Impact of era of diagnosis on cause‐specific late mortality among 77 423 five‐year European survivors of childhood and adolescent cancer: The PanCareSurFup consortium

Abstract

Late mortality of European 5-year survivors of childhood or adolescent cancer has dropped over the last 60 years, but excess mortality persists. There is little information concerning secular trends in cause-specific mortality among older European survivors.PanCareSurFup pooled data from 12 cancer registries and clinics in 11 European countries from 77 423 five-year survivors of cancer diagnosed before age 21 between 1940 and 2008 followed for an average age of 21 years and a total of 1.27 million personyears to determine their risk of death using cumulative mortality, standardized mortality ratios (SMR), absolute excess risks (AER), and multivariable proportional hazards regression analyses. At the end of follow-up 9166 survivors (11.8%) had died compared to 927 expected (SMR 9.89, 95% confidence interval [95% CI] 9.69-10.09), AER 6.47 per 1000 person-years, (95% CI 6.32-6.62). At 60 to 68 years of attained age all-cause mortality was still higher than expected (SMR = 2.41, 95% CI 1.90-3.02). Overall cumulative mortality at 25 years from diagnosis dropped from 18.4% (95% CI 16.5-20.4) to 7.3% (95% CI 6.7-8.0) over the observation period. Compared to the diagnosis period 1960 to 1969, the mortality hazard ratio declined for first neoplasms (P for trend <.0001) and for infections (P < .0001); declines in relative mortality from second neoplasms and cardiovascular causes were less pronounced (P = .1105 and P = .0829, respectively). Pan-CareSurFup is the largest study with the longest follow-up of late mortality among European childhood and adolescent cancer 5-year survivors, and documents significant mortality declines among European survivors into modern eras. However, continuing excess mortality highlights survivors' long-term care needs.cardiovascular, causes of death, European, late mortality, second malignant neoplasms, survivors of childhood cancer What's new?Children and adolescents who survive cancer have increased mortality rates compared with the general population. Here, the authors investigated trends in mortality among European cancer survivors 5 or more years after diagnosis. They pooled data on more than 77 000 patients from 12 cancer registries and clinics across Europe. Patients were diagnosed between 1940 and 2018, and all-cause mortality fell steeply during this period. However, excess mortality remained high, even for subjects in their 60s, highlighting the need for long term care for childhood cancer survivors.

Late mortality reduction among survivors of germ cell tumors in childhood and adolescence in Europe: A report from the PanCareSurFup cohort

“…Moreover, Trabert et al 32 reported that in the SEER between 1988 and 2007, there was a change in the classification of mixed GCTs, with a decline of some types of histology and the final suggestion of cautious interpretation of some data. The rules for coding underlying causes of death can also give rise to too many deaths being attributed to the first primary neoplasm 1 and to deaths due to other causes being underestimated. The median followup of the cohort is 14 years beyond the fifth year after diagnosis and thus, new mortality and morbidity patterns could emerge with greater follow-up.…”

“…Greater success in the treatment of children and adolescents with cancer and more expertise in supportive care have contributed to improving 5‐year survival for most cancers. Improving 5‐year survival has shown, however, that long‐term survivors remain persistently at greater risk of severe late effects, including excess late mortality, whatever the type of primary tumor 1 …”

“…Improving 5-year survival has shown, however, that long-term survivors remain persistently at greater risk of severe late effects, including excess late mortality, whatever the type of primary tumor. 1 Data regarding late mortality reduction and excess late mortality in survivors of germ cell tumors (GCTs) in childhood and adolescence are more limited than for other more common childhood and adolescent cancers. This could be due to the fact that GCTs are more difficult to study because they form a heterogeneous group in terms of histology, age at diagnosis, anatomical site, and prognosis 2 and are rare (in Europe incidence rates in 0-19 years old per 100,000: 0.43 in females, 1.6 in males).…”

Late mortality among 5‐year survivors of childhood cancer: A systematic review and meta‐analysis

“…Evolving treatment options and reductions in treatment intensity over time have resulted in significant reductions in the cumulative incidence of late mortality (both all-cause and cause-specific mortality) at various follow-up intervals among survivors treated in past decades. 2,3 Using cumulative incidence to examine trends in late mortality can identify differences between subgroups of survivors but cannot contextualize more broadly whether the mortality experienced among survivors varies significantly from what is expected in the general population. Relative and excess mortality are additional metrics that can be used to measure progress in cancer treatment and reduction in long-term adverse health effects among survivors.…”

Treating secondary malignant neoplasms: A burden of childhood cancer survivors

“…The radiotherapy and chemotherapy regimens responsible for improving the survival rates for children and adolescents with cancer are not devoid of carcinogenic effects, and second malignancies are an important cause of death in long-term survivors. 11,12 The incidence of SMN is known to increase after radiotherapy, and the related risk persists for decades, long after the first tumor was diagnosed. 13 Many reports have been published, especially on Hodgkin lymphoma 14 and pediatric and adolescent cancer survivors, on the risk factors, the radiotherapy fields and doses, the type and dosage of chemotherapy, and the timing and type of follow up adopted in such patients.…”