Marked Prognostic Impact of Minimal Lymphatic Tumor Spread in Prostate Cancer

Background: Nodal metastasis (N1) is a strong prognostic parameter in prostate cancer; however, lymph node evaluation is always incomplete. Objective: To study the prognostic value of lymphatic invasion (L1) and whether it might complement or even replace lymph node analysis in clinical practice. Design, setting, and participants: Retrospective analysis of pathological and clinical data from 14 528 consecutive patients. Intervention: Radical prostatectomy. Outcome measurements and statistical analysis: The impact of L1 and N1 on patient prognosis was measured with time to biochemical recurrence as the primary endpoint. Results and limitations: Nodal metastases were found in 1602 (12%) of 13 070 patients with lymph node dissection. L1 was seen in 2027 of 14 528 patients (14%) for whom lymphatic vessels had been visualized by immunohistochemistry. N1 and L1 continuously increased with unfavorable Gleason grade, advanced pT stage, and preoperative prostate-specific antigen (PSA) values (p < 0.0001 each). N1 was found in 4.3% of 12 501 L0 and in 41% of 2027 L1 carcinomas (p < 0.0001). L1 was seen in 11% of 9868 N0 and in 61% of 1360 N1 carcinomas (p < 0.0001). Both N1 and L1 were linked to PSA recurrence (p < 0.0001 each). This was also true for 17 patients with isolated tumor cells (ie, <200 unequivocal cancer cells without invasive growth) and 193 metastases ≤1 mm. Combined analysis of N and L status showed that L1 had no prognostic effect in N1 patients but L1 was strikingly linked to PSA recurrence in N0 patients. N0L1 patients showed a similar outcome as N1 patients. Conclusions: Analysis of lymphatic invasion provides comparable prognostic information than lymph node analysis. Even minimal involvement of the lymphatic system has pivotal prognostic impact in prostate cancer. Thus, a thorough search for lymphatic involvement helps to identify more patients with an increased risk for disease recurrence. Patient summary: Already minimal amounts of tumor cells inside the lymph nodes or intraprostatic lymphatic vessels have a severe impact on patient prognosis. To replace morbidity-prone lymph node analysis, we tested immunohistochemical analysis of lymphatic vessels to predict prognosis after radical prostatectomy. We found that minimal lymphatic invasion had a pivotal prognostic impact.