Marked Prognostic Impact of Minimal Lymphatic Tumor Spread in Prostate Cancer

Nodal metastasis (N1) is a strong prognostic parameter in prostate cancer; however, lymph node evaluation is always incomplete.

To study the prognostic value of lymphatic invasion (L1) and whether it might complement or even replace lymph node analysis in clinical practice.

Retrospective analysis of pathological and clinical data from 14 528 consecutive patients.

Radical prostatectomy.

The impact of L1 and N1 on patient prognosis was measured with time to biochemical recurrence as the primary endpoint.

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 ≤1mm. 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.

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.

Already minimal amounts of tumor cells inside the lymph nodes or intraprostatic lymphatic vessels have a severe impact on patient prognosis.