Impact of Lymph Node Burden on Survival of High-risk Prostate Cancer Patients Following Radical Prostatectomy and Pelvic Lymph Node Dissection

Abstract

AimTo determine the impact of the extent of lymph node invasion (LNI) on long-term oncological outcomes after radical prostatectomy (RP).Material and methodsIn this retrospective study, we examined the data of 1,249 high-risk, non-metastatic PCa patients treated with RP and pelvic lymph node dissection (PLND) between 1989 and 2011 at eight different tertiary institutions. We fitted univariate and multivariate Cox models to assess independent predictors of cancer-specific survival (CSS) and overall survival (OS). The number of positive lymph node (LN) was dichotomized according to the most informative cutoff predicting CSS. Kaplan–Meier curves assessed CSS and OS rates. Only patients with at least 10 LNs removed at PLND were included. This cutoff was chosen as a surrogate for a well performed PNLD.ResultsMean age was 65 years (median: 66, IQR 60–70). Positive surgical margins were present in 53.7% (n = 671). Final Gleason score (GS) was 2–6 in 12.7% (n = 158), 7 in 52% (n = 649), and 8–10 in 35.4% (n = 442). The median number of LNs removed during PLND was 15 (IQR 12–17). Of all patients, 1,128 (90.3%) had 0–3 positive LNs, while 126 (9.7%) had ≥4 positive LNs. Patients with 0–3 positive LNs had significantly better CSS outcome at 10-year follow-up compared to patients with ≥4 positive LNs (87 vs. 50%; p < 0.0001). Similar results were obtained for OS, with a 72 vs. 37% (p < 0.0001) survival at 10 years for patients with 0–3 vs. ≥4 positive LNs, respectively. At multivariate analysis, final GS of 8–10, salvage ADT therapy, and ≥4 (vs. <4) positive LNs were predictors of worse CSS and OS. Pathological stage pT4 was an additional predictor of worse CSS.ConclusionFour or more positive LNs, pathological stage pT4, and final GS of 8–10 represent independent predictors for worse CSS in patients with high-risk PCa. Primary tumor biology remains a strong driver of tumor progression and patients having ≥4 positive LNs could be considered an enriched patient group in which novel treatment strategies should be studied.

Surgical margin status and its impact on prostate cancer prognosis after radical prostatectomy: a meta-analysis

“…A total of 141,222 patients (ranging from 51 to 65,633) underwent RP for PCa management, of which 31,421 patients were reported to have PSMs. Nine studies [ 8 , 17 , 19 , 20 , 30 , 32 , 34 , 36 , 37 , 42 ] reported the use of radiotherapy as an adjuvant therapy after RP, and the proportion of patients who received aRT was 0.2–69%. Of the 32 studies, 11 were conducted in North America, 10 in Asia, 8 in Europe and 3 at international multi-centres.…”

Clinical Factors Predicting Bilateral Lymph Node Invasion in High-Risk Prostate Cancer

“…However, there is increasing evidence that the number of metastatic nodes can stratify subpopulations with different prognosis. In high-risk PCA, it has been shown that the lymph node burden is an independent prognostic factor associated with both cancer-specific and overall survival [10,20]. So far, clinical factors predicting the loads of LNI are important for stratifying the high-risk PCA population who is subject to multimodality treatments.…”

“…A large multicenter retrospective study including an old cohort has shown that in high-risk selected patients with at least 10 nodes removed (median 15), the rate of LNI was 36.1%, which included ROC, receiverreceiver operating characteristic; AUC, area under the curve; pN, pathologic nodal staging status; pN0, absence of nodal metastases; pN1(u), prostate cancer with unilateral metastatic nodes; pN1(b), prostate cancer with bilateral nodal metastases; PSA, prostate-specific antigen; P(p), proportion of biopsy positive cores. 26.4% of cases having 1-3 positive nodes and 9.7% of patients with more than 3 positive lymph nodes [10]. In a dated North American cohort, a nomogram predicting pathological outcomes in high-risk patients has been proposed by evaluating a median LN(n) of 5 [18].…”

“…Indeed, a large retrospective multi-center study has shown that a number of 4 or more positive nodes was a negative prognostic factor of cancer-specific survival [10]; moreover, it has been shown that the rate of bilateral LNI is not negligible (6.4%) in localized PCA and associates with extensive nodal metastatic load [11]. Factors associated with LNI are well known from the literature [2][3][4][5]7]; however, analysis of factors associated with bilateral lymph node metastases, which means extensive LNI, is missing.…”

Impact of daily soft‐tissue image guidance to prostate on pelvic lymph node (PLN) irradiation for prostate patients receiving SBRT

“…Therefore, it is recommended that pelvic lymph nodes (PLN) be included in the target volume for those patients. In addition, there is evidence of clinical benefit from PLN treatment in the high‐risk population . Given the low α/β ratio attributed to prostate cancer, (approximately 1.5–1.8), hypofractionation is potentially more beneficial for occult nodal metastases in high‐risk patients .…”