Role of lymphatic invasion in predicting biochemical recurrence after radical prostatectomy

Lymphatic invasion in prostate cancer is associated with poor prognosis. However, there is no consensus regarding the clinical and prognostic value of lymphatic invasion. This study aimed to investigate the prognostic value of lymphatic invasion in biochemical recurrence (BCR) and compare the recurrence rates between patients with lymphatic invasion and lymph node metastasis.We retrospectively analyzed 2,207 patients who underwent radical prostatectomy (RP) without pelvic lymph node dissection (PLND) and 742 patients who underwent RP with PLND for clinically localized or locally advanced prostate cancer, between 1993 and 2020, at Seoul National University Hospital. Kaplan–Meier analysis was performed to estimate BCR-free survival (BCRFS) using the log-rank test. The Cox proportional hazards model was used to identify the significant factors for BCR. Propensity score matching was performed with a 1:2 ratio to match age, initial PSA level, pathological T stage, and Gleason score to exclude confounding effects.Of the 2,207 patients who underwent RP without PLND, lymphatic invasion (L1Nx) was observed in 79 (3.5%) individuals. Among the 742 patients who underwent RP with PLND, lymph node metastases were found in 105 patients (14.2%). In patients with lymph node metastasis, lymphatic invasion was observed in 50 patients (47.6%), whereas lymphatic invasion was observed in 53 patients (8.3%) among those without lymph node metastasis. In patients who underwent RP without PLND, Kaplan–Meier analysis showed significantly poorer BCR-free survival in the L1Nx group than in the L0Nx group (p < 0.001). In patients who underwent RP with PLND, the L1N0, L0N1, and L1N1 groups showed significantly worse prognoses than the L0N0 group (p < 0.001). However, there was no significant difference in BCRFS between the L1N0 and lymph node metastasis groups, including the L0N1 and L1N1 groups. After propensity score matching at a 1:2 ratio, the L1Nx group showed significantly poorer outcomes in terms of BCRFS than the L0Nx group (p = 0.05). In addition, the L1N0 group showed a significantly worse prognosis than the L0N0 group after propensity score matching.Lymphatic invasion in radical prostatectomy specimens is an independent prognostic factor, which can complement lymph node status for predicting biochemical recurrence. Considering lymphatic invasion as an adverse pathological finding, similar to lymph node metastasis, adjuvant therapy could be considered in patients with lymphatic invasion.

[1]  M. Muders,et al.  The Role of Perineural Invasion in Prostate Cancer and Its Prognostic Significance , 2022, Cancers.

[2]  Y. Kohjimoto,et al.  Prognostic Impact of Lymphatic Invasion in Patients with High-Risk Prostate Cancer after Robot-Assisted Radical Prostatectomy and Extended Lymph Node Dissection: A Single-Institution Prospective Cohort Study , 2022, Cancers.

[3]  F. Montorsi,et al.  Management of Patients with Node-positive Prostate Cancer at Radical Prostatectomy and Pelvic Lymph Node Dissection: A Systematic Review. , 2020, European urology oncology.

[4]  B. Delahunt,et al.  Dataset for the reporting of prostate carcinoma in radical prostatectomy specimens: updated recommendations from the International Collaboration on Cancer Reporting , 2019, Virchows Archiv.

[5]  A. Partin,et al.  Adjuvant radiation with androgen‐deprivation therapy for men with lymph node metastases after radical prostatectomy: identifying men who benefit , 2019, BJU international.

[6]  A. Haese*,et al.  Marked Prognostic Impact of Minimal Lymphatic Tumor Spread in Prostate Cancer. , 2018, European urology.

[7]  Hu Zhao,et al.  Perineural invasion as an independent predictor of biochemical recurrence in prostate cancer following radical prostatectomy or radiotherapy: a systematic review and meta-analysis , 2018, BMC Urology.

[8]  Ronald C. Chen,et al.  Contemporary Incidence and Outcomes of Prostate Cancer Lymph Node Metastases , 2017, The Journal of urology.

[9]  W. Lowrance,et al.  Prognostic significance of lymphovascular invasion in radical prostatectomy specimens , 2011, BJU international.

[10]  P. V. van Diest,et al.  Micrometastases or isolated tumor cells and the outcome of breast cancer. , 2009, The New England journal of medicine.

[11]  N. Baxter,et al.  Increasing negative lymph node count is independently associated with improved long-term survival in stage IIIB and IIIC colon cancer. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[12]  Jorge Yao,et al.  Immediate versus deferred androgen deprivation treatment in patients with node-positive prostate cancer after radical prostatectomy and pelvic lymphadenectomy. , 2006, The Lancet. Oncology.

[13]  C. Magi-Galluzzi,et al.  Peritumoral lymphatic invasion is associated with regional lymph node metastases in prostate adenocarcinoma , 2006, Modern Pathology.

[14]  Haiqun Lin,et al.  Lymphovascular invasion is an independent prognostic factor in prostatic adenocarcinoma. , 2005, The Journal of urology.

[15]  H. Matsubara,et al.  Prognostic Significance of the Number of Metastatic Lymph Nodes in Early Gastric Cancer , 2003, Digestive Surgery.

[16]  P. Scardino,et al.  Long-term outcomes of patients with lymph node metastasis treated with radical prostatectomy without adjuvant androgen-deprivation therapy. , 2014, European urology.

[17]  M. Pepper,et al.  Lymphatic dissemination of tumour cells and the formation of micrometastases. , 2002, The Lancet. Oncology.

[18]  D. Bostwick,et al.  Risk of prostate carcinoma death in patients with lymph node metastasis , 2001, Cancer.

[19]  J. Sleeman The lymph node as a bridgehead in the metastatic dissemination of tumors. , 2000, Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer.