cancers Article Cancer Survival in Adults in Spain: A Population-Based Study of the Spanish Network of Cancer Registries (REDECAN) Marcela Guevara 1,2,3, * , Amaia Molinuevo 4 , Diego Salmerón 2,5 , Rafael Marcos-Gragera 2,6,7,8,9 , Marià Carulla 10,11,12 , María-Dolores Chirlaque 2,5,13 , Marta Rodríguez Camblor 14 , Araceli Alemán 15 , Dolores Rojas 15 , Ana Vizcaíno Batllés 16 , Matilde Chico 17 , Rosario Jiménez Chillarón 18 , Arantza López de Munain 19 , Visitación de Castro 19 , Maria-José Sánchez 2,20,21,22 , Enrique Ramalle-Gómara 23 , Paula Franch 24,25 , Jaume Galceran 10,11,12 and Eva Ardanaz 1,2,3 1 Navarra Public Health Institute, 31003 Pamplona, Spain; me.ardanaz.aicua@navarra.es 2 Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), 28029 Madrid, Spain; dsm@um.es (D.S.); rmarcos@iconcologia.net (R.M.-G.); mdolores.chirlaque@carm.es (M.-D.C.); mariajose.sanchez.easp@juntadeandalucia.es (M.-J.S.) 3 Navarra Institute for Health Research (IdiSNA), 31008 Pamplona, Spain 4 Biodonostia Health Research Institute, 20014 San Sebastian, Spain; au-molinuevo@euskadi.eus 5 Departamento de Ciencias Sociosanitarias, IMIB-Arrixaca, Universidad de Murcia, 30100 Murcia, Spain 6 Epidemiology Unit and Girona Cancer Registry, Oncology Coordination Plan, Catalan Institute of Oncology, Department of Health, Government of Catalonia, 17007 Girona, Spain 7 Descriptive Epidemiology, Genetics and Cancer Prevention Research Group, Girona Biomedical Research Institute (IdiBGi), 17190 Girona, Spain 8 Faculty of Medicine, University of Girona, 17071 Girona, Spain 9 Josep Carreras Leukemia Research Institute, 17003 Girona, Spain 10 Tarragona Cancer Registry, Cancer Epidemiology and Prevention Service, Hospital Universitari Sant Joan de Citation: Guevara, M.; Molinuevo, Reus, CatSalut, 43204 Reus, Spain; maria.carulla@salutsantjoan.cat (M.C.); A.; Salmerón, D.; Marcos-Gragera, R.; jaume.galceran@salutsantjoan.cat (J.G.) Carulla, M.; Chirlaque, M.-D.; 11 Pere Virgili Health Research Institute (IISPV), 43204 Reus, Spain 12 Faculty of Medicine and Health Sciences, Rovira i Virgili University, 43204 Reus, Spain Rodríguez Camblor, M.; Alemán, A.; 13 Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, 30008 Murcia, Spain Rojas, D.; Vizcaíno Batllés, A.; et al. 14 Public Health Directorate of Asturias, 33006 Oviedo, Spain; marta.rodriguezcamblor@asturias.org Cancer Survival in Adults in Spain: A 15 Canary Islands Cancer Registry, Public Health Directorate, Canary Health Service, Population-Based Study of the 35003 Las Palmas de Gran Canaria, Spain; maleher@gobiernodecanarias.org (A.A.); Spanish Network of Cancer mrojmar@gobiernodecanarias.org (D.R.) Registries (REDECAN). Cancers 2022, 16 Castellón Cancer Registry, Public Health Directorate, General Health Department, Generalitat Valenciana, 14, 2441. https://doi.org/10.3390/ 46020 Valencia, Spain; vizcaino_ana@gva.es cancers14102441 17 Ciudad Real Cancer Registry, Health and Social Welfare Authority, Castile-La Mancha, 13071 Ciudad Real, Spain; matildec@jccm.es Academic Editor: Eduardo Nagore 18 Cuenca Cancer Registry, Health and Social Welfare Authority, Castile-La Mancha, 16071 Cuenca, Spain; Received: 30 April 2022 rjimenez@jccm.es 19 Basque Country Cancer Registry, Health Department, 01010 Vitoria, Spain; Accepted: 13 May 2022 arantza-lopez@euskadi.eus (A.L.d.M.); v-castro@euskadi.eus (V.d.C.) Published: 15 May 2022 20 Escuela Andaluza de Salud Pública (EASP), 18011 Granada, Spain 21 Instituto de Investigación Biosanitaria ibs.GRANADA, 18012 Granada, Spain Publisher’s Note: MDPI stays neutral 22 Department of Preventive Medicine and Public Health, University of Granada, 18071 Granada, Spain with regard to jurisdictional claims in 23 Department of Epidemiology and Prevention, La Rioja Regional Health Authority, 26071 Logroño, Spain; published maps and institutional affil- eramalle@larioja.org iations. 24 Balearic Islands Health Research Institute (IdISBa), Illes Balears, 07120 Palma, Spain; pfranch@dgsanita.caib.es 25 Mallorca Cancer Registry, Balearic Islands Public Health Department, 07010 Palma, Spain * Correspondence: mguevare@navarra.es Copyright: © 2022 by the authors. Simple Summary: We studied cancer survival and its trends in adult patients in Spain. We included Licensee MDPI, Basel, Switzerland. more than 600,000 patients with primary cancer diagnosed during 2002–2013 and followed them up This article is an open access article distributed under the terms and to 2015. The study provides cancer survival estimates up to five years after diagnosis by sex and age conditions of the Creative Commons for 29 cancer groups. We found survival improvements for most cancer groups from 2002–2007 to Attribution (CC BY) license (https:// 2008–2013, although with differences by age, being greater for patients younger than 75 years than creativecommons.org/licenses/by/ for older patients. The persistent poor prognosis for some cancers emphasizes the need to reinforce 4.0/). Cancers 2022, 14, 2441. https://doi.org/10.3390/cancers14102441 https://www.mdpi.com/journal/cancers Cancers 2022, 14, 2441 2 of 18 actions along the cancer continuum, from primary prevention to early diagnosis, optimal treatment, and supportive care. Further examination of possible sociodemographic inequalities is warranted. Abstract: The assessment of cancer survival at the population level is essential for monitoring progress in cancer control. We aimed to assess cancer survival and its trends in adults in Spain. Individual records of 601,250 adults with primary cancer diagnosed during 2002–2013 and followed up to 2015 were included from 13 population-based cancer registries. We estimated net survival up to five years after diagnosis and analyzed absolute changes between 2002–2007 and 2008–2013. Estimates were age-standardized. Analyses were performed for 29 cancer groups, by age and sex. Overall, age- standardized five-year net survival was higher in women (61.7%, 95% CI 61.4–62.1%) than in men (55.3%, 95% CI 55.0–55.6%), and ranged by cancer from 7.2% (pancreas) to 89.6% (prostate) in men, and from 10.0% (pancreas) to 93.1% (thyroid) in women in the last period. Survival declined with age, showing different patterns by cancer. Between both periods, age-standardized five-year net survival increased overall by 3.3% (95% CI 3.0–3.7%) in men and 2.5% (95% CI 2.0–3.0%) in women, and for most cancer groups. Improvements were greater in patients younger than 75 years than in older patients. Chronic myeloid leukemia and myeloma showed the largest increases. Among the most common malignancies, the greatest absolute increases in survival were observed for colon (5.0%, 95% CI 4.0–6.0%) and rectal cancers (4.5%, 95% CI 3.2–5.9%). Survival improved even for some cancers with poor prognosis (pancreas, esophagus, lung, liver, and brain cancer). Further investigation of possible sociodemographic inequalities is warranted. This study contributes to the evaluation of cancer control and health services’ effectiveness. Keywords: cancer; survival; prognosis; epidemiology; population-based study; cancer registries 1. Introduction Cancer is a major cause of morbidity and mortality globally. Recent World Health Organization (WHO) estimates showed that cancer is the first leading cause of premature death (before 70 years of age) in 57 of 183 countries, including Spain, and ranks second in a further 55 countries [1]. In 2020 in Spain, with projected 280,000 new cancer cases [2], and 113,000 cancer deaths, the disease remains the first cause of death in men and the second in women, accounting for 27% and 19% of all deaths, respectively [3]. Population-based cancer survival, in addition to being a fundamental measure to describe the prognosis of cancer patients, is an indicator of the overall performance of health services across the patient pathway, from early detection and diagnosis to treat- ment and follow-up. Moreover, wide regional and international differences have been revealed, largely reflecting socioeconomic inequalities and differences in the effectiveness of health systems [4–6]. Hence, cancer survival estimates are of great importance to patients, clinicians, public health professionals, and policymakers. The CONCORD-3 Programme updated the worldwide 5-year survival estimates to 2014 (2013 for Spanish adults) for 18 groups of cancers, however it did not provide data by sex nor by age group at the country level [4]. The latest specific study on survival of cancer patients in Spain, performed by the Spanish Network of Cancer Registries (REDECAN), provided results for patients diagnosed up to 2007 [7], therefore, detailed and more up-to- date estimates are needed. The aims of this study were (1) to provide cancer survival estimates for adult patients, diagnosed during 2008–2013 in Spain, overall and for 29 cancer groups by sex and age group, and (2) to assess survival trends between 2002–2007 and 2008–2013. Cancers 2022, 14, 2441 3 of 18 2. Materials and Methods 2.1. Study Design and Population We conducted an observational study using data from 13 population-based cancer registries (Asturias, Canary Islands, Castellón, Ciudad Real, Cuenca, Basque Country, Girona, Granada, La Rioja, Mallorca, Murcia, Navarra and Tarragona), covering more than 12 million inhabitants that represent ~26% of the Spanish population of 2013. All the participating cancer registries follow standard registration procedures and have met the high standards of comparability, completeness and validity for inclusion in the series Cancer Incidence in Five Continents, published quinquennially by the International Agency for Research on Cancer (IARC) [8]. Most registries provided data for the entire study period and all included at least three years of each comparison period (Supplementary Table S1). We selected the cancer registration records for adults (aged 15–99 years) diagnosed between 2002 and 2013 with a primary malignant neoplasm, except non-melanoma skin cancer. Tumor anatomical site (topography) and morphology were coded according to the International Classification of Disease for Oncology, 3rd edition (ICD-O-3) [9]. The international rules for registering multiple primary neoplasms were applied [10], to enable comparison of the results with other studies. Patients who had more than one primary cancer were included in the analyses for each cancer. Only invasive malignancies (ICD-O-3 behaviour code 3) were included, except for the bladder, for which tumors with uncertain or borderline malignancy and in situ (behavior codes 1 and 2) were also included, to ensure comparability. Cases known to the registry only through the death certificate (DCO) and cases diagnosed at autopsy were excluded from the analyses, since their survival time was unknown. Analyses were performed for all cancers combined and separately for 29 cancer groups that jointly represent more than 90% of all cancer cases. Cancer groups were defined by topography and morphology. The WHO classification and the HAEMACARE guidelines were followed for grouping the hematological malignancies [11,12]. For presentation, the ICD-O-3 codes were converted to the International Classification of Diseases, Tenth Revision (ICD-10) codes by using the software IARCcrg Tools v2.13 (IARC, Lyon, France). Table 1 shows the cancer groups analyzed and the respective ICD-10 codes. 2.2. Follow-Up for Vital Status Vital status follow-up until the end of 2015 was carried out using multiple sources of information in all cancer registries, such as the regional mortality registries, National Death Index, social security database, hospital and primary care records and population censuses, as needed and available in each registry. 2.3. Quality Control In addition to the quality controls performed in each cancer registry, extensive data quality checks were undertaken on the joint database, including those proposed by EUROCARE- 5 [13], using IARCcrg Tools v2.13 (IARC, Lyon, France), JRC-ENCR Quality Check Software v1.8.1 (ENCR, Ispra, Italy), and automated ad-hoc checks. The records with definite or possible errors were returned to the registries for verification, correction and resubmission. We assessed the proportions of cases microscopically verified and cases with non- specific morphology. We also evaluated the percentage of patients lost to follow-up, defined as cases censored alive before five years from diagnosis unless they were censored due to the end of follow-up (31 December 2015). Cancers 2022, 14, 2441 4 of 18 Table 1. Cancer groups, number of cases included and data quality indicators, 2002–2013. Excluded, % Data Quality Indicators, % Cancer Groups ICD-10 Codes Number of Eligible Number of Cases Cases Included (%) Microscopically Non-Specific DCO Diagnosed at Autopsy Verified Morphology a Lost to Follow-Up b Oral cavity and C01–C06, C09–14 14,939 0.64 0.11 14,828 (99.26) 98.73 1.50 0.26 pharynx Esophagus C15 6442 1.60 0.20 6326 (98.20) 95.78 4.47 0.40 Stomach C16 21,748 2.21 0.43 21,175 (97.37) 94.63 5.77 0.25 Colon C18 58,307 1.75 0.32 57,097 (97.92) 94.93 5.38 0.14 Rectum C19–C20 28,990 0.63 0.20 28,750 (99.17) 97.26 3.01 0.15 Liver C22 14,863 4.44 0.69 14,101 (94.87) 43.93 37.08 0.35 Gallbladder and bile C23–C24 6865 2.08 0.52 65.99 34.89 0.27 6686 (97.39) ducts c Pancreas C25 15,685 4.07 0.54 14,962 (95.39) 61.72 40.22 0.30 Larynx C32 10,636 0.80 0.03 10,548 (99.17) 98.52 1.80 0.20 Lung, bronchus and C33–34 66,692 2.21 0.42 64,938 (97.37) 87.20 13.62 0.32 trachea c Skin melanoma C43 12,857 0.32 0.05 12,809 (99.63) 99.63 0.00 0.30 Breast (women only) C50 67,186 0.75 0.01 66,670 (99.23) 98.55 1.69 0.25 Cervix uteri C53 5674 0.55 0.00 5643 (99.45) 98.90 1.45 0.87 Corpus uteri C54 14,912 0.50 0.07 14,827 (99.43) 98.14 1.98 0.20 Ovary and annexes C56, C570–C574, C577 8635 1.97 0.24 8444 (97.79) 91.38 9.53 0.28 Prostate C61 77,920 1.40 0.19 76,682 (98.41) 91.38 8.62 0.16 Testicle C62 3102 0.16 0.10 3094 (99.74) 99.22 0.94 0.52 Kidney C64 13,912 1.32 0.71 13,630 (97.97) 83.09 17.23 0.21 Urinary bladder C67, D090, D414 47,058 0.76 0.09 46,659 (99.15) 95.75 4.94 0.12 Brain C71 9404 2.46 0.38 9137 (97.16) 69.94 18.44 0.42 Thyroid C73 9176 0.20 0.73 9091 (99.07) 99.33 0.79 0.34 Hodgkin lymphoma C81 3531 0.03 0.57 3510 (99.41) 99.97 0.00 0.34 Non-Hodgkin C82–C86, C96 18,691 0.81 0.56 18,435 (98.63) 98.06 9.74 0.23 lymphoma Myeloma C90 7421 1.68 0.19 7282 (98.13) 93.79 0.00 0.15 Acute lymphoid C910 760 0.53 0.26 754 (99.21) 99.73 0.00 0.13 leukemia Chronic lymphoid C911 5293 0.36 0.06 5271 (99.58) 99.37 0.00 0.23 leukemia Acute myeloid C920, C923–C928, C930, 4246 0.00 0.00 4246 (100.00) 99.48 0.00 0.33 leukemia C940–C946 Chronic myeloid C921 1302 0.69 0.00 1293 (99.31) 99.85 0.00 0.23 leukemia C913; C914; C915; C916; Leukemia NOS and C917; C918; C919; C929; 2321 11.72 0.26 90.16 39.94 0.34 2043 (88.02) others C931; C947; C950; C959 d 54,405 3.46 0.37 52,319 (96.17) 85.91 14.68 0.23 Other cancers C00–C96 (except C44), All cancers d D090, D414, D45–D47 612,973 1.64 0.27 601,250 (98.09) 91.03 8.97 0.23 a Abbreviations: ICD-10, International Classification of Diseases—10th revision; DCO, Cases known by death certificate only; NOS, not otherwise specified. Non-specific morphology: International Classification of Diseases for Oncology codes, 3rd edition, 8000–8005 (solid tumors) and 9590, 9591, 9800, 9801, 9805, 9820, 9832 or 9860 (hematological neoplasms). b Cases censored alive before five years from diagnosis unless they were censored due to the end of follow-up (31 December 2015). c Note that the group referred in the text to as “gallbladder” includes gallbladder and bile ducts; and the group referred to as “lung” includes lung, bronchus and trachea. d Excluding non-melanoma skin cancer. Cancers 2022, 14, 2441 5 of 18 2.4. Statistical Analyses We estimated observed and net survival up to five years after diagnosis, with 95% confidence intervals (CIs), for adults diagnosed during 2002 through 2007 and 2008 through 2013, by sex and age group for each cancer group. The Kaplan-Meier and Pohar-Perme methods were used to obtain observed and net survival estimates, respectively [14]. Net sur- vival is the probability of being alive at a certain time following diagnosis after controlling for other causes of death (background mortality). To control for background mortality, we built life tables of all-cause death rates in the general population for each province, by single year of age, sex, and calendar year of death. The source of population and death data was the Spanish National Institute of Statistics. Life tables were interpolated and smoothed by the Elandt-Johnson method [15]. The cohort approach was adopted for patients diagnosed in 2002–2007 and the period approach for those diagnosed in 2008–2013 [16], given that follow-up was carried out up to 2015, thus a complete 5-year follow-up was not available for all the cases incident during the latter period. To allow comparisons over time and with other studies, net survival estimates were age-standardized using the cancer-specific weights from the International Cancer Survival Standards (ICSS) [17]. The ICSS age groups are defined as 15–44, 45–54, 55–64, 65–74 and ≥75 years, with a variation for prostate cancer patients (15–54, 55–64, 65–74, 75–84 and ≥85). We present age-standardized net survival (ASNS) at 1, 3 and 5 years post-diagnosis and at 5 years post-diagnosis, conditional on having survived 1 year. The latter was obtained by restricting the analysis to patients who survived at least 1 year. The 95% CIs were calculated from the standard errors using the Greenwood formula [18]. Absolute changes in survival between both periods were measured as the arithmetic difference between ASNS estimates (ASNS 2008–2013 —ASNS 2002–2007 ), for instance, a change in survival from 10% to 15% is reported as an increase of 5% (not 50%). A change was considered statistically significant if the 95% CI did not include zero. Trends were analyzed for all ages by sex and for two broad age groups (<75 and ≥75 years at diagnosis). The analyses were performed using STATA 15.1 (Stata Corporation, College Station, TX, USA), and specifically the stns command to estimate net survival [19]. 3. Results 3.1. Study Population and Quality Indicators A total of 601,250 adult patients diagnosed with cancer (except non-melanoma skin cancer) over the 12-year period were included in the study, representing 98.1% of the eligible cases. The remaining 1.9% (11,723 cases) were excluded because they were DCO or diagnosed at autopsy. Men accounted for 60.4% (363,144 cases) of the study population and the mean age ±SD was 68 ±13 and 65 ±16 years in men and women, respectively. The number of cases and data quality indicators by cancer group are shown in Table 1. A high proportion of diagnoses were microscopically verified: 91% overall and ≥80% in all cancer groups with the exception of liver, pancreas, gallbladder and brain cancers. About 9% of tumors were recorded with a non-specific morphology, and only 0.23% of patients were lost to follow-up. 3.2. Cancer Survival in Patients Diagnosed in 2008–2013 The 5-year observed survival (5y-OS) and net survival (5y-NS) estimates in patients diagnosed during the last six-year period (2008–2013) are shown in Table 2. For all cancers combined, 5y-OS was 47.4% and 57.4% in men and women, respectively; and 5y-NS, i.e., survival after controlling for other causes of death, was 54.3% and 62.0% in men and women, respectively. By cancer group, the lowest 5y-NS (<10%) was found for pancreatic cancer in men and women while the highest (≥95%) was observed for testicular cancer in men and thyroid cancer in women. The largest differences between 5y-OS and 5y-NS were found for prostate cancer (78% vs. 90%) and chronic lymphoid leukemia (62.5% vs. 73.6% in both sexes), while the smallest differences were seen for brain cancer (13.7% vs. 14.1% in both sexes). Cancers 2022, 14, 2441 6 of 18 Table 2. Five-year observed survival (OS) and net survival (NS) by sex in adult patients diagnosed with cancer in Spain in 2008–2013. Men Women Both Cancer Group Number of Cases OS (95% CI), % NS (95% CI), % Number of Cases OS (95% CI), % NS (95% CI), % Number of Cases OS (95% CI), % NS (95% CI), % Oral cavity and 5573 37.2 (35.9–38.6) 40.5 (39.0–42.0) 1733 53.1 (50.5–55.5) 57.6 (54.7–60.6) 7306 41.0 (39.8–42.2) 44.5 (43.2–45.9) pharynx Esophagus 2619 11.5 (10.2–12.9) 12.7 (11.3–14.2) 472 13.8 (10.7–17.3) 14.6 (11.0–18.1) 3091 11.9 (10.7–13.1) 13.0 (11.7–14.4) Stomach 6533 20.8 (19.8–21.8) 24.0 (22.7–25.2) 3880 23.3 (21.9–24.7) 26.1 (24.5–27.7) 10,413 21.7 (20.9–22.6) 24.8 (23.8–25.8) Colon 18,121 51.2 (50.4–52.0) 60.5 (59.5–61.5) 12,488 53.3 (52.3–54.2) 60.2 (59.1–61.3) 30,609 52.1 (51.5–52.7) 60.4 (59.7–61.1) Rectum 9580 51.2 (50.1–52.3) 59.0 (57.7–60.4) 5136 53.9 (52.4–55.3) 59.7 (57.9–61.4) 14,716 52.1 (51.3–53.0) 59.3 (58.2–60.3) Liver 5440 16.1 (15.1–17.2) 17.6 (16.4–18.8) 2028 10.3 (8.8–11.8) 11.2 (9.5–12.8) 7468 14.6 (13.7–15.5) 15.9 (14.9–16.9) Gallbladder and 1584 1766 3350 bile ducts 14.8 (12.9–16.7) 17.2 (14.9–19.5) 12.0 (10.4–13.7) 14.2 (12.1–16.3) 13.3 (12.1–14.6) 15.6 (14.1–17.2) Pancreas 4427 5.7 (5.0–6.5) 6.2 (5.4–7.1) 3881 6.3 (5.5–7.2) 6.9 (5.9–7.8) 8308 6.0 (5.5–6.6) 6.5 (5.9–7.2) Larynx 4460 55.2 (53.6–56.7) 61.5 (59.7–63.3) 355 64.7 (59.1–69.8) 68.0 (62.2–73.8) 4815 55.9 (54.3–57.3) 62.0 (60.3–63.7) Lung 26,981 10.9 (10.5–11.3) 12.1 (11.6–12.6) 6352 17.3 (16.3–18.4) 18.0 (16.9–19.2) 33,333 12.1 (11.7–12.5) 13.2 (12.8–13.6) Skin melanoma 3140 70.9 (69.2–72.6) 80.3 (78.1–82.5) 3480 81.4 (79.9–82.7) 87.5 (85.7–89.3) 6620 76.4 (75.3–77.5) 84.1 (82.7–85.5) Breast (women) 34,294 82.0 (81.6–82.5) 87.3 (86.8–87.9) 34,294 Cervix uteri 2726 65.8 (63.9–67.6) 67.6 (65.7–69.6) 2726 Corpus uteri 7432 70.2 (69.1–71.3) 75.1 (73.8–76.4) 7432 Ovary and 4199 4199 annexes 43.0 (41.3–44.6) 44.7 (43.0–46.4) Prostate 38,929 78.0 (77.5–78.4) 90.0 (89.4–90.6) 38,929 Testicle 1671 95.1 (93.9–96.1) 95.9 (94.8–97.0) 1671 Kidney 5069 58.5 (57.0–59.9) 65.4 (63.6–67.2) 2374 59.6 (57.4–61.6) 64.1 (61.7–66.5) 7443 58.8 (57.6–60.0) 65.0 (63.5–66.4) Urinary bladder 20,022 60.3 (59.5–61.0) 70.8 (69.9–71.8) 3973 61.6 (60.0–63.2) 70.7 (68.6–72.8) 23,995 60.5 (59.8–61.1) 70.8 (69.9–71.7) Brain 2613 13.5 (12.2–14.9) 13.9 (12.5–15.4) 2104 14.0 (12.4–15.6) 14.3 (12.7–15.9) 4717 13.7 (12.7–14.8) 14.1 (13.0–15.2) Thyroid 1186 84.8 (82.5–86.9) 88.9 (86.5–91.4) 4151 93.0 (92.1–93.7) 95.3 (94.5–96.2) 5337 91.2 (90.4–92.0) 93.9 (93.1–94.8) Hodgkin 1026 78.5 (75.8–81.0) 81.1 (78.3–83.8) 725 82.4 (79.4–85.1) 83.5 (80.6–86.5) 1751 80.2 (78.1–82.0) 82.1 (80.0–84.1) lymphoma Non-Hodgkin 5188 57.6 (56.1–59.0) 63.8 (62.1–65.4) 4395 62.2 (60.7–63.7) 66.7 (64.9–68.4) 9583 59.7 (58.6–60.7) 65.1 (63.9–66.3) lymphoma Myeloma 1989 35.1 (32.8–37.4) 40.2 (37.4–43.0) 1747 41.2 (38.7–43.7) 45.0 (42.2–47.9) 3736 38.0 (36.3–39.7) 42.5 (40.5–44.5) Acute lymphoid 189 36.5 (29.5–43.6) 38.0 (30.6–45.4) 147 32.1 (24.5–39.9) 32.7 (24.6–40.7) 336 34.6 (29.4–39.8) 35.7 (30.2–41.1) leukemia Chronic lymphoid 1446 61.4 (58.6–64.0) 73.1 (69.4–76.9) 995 64.1 (60.8–67.1) 74.2 (70.1–78.2) 2441 62.5 (60.4–64.5) 73.6 (70.8–76.3) leukemia Acute myeloid 1192 19.3 (17.0–21.7) 20.1 (17.6–22.6) 1022 25.9 (23.1–28.7) 26.3 (23.3–29.3) 2214 22.3 (20.5–24.2) 22.9 (21.0–24.9) leukemia Chronic myeloid 366 69.9 (64.7–74.4) 75.1 (69.5–80.8) 240 70.3 (63.7–75.9) 74.2 (67.0–81.3) 606 70.0 (66.0–73.7) 74.8 (70.4–79.2) leukemia Leukemia NOS 658 32.8 (28.9–36.8) 37.8 (32.5–43.1) 405 30.0 (25.1–35.0) 33.2 (27.3–39.1) 1063 31.7 (28.6–34.8) 36.0 (32.0–40.0) and others All cancers a 184,991 47.4 (47.1–47.6) 54.3 (54.0–54.6) 123,769 57.4 (57.1–57.7) 62.0 (61.6–62.3) 308,760 51.4 (51.2–51.6) 57.4 (57.2–57.6) Survival estimates are non-age standardized. Abbreviations: NOS, not otherwise specified. a Excluding non-melanoma skin cancer. Cancers 2022, 14, 2441 7 of 18 Cancers 2022, 14, x FOR PEER REVIEW 11 of 26 Age-specific 5y-NS estimates by sex for each cancer group in 2008–2013 are shown in Figure 1 and are detailed5y-NS Age-specific for men, women estimates andforboth by sex eachsexes canceringroup Supplementary Table in 2008–2013 are S2. in shown Survival declined Figure with 1 andageare at diagnosis, detailed although for men, womenfor some and bothcancers sexes initSupplementary occurred onlyTable after S2. a certain age, for instance, Survival declinedfor withcolon, age atrectal, breast diagnosis, and testicular although for some cancers cancers itafter the age occurred onlyof after 65 years anda for certain age, for prostate instance, cancer afterfor75colon, years.rectal, The breast and testicular downward cancers trend over ageafter wasthe age of 65 steeper years and for chronic myeloid for prostate leukemia, cancer after myeloma, 75 years. prostate and The downward brain cancer in trend overfor men and ageHodgkin was steeper lymphoma, for chronic acute myeloid myeloid leukemia, leukemia, myeloma, brain prostatecancer and ovarian and brain cancer in men and for Hodg- in women. kin lymphoma, acute myeloid leukemia, brain and ovarian cancer in women. Oral cavity and pharynx Esophagus Stomach 100 100 100 90 90 90 80 80 80 70 70 70 60 60 60 50 50 50 40 40 40 30 30 30 20 20 20 10 10 10 0 0 0 15–44 45–54 55–64 65–74 ≥75 15–44 45–54 55–64 65–74 ≥75 15–44 45–54 55–64 65–74 ≥75 Colon Rectum Liver 100 100 100 90 90 90 80 80 80 70 70 70 60 60 60 50 50 50 40 40 40 30 30 30 20 20 20 10 10 10 0 0 0 15–44 45–54 55–64 65–74 ≥75 15–44 45–54 55–64 65–74 ≥75 15–44 45–54 55–64 65–74 ≥75 Gallbladder and bile ducts Pancreas Larynx 100 100 100 90 90 90 80 80 80 70 70 70 60 60 60 50 50 50 40 40 40 30 30 30 20 20 20 10 10 10 0 0 0 15–44 45–54 55–64 65–74 ≥75 15–44 45–54 55–64 65–74 ≥75 15–44 45–54 55–64 65–74 ≥75 Lung Skin melanoma Breast 100 100 100 90 90 90 80 80 80 70 70 70 60 60 60 50 50 50 40 40 40 30 30 30 20 20 20 10 10 10 0 0 0 15–44 45–54 55–64 65–74 ≥75 15–44 45–54 55–64 65–74 ≥75 15–44 45–54 55–64 65–74 ≥75 Cervix uteri Corpus uteri Ovary and annexes 100 100 100 90 90 90 80 80 80 70 70 70 60 60 60 50 50 50 40 40 40 30 30 30 20 20 20 10 10 10 0 0 0 15–44 45–54 55–64 65–74 ≥75 15–44 45–54 55–64 65–74 ≥75 15–44 45–54 55–64 65–74 ≥75 Age at diagnosis (years) Men Women Figure continued on next page Figure 1. Cont. Cancers 2022, 14, 2441 Cancers 2022, 14, x FOR PEER REVIEW 8 of 18 12 of 26 Prostate Testicle Kidney 100 100 100 90 90 90 80 80 80 70 70 70 60 60 60 50 50 50 40 40 40 30 30 30 20 20 20 10 10 10 0 0 0 15–54 55–64 65–74 75–84 ≥85 15–44 45–54 55–64 65–74 ≥75 15–44 45–54 55–64 65–74 ≥75 Urinary bladder Brain Thyroid 100 100 100 90 90 90 80 80 80 70 70 70 60 60 60 50 50 50 40 40 40 30 30 30 20 20 20 10 10 10 0 0 0 15–44 45–54 55–64 65–74 ≥75 15–44 45–54 55–64 65–74 ≥75 15–44 45–54 55–64 65–74 ≥75 Hodgkin lymphoma Non-Hodgkin lymphoma Myeloma 100 100 100 90 90 90 80 80 80 70 70 70 60 60 60 50 50 50 40 40 40 30 30 30 20 20 20 10 10 10 0 0 0 15–44 45–54 55–64 65–74 ≥75 15–44 45–54 55–64 65–74 ≥75 15–44 45–54 55–64 65–74 ≥75 Acute lymphoid leukemia Chronic lymphoid leukemia Acute myeloid leukemia 100 100 100 90 90 90 80 80 80 70 70 70 60 60 60 50 50 50 40 40 40 30 30 30 20 20 20 10 10 10 0 0 0 15–44 45–54 55–64 65–74 ≥75 15–44 45–54 55–64 65–74 ≥75 15–44 45–54 55–64 65–74 ≥75 Chronic myeloid leukemia Leukemia NOS and others All cancers 100 100 100 90 90 90 80 80 80 70 70 70 60 60 60 50 50 50 40 40 40 30 30 30 20 20 20 10 10 10 0 0 0 15–44 45–54 55–64 65–74 ≥75 15–44 45–54 55–64 65–74 ≥75 15–44 45–54 55–64 65–74 ≥75 Age at diagnosis (years) Men Women Figure 1. Five-year net survival by age group and sex in adult patients diagnosed with cancer in Figure 1. Five-year net survival by age group and sex in adult patients diagnosed with cancer in Spain in 2008–2013. Error Spain bars are 95% in 2008–2013. CIs. Error barsThe are “all 95%cancers” category CIs. The “all excludes cancers” categorynon-melanoma skin excludes non-melanoma skin cancer. Abbreviations: NOS, not otherwise specified. cancer. Abbreviations: NOS, not otherwise specified. Table 3 shows the ASNS at one, three, and five years following diagnosis, and at five years following diagnosis conditional on having survived 1 year (5|1 years). The ASNS at the first year was 74.7% (95% CI 74.6–74.9%) overall and varied by cancer group from <40% for pancreas, esophagus and lung cancers to ≥95% for skin melanoma, female breast and prostate cancers. We observed a 5y-ASNS of 58.2% (95% CI 58.0–58.4%) overall, ranging Cancers 2022, 14, 2441 9 of 18 from <20% for the pancreas, esophagus, lung, and liver cancer to ≥80% for cancers of the thyroid, prostate, testicle, skin melanoma, female breast, and Hodgkin lymphoma. The 5|1y-ASNS was 77.1% (95% CI 76.8–77.3%) for all cancers combined, and it was more than 20 percentage points higher than the 5y-ASNS for cancer of the esophagus, stomach, gallbladder and acute lymphoid leukemia. Table 3. Age-standardised net survival at one, three and five years post-diagnosis and at five years post-diagnosis conditional on having survived one year, in adult patients diagnosed with cancer in Spain in 2008–2013. Age-Standardised Net Survival (95% CI), % Cancer Groups 1 Year 3 Years 5 Years 5 Years Conditional Oral cavity and 70.2 (69.1–71.4) 51.0 (49.7–52.3) 42.9 (41.5–44.4) 60.7 (58.7–62.7) pharynx Esophagus 38.1 (36.3–39.9) 17.4 (16.0–19.0) 13.5 (12.1–15.0) 34.3 (31.0–37.9) Stomach 51.2 (50.2–52.2) 31.7 (30.7–32.7) 27.4 (26.4–28.4) 52.8 (51.1–54.6) Colon 81.3 (80.8–81.7) 69.1 (68.5–69.7) 63.3 (62.6–64.0) 77.6 (76.9–78.4) Rectum 83.4 (82.8–84.0) 68.7 (67.9–69.5) 61.1 (60.1–62.1) 72.8 (71.7–73.9) Liver 45.8 (44.6–47.0) 25.1 (24.0–26.2) 17.4 (16.4–18.5) 36.0 (34.0–38.0) Gallbladder and bile 45.0 (42.9–47.2) 27.3 (25.3–29.4) 20.9 (18.9–23.1) 44.3 (40.9–48.0) ducts Pancreas 27.9 (26.9–29.0) 11.5 (10.7–12.3) 8.3 (7.5–9.1) 26.8 (24.4–29.4) Larynx 84.1 (82.9–85.3) 68.1 (66.5–69.8) 60.5 (58.6–62.5) 71.6 (69.5–73.9) Lung 39.0 (38.5–39.6) 18.6 (18.2–19.1) 13.8 (13.3–14.2) 33.7 (32.6–34.7) Skin melanoma 95.6 (95.1–96.2) 89.4 (88.5–90.2) 85.8 (84.7–86.9) 89.6 (88.6–90.7) Breast (women) 96.0 (95.7–96.3) 90.1 (89.6–90.5) 85.5 (84.8–86.2) 88.8 (88.1–89.5) Cervix uteri 84.3 (82.8–85.7) 70.7 (68.9–72.6) 65.5 (63.5–67.5) 76.6 (74.3–78.9) Corpus uteri 89.2 (88.4–89.9) 78.5 (77.5–79.6) 74.0 (72.8–75.3) 82.3 (80.9–83.7) Ovary and annexes 70.4 (69.1–71.8) 50.8 (49.2–52.4) 40.9 (39.3–42.6) 55.7 (53.3–58.1) Prostate 96.4 (96.1–96.6) 92.2 (91.7–92.6) 89.6 (89.0–90.1) 92.3 (91.7–92.9) Testicle 93.2 (90.6–95.9) 91.5 (88.2–95.0) 89.4 (85.2–93.9) 95.3 (90.6–100.0) Kidney 78.9 (78.0–79.9) 70.2 (69.0–71.3) 65.0 (63.6–66.4) 81.6 (80.0–83.2) Urinary bladder 87.9 (87.5–88.4) 78.6 (78.0–79.2) 74.1 (73.3–74.8) 83.7 (83.0–84.5) Brain 48.9 (47.5–50.2) 26.8 (25.5–28.2) 22.2 (20.8–23.6) 36.2 (33.7–38.8) Thyroid 93.9 (93.1–94.7) 92.3 (91.3–93.2) 91.4 (90.2–92.6) 97.1 (95.9–98.3) Hodgkin lymphoma 89.4 (88.1–90.8) 83.1 (81.4–84.8) 81.2 (79.3–83.1) 89.5 (87.3–91.8) Non-Hodgkin 78.1 (77.2–78.9) 68.9 (67.9–69.9) 65.0 (63.8–66.2) 82.2 (80.9–83.6) lymphoma Myeloma 79.5 (78.2–80.8) 60.4 (58.7–62.1) 47.8 (45.9–49.8) 58.6 (56.4–60.9) Acute lymphoid 64.1 (59.3–69.2) 43.7 (38.5–49.5) 40.6 (35.4–46.7) 61.9 (54.8–69.9) leukemia Chronic lymphoid 87.2 (86.2–88.2) 86.7 (85.2–88.3) 78.9 (76.7–81.1) 83.2 (80.9–85.5) leukemia Acute myeloid 42.9 (40.9–45.1) 25.1 (23.3–27.1) 21.7 (19.9–23.7) 40.4 (36.6–44.6) leukemia Chronic myeloid 86.4 (83.4–89.5) 76.9 (73.0–81.0) 70.8 (66.2–75.6) 79.6 (74.4–85.2) leukemia Leukemia NOS and 68.5 (65.5–71.8) 51.4 (47.9–55.1) 44.3 (40.6–48.3) 61.9 (57.4–66.9) others All cancers a 74.7 (74.6–74.9) 63.0 (62.8–63.2) 58.2 (58.0–58.4) 77.1 (76.8–77.3) a Abbreviations: NOS, not otherwise specified. Excluding non-melanoma skin cancer. The 5y-ASNS in 2008–2013 was higher in women than in men overall and for 12 cancer groups: oral cavity and pharynx, stomach, rectum, pancreas, lung, skin melanoma, urinary bladder, brain, thyroid, non-Hodgkin lymphoma, myeloma and acute myeloid leukemia (Table 4). For the remaining cancer groups, the 5y-ASNS was similar in both sexes. The most pronounced female survival advantage was found for cancer of the oral cavity and pharynx, with 5y-ASNS of 38.2% (95% CI 36.6–39.9%) in men vs. 57.2% (95% CI 54.4–60.2%) in women. Cancers 2022, 14, 2441 10 of 18 Table 4. Five-year age-standardised net survival (ASNS) in men and women diagnosed with cancer in Spain in 2002–2007 and 2008–2013 and absolute change between periods. Men Women Cancer Group ASNS (95% CI), % ASNS (95% CI), % Absolute Change a (95% CI), % Absolute Change a (95% CI), % 2002–2007 2008–2013 2002–2007 2008–2013 Oral cavity and pharynx 37.4 (35.7, 39.1) 38.2 (36.6, 39.9) 0.9 (−1.5, 3.2) 51.6 (48.7, 54.6) 57.2 (54.4, 60.2) 5.6 (1.5, 9.8) Esophagus 9.7 (8.6, 11.0) 13.1 (11.6, 14.7) 3.4 (1.4, 5.3) 17.3 (13.8, 21.6) 16.5 (13.1, 20.8) −0.8 (−6.2, 4.6) Stomach 24.6 (23.5, 25.8) 26.0 (24.8, 27.4) 1.4 (−0.3, 3.2) 30.6 (29.0, 32.3) 30.3 (28.6, 32.2) −0.3 (−2.8, 2.2) Colon 57.5 (56.5, 58.4) 63.1 (62.2, 64.1) 5.6 (4.3, 7.0) 59.8 (58.7, 60.8) 63.9 (62.8, 64.9) 4.1 (2.6, 5.6) Rectum 55.8 (54.6, 57.1) 60.4 (59.1, 61.7) 4.6 (2.8, 6.4) 58.1 (56.6, 59.7) 62.7 (61.1, 64.3) 4.6 (2.3, 6.8) Liver 15.2 (14.1, 16.3) 17.9 (16.7, 19.2) 2.8 (1.1, 4.4) 16.4 (14.3, 18.7) 16.2 (14.1, 18.6) −0.2 (−3.4, 2.9) Gallbladder and bile ducts 18.7 (16.2, 21.6) 22.3 (19.6, 25.3) 3.6 (−0.3, 7.5) 18.1 (15.7, 20.8) 19.2 (16.5, 22.4) 1.1 (−2.8, 5.0) Pancreas 5.7 (4.9, 6.6) 7.2 (6.3, 8.2) 1.5 (0.2, 2.8) 7.3 (6.2, 8.5) 10.0 (8.7, 11.4) 2.7 (1.0, 4.5) Larynx 60.6 (58.8, 62.4) 60.0 (58.0, 62.1) −0.5 (−3.2, 2.2) 68.5 (62.4, 75.1) 66.1 (58.8, 74.2) −2.4 (−12.4, 7.5) Lung 11.2 (10.7, 11.6) 12.7 (12.2, 13.2) 1.6 (0.9, 2.2) 16.2 (15.1, 17.4) 17.6 (16.5, 18.8) 1.4 (−0.3, 3.0) Skin melanoma 79.1 (77.3, 81.0) 82.3 (80.5, 84.1) 3.2 (0.6, 5.7) 88.6 (87.2, 90.0) 88.9 (87.5, 90.3) 0.3 (−1.7, 2.3) Breast (women) 83.2 (82.5, 83.9) 85.5 (84.8, 86.2) 2.3 (1.3, 3.3) Cervix uteri 64.4 (62.5, 66.3) 65.5 (63.5, 67.5) 1.1 (−1.7, 3.8) Corpus uteri 74.6 (73.4, 75.9) 74.0 (72.8, 75.3) −0.6 (−2.4, 1.1) Ovary and annexes 37.5 (36.0, 39.0) 40.9 (39.3, 42.6) 3.5 (1.2, 5.7) Prostate 87.8 (87.2, 88.4) 89.6 (89.0, 90.1) 1.7 (0.9, 2.6) Testicle 85.2 (81.0, 89.6) 89.4 (85.2, 93.9) 4.2 (−1.9, 10.3) Kidney 59.8 (58.1, 61.6) 64.8 (63.0, 66.6) 5.0 (2.4, 7.5) 61.4 (59.1, 63.7) 65.8 (63.7, 68.0) 4.4 (1.3, 7.6) Urinary bladder 72.3 (71.5, 73.1) 73.8 (73.0, 74.7) 1.6 (0.4, 2.7) 72.9 (71.1, 74.8) 75.9 (74.2, 77.6) 3.0 (0.5, 5.5) Brain 19.3 (17.8, 21.0) 20.8 (19.2, 22.6) 1.5 (−0.9, 3.9) 21.2 (19.3, 23.2) 24.2 (22.1, 26.5) 3.1 (0.2, 6.0) Thyroid 78.3 (74.9, 81.8) 86.1 (83.2, 89.1) 7.8 (3.3, 12.3) 88.8 (87.3, 90.3) 93.1 (91.8, 94.4) 4.3 (2.3, 6.3) Hodgkin lymphoma 80.0 (77.3, 82.7) 80.6 (77.8, 83.4) 0.6 (−3.3, 4.5) 83.3 (80.8, 85.9) 82.6 (80.0, 85.3) −0.7 (−4.4, 3.0) Non-Hodgkin lymphoma 57.2 (55.4, 58.9) 62.4 (60.7, 64.1) 5.2 (2.8, 7.6) 63.0 (61.4, 64.6) 68.4 (66.8, 70.0) 5.4 (3.2, 7.7) Myeloma 40.1 (37.7, 42.7) 44.8 (42.2, 47.5) 4.6 (1.0, 8.3) 42.5 (40.0, 45.2) 51.2 (48.5, 54.1) 8.7 (4.9, 12.5) Acute lymphoid leukemia 35.1 (29.9, 41.3) 41.6 (34.8, 49.6) 6.5 (−2.9, 15.8) 37.1 (30.4, 45.3) 40.0 (32.1, 49.7) 2.9 (−8.5, 14.3) Chronic lymphoid leukemia 78.8 (76.2, 81.5) 77.7 (74.6, 80.8) −1.1 (−5.2, 2.9) 80.7 (77.7, 83.9) 80.7 (77.7, 83.8) −0.0 (−4.4, 4.3) Acute myeloid leukemia 17.0 (14.9, 19.4) 19.2 (16.9, 21.8) 2.2 (−1.1, 5.5) 19.8 (17.3, 22.6) 24.9 (22.1, 28.0) 5.1 (1.2, 9.0) Chronic myeloid leukemia 59.2 (53.6, 65.3) 68.8 (62.7, 75.4) 9.6 (1.0, 18.2) 67.5 (59.6, 76.5) 73.0 (66.4, 80.3) 5.5 (−5.4, 16.4) Leukemia NOS and others 42.5 (38.2, 47.2) 45.9 (41.4, 50.9) 3.4 (−3.1, 10.0) 33.5 (28.5, 39.5) 41.9 (36.1, 48.7) 8.4 (0.0, 16.8) All cancers b 52.0 (51.7, 52.2) 55.3 (55.0, 55.6) 3.3 (3.0, 3.7) 59.2 (58.9, 59.6) 61.7 (61.4, 62.1) 2.5 (2.0, 3.0) Abbreviations: NOS, not otherwise specified. a Absolute difference = ASNS 2nd period—ASNS 1st period. Bold identifies statistically significant changes. b Excluding non-melanoma skin cancer. Cancers 2022, 14, x FOR PEER REVIEW 17 of 26 Cancers 2022, 14, 2441 11 of 18 3.3. Survival Trends Between 2002–2007 and 2008–2013 3.3. Survival Trends between 2002–2007 and 2008–2013 In both sexes together, there were significant increases in survival overall and for most of Inthe both sexes groups cancer together, there were between significant 2002–2007 andincreases in survival 2008–2013, as shown overall and for in Figure most 2. The of the cancer groups between 2002–2007 and 2008–2013, as shown in Figure 2. The 5y-ASNS increased by more than 5% in patients with thyroid cancer, chronic myeloid leu- 5y-ASNS increased kemia, by more lymphoma non-Hodgkin than 5% in and patients with Absolute myeloma. thyroid cancer, increaseschronic myeloid of 3–5% leukemia, were observed non-Hodgkin lymphoma and myeloma. Absolute increases of 3–5% were for kidney, colon, rectum, ovary and annexes, acute myeloid leukemia and esophageal observed for kidney, colon, rectum, ovary and annexes, acute myeloid leukemia and esophageal cancer. cancer. In addition, increases of 1–3% in the 5y-ASNS were found in patients with cancer In addition, increases of 1–3% in the 5y-ASNS were found in patients with cancer of the of the prostate, skin melanoma, female breast, urinary bladder, oral cavity and pharynx, prostate, skin melanoma, female breast, urinary bladder, oral cavity and pharynx, brain, brain, liver, lung, and pancreas. The trend was stable for the remaining cancer groups liver, lung, and pancreas. The trend was stable for the remaining cancer groups. 2008–2013 Change from 2002–2007 to 2008–2013 Thyroid Thyroid Prostate Prostate Testicle Testicle Skin melanoma Skin melanoma Breast (women) Breast (women) Hodgkin lymphoma Hodgkin lymphoma Chronic lymphoid leukemia Chronic lymphoid leukemia Urinary bladder Urinary bladder Corpus uteri Corpus uteri Chronic myeloid leukemia Chronic myeloid leukemia Cervix uteri Cervix uteri Non-Hodgkin lymphoma Non-Hodgkin lymphoma n.s. Kidney Kidney Colon Colon Rectum Rectum 1-3% Larynx Larynx c a nc eror c a nc eror All cancers All cancers 3-5% Myeloma Myeloma Leukemia NOS and others Leukemia NOS and others Oral cavity and pharynx Oral cavity and pharynx >5% Ovary and annexes Ovary and annexes Acute lymphoid leukemia Acute lymphoid leukemia Stomach Stomach Brain Brain Acute myeloid leukemia Acute myeloid leukemia Gallbladder and bile ducts Gallbladder and bile ducts Liver Liver Lung Lung Esophagus Esophagus Pancreas Pancreas 0 10 20 30 40 50 60 70 80 90 100 -5 -3 -1 1 3 5 7 9 11 13 15 5-year ASNS (%) Absolute change in 5-year ASNS (%) Figure 2. Five-year age-standardized net survival by cancer group in patients diagnosed with cancer Figure 2. Five-year age-standardized net survival by cancer group in patients diagnosed with cancer in Spain in 2008–2013 (left panel) and absolute change from 2002–2007 to 2008–2013 (right panel). in Spain in 2008–2013 (left panel) and absolute change from 2002–2007 to 2008–2013 (right panel). Errorbars Error barsare are95% 95%CIs. CIs.Abbreviations: Abbreviations:ASNS, ASNS,age-standardized age-standardized netsurvival; net survival;n.s., n.s.,non-statistically non-statistically significantchange significant change(i.e., (i.e.,95% 95%CICIincludes includeszero). zero). The trend analysis by sex (Table 4) showed that the 5y-ASNS for all cancers combined The trend analysis by sex (Table 4) showed that the 5y-ASNS for all cancers combined increased between the two periods from 52.0% (95% CI 51.7–52.2%) to 55.3% (95% CI increased between the two periods from 52.0% (95% CI 51.7–52.2%) to 55.3% (95% CI 55.0– 55.0–55.6%) in men, and from 59.2% (95% CI 58.9–59.6%) to 61.7% (95% CI 61.4–62.1%) 55.6%) in men, and from 59.2% (95% CI 58.9–59.6%) to 61.7% (95% CI 61.4–62.1%) in in women. The increases in 5y-ASNS for cancer of the colon, rectum, pancreas, kidney, women. The increases in 5y-ASNS for cancer of the colon, rectum, pancreas, kidney, uri- urinary bladder, thyroid, non-Hodgkin lymphoma and myeloma were observed in both nary bladder, thyroid, non-Hodgkin lymphoma and myeloma were observed in both men men and women. An upward trend in 5y-ASNS for cancer of the esophagus, liver, lung, Cancers 2022, 14, 2441 12 of 18 skin melanoma, and chronic myeloid leukemia was found only in men, while it remained stable in women. Increased 5y-ASNS for cancer of the oral cavity and pharynx, brain, acute myeloid leukemia, and the group of leukemia not otherwise specified (NOS) and others was observed only in women, whereas it did not change in men. There were no significant decreases in survival in men or women for any cancer group. Among the most common cancers, the largest increases in the 5y-ASNS were found for colon cancer, from 57.5% to 63.1% in men and from 59.8% to 63.9% in women, and for rectal cancer, from 55.8% to 60.4% in men and from 58.1% to 62.7% in women. In addition, the 5y-ASNS for prostate cancer increased from 87.8% to 89.6%, and for female breast cancer from 83.2% to 85.5%. For patients with lung cancer the figures moved from 11.2% to 12.7% in men and from 16.2% to 17.6% in women, although the change in women was not statistically significant. Increases in the 5y-ASNS were also seen for urinary bladder tumors in men (by 1.6%) and women (by 3.0%). However, for corpus uteri cancer the 5y-ASNS remained unchanged between the first and second periods, 74.6% vs. 74.0%, respectively (Table 4). The results of the trend analysis according to age group at diagnosis are shown in Table 5. In patients younger than 75 years, the 5y-ASNS increased for all cancers combined (by 4.5%, 95% CI 4.1 to 4.8%) and for 20 cancer groups. By contrast, in patients aged 75 years and older, the 5y-ASNS was stable for all cancers combined (absolute change of −0.1%, 95% CI −0.8 to 0.5%) and increased only for five cancer groups (colon, thyroid, non-Hodgkin lymphoma, myeloma, and acute lymphoid leukemia). Although an upward trend was observed mainly in patients younger than 75 years, in the older age group there were larger increases for thyroid cancer and acute lymphoid leukemia. Table 5. Five-year age-standardised net survival (ASNS) in patients diagnosed with cancer in Spain in 2002–2007 and 2008–2013 and absolute change between periods according to age group at diagnosis. Younger Than 75 Years Aged 75 Years and Older Cancer Group ASNS (95% CI), % a ASNS (95% CI), % Absolute Change Absolute Change a 2002–2007 2008–2013 (95% CI), % 2002–2007 2008–2013 (95% CI), % Oral cavity and 41.6 (40.3, 42.9) 46.6 (45.2, 48.2) 5.1 (3.1, 7.1) 35.9 (32.1, 39.6) 33.8 (30.3–37.3) −2.1 (−7.2, 3.1) pharynx Esophagus 12.8 (11.4, 14.3) 16.2 (14.4, 18.1) 3.4 (1.1, 5.7) 4.5 (2.7, 6.2) 7.0 (4.8–9.2) 2.5 (−0.2, 5.3) Stomach 30.5 (29.3, 31.8) 31.5 (30.2, 32.9) 1.0 (−0.8, 2.8) 17.2 (15.7, 18.6) 17.3 (15.8–18.7) 0.1 (−1.9, 2.1) Colon 63.0 (62.1, 63.8) 68.9 (68.1, 69.8) 6.0 (4.8, 7.1) 47.1 (45.7, 48.5) 49.7 (48.4–51.0) 2.5 (0.6, 4.4) Rectum 61.8 (60.8, 62.9) 67.3 (66.2, 68.5) 5.5 (3.9, 7.1) 43.7 (41.7, 45.7) 45.9 (43.9–48.0) 2.3 (−0.6, 5.1) Liver 18.8 (17.6, 20.1) 21.6 (20.2, 23.0) 2.8 (0.9, 4.6) 6.3 (5.1, 7.6) 7.1 (5.8–8.4) 0.8 (−1.0, 2.6) Gallbladder and bile ducts 21.5 (19.2, 24.1) 25.2 (22.6, 28.2) 3.7 (0.0, 7.4) 10.6 (8.4, 12.8) 10.3 (8.4–12.3) −0.3 (−3.2, 2.7) Pancreas 7.9 (7.0, 8.8) 10.7 (9.7, 11.8) 2.8 (1.4, 4.2) 2.0 (1.3, 2.7) 2.3 (1.6–3.0) 0.3 (−0.7, 1.3) Larynx 64.5 (63.0, 66.1) 65.2 (63.3, 67.0) 0.7 (−1.8, 3.1) 51.5 (47.0, 56.0) 49.1 (44.1–54.0) −2.4 (−9.1, 4.3) Lung 14.2 (13.8, 14.7) 17.0 (16.4, 17.6) 2.7 (2.0, 3.5) 5.9 (5.3, 6.5) 5.9 (5.3–6.6) 0.0 (−0.8, 0.9) Skin melanoma 86.3 (85.2, 87.3) 87.8 (86.7, 88.9) 1.5 (0.0, 3.1) 71.3 (66.5, 76.2) 73.6 (69.2–78.0) 2.2 (−4.3, 8.8) Breast (women) 87.5 (87.0, 88.1) 90.6 (90.1, 91.1) 3.1 (2.3, 3.8) 72.5 (70.4, 74.7) 72.8 (70.8–74.9) 0.3 (−2.6, 3.3) Cervix uteri 69.6 (67.6, 71.5) 70.2 (68.1, 72.3) 0.6 (−2.3, 3.5) 32.8 (26.6, 39.0) 36.5 (30.1–42.9) 3.7 (−5.2, 12.6) Corpus uteri 81.3 (80.2, 82.4) 82.3 (81.1, 83.5) 1.0 (−0.6, 2.6) 58.4 (55.3, 61.5) 53.8 (50.5–57.1) −4.6 (−9.1, 0.0) Ovary and annexes 46.1 (44.3, 48.0) 49.8 (47.8, 51.9) 3.7 (1.0, 6.5) 16.3 (13.5, 19.1) 19.1 (16.1–22.0) 2.8 (−1.3, 6.9) Prostate 92.5 (92.0, 93.1) 95.6 (95.1, 96.1) 3.1 (2.3, 3.9) 76.3 (74.8, 77.9) 74.7 (73.2, 76.3) −1.6 (−3.8, 0.6) Testicle 91.3 (88.2, 94.6) 93.0 (89.6, 96.6) 1.7 (−3.1, 6.4) 29.9 (0.0, 62.0) 57.0 (27.4–86.7) 27.1 (−16.6, 70.7) Kidney 67.3 (65.8, 68.8) 72.7 (71.3, 74.2) 5.5 (3.4, 7.6) 42.5 (39.4, 45.7) 46.0 (42.8–49.2) 3.5 (−1.1, 8.0) Urinary bladder 78.6 (77.8, 79.4) 80.9 (80.1, 81.7) 2.3 (1.2, 3.4) 56.7 (55.0, 58.4) 57.3 (55.7–59.0) 0.7 (−1.7, 3.1) Brain 22.8 (21.4, 24.2) 25.4 (23.9, 27.0) 2.6 (0.5, 4.7) 3.5 (2.2, 4.8) 2.4 (1.3–3.4) −1.1 (−2.8, 0.5) Thyroid 92.1 (91.0, 93.3) 95.4 (94.5, 96.3) 3.3 (1.8, 4.8) 50.3 (43.1, 57.6) 67.0 (60.5–73.4) 16.6 (6.9, 26.3) Hodgkin 85.8 (84.1, 87.6) 86.2 (84.4, 88.1) 0.4 (−2.2, 2.9) 40.3 (30.2, 50.3) 36.0 (26.1–45.9) −4.2 (−18.4, 9.9) lymphoma Non-Hodgkin 68.0 (66.7, 69.3) 73.8 (72.5, 75.1) 5.8 (4.0, 7.7) 39.2 (36.7, 41.8) 43.5 (40.9–46.1) 4.3 (0.6, 7.9) lymphoma Myeloma 49.1 (46.8, 51.4) 56.3 (53.9, 58.8) 7.2 (3.9, 10.6) 22.2 (19.5, 24.9) 26.9 (23.9–30.0) 4.7 (0.7, 8.8) Acute lymphoid 39.3 (34.6, 44.7) 43.5 (37.8, 50.1) 4.2 (−3.8, 12.1) 2.6 (0.0, 6.6) 14.8 (4.4–25.1) 12.2 (1.1, 23.3) leukemia Chronic lymphoid 85.5 (83.5, 87.6) 86.4 (84.0, 88.9) 0.9 (−2.2, 4.0) 64.9 (59.8, 70.0) 60.4 (55.5–65.3) −4.5 (−11.6, 2.6) leukemia Acute myeloid 24.3 (22.1, 26.8) 29.8 (27.3, 32.5) 5.4 (1.9, 8.9) 3.2 (1.6, 4.8) 2.1 (0.7–3.4) −1.2 (−3.3, 0.9) leukemia Chronic myeloid 75.0 (70.1, 80.1) 83.7 (78.9, 88.9) 8.8 (1.7, 15.8) 31.6 (18.7, 44.5) 39.0 (28.3–49.7) 7.4 (−9.4, 24.2) leukemia Leukemia NOS and 47.5 (43.2, 52.3) 53.9 (49.2, 59.1) 6.4 (−0.3, 13.1) 18.7 (14.4, 23.0) 20.7 (15.4–26.1) 2.0 (−4.9, 8.9) others All cancers b 60.6 (60.4, 60.8) 65.1 (64.8, 65.3) 4.5 (4.1, 4.8) 41.5 (41.0, 42.0) 41.4 (40.9–41.8) −0.1 (−0.8, 0.5) Abbreviations: NOS, not otherwise specified. a Absolute difference = ASNS 2nd period—ASNS 1st period. Bold identifies statistically significant changes. b Excluding non-melanoma skin cancer. Cancers 2022, 14, 2441 13 of 18 4. Discussion The present study provides a comprehensive overview of cancer survival in Spain using the most up-to-date data from population-based cancer registries. More than 600,000 adult patients diagnosed until 2013 and followed up to 2015 were included. This study updates a previous publication incorporating six additional years of incidence [7], and also expands coverage as more registries were able to contribute data, reaching more than a quarter of the Spanish population. Survival estimates vary widely by cancer group [4,5,7]. The range of variation we found is broadly consistent with that reported by other population-based studies [4,20–22]. Very good prognosis (5y-ASNS ≥ 80%) was observed for cancers of the thyroid, prostate, testicle, female breast, skin melanoma and Hodgkin lymphoma. According to incidence estimates [23], these cancers represent 29% of all cancer cases in Spain, and account for a greater proportion in women than in men, 34% vs. 26%, respectively. Other frequent cancers, including those of the colon, rectum, urinary bladder and corpus uteri, had good prognosis (5y-ASNS 60–79%). However, cancers of the pancreas, esophagus, lung and liver showed 5y-ASNS < 20%. These malignancies represent 18% of the incident cancer cases, making up 11% and 22% for women and men, respectively [23]. For all malignancies combined, better survival was observed in women than in men, which is largely explained by the different distribution of cancer groups by sex, as has been mentioned above. Furthermore, women showed higher survival than did men for 12 out of 23 non-sex specific cancer groups. A better prognosis in women for several cancers has been consistently reported in other studies [24–26]. A biological advantage mediated by sexual hormones has been hypothesized [25,27]. Other considerations are that stage at diagnosis, tumor subsite and histology, and patients’ comorbidity may differ between the sexes [25,26]. Our study revealed a remarkable male survival disadvantage for oral cavity and pharynx cancer (absolute difference in 5y-ASNS point estimates of 19%), which could be partly related to differences in the prevalence of risk factors between sexes, such as smoking and alcohol consumption, that in turn are associated with histological type, subsite and comorbidity [25,28]. Nevertheless, the gender gap we observed for this cancer group warrants deeper examination, as it appears to be wider than described in other studies [28,29]. Survival generally decreased with age, consistent with other population-based stud- ies [5,21,30,31]. Several factors may be contributing to age-related differences in survival, including comorbidity, frailty, socioeconomic factors, suboptimal cancer management, di- agnostic delays, and patient’s preferences for treatment options [32–34]. Further studies are needed to better understand this age-related disparity and to guide strategies to reduce it. Differences between observed and net survival were smaller for cancers that tend to occur among younger patients (e.g., testicle cancer or Hodgkin lymphoma) than for those cancers occurring in older patients (e.g., prostate cancer or chronic lymphoid leukemia), which is explained by less competing risks for death at a younger age. Likewise, as expected, these differences also tended to be smaller for cancers with poorer prognosis (e.g., pancreas or brain cancers). The large difference (>20 percentage points) between the 5y-ASNS and the conditional 5|1y-ASNS in patients with cancer of the esophagus, stomach and gallbladder possibly reflects the impact of postoperative mortality and/or comorbidity on first-year survival, as these patients frequently require high-risk procedures with a considerable incidence of major complications [35]. The CONCORD-3 study reported worldwide survival estimates for 15 cancer groups in adults, both sexes combined, up to the period 2010–2014 [4]. Spanish figures were within the ranges of most countries globally; however, the 5y-ASNS for esophageal, lung and brain cancer seem to be lower in Spain than in most high-income countries. Similarly, our 5y-ASNS estimates for esophageal and lung cancer tended to be lower than those of seven high-income countries published by the ICBP-SURVMARK2 project for 2010–2014 [31]. Different distribution by sex and smoking habits could be among the reasons for these differences, and variation in registration practices across countries may partly contribute. Cancers 2022, 14, 2441 14 of 18 However, further investigation is required to determine whether potentially modifiable factors that could be intervened on, such as stage at diagnosis and access to timely and optimal treatment, are contributing to the poor prognosis for these tumors. A previous study found regional differences in survival for various cancers in Spain, most notably for lung cancer [36]. Indications that there is room for improvement have been seen in some high-resolution studies showing geographical variation in the early diagnosis and management of cancer patients in Spain [37,38]. Furthermore, some Spanish studies have reported geographical disparities in infrastructure and equipment for radiation oncology, and in access to oncology drugs and predictive biomarkers [39,40]. We observed significant increases in survival between periods of diagnosis, 2002–2007 and 2008–2013, for all cancers combined and for 19 of 29 cancer groups in both sexes (14 of 25 in men and 14 of 27 in women), and no significant decrease was found for any cancer group. For most cancers, larger improvements were found in patients younger than 75 years at diagnosis than in those aged 75 years and older, as described in other studies [31], and various factors might play a role in these differences, as mentioned previously. Some of the largest increases were seen for some hematological malignancies: chronic myeloid leukemia, myeloma, non-Hodgkin lymphoma, acute myeloid leukemia, acute lym- phoid leukemia and the group of leukemia NOS and others, although the increases were not statistically significant for the two latter groups. Chronic myeloid leukemia was the malignancy that showed the greatest increase in survival in the period 2000–2007 compared to 1995–1999 [7] and continued to rise considerably in 2008–2013. This results mostly from the introduction in 2001 of treatments with tyrosine kinase inhibitors, which dramatically changed the course and prognosis of the disease [41,42]. The increased survival in patients with myeloma is probably largely due to changes in the therapeutic arsenal in the last decade [43]. For non-Hodgkin lymphoma and some leukemias, advances in molecular biol- ogy and cytogenetic techniques have led to better diagnostic and therapeutic approaches that may be reflected in the observed improved survival [44,45]. Despite the aforemen- tioned advances, no increased survival was observed for chronic lymphoid leukemia, but this may be at least partially due to a bias resulting from the change of diagnostic criteria in the 2008 WHO classification [46]. This change might have led to classification of some patients who formerly would have been diagnosed with chronic lymphoid leukemia, as monoclonal B-cell lymphocytosis, a premalignant condition [47]. Among the most common cancers, survival increases were particularly large for those of the colon and rectum, probably related to earlier diagnosis and better patient management [48]. Only a few regions of Spain had started population-based organized screening programs for colorectal cancer in the studied period, therefore, it is unlikely that there was already an impact on survival from these programs. An increase in survival was also observed for breast cancer, for which there are well-established screening programs in all Spanish regions. Regarding thyroid and kidney cancers, it should be note that some of the apparent improvement in survival might be caused by the increased diagnosis of indolent tumors [49–51]. Improved survival was also seen for some of the tumors with poor prognosis including pancreatic, esophageal, lung, liver and brain cancer, possibly due to advancements in diagnosis and treatment, together with enhanced supportive care [52,53]. However, we did not detect changes for gallbladder and stomach cancer, two other neoplasms that showed low survival. Moreover, for stomach cancer, the survival we found in the last period is very similar to that in 1995–1999 reported in a previous study [7]. The persisting poor prognosis for all these cancers underscores the need to strengthen primary prevention and early diagnosis whenever possible. The main strengths of this study include its population-based setting, which mini- mized the selection bias present in most clinical trials; the use of standardized registration procedures and high-quality data; and the reliable follow-up of vital status. Among the lim- itations, we acknowledge that our data covered only about 26% of the Spanish population, nevertheless this is the most complete and accurate information available on the survival Cancers 2022, 14, 2441 15 of 18 of cancer patients in Spain. Another limitation is that some important explanatory factors, such as stage at diagnosis, treatments, or socioeconomic status, could not be considered because these data were not available. Finally, the fact that survival was estimated using the cohort approach for patients diagnosed in 2002–2007 and the period approach for those diagnosed in 2008–2013, might have slightly underestimated the level of survival improvement achieved [54]. 5. Conclusions We provided cancer survival estimates and analyzed survival trends among adult pa- tients in Spain by cancer group, sex, and age. These survival estimates are crucial indicators for assessing the cancer strategy of the Spanish National Health System and the overall ef- fectiveness of health services for cancer patients. We found survival improvements for most cancer groups and there may be multiple reasons for these findings, including earlier diag- nosis and improved treatment options. However, the persistent poor prognosis observed for some cancers emphasizes the need to reinforce actions along the cancer continuum, from primary prevention to early diagnosis, optimal treatment, and supportive care. Further investigation of possible sociodemographic inequalities is warranted. Population-based cancer registries are fundamental to continue monitoring cancer survival. Supplementary Materials: The following supporting information can be downloaded at: https:// www.mdpi.com/article/10.3390/cancers14102441/s1, Table S1: Participating cancer registries, number of cases and periods of diagnosis included; Table S2: Five-year net survival by age group and sex for adult patients diagnosed with cancer in Spain in 2008–2013. Author Contributions: Conceptualization, M.G., E.A., R.M.-G., M.-D.C. and J.G.; Methodology, M.G., E.A., D.S. and R.M.-G.; Data Collection and Validation, M.G., R.M.-G., M.C. (Marià Carulla), M.-D.C., M.R.C., A.A., D.R., A.V.B., M.C. (Matilde Chico), R.J.C., A.L.d.M., V.d.C., M.-J.S., E.R.-G., P.F., J.G. and E.A.; Data Curation, M.C. (Marià Carulla), J.G., A.M. and M.G.; Formal Analysis, M.G. and A.M.; Investigation, all authors; Visualization, M.G.; Writing—Original Draft Preparation, M.G. and E.A.; Writing—Review and Editing, all authors. All authors have read and agreed to the published version of the manuscript. Funding: This research received no external funding. Institutional Review Board Statement: This study is based on data collected in cancer registries for public health surveillance. All the participating cancer registries comply with current European and national regulations on data protection. The public health administration of each region/province authorized the collection and use of these data for their analysis without requirement of informed consent and ethical approval, covered by the Spanish General Health Law 14/1986 and the Public Health General Law 33/2011. The authorizing bodies for each region/province can be seen on https://stage.redecan.org/es/registros-de-cancer (accessed on 29 April 2022). The study was carried out in accordance with the principles of the Declaration of Helsinki. Informed Consent Statement: Patient consent was waived due to the deidentified nature of the data. Data Availability Statement: Data are available from the authors on reasonable request with the permission of the cancer registries. Data requestors will need to sign a data access agreement. Acknowledgments: The authors acknowledge Nerea Larrañaga (Basque Country Cancer Registry) and Josefina Perucha-González (La Rioja Cancer Registry) for their valuable contribution to this work. Conflicts of Interest: The authors declare that they have no conflict of interest. References 1. Sung, H.; Ferlay, J.; Siegel, R.L.; Laversanne, M.; Soerjomataram, I.; Jemal, A.; Bray, F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J. Clin. 2021, 71, 209–249. [CrossRef] [PubMed] 2. Red Española de Registros de Cáncer (REDECAN). Estimaciones de la Incidencia del Cáncer en España. 2022. Available online: https://redecan.org (accessed on 14 May 2022). Cancers 2022, 14, 2441 16 of 18 3. Instituto Nacional de Estadística. 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