Response: Methods for second primary cancers evaluation have to be standardized

We read carefully through the Letter to the Editor entitled “Methods for second primary cancers evaluation have to be standardized” by Crocetti et al.1 In our study,2 standardized incidence ratios (SIRs) of ovarian cancers diagnosed within the first year after endometrial cancer diagnosis were high (Table 3), which might suggest the existence of synchronous ovarian cancer. However, all second primary cancers (SPCs) included in our study were real cancers occurring at different sites/histology rather than two concomitant presentations of the same malignancy, as mentioned in the materials and methods section. For instance, the Swedish Cancer Registry only records primary malignancies. Metastasized cancers to other sites were only registered at primary sites and, for multiple primary cancers occurring in the same organ or same organ system, only clearly separated malignancies were accepted as multiple primaries and registered. Close to 100% of the registered neoplasms were histologically verified and ∼98% of second neoplasms were correctly verified according to a re-evaluation study of 209 multiple primary tumors.3, 4 A few of the first primary cancers reported in the early years of German cancer registry might be actually second primary cancers because the German cancer registries included in this study were generally established in 1997 (except that four German registries even started data collection after 1997); nevertheless, for comparability and consistency, the same criteria were also adopted for Swedish data, i.e., the definition of first and second primary cancers was recorded according to the study period 1997–2012. Our overview paper also indicated this point.5 Coexisting ovarian malignancy in young women with endometrial cancer is common. If histology of ovarian cancer is different from endometrial cancer, it is likely that the ovarian cancer is a secondary cancer. While if the histology types are the same (e.g., both are endometrioid) and at the same time, if the time interval is short (e.g., <2 months) after endometrial cancer diagnosis, ovarian recurrence of endometrial cancer is likely. Actually in our study,2 in Sweden there was only one case with same endometrioid histology for endometrial and ovarian cancers (Appendix 3), while in Germany there were 24 cases (Table 5) and all those 24 cases occurred within the first year of diagnosis of endometrial cancer (Table 3). Therefore, in Sweden there should be no concurrent cancer (or just one case), while in Germany we found 2.3-fold elevated risk of second endometrioid cancer for the follow-up 1–4 years, consistent with the overall finding of 4.8-fold elevated risk of second endometrioid cancer (Table 2). Actually, we already highlighted in our paper that elevated risks of second ovarian and kidney cancers found within one year of follow-up might most likely be attributed to increased medical surveillance after the diagnosis of endometrial cancer, as suggested by studies from our group [treatments for patients with endometrial cancer usually involve major surgery, which (especially within first year) leads to a careful examination of the patient and diagnosis of tumors at a variety of sites]. Numerous studies on second primary cancers using data from the Nordic cancer registries, the US Surveillance, Epidemiology and End Results (SEER) Program and the IARC have been conducted.6-9 Nevertheless, there is no consensus on whether or not including data on within first two months after the follow-up of first primary cancer.2, 5, 10 Therefore, we also agree that methods for second primary cancers evaluation should be standardized by international cancer agencies. List of the consortia (GEKID Cancer Survival Working Group) members: Martin Meyer6, Andrea Eberle9, Roland Stabenow14, Stefan Hentschel15, Alice Nennecke15, Joachim Kieschke16, Eunice Sirri16, Katharina Emrich17, Hiltraud Kajüter18, Volkmar Mattauch18, Nora Eisemann8 and Klaus Kraywinkel19 14 Cancer Registry of Berlin and the New Federal States, Berlin, Germany 15 Hamburg Cancer Registry, Hamburg, Germany 16 Cancer Registry of Lower Saxony, Hannover, Germany 17 Cancer Registry of Rhineland-Palatinate, Institute for Medical Biostatistics, Epidemiology and Informatics, University Medical Center, Johannes Gutenberg 18 Cancer Registry of North Rhine-Westphalia, Münster, Germany 19 Robert Koch Institute, Berlin, Germany The study sponsors were not involved in the study design, data collection, data analysis, interpretation of results, writing of the manuscript and in the decision to submit the manuscript for publication.