It’s time to move forward in geriatric oncology

The greatest risk factor of developing malignancy is aging. In the Nordic countries, approximately 45% of newly diagnosed cancer patients and the major part of cancer survivors are aged 70 years or older [1,2]. However, most studies are conducted in highly selected groups of younger patients without significant comorbidity, and results from these studies set the standard of treatment for all cancer patients. It has been shown that whereas 67% of newly diagnosed cancer patients in the US are 65 years or older, only 33% of patients in oncologic clinical trials are in this age group. This distribution has not changed throughout the past decade [3,4]. This is also seen in the Nordic countries [5]. This fact raises concerns that many older patients will be undertreated because physicians worry they might not tolerate standard treatment regimens. Others might suffer from severe treatment toxicity due to frailty, not found by a routine examination.

For quite some years now, there has been a special and increasing clinical interest in geriatric oncology. Aging is a heterogeneous process that involves a progressive decline in the functional reserve of multiple organs and systems, which increases the susceptibility to stress caused by disease, treatment, and complications to both [6]. The course of this process is highly individual, and a person’s functional status cannot be established on chronological age alone [7]. Recognizing these issues, there has been a major interest in developing tools for identifying patients who might and might not tolerate and benefit from routine oncologic treatment. In 2000, the International Society of Geriatric Oncology (SIOG) was founded. The goal of SIOG is to “foster the development of health professionals in the field of geriatric oncology, in order to optimize treatment of older adults with cancer” (www.siog.org).

A comprehensive geriatric assessment (CGA) is defined as “a multidimensional, interdisciplinary diagnostic process focusing on determining an older person’s medical, psychosocial, and functional capabilities to develop a coordinated and integrated plan for treatment and long-term follow-up”. In a non-oncologic geriatric population, a CGA can detect frailty and additionally CGA creates opportunities to improve functional status thus improving physical function, overall survival, and quality of life [8].

In older oncologic patients, a CGA identifies problems that are not found by a routine history or physical examination [9], but it also has potential to predict treatment-related toxicity and mortality [10,11]. However, most studies are small, retrospective and/or with very heterogeneous study populations, and further prospective studies in larger and more homogenous groups are warranted to establish the most important predictive parameters and their cut-off points. In two reviews of the literature on CGA in geriatric oncology up to 2012, it has not been possible to conduct a meta-analysis on the effect of a CGA on treatment toxicity and overall survival. This is due to the heterogeneity of both populations and the assessment methods used [12,13].

A CGA is time consuming, and many screening tools and models have been developed and tested to find patients in need of a CGA or simply to replace it. Up until now, no screening tool has been found adequate to replace a full CGA, and an SIOG expert panel could not recommend one over another [14].

Comparing results of a full CGA and various screening tools, the G8 and VES-13 and especially a combination of both, seem to have the highest sensitivity and specificity. Some studies have found G8 and VES-13 to predict both toxicity to chemotherapy and prognosis but again; others have not. An important point is that a CGA performed in collaboration with a geriatric specialist includes an intervention aimed at improving the patients’ condition, and this intervention might make the difference for the patient. As a physician in a busy everyday clinic, however, a quick tool that could help us differentiate the patients who would tolerate chemotherapy and benefit from it, from those who would not, would be invaluable.

Published in this issue of Acta Oncologica is a prospective cohort study by Aaldriks et al., “Prognostic factors for the feasibility of chemotherapy and the Geriatric Prognostic Index (GPI) as risk profile for mortality before chemotherapy in the Elderly”. A CGA was performed in 496 senior cancer patients before starting chemotherapy in four different hospitals during almost six years. The authors developed a three-item screening tool for prediction of chemotherapy feasibility and one for determining patient prognosis (GPI). The domains evaluated in this GA were nutritional status, cognitive status, co-medication, functional status, and psychosocial status. The authors found three items to be independently associated with feasibility of chemotherapy, and three items to be associated with prognosis. Overall, the study shows that nutrition, functional status, and co-medication all influence feasibility of receiving at least four cycles of chemotherapy and on mortality. As many other studies, this comprises a heterogeneous study population receiving heterogeneous treatment regimens. However, analyses have been adjusted for type of malignancy, purpose of treatment, and for multiple testing. Of course, results of this study will need further validation, before being able to guide us when planning treatment for our senior patients. Unfortunately, traditional baseline blood tests and ECOG performance status were not reported and adjusted for in this study. This diversity in the selection of baseline factors makes comparison across trials almost impossible and may add to the lack of an established GA. We recommend that traditional baseline parameters with some of the well known GA parameters and screening tools should be evaluated before starting therapy in older oncologic patients.

All in all, we need further studies focusing on the capability of a GA and screening tools to improve outcomes for older patients. We need to establish solid evidence that extra focus on this group, the major group of cancer patients, is cost effective. We need to do this also in order to raise awareness among politicians that this is an area worth investing in. The time has come to start validating the already existing tools in order to establish this evidence. SIOG has found the G8 and the VES-13 to be screening tools with high sensitivity and specificity, especially in combination. Even in institutions that do not have an opportunity to perform a GA, these screenings can and should be done, and their association with treatment tolerance and prognosis should be registered prospectively and published. Two other screening tools were developed through large prospective studies to predict treatment toxicity, both created after large prospective studies, and both easily accessible online [15,16]. Last but certainly not least, more randomized clinical trials recruiting older cancer patients are warranted in order to secure the major group of cancer patients an evidence-based anti-neoplastic treatment. In April 2015, NORDIC9 was launched. NORDIC9 is a Nordic multicenter randomized trial comparing a full dose monotherapy strategy (S-1 followed by irinotecan at the time of progression) to reduced dose combination therapy strategy (S-1 and oxaliplatin followed by S-1 and irinotecan) as first-line therapy. For this study, 150 older patients (70 + years) with non-resectable metastatic colorectal cancer (mCRC) who are not candidates for full-dose standard combination therapy will be included. Elderly patients with mCRC have a much poorer prognosis compared with younger patients, and this has not improved during the past decade as it has in the younger ones [17]. Patients will be included based on performance status and routine blood tests but simple GA parameters and screening tools (G8, VES13, Timed-Up-and-Go, Grip strength and Charlson Comorbidity Index) and quality of life (EORTC QLQ-30) will be registered at baseline. The primary endpoint is progression-free survival but secondary endpoints are simple GAs as predictive markers for efficacy and toxicity. The present and other ongoing prospective studies will increase our understanding of the tolerability of oncological therapy and broaden our possibilities to tailor treatment in this fast growing group of older cancer patients.