Simple SummaryLymph node invasion represents a poor prognostic factor after primary radical prostatectomy for prostate cancer. However, its impact on oncologic outcomes in salvage radical prostatectomy patients is unknown. Within this study we investigated the impact of lymph node invasion and dissection on the oncologic outcomes after salvage prostatectomy. Our results show that lymph node invasion represents are poor prognostic factor after salvage prostatectomy. Conversely, we recorded no benefit for lymph node dissection compared to no lymph node dissection during salvage prostatectomy. These findings underline the need for a cautious indication of lymph node dissection in salvage prostatectomy patients as well as strict postoperative monitoring of patients with lymph node invasion.AbstractBackground: Lymph node invasion (LNI) represents a poor prognostic factor after primary radical prostatectomy (RP) for prostate cancer (PCa). However, the impact of LNI on oncologic outcomes in salvage radical prostatectomy (SRP) patients is unknown. Objective: To investigate the impact of lymph node dissection (LND) and pathological lymph node status (pNX vs. pN0 vs. pN1) on long-term oncologic outcomes of SRP patients. Patients and methods: Patients who underwent SRP for recurrent PCa between 2000 and 2021 were identified from 12 high-volume centers. Kaplan–Meier analyses and multivariable Cox regression models were used. Endpoints were biochemical recurrence (BCR), overall survival (OS), and cancer-specific survival (CSS). Results: Of 853 SRP patients, 87% (n= 727) underwent LND, and 21% (n= 151) harbored LNI. The median follow-up was 27 months. The mean number of removed lymph nodes was 13 in the LND cohort. At 72 months after SRP, BCR-free survival was 54% vs. 47% vs. 7.2% for patients with pNX vs. pN0 vs. pN1 (p< 0.001), respectively. At 120 months after SRP, OS rates were 89% vs. 81% vs. 41% (p< 0.001), and CSS rates were 94% vs. 96% vs. 82% (p= 0.02) for patients with pNX vs. pN0 vs. pN1, respectively. In multivariable Cox regression analyses, pN1 status was independently associated with BCR (HR: 1.77,p< 0.001) and death (HR: 2.89,p< 0.001). Conclusions: In SRP patients, LNI represents an independent poor prognostic factor. However, the oncologic benefit of LND in SRP remains debatable. These findings underline the need for a cautious LND indication in SRP patients as well as strict postoperative monitoring of SRP patients with LNI.