Management of Bladder Cancer Patients with Clinical Evidence of Lymph Node Invasion (cN+)

SIMPLE SUMMARY: This review presents the current status of diagnostic and treatment options in bladder cancer (BCa) patients with clinically positive lymph nodes (cN+). There is no conclusive evidence regarding the management of cN+ patients, as most scientific associations do not distinguish the group in their guidelines or differ in the treatment options. A multimodal approach with a combination of neoadjuvant chemotherapy (NAC) and radical cystectomy (RC) with pelvic lymph node dissection (PLND) is associated with the best long-term survival in cN+ patients. In those patients, the extended template of PLND (ePLND) is recommended. Emerging evidence indicates that it is comparable to NAC results of adjuvant chemotherapy (AC); however, there is a lack of studies focusing on cN+ patients. The response to chemotherapy (ChT) is crucial for the prognosis of cN+ patients. Therefore, with a significant percentage of ChT-ineligible patients, immunotherapy has achieved growing importance in neoadjuvant and adjuvant treatment. Patients with cN+ BCa demand special attention, as the oncological outcomes are significantly worse for this group. ABSTRACT: The purpose of this review is to present the current knowledge about the diagnostic and treatment options for bladder cancer (BCa) patients with clinically positive lymph nodes (cN+). This review shows compaction of CT and MRI performance in preoperative prediction of lymph node invasion (LNI) in BCa patients, along with other diagnostic methods. Most scientific societies do not distinguish cN+ patients in their guidelines; recommendations concern muscle-invasive bladder cancer (MIBC) and differ between associations. The curative treatment that provides the best long-term survival in cN+ patients is a multimodal approach, with a combination of neoadjuvant chemotherapy (NAC) and radical cystectomy (RC) with extended pelvic lymph node dissection (ePLND). The role of adjuvant chemotherapy (AC) remains uncertain; however, emerging evidence indicates comparable outcomes to NAC. Therefore, in cN+ patients who have not received NAC, AC should be implemented. The response to ChT is a crucial prognostic factor for cN+ patients. Recent studies demonstrated the growing importance of immunotherapy, especially in ChT-ineligible patients. Moreover, immunotherapy can be suitable as adjuvant therapy in selected cases. In cN+ patients, the extended template of PLND should be utilized, with the total resected node count being less important than the template. This review is intended to draw special attention to cN+ BCa patients, as the oncological outcomes are significantly worse for this group.