Extended pelvic lymphadenectomy for prostate cancer: should the Cloquet's nodes dissection be considered only an option?

BACKGROUND: The aim of this study was to assess the anatomical prevalence and secondary involvement of Cloquet's nodes in patients undergoing robotic radical prostatectomy (RRP) and extended pelvic lymph node dissection (ePLND) for prostate cancer (PCa). METHODS: RRP and ePLND were performed by two expert surgeons (WA and VDM). Data were prospectively collected and retrospectively analyzed. Dissected pelvic lymph nodes were sampled according to an anatomical template as follows: external iliac, obturator, Marcille's, and Cloquet's. Node packages were sent to the dedicated pathologist separately. Baseline characteristics, perioperative and pathological outcomes were analyzed. RESULTS: Between January 2014 and December 2017 a total of 258 patients were evaluated. In aggregate 247 out of 258 patients (95.7%) presented at least a lymph node in the in the Cloquet's fossa tissue and 105 (40.6%) had more than one node. Patients with multiple nodes in Cloquet fossa presented higher median lymph node amount (27 vs. 33; P<0.0001). 13.5% of patients had lymph node invasion Pathological evaluation of the Cloquet's nodes showed metastatic PCa in 3 out of 35 (8.6%) pN+ patients. No differences were found when patients with metastatic Cloquet's nodes were compared with the pN+ population in terms of demographics, PSA, D'Amico classification, biopsy and pathological Gleason Grouping, clinical and pathological stage and complications. CONCLUSIONS: To the best of our knowledge this is the first study that analyses specifically the quantitative prevalence of Cloquet's nodes and the incidence of malignancy involvement in patients undergoing RRP and ePLND for PCa. The occurrence of multiple lymph nodes in the Cloquet fossa is a rare event. Our series showed that Cloquet involvement seems to be associated with multiple nodes cohabitation and contemporarily multiple lymph node metastases in other template locations. Related morbidity rate is sporadic and cannot justify the Cloquet preservation. Wider series are required to comprehend predictor factors of Cloquet nodes involvement. Until then the Cloquet lymphadenectomy would be recommended and should not be an option.

Cathepsin K expression in castration-resistant prostate carcinoma: a therapeutical target for patients at risk for bone metastases.

BACKGROUND: The lysosomal cysteine protease cathepsin K is involved in bone remodeling and is also expressed in the peritumoral stroma of carcinomas arising from different organs. A new generation of cathepsin K inhibitors blocking the RANKL/RANK pathway are being developed. We sought to investigate cathepsin K expression in a cohort of castration-resistant prostate carcinomas. METHODS: Sixteen cases of castration-resistant disease with at least 5 years of follow-up were selected from a cohort of 280 patients who underwent surgery. Cathepsin K was evaluated on formalin-fixed and paraffin-embedded tissue microarrays with 5 tissue spots per case. These were scored as high 2+ (≥30% of cells), low 1+ (<30% of cells) or zero (absence), distinguishing tumor cells and peritumoral stroma cells. Low (1+) and absence (0) of scoring were interpreted as negative, and high (2+) as positive. RESULTS: The castration-resistant group was composed of 15 acinar adenocarcinomas and 1 neuroendocrine carcinoma, and all showed at least Gleason score 8 at prostatectomy. Two out of 16 cases (12%) scored positive for cathepsin K in tumor cells; and 5 of 16 cases (31%) scored positive in peritumoral stroma cells. The neuroendocrine and acinar subtypes of carcinoma with positive immunoexpression in neoplastic cells developed bone metastases after 4 and 5 years, respectively, and subsequently died. CONCLUSIONS: Patients affected by castration-resistant prostate carcinoma may be tested for cathepsin K, and a positive strong expression (2+) could be a useful predictive biomarker of response to targeted agents, aiding in the selection of patients eligible for these treatments.