Das Urothelkarzinom des oberen Harntrakts: Umfassende retrospektive Analyse des Marburger Kollektivs von 2004 bis 2015

Urothelial carcinoma of the upper urinary tract occurs in about 5 per 100.000 inhabitants, incidence is increasing. Affected people are 70–73 years old in median. Men are falling ill twice as often compared to women. Overall mortality is about 0,6 per 100.000 people. The main risk factors are tobacco consumption, in part occupational exposure to various hazardous substances, alcohol consumption, older age, male gender, obesity, previous bladder cancer, kidney stones, kidney failure requiring dialysis, chronic urinary tract infections and radiotherapy in the small pelvis. Pathogenetically relevant are missense and nonsense mutations, gene fusions, amplifications, deletions, loss of chromosome 9 and mutations in promoter regions. The malignancy usually presents clinically through hematuria or flank pain. It represents 5–10 % of all urothelial carcinomas, with the renal pelvis affected twice as often as the ureter. The diagnosis is primarily successful through ureterorenoscopy, computed tomography urography and biopsy. Therapeutic gold standard is realised by open radical nephroureterectomy. When diagnosed, more than half of the tumours have progressed locally (> pT2) mostly with G2 closely followed by G3 differentiation, about 8–11 % of the patients already have lymph node and about 5–9 % distant metastases. Cancer specific 5-year survival is 64–76 %. The aim of this retrospective study was to present a detailed presentation of the Marburg collective of patients with malignancy of the upper urinary tract in the period from 2004 to 2015, taking into account all factors relevant to the disease. In addition, the form of internationally recognized risk factors was examined on the basis of group analysis and special attention was paid to the tumour classification as an endpoint that cannot be influenced and to the form of the Clavien classification. Also included in the examination was the detection and analysis of other significant results in a group comparison. The cohort consisted of male and female patients at a ratio of approximately 2:1. Patients fell ill at a median age of 72. 42,9 % were smokers. The average body mass index was classified in the range of pre-obesity. 15,5 % of the patients performed a job with risk of developing cancer. The main symptom was gross hematuria. Notable was the frequent occurrence of previous bladder cancer (22,9 %). Metachronous bladder carcinomas and distant metastases developed at a comparable frequency with 20 % and 19 %. The side involvement was left-accentuated, whereby the renal pelvis was affected much more often than the ureter (55,7 % to 34,9 %). The diagnosis was made primarily by means of computer and magnetic resonance tomographic imaging, urine cytology and ureterorenoscopy. 75 % of the patients were treated with radical nephroureterectomy. Most of the tumours were pT3 classified, whereas pTis were the fewest. About one fifth of the patients had local lymph node metastases and about one tenth had distant metastases. Little more than 50 % of the tumours were moderately, about one third was poorly differentiated. More than 95 % of the tumours were transitional cell carcinomas, less than 5 % sarcomatoid and squamous cell carcinomas. Our cohort presented more advanced tumour stages in comparison to other studies, maybe based on an insufficient number of local urological surgery in Marburg’s surrounding region. However, local recurrences were less common with us, suggesting favorable quality of therapy and follow-up care in Marburg. Correspondingly, the periods of time until the appearance of metachronic secondary tumours were longer. The analysis of our comparison groups showed that men smoked significantly more frequently and had more metachronous bladder carcinomas with transurethral resection than women. The time to develop contralateral tumours of the upper urinary tract was correspondingly shorter. This confirmed the suspicion that smoking is a significant carcinogenic risk factor. This was further illustrated by the fact that the age of disease onset in smokers was significantly earlier than in non-smokers. However, invasiveness or aggressiveness were comparable among smokers and non-smokers. Patients younger than 72 years smoked significantly more often and had significantly more flank pain but similar tumour stages. Significantly more previous and, in trend, more synchronous bladder carcinomas in over 72-year-olds who smoked less favored the risk factor “age” in comparison to “smoking”. The effect of weight seems contradictory. Distant metastases at diagnosis as well as synchronous bladder carcinomas occurred significantly more frequently with a body mass index < 25 kg/m2, whereas local recurrences and metachronous distant metastases occurred significantly more frequently with ≥ 25 kg/m2. Previous bladder carcinomas did not have a negative impact on the TNM classification or the differentiation of the tumours, contrary to the presumption. Interestingly however, patients with previous bladder cancer showed significantly more frequent ureter and less common renal pelvic cancer.