Pathological Features of Lymph Node Metastasis for Predicting Biochemical Recurrence After Radical Prostatectomy for Prostate Cancer

Abstract

Purpose Subclassification of nodal stage may be of prognostic value in men with lymph node metastases (LNM) at the time of radical prostatectomy (RP). We explored the role of extranodal extension (ENE), size of the largest metastatic LN, size of the largest metastasis and LN density (LND) as predictors of biochemical recurrence (BCR). Materials and Methods We reviewed pathological material from 261 node-positive prostate cancer patients. We examined the predictive value when adding the additional pathology findings to a base model including extraprostatic extension (EPE), seminal vesicle invasion (SVI), RP Gleason score, Prostate-Specific Antigen (PSA) and number of positive LNs, using Cox proportional hazards regression and Harrell's c-index. Results The median number of LNs removed was 14 (IQR 9, 20) and the median number of positive LNs was 1 (IQR 1, 2). With a median follow-up of 4.6 years (IQR 3.2-6.0 years), 155/261 patients experienced BCR; 5-year BCR-free survival 39% [95% CI 33%, 46%]. The median diameter of the largest metastatic LN was 9 mm (IQR 5, 16). On Cox regression, RP specimen Gleason score (>7 vs. ≤7), number of positive LNs (≥3 vs. 1-2), SVI and PSA were associated with significantly increased risks of BCR. In a subset analysis, size of the metastasis significantly improved the discrimination of the model (Harrell's C 0.700 vs. 0.655 for the base model, p=0.032). Conclusion Our study confirms that the number of positive LNs is a predictor of BCR in men with node-positive disease. The improvement in prognostic value of measuring the metastatic focus warrants further investigation.

Gleason grade patterns in nodal metastasis and corresponding prostatectomy specimens: impact on patient outcome

“…In this work we identified the number of positive nodes to be a relevant predictor of outcome, in that two or more positive nodes associated with worse patient outcomes. This is in accordance with previous publications which also found >1 positive node to be a prognostic factor . When we assessed the nodal cancer volume (using metastasis in the largest involved lymph node as a surrogate) and binarised the metastases as micro‐ (≤2.0 mm) or macrometastasis (>2.0 mm), we did not find any association of macrometastatic nodal disease with outcome in this cohort.…”

“…This is in accordance with previous publications which also found >1 positive node to be a prognostic factor. 5,6,8,9,31 When we assessed the nodal cancer volume (using metastasis in the largest involved lymph node as a surrogate) and binarised the metastases as micro-(≤2.0 mm) or macrometastasis (>2.0 mm), we did not find any association of macrometastatic nodal disease with outcome in this cohort. A variety of metastasis sizes [3 mm (eight), 10 mm (six)] have been used in previous publications as cut-offs for determining patient outcome.…”

“…3 Lymph node metastases are a critical prognostic factor 4 in determining patient outcome. Several authors have assessed parameters such as number of positive nodes, 5,6 nodal cancer burden [7][8][9][10] and the presence/absence of extranodal extension (ENE), [11][12][13] with the goal of determining which pathological features are the most relevant contributors to outcome.…”

Contemporary Patterns of Care and Outcomes of Men Found to Have Lymph Node Metastases at the Time of Radical Prostatectomy

“…2 Although the present study confirms that the majority of men with pN1 prostate cancer have favorable outcomes (89% and 66% of men in our cohort were alive five and ten years after RP, respectively), it also draws attention to substantial variation in the prognosis of individual patients. As reported by several prior single-institution series, we found grade group 4-5 disease, pT3b-T4 disease, positive surgical margins and an increasing number of positive LN to be independent predictors of worse OS, 17,18 which highlights the fact that the natural history of pN1 prostate cancer is driven as much by the characteristics of the primary tumor as the burden of LN metastases.…”

Kallikrein markers performance in pretreatment blood to predict early prostate cancer recurrence and metastasis after radical prostatectomy among very high‐risk men

“…In this very high‐risk setting, we did not find that total PSA aided in predicting BCR or metastasis. This differs from the report from Carlsson et al, which established the predictive value of total PSA in predicting BCR in patients with established lymph node‐positive disease on RP. That we were not able to establish this relationship might be explained by our smaller sample size (261 vs 106) and that the men in our study had higher risk disease including higher rates of SVI (54% vs 43%) and Gleason ≥8 disease (69% vs 52%) by our cohort definition.…”