assessment.

[Geriatric specificities of localized renal cell carcinoma]. / Spécificités gériatriques du cancer du rein localisé.

PURPOSE: To describe the epidemiology of renal cell carcinoma (RCC) and its natural history in the elderly patient. To propose adaptations of geriatric evaluation specific to RCC. Recall therapeutic options and the treatment options specific to elderly patients. METHOD: Bibliographic research from the Medline bibliographic database (NLM Pubmed tool) and Embase, as well as on the websites of scientific societies of geriatrics, from the National Cancer Institute using the following keywords: elderly, geriatrics, renal cell carcinoma, small renal mass, diagnosis, treatment. RESULTS: The incidence of RCC increases in France and peaks between 70 and 80 years. This increase in incidence is mainly due to the diagnosis of small renal masses (SMR). The specific mortality of RCC increases with age (at least between 75 and 95 years). Tumor biopsy, especially of SMR, should be considered in the elderly patient. The geriatric assessment of patients with CaR has no specificity apart from specific evaluation of renal function and operative risk. There is no prospective therapeutic trials dedicated to elderly patients with localized RCC. Surgical treatment requires the use of fast track protocol (the modalities of which are being elaborated) in which geriatricians play a key role throughout the process. The role of percutaneous ablative treatment should be better defined in elderly patients. However, given their low specific mortality, surveillance of SRM (at least initially) is probably an interesting option, certainly under-used, although its impact on quality of life remains to be clarified. The overarching goal of geriatric oncology must guide the decisions of care in the older patient with CaR: first, the respect of patient-specific expectations and secondly the search for an overall clinical benefit; objectives that have no reason to be restricted to elderly patients. CONCLUSION: RCC is becoming a predominantly elderly cancer. It responds to the current general diagnostic and therapeutic guidelines. It is desirable that clinical research help to better define the respective roles of percutaneous biopsy and treatment of localized RCC.

[Specificity of the management of metastatic renal cancer in the older patient]. / Spécificité de la prise en charge du cancer du rein métastatique chez le patient âgé.

AIM: To define the necessary arrangements of medical treatment with anti-angiogenics, mTOR inhibitor or systemic immunotherapies in the management of metastatic renal cell carcinoma in elderly patients. METHOD: Bibliographical search was performed from the Medline bibliographic database (NLM Pubmed tool) and Embase focused on: metastatic renal cell carcinoma, elderly, treatment. RESULTS: The selection criteria for the medical treatment of metastatic renal cell carcinoma in elderly patients are the IMDC score, necessarily complemented by performance status, the tolerability profile of treatments, more frequent drug interactions, treatment adherence, management capacity of side effects, and patient preference. Each of these criteria is detailed in critical ways. CONCLUSION: The efficacy and tolerability of medical treatments for metastatic renal cancer have not been reported as different depending on age. No dosage adjustment is recommended in principle. However, prevention and early treatment of side effects of treatment should be strengthened in elderly patients.

[Epidemiological, pathological and prognostic characteristics of bladder cancer in elderly patients]. / Spécificités épidémiologiques, pathologiques et pronostiques du cancer de la vessie chez les patients âgés.

AIM: To define and present explanations for the epidemiological, pathological and prognostic differences in bladder cancer in elderly patients. METHOD: Bibliographical search was performed from the Medline bibliographic database (NLM Pubmed tool) and Embase focused on: bladder cancer, carcinogenesis, elderly, epidemiology, prognosis. RESULTS: Bladder cancer is a growing concern for the elderly first and foremost and with an impact, mainly those who are consumers or former users of tobacco, whose therefore frequently have comorbidities associated with this consumption. The initiated carcinogenesis extends with the life length of patients, increasing the prevalence of bladder cancer. Aging promotes carcinogenesis by both potentiating its genetic abnormalities and reducing the immune system performance of the aged host to destroy cancer cells. The delay in the diagnosis of bladder cancer in elderly patients is explained and make up for the time could improve the prognosis. CONCLUSION: Regardless of variations in therapeutic effect and morbidity and mortality of treatments, aging promotes the occurrence and aggressiveness of bladder cancer. The incentive to stop exposure to carcinogens and the search for bladder cancer in patients with hematuria should not reduce with advanced age but instead be promoted in order to improve the prognosis.

Multidisciplinary development of the Geriatric Core Dataset for clinical research in older patients with cancer: A French initiative with international survey.

BACKGROUND: To define a core set of geriatric data to be methodically collected in clinical cancer trials of older adults, enabling comparison across trials. PATIENTS AND METHODS: Following a consensus approach, a panel of 14 geriatricians from oncology clinics identified seven domains of importance in geriatric assessment. Based on the international recommendations, geriatricians selected the mostly commonly used tools/items for geriatric assessment by domain (January-October 2015). The Geriatric Core Dataset (G-CODE) was progressively developed according to RAND appropriateness ratings and feedback during three successive Delphi rounds (July-September 2016). The face validity of the G-CODE was assessed with two large panels of health professionals (55 national and 42 international experts) involved both in clinical practice and cancer trials (March-September 2017). RESULTS AND DISCUSSION: After the last Delphi round, the tools/items proposed for the G-CODE were the following: (1) social assessment: living alone or support requested to stay at home; (2) functional autonomy: Activities of Daily Living (ADL) questionnaire and short instrumental ADL questionnaire; (3) mobility: Timed Up and Go test; (4) nutrition: weight loss during the past 6 months and body mass index; (5) cognition: Mini-Cog test; (6) mood: mini-Geriatric Depression Scale and (7) comorbidity: updated Charlson Comorbidity Index. More than 70% of national experts (42 from 20 cities) and international experts (31 from 13 countries) participated. National and international surveys showed good acceptability of the G-CODE. Specific points discussed included age-year cut-off, threshold of each tool/item and information about social support, but no additional item was proposed. CONCLUSION: We achieved formal consensus on a set of geriatric data to be collected in cancer trials of older patients. The dissemination and prospective use of the G-CODE is needed to assess its utility.

Geriatric analysis from PRODIGE 20 randomized phase II trial evaluating bevacizumab + chemotherapy versus chemotherapy alone in older patients with untreated metastatic colorectal cancer.

BACKGROUND: Older patients have frailty characteristics that impair the transposition of treatment results found in younger patients. Predictive factors are needed to help with treatment choices for older patients. The PRODIGE 20 study is a randomized phase II study that evaluated chemotherapy associated with bevacizumab (BEV) or not (CT) in patients aged 75 years or older. PATIENTS AND METHODS: Patients underwent a geriatric assessment at randomization and at each evaluation. The predictive value of geriatric and oncologic factors was determined for the primary composite end-point assessing safety and efficacy of treatment (BEV or CT) simultaneously and also progression-free survival (PFS) and overall survival (OS). RESULTS: 102 patients were randomized (51 BEV and 51 CT; median age 80 years [range 75-91]). On multivariate analysis, baseline normal independent activity of daily living (IADL) score and no previous cardiovascular disease predicted the primary end-point. High (versus low) baseline Köhne score predicted short PFS and baseline Spitzer quality of life (QoL) score <8, albumin level ≤35 g/L, CA19.9 >2 LN levels above normal and high baseline Köhne score predicted short OS. Survival without deteriorated QoL and autonomy was similar with BEV and CT. On subgroup analyses, the benefit of bevacizumab seemed to be maintained in patients with baseline impaired IADL or nutritional status. CONCLUSION: Normal IADL score was associated with a good efficacy and safety of both BEV and CT. Köhne criteria may be relevant prognostic factors in older patients. Adding bevacizumab to chemotherapy does not impair patient autonomy or QoL.

Bevacizumab+chemotherapy versus chemotherapy alone in elderly patients with untreated metastatic colorectal cancer: a randomized phase II trial-PRODIGE 20 study results.

Background: Metastatic colorectal cancer frequently occurs in elderly patients. Bevacizumab in combination with front line chemotherapy (CT) is a standard treatment but some concern raised about tolerance of bevacizumab for these patients. The purpose of PRODIGE 20 was to evaluate tolerance and efficacy of bevacizumab according to specific end points in this population. Patients and methods: Patients aged 75 years and over were randomly assigned to bevacizumab + CT (BEV) versus CT. LV5FU2, FOLFOX and FOLFIRI regimen were prescribed according to investigator's choice. The composite co-primary end point, assessed 4 months after randomization, was based on efficacy (tumor control and absence of decrease of the Spitzer QoL index) and safety (absence of severe cardiovascular toxicities and unexpected hospitalization). For each arm, the treatment will be consider as inefficient if 20% or less of the patients met the efficacy criteria and not safe if 40% or less met the safety criteria. Results: About 102 patients were randomized (51 BEV and 51 CT), median age was 80 years (range 75-91). Primary end point was met for efficacy in 50% and 58% and for safety in 61% and 71% of patients in BEV and CT, respectively. Median progression-free survival was 9.7 months in BEV and 7.8 months in CT. Median overall survival was 21.7 months in BEV and 19.8 months in CT. The 36-month overall survival rate was 27% in BEV and 10.1% in CT. Severe toxicities grade 3/4 were mainly non-hematologic toxicities (80.4% in BEV, 63.3% in CT). Conclusion: Bevacizumab combined with CT was safe and efficient. Both arms met the primary safety and efficacy criteria.

Slow Gait Speed Is an Independent Predictor of Early Death in Older Cancer Outpatients: Results from a Prospective Cohort Study.

OBJECTIVE: To assess the predictive value of gait speed for early death in older outpatients with cancer. DESIGN: Prospective bicentric observational cohort study. SETTING: The Physical Frailty in Elder Cancer patients (PF-EC) study (France). PARTICIPANTS: One hundred and ninety outpatients with cancer during the first 6 months of follow up in the PF-EC study. MEASUREMENTS: The association between usual gait speed over 4 m alone (GS) or included in the short physical performance battery (SPPB) and overall survival within 6 months following a comprehensive geriatric assessment (CGA). A Cox proportional-hazard regression model was performed in non-survivors for clinical factors from the CGA, along with c reactive protein (CRP). Two models were created to assess GS alone and from inclusion in the SPPB. RESULTS: The mean age was 80.6 years, and 50.5% of the participants were men. Death occurred in 11% (n=22) of the participants within the 6 month follow up period. Of these participants, 98% had solid cancers, and 33% had a metastatic disease. A GS < 0.8 m/s (HR=5.6, 95%CI=1.6-19.7, p=0.007), a SPPB < 9 (HR=5.8, 95%CI=1.6-20.9, p=0.007) and a CRP of 50 mg/l or greater (p<0.0001) were significantly associated with early death in the two multivariate analyses. Cancer site and extension were not significantly associated with early death. CONCLUSION: Walking tests are associated with early death within the 6 month follow up period after a CGA independent of cancer site and cancer extension. GS alone < 0.8 m/s is at least as efficacious as the SPPB in predicting this outcome. GS alone could be used routinely as a marker of early death to adapt oncologic therapeutics. Further studies are needed to validate these preliminary data.

[Comprehensive geriatric assessment (CGA) in elderly with cancer: For whom?]. / Évaluation gériatrique en oncologie : pour quels patients ?

Scientific societies recommend the implementation of a comprehensive geriatric assessment (CGA) in cancer patients aged 70 and older. The EGA is an interdisciplinary multidimensional diagnostic process seeking to assess the frail older person in order to develop a coordinated plan of treatment and long-term follow-up. Identification of comorbidities and age-induced physiological changes that may increase the risk of anticancer treatment toxicities is essential to better assess the risk-benefit ratio in elderly cancer patients. The systematic implementation of a CGA for each patient is difficult to perform in daily practice. Therefore, it is recommended to screen vulnerable patients who will benefit from a complete CGA. Our work presents the vulnerability screening tools validated by at least two independent studies in a cancer elderly population setting. Among seven screening tools, the G8 and the VES13 are the most effective, and have been validated specifically in older population with cancer. The G8 is recommended by scientific societies and the French National Cancer Institute (INCa) because of its easy implementation in daily clinical practice, its high sensitivity and fair specificity. Although studies are underway to improve its performance, the G8 is currently the simplest tool to routinely identify older cancer patients who should have a complete assessment in geriatric oncology.

Frailty and nutrition: searching for evidence.

Frailty is a geriatric syndrome that predicts disability, morbidity and mortality in the elderly. Poor nutritional status is one of the main risk factors for frailty. Macronutrients and micronutrients deficiencies are associated with frailty. Recent studies suggest that improving nutritional status for macronutrients and micronutrients may reduce the risk of frailty. Specific diets such as the Mediterranean diet rich in anti-oxidants, is currently investigated in the prevention of frailty. The aim of this paper is to summarize the current body of knowledge on the relations between nutrition and frailty, and provide recommendations for future nutritional research on the field of frailty.

Interrelations of immunological parameters, nutrition, and healthcare-associated infections: prospective study in elderly in-patients.

BACKGROUND & AIMS: Healthcare-associated infections [HAI] are common in elderly individuals and may be related to both nutritional deficiencies and immunosenescence. Here, we assessed whether overall malnutrition and/or specific nutrient deficiencies were associated with HAI via alterations in immune parameters. METHODS: Prospective observational cohort study in patients aged ≥ 70 years admitted to the geriatric rehabilitation unit of a teaching hospital in France between July 2006 and November 2008. Clinical and laboratory parameters reflecting nutritional status and immune function were collected at baseline. Flow cytometry was used to assess blood lymphocyte subsets including the naive CD4 T-cell count, naive and memory CD8 T-cell counts, effector CD8 T-cell count, and CD4/CD8 ratio. Patients were monitored for HAI for 3 months or until discharge from the geriatric unit or death. RESULTS: Of 252 consecutive in-patients aged ≥ 70 years [mean age, 85 ± 6.2 years], 181 [72%] met French National Authority for Health criteria for malnutrition and 97 [38%] experienced one or more HAI. Patients who subsequently experienced HAI had significantly lower baseline values for energy intake [odds ratio (OR), 0.76; 95% confidence interval (95%CI), 0.59-0.99], serum albumin [OR, 0.43; 95%CI, 0.32-0.58], serum zinc [OR, 0.77; 95%CI, 0.62-0.97], selenium [OR, 0.76; 95%CI, 0.61-0.95], and vitamin C [OR, 0.71; 95%CI, 0.54-0.93]. Associations linking these five variables to HAI were not significantly changed by adjusting for flow cytometry T-cell subset values. CONCLUSION: Our results suggest a direct effect of nutritional parameters on HAI rather than an indirect effect mediated by immune parameters.