Cancer incidence and mortality trends in France over 1990-2018 for solid tumors: the sex gap is narrowing.

OBJECTIVE: To analyze trends in cancer incidence and mortality (France, 1990-2018), with a focus on men-women disparities. METHODS: Incidence data stemmed from cancer registries (FRANCIM) and mortality data from national statistics (CépiDc). Incidence and mortality rates were modelled using bidimensional penalized splines of age and year (at diagnosis and at death, respectively). Trends in age-standardized rates were summarized by the average annual percent changes (AAPC) for all-cancers combined, 19 solid tumors, and 8 subsites. Sex gaps were indicated using male-to-female rate ratios (relative difference) and male-to-female rate differences (absolute difference) in 1990 and 2018, for incidence and mortality, respectively. RESULTS: For all-cancers, the sex gap narrowed over 1990-2018 in incidence (1.6 to 1.2) and mortality (2.3 to 1.7). The largest decreases of the male-to-female incidence rate ratio were for cancers of the lung (9.5 to 2.2), lip - oral cavity - pharynx (10.9 to 3.1), esophagus (12.6 to 4.5) and larynx (17.1 to 7.1). Mixed trends emerged in lung and oesophageal cancers, probably explained by differing risk factors for the two main histological subtypes. Sex incidence gaps narrowed due to increasing trends in men and women for skin melanoma (0.7 to 1, due to initially higher rates in women), cancers of the liver (7.4 to 4.4) and pancreas (2.0 to 1.4). Sex incidence gaps narrowed for colon-rectum (1.7 to 1.4), urinary bladder (6.9 to 6.1) and stomach (2.7 to 2.4) driven by decreasing trends among men. Other cancers showed similar increasing incidence trends in both sexes leading to stable sex gaps: thyroid gland (0.3 to 0.3), kidney (2.2 to 2.4) and central nervous system (1.4 to 1.5). CONCLUSION: In France in 2018, while men still had higher risks of developing or dying from most cancers, the sex gap was narrowing. Efforts should focus on avoiding risk factors (e.g., smoking) and developing etiological studies to understand currently unexplained increasing trends.

Contamination in control group led to no effect of PSA-based screening on prostate cancer mortality at 9 years follow-up: Results of the French section of European Randomized Study of Screening for Prostate Cancer (ERSPC).

INTRODUCTION: European Randomized Study of Screening for Prostate Cancer (ERSPC) mortality results were reported for 7 European countries (excluding France) and showed a significant reduction in Prostate cancer (PCa) mortality. As those results have not been part of the global ERSPC results, it is of interest to report PCa mortality at a median follow-up of 9 years for French section of ERSPC. MATERIAL AND METHODS: Two administrative departments were involved in the study. Only men after randomization in the screening group were invited by mail to be screened by PSA testing with two rounds at 4-6 year intervals. Biopsy was recommended if PSA>=3.0 ng/mL. No information other that the French Association of Urology recommandations on the use of PSA was offered to the control group (own decision of physicians and patients). Follow up was based on cancer registry database. Contamination defined as the receipt of PSA testing in control arm was measured. Poisson regression models were used to estimate the Rate Ratio (RR) of PCa mortality and incidence in the screening vs. control arm. RESULTS: Starting from 2003, 80,696 men aged 55-69 years were included. The percentage of men in the screening arm with at least one PSA test (compliance) was 31%. Compared to the control arm, PCa incidence increased by 10% in the screening arm (RR=1.10; 95% CI=[1.04-1.16], P=0.001), but PCa mortality did not differ (0.222 and 0.215 deaths/1000 person-years; RR=1.03[0.75-1.42], P=0.9). DISCUSSION: Limitations include low participation rate. PSA testing in the control arm was observed in 32% of men (contamination). CONCLUSIONS: Contamination in control group led to no effect of PSA-based screening on prostate cancer mortality at 9 years follow-up. LEVEL OF EVIDENCE: 3.

Are comorbidities associated with long-term survival of lung cancer? A population-based cohort study from French cancer registries.

BACKGROUND: Survival rates of lung cancer remains poor and the impact of comorbidities on the prognosis is discussed. The objective of this study was to assess if the Charlson Comorbidity Index (CCI) was associated with 8-year survival rates by histological type. METHODS: A cohort study was conducted using randomly selected cases from 10 French cancer registries. Net survival rates were computed using the Pohar-Perme estimator of the net cumulative rate. Three Cox models were independently built for adenocarcinomas, squamous cell and small cell cancers to estimate prognostic factors including CCI grade. RESULTS: A total of 646 adenocarcinomas, 524 squamous cell and 233 small cell cancers were included in the analysis. The net 8-year survival rate ranged from 12.6% (95% CI: 9.8-15.4%) for adenocarcinomas and 13.4% (95% CI: 10.1-16.7%) for squamous cell carcinomas, to 3.7% (95% CI: 1.1-6.3%) for small cell cancers. Observed and net survival rates decreased for CCI grades ≥3 for all histological group considered. After adjustment for sex, age group, stage and diagnostic mode, CCI grades 1 (HR = 1.6 [95% CI: 1.1-2.3]), 2 (HR = 1.7 [95% CI: 1.1-2.7]) and ≥ 3 (HR = 2.7 [95% CI: 1.7-4.4]) were associated with lower survival rates only for small cell cancers. CONCLUSION: After adjustment for age, sex, stage and diagnostic mode, the presence of comorbidity based on CCI grades 1-2 and ≥ 3 was associated with lower survival rates for small cell cancers whereas no differences were observed for adenocarcinomas and squamous cell cancers.

Merkel cell carcinoma in France: a registries-based, comprehensive epidemiological survey.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare primary cutaneous neuroendocrine carcinoma. Owing to its low incidence, epidemiological data are scarce and have never been analysed in France to identify the main epidemiological trends. METHODS: Data from MCC patients diagnosed between 1998 and 2010 were obtained from 11 French cancer registries in the FRANCIM network. The main epidemiological characteristics of MCC were investigated between 2006 and 2010 because comprehensive data were only available for this period. The main focus was tumour incidence and mortality over time. RESULTS: Between 1998 and 2010, 562 cases of MCC were reported in the registries. From 2006 to 2010 (290 cases), European- and world-standardized incidence rates were 0.26 and 0.43 per 100,000 person-years in men and 0.24 and 0.38 per 100,000 person-years in women. MCC is more frequent in females in France (56.9%) with male/female ratio 1.1. Relative survival rates were 84%, 56% and 42% at one, three and 5 years, respectively. CONCLUSIONS: The incidence of MCC clearly increased over time in all areas under focus. The standardized incidence in France was comparable to the incidence observed in other countries for the same period, but French data are too recent to conclude on an increase in MCC incidence. Prognosis remains poor in all countries in which data are available.

[Prostate cancer: Quality assessment of clinical management in the Midi-Pyrenean region in 2011]. / Cancer de la prostate : qualité de la prise en charge en Midi-Pyrénées en 2011.

OBJECTIVES: Assessing the quality of the clinical management of prostate cancer in the Midi-Pyrenean region in 2011. METHODS: The study population was randomly selected among new cases of prostate cancer presented in Multidisciplinary Team Meeting (MTM) in 2011. The indicators defined with the professionals have evaluated the quality of the diagnostic care, when treatment started and at the time of the MTM. RESULTS: Six hundred and thirty-three new patients were included (median age at diagnosis=69years, min: 48; max: 93). In diagnostic period, 92% of patients had a prostate biopsy. Performing a pelvic MRI, an abdomino-pelvic CT and bone scintigraphy concerned respectively 53%, 55% and 61% of intermediate or high-risk patients. The Gleason score, surgical margins and pathological stage were included in over 98% patient records treated by radical prostatectomy. A PSA assay in 3months after prostatectomy was found in 59% of surgical patients. The MTM was performed before treatment to 83% of patients. About three-quarters of surgical patients with stage pT≥3 or pN1 or with no healthy margins were discussed in MTM after surgery. CONCLUSION: Most of the studied indicators reach a high level. However, the lower level of realization of complementary examinations may question about their real place, accessibility and traceability. LEVEL OF EVIDENCE: 4.

The care center influences the management of lymphoma patients in a universal health care system: an observational cohort study.

BACKGROUND: Healthcare providers-related disparities in adherence to the treatment plan among lymphoma patients are found even in a universal healthcare system, but the mechanism remains unclear. We investigated the association between the type of care center and the relative dose intensity and determined whether it persists after adjustment for patients' recruitment differences. METHODS: Prospective observational cohort study of 294 patients treated with standard protocols for diffuse large B-cell lymphoma (DLBCL) in teaching or community public hospitals or in private centers in the French Midi-Pyrénées region from 2006-2013. To test our assumptions, we used multinomial and mixed-effect logistic models progressively adjusted for patients' biomedical characteristics, socio-spatial characteristics and treatment-related toxicity events. RESULTS: Patients treated using standard protocols in the teaching hospital had more advanced stage and poorer initial prognosis without limitation regarding the distance from the residence to the care center. Patients' recruitment profile across the different types of care center failed to explain the difference in relative dose intensity. Low relative dose intensity was less often observed in teaching hospital than elsewhere. CONCLUSION: We showed that even in a universal healthcare system, disparities in the management of DLBCL patients' do exist according to the types of care center. A main issue may be to find and diffuse the reasons of this benefit in cancer management in the teaching hospital to the other centers.

Guidelines for time-to-event end point definitions in sarcomas and gastrointestinal stromal tumors (GIST) trials: results of the DATECAN initiative (Definition for the Assessment of Time-to-event Endpoints in CANcer trials)†.

BACKGROUND: The use of potential surrogate end points for overall survival, such as disease-free survival (DFS) or time-to-treatment failure (TTF) is increasingly common in randomized controlled trials (RCTs) in cancer. However, the definition of time-to-event (TTE) end points is rarely precise and lacks uniformity across trials. End point definition can impact trial results by affecting estimation of treatment effect and statistical power. The DATECAN initiative (Definition for the Assessment of Time-to-event End points in CANcer trials) aims to provide recommendations for definitions of TTE end points. We report guidelines for RCT in sarcomas and gastrointestinal stromal tumors (GIST). METHODS: We first carried out a literature review to identify TTE end points (primary or secondary) reported in publications of RCT. An international multidisciplinary panel of experts proposed recommendations for the definitions of these end points. Recommendations were developed through a validated consensus method formalizing the degree of agreement among experts. RESULTS: Recommended guidelines for the definition of TTE end points commonly used in RCT for sarcomas and GIST are provided for adjuvant and metastatic settings, including DFS, TTF, time to progression and others. CONCLUSION: Use of standardized definitions should facilitate comparison of trials' results, and improve the quality of trial design and reporting. These guidelines could be of particular interest to research scientists involved in the design, conduct, reporting or assessment of RCT such as investigators, statisticians, reviewers, editors or regulatory authorities.

[Prostate cancer incidence and mortality trends in France from 1980 to 2011]. / Le cancer de la prostate, évolution de l'incidence et de la mortalité en France entre 1980 et 2011.

UNLABELLED: The prostate cancer became for two decades the most frequent cancer in men. We describe the evolution of its incidence and mortality from 1980 to 2011 for France. METHODS: Incidence data were collected from registries and national incidence estimates were based on the use of mortality as a correlate of incidence. RESULTS: After a very strong increase of incidence between 1980 (24.8/100,000) and 2005 (124.5/100,000), we observe a net decline since (97.7/100,000, in 2011). The reduction began earlier for the old patients. The evolution of mortality is very different. We observe a regular reduction since the end of 1990s (from 18.0/100,000 in 1990 to 10.5/100,000 in 2011). The reduction began earlier for the young patients. CONCLUSION: This pattern of evolution is observed in all the countries where the use of the PSA had caused an important increase of the diagnosis of prostate cancer. LEVEL OF EVIDENCE: 3.

Adherence to consensus-based diagnosis and treatment guidelines in adult soft-tissue sarcoma patients: a French prospective population-based study.

BACKGROUND: Soft-tissue sarcomas (STSs) are rare tumors with varied histological presentations. Management and treatment are thus complex, but crucial for patient outcomes. We assess adherence to adult STS management guidelines across two French regions (10% of the French population). We also report standardized incidence. PATIENTS AND METHODS: STS patients diagnosed from 1 November 2006 to 31 December 2007 were identified from pathology reports, medical hospital records, and cancer registries. Guideline adherence was assessed by 23 criteria (validated by Delphi consensus method), and age and sex-standardized incidence rates estimated. Associations between patient, treatment, and institutional factors and adherence with three major composite criteria relating to diagnostic imaging and biopsy as well as multidisciplinary team (MDT) case-review are reported. RESULTS: Two hundred and seventy-four patients were included (57.7% male, mean age 60.8 years). Practices were relatively compliant overall, with over 70% adherence for 10 criteria. Three criteria with perfect Delphi consensus had low adherence: receiving histological diagnosis before surgery, adequacy of histological diagnosis (adherence around 50% for both), and MDT discussion before surgery (adherence <30%). Treatment outside of specialized centers was associated with lower adherence for all three composite criteria, and specific tumor sites and/or features were associated with lower adherence for diagnostic imaging, methods, and MDT meetings. STS standardized incidence rates were 4.09 (European population) and 3.33 (World) /100 000 inhabitants. CONCLUSIONS: Initial STS diagnosis and treatment across all stages (imaging, biopsy, and MDT meetings) need improving, particularly outside specialized centers. Educational interventions to increase surgeon's sarcoma awareness and knowledge and to raise patients' awareness of the importance of seeking expert care are necessary.

[Incidence and mortality of urological cancers in 2012 in France]. / Projection de l'incidence et de la mortalité par cancer urologique en France en 2012.

OBJECTIVES: Present national estimations of the incidence and mortality trends in urological cancers in France between 1980 and 2012. MATERIAL AND METHODS: Francim database and French Register of Cancers. RESULTS: Analysis of the current data shows a regular increase of the incidence of renal cancer in men and women (7,781 cases in men and 3,792 in women in 2012). For bladder cancer, trends are divergent. There is a small reduction in incidence for men and an increase for women (9,549 cases in men and 2,416 in women in 2012). Testicular cancer is still increasing slightly (2,317 incidental cases in 2012). The incidence of prostate cancer experienced a huge increase up until 2005, and thereafter it decreased sharply, though it is difficult to discern whether this drop (which was observed up until 2008) continued at the same rate after that point (56,841 incidences in 2012 based on the rates calculated for 2009). CONCLUSION: The analyses by organ database show that there are significant variations in the incidence of urological cancers, particularly for prostate cancer, which shows that both the natural history of urological tumours and the methods of detection have an impact on incidence.

[Is statin use associated with D'Amico risk groups and biochemical recurrence after radical prostatectomy?]. / Impact de la prise de statines sur les groupes à risques de progression de D'Amico et la survie sans récidive biologique après prostatectomie totale.

OBJECTIVE: To examine the association between statin use and prostate cancer (PC) stratified with D'Amico risk groups and biochemical recurrence (BR) in patients undergoing radical prostatectomy (RP). PATIENTS AND METHODS: All medical charts of patients managed from 2004 to 2008 for PC with RP were reviewed retrospectively. The use and the type of statin were identified. Patients were split according to the use (S+) or not (S-) of statin. The two groups were compared using the Chi(2) test. A logistic regression was performed for multivariate analysis. RESULTS: Overall, 377 patients were included. Mean age was 64 (48-76) (median, range). Ninety-seven patients (27.5%) used statin for at least a year. Groups S- and S+ were comparable in terms of age, obesity, diabetes, preoperative PSA, biopsy Gleason score or clinical stage. The use of statin was statistically associated with D'Amico risk groups (P=0.003). The number of high-risk PC was higher in Group S+ (23.7% vs. 10.7%) with an odds ratio of 2.4 (P=0.009). With a mean follow up of 33±10 months, the overall 2-years-BR was 89%. The 2-years-BR was higher in the S+ (93% vs. 88%, P=0.16). After adjustment, this difference was statistically significant with a hazard ratio of 0.46 (P=0.036). CONCLUSION: The use of statin was associated with high risk PC in this study. Surprisingly, the statin use seem also to be associated with better disease-free survival, independently of other risk factors.

Breast cancer incidence and time trend in France from 1990 to 2007: a population-based study from two French cancer registries.

BACKGROUND: The hypothesis of a link between breast cancer and hormone replacement therapy (HRT) is evoked to explain the recent decrease of incidence observed in several countries. The purpose of our study is to analyse the evolution of breast cancer incidence by stage. MATERIALS AND METHODS: We used data from Tarn and Isère French cancer registries for the period 1990-2007. Trends of annual world population standardised incidence rates were studied using the Joinpoint method. RESULTS: From 1990 to 1999, the incidence of invasive breast cancer increased annually by 1.2%, then by 4.8% from 1999 till 2003 and then decreased by 1.7%. For the women aged 50-74 years, annual changes were, respectively, 1.5%, 6.0% and 3.4%. In this group, the incidence of T1/T2-N0-M0 stages increased annually by 4.6% until 2003 and then decreased by 2.2%. Since 1990, the incidence of in situ breast cancer increased annually by 5%. From 2003 to 2004, prescribing of HRT decreased substantially. CONCLUSIONS: : Since 2003, the incidence of invasive breast cancer decreased for women aged 50-74 years, mainly involving T1/T2-N0-M0 stages. The reduction in HRT prescription may partly explain this decrease. The incidence of in situ breast cancer didn't decrease during the whole period.

[Completeness and quality of multidisciplinary team meetings: the example of prostate cancer in the Mid-Pyrenees region]. / Exhaustivité et qualité des réunions de concertation pluridisciplinaire: l'exemple des cancers prostatiques en Midi-Pyrénées.

OBJECTIVES: To determine the completeness of the examination of cancer patient cases in a multidisciplinary team meeting (MDTM), to study the factors that can affect this examination and to assess the quality of the MDTM concerning prostate cancer in Tarn. METHODS: Completeness was estimated by comparing the database of the Tarn cancer registry containing all the inhabitants of this department for whom prostate cancer was diagnosed in 2007 with the list of patients living in Tarn whose cases were discussed during a Midi-Pyrénées MDTM. Determinants of the case discussion in MDTM were studied from data collected in medical records (age, stage at diagnosis, PSA level, Gleason score, treatment). The MDTM quality study (delay in management, whether the case was seen before or after treatment, required elements for MDTM, clinical data, conformity between suggested treatment and guidelines, adequacy between suggested and performed treatments) was based on the MDTM forms retrieved from the DCO and from medical records. RESULTS: Four hundred and fifty-nine patients were re-examined. The pretherapeutic passage rate within three months after diagnosis was 56.2%. The probability of a discussion in MDTM decreased for people over 85 years of age (OR=0.10) compared with the 70-74 year-old people and it increased for the N+M+ (OR=4.23) compared with the T1-T2. Patients for whom radiotherapy was considered were presented more frequently than the others. The MDTM quality was studied based on 220 DCO forms. The patient's physician attended the MDTM in 65% of the cases, 97% of the suggested treatments were consistent with the guidelines and 90% of the performed treatments complied with the suggested treatment. CONCLUSION: The discussion rate in MDTM has not reached the 100% planned by the first "plan cancer" yet, but when a MDTM was carried out, its compliance and adequacy were high. While seniors' cases require interdisciplinarity because of a complicated management, they were less discussed in MDTM.

Evolution of pleural cancers and malignant pleural mesothelioma incidence in France between 1980 and 2005.

The evolution of pleural cancers and malignant pleural mesothelioma incidence in France between 1980 and 2005 was analysed using data derived from the French network of cancer registries (FRANCIM) and the French National Mesothelioma Surveillance Program (PNSM). Mesothelioma proportions in pleural cancers were calculated by diagnosis year in the 1980-2000 period. Our results suggest that the incidences of pleural cancer and mesothelioma levelled off in French men since 2000 and continued to increase in French women. A decrease of the annual pleural cancer incidence average in men was noticed (-3.4% of annual rate of change) between 2000 and 2005. The proportion of pleural cancers that were mesothelioma was unchanged between 1980 and 2003 with an average of 86%. The age standardised incidence rate of pleural mesothelioma remained relatively stable between 1998 and 2005 with a slight falling trend. For women, the age standardised incidence rate of pleural cancers and mesothelioma increased during the period 1998-2005. Additionally, the proportion of pleural cancers that were mesothelioma increased during the same period of time. Finally, the increased trend observed in the incidence of pleural mesothelioma and cancers in women is credibly due to their under diagnosis in the 1980-1997 period. The comparison between the French incidence and the American and British ones shows that the decreasing trend in incidence of mesothelioma and pleural cancers in French men since 2000 is potentially associated with a lower amphibole consumption and by the implementation of safety regulations at work from 1977.

A population-based study of adjuvant chemotherapy for stage-II and -III colon cancers.

BACKGROUND: Although clinical trials have demonstrated that adjuvant chemotherapy improves survival for stage-III colon cancer, the benefits remain controversial for stage-II lesions. The objective of the present study was to determine the extent to which adjuvant chemotherapy is used for patients with stage-II and -III colon cancers. METHODS: The study population comprised 1074 patients with stage-II and -III colon cancers diagnosed in 2000 in 12 French administrative districts and recorded in population-based cancer registries. Data were collected using a standardized procedure. RESULTS: Overall, 20.4% of patients with stage II and 61.9% with stage III received adjuvant chemotherapy. Age at diagnosis was the strongest determinant of chemotherapy. Among stage-II patients, those receiving chemotherapy decreased from 57.6% in patients aged or=85. The corresponding percentages with stage III were 93.6% and 1.4%. In multivariate analyses, other factors found to be independently and significantly associated with administration of adjuvant chemotherapy for stage II were extension of the cancer (stage IIA vs. stage IIB), clinical presentation (obstruction or perforation vs. uncomplicated cancer) and discussion of the case at a multidisciplinary case-review meeting. For stage III, apart from age, discussion of the case at a multidisciplinary meeting was the only factor independently associated with administration of chemotherapy. CONCLUSION: Adjuvant chemotherapy for stage-III colon cancer is used extensively for patients under 75 years of age. However, many elderly patients do not receive such treatment. On the other hand, a substantial percentage of stage-II colon cancer patients receive adjuvant chemotherapy despite its uncertain benefits.

[Prostate cancer management and factors associated with radical prostatectomy in France in 2001]. / Le cancer de la prostate en France en 2001: état des pratiques et facteurs associés à la réalisation d'une prostatectomie totale.

INTRODUCTION: Prostate cancer was the most common cancer in men in France in 2005, and the second cause of male death from cancer. In this study, we analyzed clinical characteristics of patients with prostate cancer diagnosed in France in 2001 with a focus on therapeutic management of localized prostate cancers. PATIENTS AND METHODS: A total of 2181 cases of prostate cancer diagnosed in 2001 from 11 French counties covered by a cancer registry were analyzed. A descriptive study of the clinical characteristics of patients was performed. Parameters studied included age, county, TNM stage, PSA value, Gleason score, D'Amico prognostic group, Charlson's comorbidity index and initial treatment modalities. For localized cancers, multivariate logistic regression analysis identified factors associated with radical prostatectomy. RESULTS: The proportion of localized prostate cancer (T1 or T2) was 86.6 %. The use of invasive curative treatment (radical prostatectomy and radiotherapy) was 58.4 % for localized cancers. Significant differences in therapeutic management were found between counties. Radical prostatectomy was associated with age at diagnosis, D'Amico prognostic group and the presence of comorbidities. CONCLUSIONS: Most of prostate cancers diagnosed in France in 2001 were clinically localized and were treated by invasive therapy. The consequences of these practices remain to be determined given the limited evolution of many prostate cancers and the frequency of adverse events related to invasive treatments.

[Current management and prognosis of intrahepatic cholangiocarcinoma in France]. / Prise en charge et pronostic du cholangiocarcinome intrahépatique en France.

INTRODUCTION: Intrahepatic cholangiocarcinoma (ICC) is a rare tumor with a poor prognosis. The aim of this study was to evaluate current management and prognosis of ICC in nine French administrative areas, which are covered by population-based cancer registries. METHODS: Between 1997 and 1998, 1100 cases of primary liver cancer were observed in nine French departments: 68 were ICC. Clinicopathological characteristics and applied treatments were recorded and a comparative analysis and a 5-year survival study were performed. RESULTS: In most cases (85%), the presence of symptoms was the principal mode of discovery. Histological confirmation revealed ICC in two thirds of cases. The remaining liver was normal in 72% of cases (patients with cirrhosis: 12%). The mean size of tumours was 6 cm. Metastases were present in one out of four cases. Surgical management, chemotherapy and radiotherapy were performed in 40%, 20% and 11.5% of patients, respectively. Hepatic surgical resection was correlated with age and bilirubin level. One third of the patients were treated for symptoms. Five-year survival rate was 7.4% and median survival was 7 months. Patients with hepatic surgical resection had 5-year survival rate of 24.5%. CONCLUSION: At present, complete resection is the only therapy offering possible long-term survival in this entity. New adjuvant chemotherapy after surgery must be offered to these patients.