From trends to transformation: where cardio-oncology is to make a difference

This editorial refers to ‘A population-based study of cardiovascular disease mortality risk in US cancer patients’†, by K.M. Sturgeon et al., on page 3889. Ashes to ashes, dust to dust, if the cancer don’t get us, the arteriosclerosis must. Richard Gordon in The Alarming History of Medicine, 1993 Over the past decade a tremendous movement has been seen: cardio-oncology. Though not defined in detail, this discipline sees itself at the intersection of oncology/haematology and cardiology, with a particular focus on mitigating and managing the cardiovascular diseases (CVDs) of cancer patients, either pre-existing or developing.1 , 2 It is uncertain how many cardio-oncology clinics and service lines currently exist worldwide, but these will most certainly keep growing, and many healthcare systems across the globe either already have them or will have access to them in the near future.3 , 4 While acknowledging the excitement and momentum of cardio-oncology, the sceptic may ask what difference it makes, what role it plays, and where in the global picture it fits in. In this issue of the European Heart Journal, Sturgeon et al. provide important information and trends for the trendy business of cardio-oncology.5 The authors inquired the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute (NCI), a national registry of cancer patients in the USA, identifying >3 million patients with 28 different cancer types over four decades (1973–2015). The mortality data reported by SEER are provided by the National Center for Health Statistics, which makes it an attractive approach for comparisons with the general US population. Taking all cancer patients into account, 38% succumbed to the malignant disease process and 11% died of CVD, with the leading cause being heart disease in three out of four cases. Thus, the first message is that CVD is not an uncommon cause of death in cancer patients, and heart disease may be regarded as the final common pathway. While these are important data, the work by Sturgeon et al. goes much deeper, with implications that go much further. First, generally speaking, cancer patients face an increased CVD mortality risk for life. It starts with a peak in the (first) year of cancer diagnosis, probably representing the acute cancer phase with the interplay of pre-existing CVD, potential cardiovascular (CV) toxicities of cancer therapies, as well as CV risks associated with the tumour burden. For instance, previous studies from the SEER-Medicare database have outlined that the risk of arterial thrombo-embolic events peaks around the time of cancer diagnosis, starts a few months before, and remains significantly elevated for months thereafter.6 , 7 Recognizing this acute phase is extremely important and has not been made this evident across a multitude of cancers in years past. The early peak in CVD risk is followed by a chronic phase, which for the most part falls into the survivorship period. As outlined in lymphoma patients before, there might be a ‘sweet spot’ where the mortality risk remains flat over years; however, eventually it seems to increase again.8 This could be the consequence of late toxicities, or accelerated or natural progression of pre-existing disease. Most importantly, it seems that the longer the cancer survival times, the higher the chances that not malignancies but other entities, especially CVD, will terminate life expectancy.9 Recognizing this chronic phase of persistent risk is equally important and again has not been worked out this clearly from one data set for a variety of cancers. The third and very fascinating aspect is that the 28 cancers analysed in the study of Sturgeon et al. can be categorized by mortality trends over time (Figure 1). The first group includes those with high cancer mortality and relatively low CVD mortality, unchanged over the past four decades. The second group comprises those with declining cancer mortality, which, however, still significantly outweighs CVD mortality. The third group entails those with a cancer mortality that is now on a par with CVD mortality. Arguably, the importance of proper management of CVD increases as the impact of cancer mortality decreases, and one may rank the ‘making a difference level’ for cardio-oncology service lines accordingly: group 3 > group 2 >> group 1. Illustration of the three groups of cancer patients that can be categorized based on the dynamics in cancer and cardiovascular disease (CVD) mortality. Cardio-oncology approaches will probably have the greatest impact in group 2 and in particular in group 3. The cardio-oncology network includes not only oncologists/haematologists and cardiologists, but also general practitioners and primary care physicians, especially considering the long-term risks extending to decades after completion of cancer therapy. CV, cardiovascular; CVRF, cardiovascular risk factor(s). It is important to emphasize that these are conceptual views and that the impact of a cardio-oncology approach may vary by individual patient and cancer subtype. For instance, in the wake of the immune checkpoint inhibitor revolution, the prognosis of many cancers is expected to change. This includes lung cancer, and its mortality (survival) plot may need to be redrawn in the near future.10 Similarly, a number of patients with relentless malignancies (group 1) may still benefit from a cardio-oncology approach, e.g. those with pre-existing or developing CVD that can threaten cancer therapy and therefore any chance of extension of life expectancy. As exciting as these analyses are, they are not without limitations. First, they are based on SEER data, and cause of death may not be accurately defined.11 This, however, would be a systematic error that affects all patients across all cancers and even the general population. A greater issue might be the lack of information on cancer therapy, CV complications, CV therapy, CV risk factors, and pre-existing CVDs. Managing and mitigating CV risk and CVD in their interplay with cancer and its therapy is at the heart of cardio-oncology, and the field is more granular than presented herein. Last, but not least, the analysis of Sturgeon et al.5 probably misses key developments in the current era of immunotherapies and remains limited in follow-up for those cancer patients diagnosed in this millennium. Accordingly, this analysis lags behind and does not reflect the present-day environment in its entirety. This being said, cancer survival prognoses and CVD aspects in cancer patients are not expected to decline but to rise. Furthermore, one may view the fact that the current analysis pre-dates the cardio-oncology movement as a grand opportunity to assess the impact of modern-day cardio-oncology in years to come. In summary, the important work by Sturgeon et al. confirms that cancer patients have an on average 2–6 times higher CVD mortality risk than the general population. This is a key message that every cardiologist needs to hear. Secondly, the CVD mortality risk is evident throughout the continuum of cancer care, and entails an acute phase (early risk) and a chronic phase (late risk). In view of such grave and persistent consequences, a reactive management approach that comes into play solely when clinical presentations and complications arise is no longer in order. Rather, one would advocate for a proactive approach that starts before any cancer therapy is given and continues for a lifetime thereafter. Thirdly, even with the best possible cardio-oncology care, no difference in population-based outcomes may be achieved in patients with relentless malignancies, while for others it is of increasing significance. Demonstrating improvement in outcomes and that cardio-oncology can, indeed, make a difference may address the sceptic and consolidate the movement. Cardio-oncology: here it comes, cardio-oncology: here it stays. Conflict of interest: none declared. The opinions expressed in this article are not necessarily those of the Editors of the European Heart Journal or of the European Society of Cardiology.