Lymph node dissection in bladder cancer. Impact on staging and prognosis.

The present thesis consists of 8 original articles focusing on lymph node dissection (LND) in patients undergoing radical cystectomy (RC) because of bladder cancer. LND is considered an essential part of the surgical procedure when performing an RC to achieve the correct staging and for prognostic reasons. However, the boundaries of LND have been the subject of debate. Proximal limit above, at, or below the aortic bifurcation has been suggested to define the perfect LND. Two questions have driven the present thesis. First, which extent of LND is needed to make the most accurate identification of patients with nodal involvement? And second, which extent of LND is needed to provide the most favourable prognosis in patients undergoing RC? During a 5-year period, all patients undergoing RC and LND to the level of the inferior mesenteric artery at the Department of Urology, Aarhus University Hospital, Skejby, were prospectively enrolled in meticulous registration of several LN variables including burden and location of metastasis based on standard pathological examination. From these patients, mapping of the metastatic LNs were made. Moreover, we included patients from a historical cohort undergoing limited LND to evaluate the possible prognostic impact of a more extended LND. Standard pathological examination was found to be reliable regarding identification of LN metastasis. A proximal limit of LND at the aortic bifurcation was found to be sufficient from a staging perspective, whereas less extensive LND was associated with a risk of under-staging. From a prognostic perspective, LND at least to the aortic bifurcation should be performed. It is still controversial and unclarified whether LND above the aortic bifurcation has any prognostic value. By extending the limits of LND from a limited dissection involving only the LNs in the obturator fossae to a dissection including all pelvic and lower lumbar LNs, a survival benefit in at least 5% of the patients was found. We also found that an extensive LND should be performed in all patients irrespective of T-stage of the primary tumour and in patients undergoing chemotherapy before RC. Previous radiotherapy, on the other hand, apparently eradicated LN metastasis in the irradiation field within the pelvic region and made subsequent LND difficult and possibly superfluous. In evaluation of a molecular marker, KPNA2, we found that the more accurate staging and more favourable prognosis achieved by extended LND compared to a limited LND was essential in evaluation of the prognostic impact of KPNA2.