Secondary Primary Cancer Risk After Radiation Therapy in Rectal Cancer: A Population-Based Cohort Study With Propensity Score Matching.

BACKGROUND: It remains unclear whether radiation therapy (RT) has an impact on the development of secondary primary cancer (SC) in rectal cancer (RC) patients, especially within the true pelvis. AIM: To examine the incidence of SC in a population-based cohort of RC after surgical treatment with or without radiation therapy (RT, NRT). PATIENTS AND METHODS: The epidemiological cohort consisting of 13,919 RC patients with primary M0 stage diagnosed between 1998 and 2019 was collected from cancer registry data of Upper Bavaria. Competing risk analyses were conducted regarding the development of SC on 11 687 first malignancies, stratified by RT/NRT. A propensity score (PS) was generated by logistic regression modeling of RT to repeat competing risk analyses on a PS-matched cohort. RESULTS: The median age (interquartile range) of the epidemiological cohort was 68.9 years (60.4-76.7). About 60.8%, were men, 38.7% had UICC III, 35.8% of tumors were localized lower than 8 cm, 41.3% underwent RT. Only 17.1% of patients older than 80 years at diagnosis received RT. In general, RT patients were 5 years younger than NRT patients (65.9 years [58.0-73.0] vs. 71.3 years [62.4-79.2], P < .0001). The 20-year cumulative incidence of SC was 16.5% in RT and 17.4% in NRT patients (P = .2298). Men with RT had a lower risk of prostate cancer (HR = 0.55, 95%CI [0.34-0.91], P = .0168). In the PS-matched cohort, RT patients had a significantly higher risk of bladder cancer during follow-up (10-year cumulative incidence of 1.1% vs. 0.6% in NRT). The direction of the RT effects in men and women and different tumor sites may cancel each other. CONCLUSION: A protective effect of RT in rectal cancer patients on developing prostate SC by half is reproduced. Further analyses studying the long-term SC risks of RT should essentially focus on stratification by sex, and focus on more recent data.

The other colon cancer: a population-based cohort study of appendix tumour trends and prognosis.

AIM: Appendiceal neoplasms are rare subtypes of colorectal tumours that mainly affect younger patients some 20 years earlier than other colon tumours. The aim of this study was to gain more insight into the histological subtypes of this rare disease and include cases previously excluded, such as mucinous neoplasia. METHOD: The cohort study included 1097 patients from the Munich Cancer Registry (MCR) diagnosed between 1998 and 2020. Joinpoint analysis was used to determine trend in incidence. Baseline demographic comparisons and survival analyses using competing risk and univariate/multivariate methods were conducted according to tumour histology: adenocarcinoma (ADENO), neuroendocrine neoplasia (NEN), mixed adeno-neuroendocrine carcinoma (MANEC), and low- (LAMN) and high-grade mucinous neoplasia (HAMN). RESULTS: Up to 2016 the number of cases increased significantly [annual per cent change (APC) = 6.86, p < 0.001] followed by a decline in the following years (APC = -14.82, p = 0.014; average APC = 2.5, p = 0.046). Comparison of all patients showed that NEN (48.4%) and mucinous neoplasms (11.6%) had a considerably better prognosis than ADENO (36.0%) and MANEC (3.0%, p < 0.0001). A multivariate analysis within the NEN and ADENO subgroups revealed that further histological classification was not prognostically relevant, while older age and regional tumour spread at diagnosis were associated with a poor prognosis. ADENO histology with high tumour grade and appendectomy only was also associated with poorer survival. CONCLUSION: Appendiceal neoplasms are histologically heterogeneous; however, this diversity becomes less relevant compared with the marked difference from cancers of the remaining colon. The previously observed increase in cases appears to be abating; fewer cases of appendicitis and/or appendectomies or changes in histopathological assessment may be behind this trend.

Colonoscopy and polypectomy: beside age, size of polyps main factor for long-term risk of colorectal cancer in a screening population.

PURPOSE: Despite national and international guideline recommendations, few studies have been conducted to estimate the impact of colonoscopy screening on long-term colorectal cancer incidence. Aim of this study was to determine the long-term impact of a full colonoscopy with polypectomy on colorectal cancer incidence in a large screening population. METHODS: In this prospective observational cohort study, a total of 10,947 colonoscopy screening participants from within the scope of the Munich Cancer Registry were consecutively recruited from participating gastroenterology practices and their subsequent colorectal cancer incidence assessed. Predictive factors associated with colorectal cancer were also evaluated in univariate and multivariate analyses. RESULTS: After a median follow-up of 14.24 years (95% CI [14.21-14.25]), 93 colorectal cancer cases were observed. This is equivalent to a truncated age-standardized rate of 69.0 (95% CI [43.3-94.7]) for male and 43.4 (95% CI [29.4-57.5]) for female participants (≥ 50 years at colonoscopy). The ratio of this observed to the expected rate from cancer registry data showed a 67% decrease in colorectal cancer incidence in the male and 65% in the female participants (p < 0.0001). In multivariate analysis of screening patients, age at screening (p < 0.0001) was the main predictive factor for colorectal cancer. In the subgroup with positive polyp findings, age (p < 0.0001) and the polyp size (p = 0.0002) were associated with colorectal cancer. CONCLUSION: These results underline the significance of a full colonoscopy screening combined with polypectomy in reducing the total disease burden of colorectal cancer.

Age independent survival benefit for patients with hepatocellular carcinoma (HCC) without metastases at diagnosis: a population-based study.

OBJECTIVE: Hepatocellular carcinoma (HCC) is a major cause of death worldwide and its incidence is expected to increase globally. Aim of this study was to assess whether the implementation of screening policies and the improvement of treatment options translated into a real-world survival benefit in HCC patients. DESIGN: 4078 patients diagnosed with HCC between 1998 and 2016 from the Munich Cancer Registry were analysed. Tumour characteristics and outcome were analysed by time period and according to age and presence of metastases at diagnosis. Overall survival (OS) was analysed using Kaplan-Meier method and relative survival (RS) was computed for cancer-specific survival. Cox proportional hazard models were conducted to control for prognostic variables. RESULTS: While incidence of HCC remained substantially stable, tumours were diagnosed at increasingly earlier stages, although the median age at diagnosis increased. The 3 years RS in HCC improved from 19.8% in 1998-2002, 22.4% in 2003-2007, 30.6% in 2008-2012 up to 31.0% in 2013-2016. Median OS increased from 6 months in 1998-2002 to 12 months in 2008-2016. However, analysis according to the metastatic status showed that survival improved only in patients without metastases at diagnosis whereas the prognosis of patients with metastatic disease remained unchanged. CONCLUSION: These real-world data show that, in contrast to the current assumptions, the incidence of HCC did not increase in a representative German region. Earlier diagnosis, likely related to the implementation of screening programmes, translated into an increasing employment of effective therapeutic options and a clear survival benefit in patients without metastases at diagnosis, irrespective of age.

Age and Outcome in Gastrointestinal Cancers: A Population-Based Evaluation of Oesophageal, Gastric and Colorectal Cancer.

BACKGROUND: With demographic changes and partial representativeness of randomized studies the question arises which results are achieved in the treatment of the elderly. The objective was to analyse population-based data on gastrointestinal cancers in terms of age. METHODS: Analyses included data of the Munich Cancer Registry, i.e. 4,014, 10,127 and 42,809 invasive oesophageal, gastric and colorectal cancer patients, respectively, which were diagnosed between 1998 and 2014. Tumour characteristics and outcome were analysed by age groups and therapy. Overall survival was analysed using the Kaplan-Meier method, and relative survival was computed as estimation for cancer-specific survival. Additionally, conditional survival of patients surviving at least 6 or 12 months was analysed by age. RESULTS: 21, 44 and 38% of oesophageal, gastric and colorectal cancer patients, respectively, were aged >75 years. Of these, 15, 46 and 73% were surgically treated with curative intent, respectively, which is significantly less than in younger patients. The total 5-year relative survival was 24, 33 and 66%, respectively. The differences in median survival by age group were diminished by selecting those surviving at least 6 or 12 months and those with curatively intended treatment. CONCLUSION: An adequate patient selection for therapies of these gastrointestinal cancers was demonstrated at large. If the patients' general conditions allowed curatively intended treatment, it was applied and led to similar outcomes irrespective of age.

Risk of second cancer following radiotherapy for prostate cancer: a population-based analysis.

BACKGROUND: To investigate the risk of second cancer and radiation induced second cancer following prostate cancer radiotherapy. METHODS: We compared men with radiotherapy only with those treated with radical prostatectomy only and those with radiotherapy after radical prostatectomy. Cumulative incidences of second cancers were calculated. Cox analyses were performed to identify determinants influencing second cancer incidence. RESULTS: Nineteen thousand five hundred thirty eight patients were analyzed. Age and median follow-up differed significantly with radiotherapy only patients having the highest median age (70.3 years) and radical prostatectomy only patients the longest median follow-up (10.2 years). Ten-year cumulative incidence of second cancer was 15.9%, 13.2% and 10.5% for patients with radiotherapy only, radiotherapy after radical prostatectomy and radical prostatectomy only (p <0.0001). Increasing age and belonging to the radiotherapy only group were associated with a higher risk of second cancer-no significant increase was seen in radiotherapy after radical prostatectomy patients. A significantly higher rate of smoking related malignancies, like lung, bladder and non-melanoma skin cancer, was seen in radiotherapy only patients. CONCLUSIONS: No clear increase in radiation induced second cancer was found in patients after radiotherapy for prostate cancer. Whereas the rate of second cancer was increased in radiotherapy only patients, no such increase was seen in patients with radiotherapy after radical prostatectomy. The increase of second cancer following radiotherapy only is highly likely to reflect advanced age and lifestyle habits and comorbidities.

Outcome of gastric cancer in the elderly: a population-based evaluation of the Munich Cancer Registry.

BACKGROUND: Gastric cancer accounts for 5 % of cancer deaths. Proportions of older stomach cancer patients are increasing. Despite the still poor prognosis, standardised treatment has achieved improvements; nonetheless it is questionable whether all age groups have benefitted. Age and outcome need to be examined in a population-based setting. METHODS: Analyses included Munich Cancer Registry (MCR) data from 8601 invasive gastric cancer patients, diagnosed between 1998 and 2012. Tumour and therapy characteristics and outcome were analysed by two age groups (<70 vs. ≥70 years). Survival was analysed using the Kaplan-Meier method and relative survival was computed as an estimation for cancer-specific survival. Additional landmark analyses were conducted by calculating conditional survival of patients who survived more than 6 months. RESULTS: Fifty-nine per cent of the cohort were ≥70 years old. These patients had tumours with a slightly better prognosis and were treated with less radical surgery and adjuvant therapy than younger patients. The 5-year relative survival was 40 % for the youngest (<50 years) and 23 % for the oldest patients (≥80 years). Survival differences were diminished or eliminated after landmark analyses: The 5-year relative survival in age groups 50-59, 60-69 and 70-79 years was comparable (between 48 and 49.6 %) and slightly worse in the youngest and oldest (45 %), which may be explained by more aggressive tumours and effects of cellular senescence, respectively. CONCLUSION: The treatment and care of elderly gastric cancer patients in the MCR catchment area seems appropriate: if a patient's general condition allows oncologic resection and chemotherapy, it is conducted and the result is comparable between age groups.

Changes in prognostic and therapeutic parameters in prostate cancer from an epidemiological view over 20 years.

BACKGROUND: The study objective was to examine changes in prognosis and treatment of prostate cancer patients over 20 years and to evaluate their impact on survival. PATIENTS AND METHODS: 38,861 prostate cancer patients diagnosed between 1990 and 2010 and living in the catchment area of the Munich Cancer Registry were analysed. RESULTS: Pre-therapeutic prostate-specific antigen (PSA) testing increased substantially in the early 1990s. A shift from capsule-exceeding tumours to capsule-limited tumours also took place especially in the 1990s. The proportion of radical prostatectomy increased continuously over the last 20 years from 20% to almost 50% whereas hormone therapy decreased from 55% to 18%. Radiation therapy and transurethral resection of the prostate increased slightly from about 5% to 10%. The 5- and 10-year relative survival rates increased from 92% to 97% and from 86% to 92%, respectively. CONCLUSIONS: 2 reasons may account for the rise in survival rates over 20 years: First, the establishment of widely used PSA testing resulted in a shift towards more favourable T categories due to the detection of many additional small tumours as well as the noticeable change in initial treatment strategy towards more radical prostatectomies. The second factor that likely increased survival was improvements in the therapies themselves.

Level of hospital care and outcome of gastric cancer: a population-based evaluation of the Munich Cancer Registry.

BACKGROUND: Gastric cancer accounts for 5 % of cancer deaths. Successful implementation of guideline-recommended treatment procedures should result in population-based outcome improvements despite the still poor prognosis. In this context, the objective of this study was to compare the outcome of gastric cancer by different levels of hospital care. MATERIALS AND METHODS: Total of 8,601 patients with invasive gastric cancer documented between 1998 and 2012 by the Munich Cancer Registry were evaluated. Tumour and therapy characteristics and outcome were analysed in regard to five levels of hospital care: three levels were defined for general hospitals (level I-III), while university hospitals and speciality hospitals were grouped as separate classes. Survival was investigated using the Kaplan-Meier-method, computing relative survival, and by multivariate Cox proportional hazard regression. RESULTS: The average age differed between 66 years in university hospitals and 75 years in hospitals providing a basic level of care (level I). No survival differences were found for patients treated in different levels of hospital care in 75 % of the patient cohort, namely the M0 patients. A better survival could only be shown for patients with M1 at diagnosis when treated in a university or level III hospital compared to those treated in other hospitals. CONCLUSION: The outcome difference of M1 patients is most likely caused by selection effects concerning health status differences and not by processes of health care attributable to level of hospital care. Thus, this study demonstrates and confirms appropriate treatment and care of gastric cancer over all levels of hospital care.

Quality of life in women with localised breast cancer or malignant melanoma 2 years after initial treatment: a comparison.

BACKGROUND: Two thirds of female breast cancer patients and more than 80 % of malignant melanoma patients are diagnosed with localised disease and good prognosis with a 5-year relative survival of more than 90 % in Germany. PURPOSE: This study was conducted to present quality of life (QoL) data from a German population-based cohort of female breast cancer and melanoma patients without recurrence for approximately 2 years after initial diagnosis. METHODS: In 2003-2004, patients with localised breast cancer and melanoma were recruited from the Munich Cancer Registry (Upper Bavaria, Germany) to answer QoL questionnaires. Differences between breast cancer and melanoma patients were investigated with regard to age and aspects of communication with their medical caregivers. RESULTS: One thousand three hundred and four breast cancer and 348 melanoma patients were included. Breast cancer patients were about 7 years older and had significantly lower QoL and higher symptom scores than melanoma patients. Communication needs were generally similar in both groups; however, breast cancer patients experienced more empathy from their medical caregivers. In breast cancer patients, communication was an independent factor for all QoL functioning scores. CONCLUSIONS: Even when faced with a similarly good prognosis, breast cancer patients have a worse QoL than melanoma patients 2 years after diagnosis. An explanation may be more distinctive surgery and systemic therapy, older patients with comorbidities and misunderstood risk communication in breast cancer patients that may stoke anxiety and fears. Further reasons could be unceasing public discussion about breast cancer and its instrumentalisation for political purposes.

Quality of life and comorbidity in localized malignant melanoma: results of a German population-based cohort study.

BACKGROUND: Incidences of malignant melanoma continue to increase in fair-skinned populations. At least 80% of patients are diagnosed with localized disease and can expect a 5-year relative survival rate of >90%. Given that the median age at diagnosis of malignant melanoma is 59 years, many patients already suffer chronic diseases when they are confronted with cancer. OBJECTIVES: The aim of this study was to analyze the effect of additional chronic diseases on health-related quality of life (QoL) in a population-based cohort of melanoma patients two years after presumably curative treatment. METHODS: In 2003-2004, 1085 patients with localized malignant melanoma were recruited from the population-based Munich Cancer Registry to answer validated QoL questionnaires. Information about comorbidities was also obtained. Factors predicting QoL were analyzed using multivariate logistic regression models. RESULTS: A total of 781 patients (72%) returned completed questionnaires, of which 664 (61%) could be included in the analyses. Quality of life scores and differences in subgroups (e.g., sex and age) were essentially similar to those in the general population. Age, number of comorbidities, and several chronic diseases (e.g. heart and kidney disease, diabetes, former depression) were the strongest predicting factors and influenced almost every aspect of QoL. CONCLUSIONS: Localized malignant melanoma does not worsen QoL per se, compared with QoL in the general population. Comorbidities have similar effects on QoL in malignant melanoma patients as they do in the general population. Therefore, cohorts of patients with localized malignant melanoma can represent a basis for comparisons with other cohorts of cancer patients to determine the respective impacts of cancer-related and non-cancer-related factors on QoL.

Metastatic renal cell carcinoma: results of a population-based study with 25 years follow-up.

BACKGROUND: Renal cell carcinoma (RCC) is the sixth leading cause of death in developed countries. A third of all RCC patients are confronted with metastatic disease. Since their approval in 2005 and 2006 in the USA, new targeted therapies may lead to substantial progress. Thus, the aim of this cohort study was to present clinical characteristics and survival in metastatic RCC in a population-based sample before widespread implementation of these new therapies. METHODS: Patients (2264) with metastatic RCC registered between 1978 and 2005 in the cancer registry of Munich, Bavaria were analysed. RESULTS: Median survival and 5 year relative survival from the 1st metastases were 14.4 months and 21%, respectively. Median survival has slightly improved from 13.2 months in 1978-1987 to 15.6 months since 2002. CONCLUSION: Survival of patients with metastatic RCC did not substantially improve within the last three decades. Assuming that new targeted therapies are successful in the treatment of metastatic RCC, population-based data like these can provide a basis for assessing the progress shown in clinical studies and for surveying critically the future implementation of new therapies in routine care.

Quality of life following breast-conserving therapy or mastectomy: results of a 5-year prospective study.

There are many conflicting results in the literature comparing quality of life following breast-conserving therapy (BCT) and mastectomy. This study compared long-term quality of life between breast cancer patients treated by BCT or mastectomy in three age groups. Patients (n = 990) completed a quality of life survey, including the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30), at regular intervals over 5 years. In the cross-sectional data, mastectomy patients had significantly (p < 0.01) lower body image, role, and sexual functioning scores and their lives were more disrupted than BCT patients. Emotional and social functioning and financial and future health worries were significantly (p < 0.01) worse for younger patients. There were no differences in body image and lifestyle scores between age groups. There was also no interaction between age and surgery method. Even patients > or =70 years of age reported higher body image and lifestyle scores when treated with BCT. The repeated measures analysis indicated that four functioning scores, half the symptom scores, future health, and global quality of life improved significantly (p < 0.01) over time. All these variables increased significantly for BCT patients and those 50 to 69 years of age. Body image, sexual functioning, and lifestyle disruption scores did not improve over time. BCT should be encouraged in all age groups. Coping with appearance change should be addressed in patient interventions.

Predictors of quality of life of breast cancer patients.

Research has indicated that several demographic and clinical factors may affect the quality of life of breast cancer patients. Few studies, however, have sufficient sample sizes for multivariate analyses to be tested. Furthermore, several important factors, such as arm morbidity, communication and comorbid illness, have not been included in quality of life models The aim of this study was to predict the simultaneous effect of these factors on long-term quality of life. Breast cancer patients (n = 990) completed a quality of life survey, including the EORTC QLQ-C30, over five years. Clinical details were registered in the Munich Cancer Registry. Eleven predictors across eight quality of life domains were analyzed over a period of five years using a logistic regression model. Arm problems, communication, comorbidity, age, surgery. and, to a lesser extent, marital, educational and employment status were significantly associated with quality of life. Adjuvant therapy, medical insurance and pT category were not significant predictors. This study is the first to demonstrate the consistency and strength of arm dysfunction and doctor-patient communication on breast cancer patients' quality of life. These important factors in breast cancer care can be improved and should be regarded as a priority.

Quality of life in rectal cancer patients: a four-year prospective study.

OBJECTIVE: To assess long-term quality of life in a population-based sample of rectal cancer patients. SUMMARY BACKGROUND DATA: Quality of life in rectal cancer patients who suffer reduced bowel and sexual function is very important. Few studies, however, have long term follow-up data or sufficient sample sizes for reliable comparisons between operation groups. PATIENTS AND METHODS: A 4-year prospective study of rectal cancer patients' quality of life was assessed by using the European Organization for Research and Treatment of Cancer QLQ-30 and CR38 questionnaires. RESULTS: A total of 329 patients returned questionnaires. Overall, anterior resection patients had better quality of life scores than abdominoperineal extirpation patients. High-anterior resection patients had significantly better scores than both low-anterior resection and abdominoperineal extirpation patients. Low-anterior resection patients, however, overall had a better quality of life than abdominoperineal extirpation patients, especially after 4 years. Abdominoperineal extirpation patients' quality of life scores did not improve over time. Stoma patients had significantly worse quality of life scores than nonstoma patients. Quality of life improved greatly for patients whose stoma was reversed. CONCLUSIONS: Anterior resection and nonstoma patients, despite suffering micturition and defecation problems, had better quality of life scores than abdominoperineal extirpation and stoma patients. Comparisons between abdominoperineal extirpation and anterior resection patients should consider the effect of temporary stomas. Improvements in quality of life scores over time may be explained by reversal of temporary stomas or physiologic adaptation.

Doctor-patient communication: results of a four-year prospective study in rectal cancer patients.

PURPOSE: The purpose of the study was to examine the effect of communication on rectal cancer patients' quality of life over four years. Previous studies have either used short follow-up periods or examined only certain aspects of quality of life, such as anxiety and depression. METHODS: In a prospective, observational study, rectal cancer patients, recruited by clinicians over a two-year period, were sent questionnaires over four years. The clinical details of these patients were recorded by the Munich Cancer Registry. The psychological scores from the European Organization for Research and Treatment of Cancer QLQ-C30 and CR38 were the main outcome variables. RESULTS: Thirty-nine percent of the sample reported that some aspect of the communication they received was unclear (incomprehensible or too little). More than 60 percent wished to speak more with their physician. Younger patients and those in larger hospitals were more likely to report unclear communication (P < 0.05). Analyses of covariance, controlled for age, gender, adjuvant therapy, stoma, education, clinic, and comorbidity, demonstrated that role, emotional, and social functioning scores were consistently lower in patients reporting unclear communication. Additionally, these patients experienced more problems sleeping, poorer body image, more financial worries, and a worse future perspective. Repeated measures analyses indicated that sleeping problems and emotional and social functioning difficulties persisted for at least three years. CONCLUSION: Reports of unclear communication were associated with poorer quality of life in rectal cancer patients without disease progression.

Axilla surgery severely affects quality of life: results of a 5-year prospective study in breast cancer patients.

No long-term prospective study has investigated arm morbidity and patient quality of life. It is unclear to what extent breast cancer patients suffer from arm problems, how long such problems affect their lives, and whether quality of life improves as arm problems abate. This prospective cohort study aims to provide data on the clinical factors associated with arm dysfunction, to estimate its prevalence and to relate arm morbidity to quality of life. The Munich Cancer Registry records clinical details of all cancer patients in and around Munich. Quality of life information was provided directly by breast cancer patients (n = 990) over 5 years. Arm morbidity, including movement limitations, swelling and lymph drainage, and quality of life (EORTC QLQ-C30) were assessed. Up to 5 years after diagnosis, 38% of patients were still experiencing arm problems (swelling and limited movement). Consistently over the 5 years, quality of life was significantly (p < 0.001) lower for patients with arm difficulties. For those whose arm problems dissipated, quality of life significantly improved (p < 0.01). A logistic regression analysis showed that extent of axilla surgery (p < 0.003), comorbidity (CVD and diabetes) (p < 0.003), employment (p < 0.01), younger age (p < 0.02), and operating clinic (p < 0.05) significantly contributed to arm problems. Axilla surgery should be re-evaluated since arm morbidity has such a profound effect on patient quality of life.

Determinants and prognoses of locoregional and distant progression in breast cancer.

PURPOSE: To describe locoregional and distant progression in a population-based breast cancer sample. METHODS AND MATERIALS: Between 1978 and 1998, the Munich Cancer Registry evaluated 14,429 patients. The mean follow-up of survivors was 8.3 years. Metastases (MET), local recurrence (LR), and lymph node recurrence (LNR) were considered as outcome measures. The prognostic factor for, and effects of, LR and MET were assessed multivariately by the Cox and dynamic Aalen models. RESULTS: The LR and MET rate increased with increasing tumor size, with the latter described by pT category. Distant MET occurred earlier than local progression. MET was recorded even earlier for MET alone. The mean time from diagnosis to MET for MET and LR was 54.9, 43.4, 29.4, and 24.7 months and for MET only was 36.5, 31.0, 22.6, and 12.9 months for pT1, pT2, pT3, and pT4, respectively. After MET, survival varied only slightly by pT stage; after LR, a more favorable prognosis, especially for pT1 and pT2, was evident. The prognosis after MET depended mainly on the MET location; 50% of patients with cerebral or nervous system MET survived <1 year and 50% of those with skeletal MET survived >2 years. In the Cox model, the relative risk of LR for MET was 3.0. In the Aalen model, after 30 months, when the hazard rates of MET began to decline, there was still an excess risk of MET after LR. CONCLUSION: This disease description highlights the importance of long-term observational studies. Empiric evidence that LR is both an indicator for, and in part a cause of, MET has been provided. In the future, the MET location should be reported. Variations in guidelines or health care systems that influence the time to MET and survival after MET through different diagnostic procedures should also be considered.