More extended lymph node dissection template at radical prostatectomy detects metastases in the common iliac region and in the fossa of Marcille.

To assess the effect of adding lymph nodes (LNs) located along the common iliac vessels and in the fossa of Marcille to the extended pelvic LN dissection (PLND) template at radical prostatectomy (RP). A total of 485 patients underwent RP and PLND at a referral centre between 2000 and 2008 (historical cohort: classic extended PLND template) and a total of 268 patients between 2010 and 2015 (contemporary cohort: extended PLND template including LNs located along the common iliac vessels and in the fossa of Marcille). Descriptive analyses were used to compare baseline, pathological, complication and functional data between the two cohorts. A logistic regression model was used to assess the template's effect on the probability of detecting LN metastases. Of 80 patients in the historical cohort with pN+ disease, the sole location of metastasis was the external iliac/obturator fossa in 23 (29%), and the internal iliac in 18 (23%), while 39 patients (49%) had metastases in both locations. Of 72 patients in the contemporary cohort with pN+ disease, the sole location of metastasis was the external iliac/obturator fossa in 17 patients (24%), the internal iliac in 24 patients (33%), and the common iliac in one patient (1%), while 30 patients (42%) had metastases in >1 location (including fossa of Marcille in five patients). Among all 46 patients in the contemporary cohort with ≤2 metastases, three had one or both metastases in the common iliac region or the fossa of Marcille. The adjusted probability of detecting LN metastases was higher, but not significantly so, in the contemporary cohort. There were no differences between the two cohorts in complication rates and functional outcomes. A more extended template detects LN metastases in the common iliac region and the fossa of Marcille and is not associated with a higher risk of complications; however, the overall probability of detecting LN metastases was not significantly higher.

Maderthaner L ，Furrer MA ，Studer UE ，Burkhard FC ，Thalmann GN ，Nguyen DP ... -  《-》

Topography of lymph node metastases in prostate cancer patients undergoing radical prostatectomy and extended lymphadenectomy: results of a combined molecular and histopathologic mapping study.

To determine the anatomic extent of pelvic lymph node dissection (PLND) in prostate cancer (PCa) patients at the time of radical prostatectomy (RP), knowledge about the topography of lymph node (LN) metastases is required. Because small-volume LN metastases may be missed by standard histopathologic examination, we performed an anatomic mapping study combining molecular and histopathologic LN examination in PCa patients treated with RP and extended PLND (ePLND). A total of 52 patients with intermediate- (n=15) and high-risk (n=37) PCa underwent RP and ePLND without neoadjuvant treatment. ePLND included dissection of the obturator fossa and the external, internal, and common iliac vessels. LNs ≥3 mm in diameter were analysed by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) for prostate-specific antigen (PSA) expression and by standard histopathology. Topography of positive LNs was determined descriptively. Of 1469 dissected LNs (median: 27 LNs per patient), 1186 LNs were ≥3 mm. Molecular LN analysis was positive in 127 LNs of 27 patients (52%) including 32 LNs of 12 patients (23%) with histopathologic positive LNs. Molecular examination was negative in 3 of 35 histopathologic positive LNs (9%). Combining both molecular and histopathologic findings, positive LNs were located in the standard PLND field defined by obturator fossa and external iliac vessels in 71%, along the internal iliac vessels in 16%, and along the common iliac vessels in 13%. Of LN-positive patients, 63% had LN metastases outside the standard PLND field. The internal iliac field was involved in 48% and the common iliac field in 37% of node-positive patients. Notably, internal and common iliac vessels were the only positive regions in 7% and 11% of node-positive patients, respectively. A limitation is the small number of patients included. These findings underline the enhanced sensitivity of qRT-PCR in comparison with standard histopathology for detection of small-volume LN metastases in PCa patients. Our results support an ePLND including the common iliac vessels, at least up to the ureteral crossing, to optimise nodal staging and to remove LNs potentially harbouring metastases.

Heck MM ，Retz M ，Bandur M ，Souchay M ，Vitzthum E ，Weirich G ，Mollenhauer M ，Schuster T ，Autenrieth M ，Kübler H ，Maurer T ，Thalgott M ，Herkommer K ，Gschwend JE ，Nawroth R ... -  《-》

Diagnostic and therapeutic value of pelvic lymph node dissection in the fossa of Marcille in patients with clinically localized high-risk prostate cancer: Histopathological and molecular analyses.

The optimal extent of lymph node dissection in radical prostatectomy has not been determined. Lymph nodes in the fossa of Marcille, which is an important pelvic lymphatic pathway and candidate for additional dissection, have not been evaluated at the molecular level. Here, we assessed by molecular analysis the presence of occult positive lymph nodes in the fossa of Marcille in patients with clinically localized high-risk prostate cancer. Fifty-two patients with clinically localized high-risk prostate cancer underwent pelvic lymph node dissection accompanied by robot-assisted radical prostatectomy. All nodal packets were dissected separately and grouped into right and left obturator, external and internal iliac regions (including common iliac region to ureter crossing), and fossa of Marcille. All lymph nodes were bisected and evaluated by histopathological or molecular analysis using a quantitative reverse transcription-polymerase chain reaction. The number of positive lymph nodes in the fossa of Marcille and the difference in detection rate were investigated using histopathological and molecular analyses. Perioperative complication rate and predictive factors for biochemical recurrence were evaluated. In the molecular analysis, there were seven positive lymph nodes in the fossa of Marcille in three patients, which were coexistent with positive nodes in other regions. The detection rate of positive lymph nodes was significantly higher using molecular than histopathological analysis (P < .01). Perioperative complication rate within 90 days after the operation was 25.0% and no Clavien-Dindo grade ≥3 complication was confirmed. Detection of metastasis by histopathological and molecular analysis was a significant factor related to biochemical recurrence in the Cox proportional hazards regression model. No case of positive lymph nodes in the fossa of Marcille that had skipped over other regions was confirmed. Additional lymph node dissection of fossa of Marcille did not lead to complete resection of molecularly positive lymph nodes.

Bando Y ，Hinata N ，Terakawa T ，Furukawa J ，Harada K ，Nakano Y ，Fujisawa M ... -  《-》

Surgeon-led prostate cancer lymph node staging: pathological outcomes stratified by robot-assisted dissection templates and patient selection.

To evaluate the perioperative, pathological, and oncological outcomes from surgeon-led pathological staging of pelvic lymph node (LN) metastases at the time of robot-assisted radical prostatectomy (RARP). Over the 6-year period of 2006-2012, three distinct pelvic LN dissection (PLND) strategies were used in chronological order at a single cancer referral hospital. Strategies were characterised by both an omission of PLND (pNx) vs inclusion decision threshold, and standard vs extended templates for patients selected for PLND. The three cohorts included: (i) omission vs standard template (04/2006-10/2007), for dominant Gleason score 4-5 or a prostate-specific antigen (PSA) level of >10 ng/mL; (ii) omission/standard vs extended template (11/2007-12/2010), for dominant Gleason score 4-5, PSA level of >10 ng/mL, any single core >7 mm, or >3 ipsilateral positive cores; and (iii) extended template with minimal exceptions (01/2011-08/2012). Standard outcomes data compared included: Clavien-Dindo complication rates, LN metrics (yield, percentage positive), and biochemical recurrence (BCR). A novel metric comprised 'pNx regret': the rate of pNx patients upgraded/upstaged. Exploratory analyses included selection criteria for reduced PLND templates, i.e. low-yield subsets. Standard PLND yielded 8-10 LNs and a positive-LN yield of 2.2-6.2%. The addition of an extended PLND (E-PLND) significantly increased the yield to 14-20 LNs and the positive-LN yield to 17.4-18.4% (both P < 0.001). E-PLND had the highest impact on the percentage of positive LNs (%pN1) for high-risk disease (9.3 vs 32.8%, P = 0.002), modest for intermediate risk (4.2 vs 10.9%, P = 0.003), and minimal impact on low risk disease (4.1 vs 0%, P = 0.401). The combined strategies of setting a very low threshold for E-PLND and sending separate LN packets increased the LN yields (18 vs 24, P < 0.001), but did not significantly change the observed %pN1 rates by clinical risk group (P = 0.975). Efforts to reduce the need for E-PLND included omission by clinical criteria, but resulting in 'pNx regret' in 16-19%. A third of patients with unilateral disease and positive LNs were found to have contralateral disease. A subset of men with minimal biopsy volume Gleason score 4 + 3 had pN1 rates after E-PLND of three of 14 (21%) compared to minimal biopsy volume Gleason score 3 + 4 pN1 rates after E-PLND of 0 of 31. E-PLND takes about twice as long to perform but with no statistically significant difference in complications (5.0 vs 6.0%, P = 0.511). The 5-year BCR rates were higher for E-PLND, given the selection criteria, but not different for overall survival. The net benefit of E-PLND remains uncertain, and therapeutic impact will probably require a randomised trial, given the strong selection criteria. E-PLND contributes to oncological staging in a significant number of high- and intermediate-risk patients, and should be bilateral. Immediate concerns include longer operative times, but no higher complication rates.

Altok M ，Babaian K ，Achim MF ，Achim GC ，Troncoso P ，Matin SF ，Chapin BF ，Davis JW ... -  《-》

Radical cystectomy and extended pelvic lymphadenectomy: survival of patients with lymph node metastasis above the bifurcation of the common iliac vessels treated with surgery only.

We assessed the clinical outcome in patients with invasive bladder cancer and lymph node metastasis above the bifurcation of the common iliac vessels treated with radical cystectomy including extended pelvic lymph node dissection without adjunct therapy. Between 1993 and June 2005 a total of 336 consecutive patients underwent radical cystectomy and extended pelvic lymphadenectomy without preoperative or postoperative chemotherapy by 1 surgeon. A total of 263 patients (78.3%) had orthotopic bladder reconstruction. The pelvic lymph node dissection began at the distal aorta including the common and external iliac lymph nodes, and the periaortic, presacral and obturator fossa nodes. The lymphatic tissue removed above and below the bifurcation of the common iliac vessels was submitted separately for histopathological analysis. Data were prospectively entered into a database that forms the basis of this cohort study. The 5-year overall and recurrence-free survival rates in the entire study population of 336 patients were 68% and 69%, respectively. Overall 64 patients (19%) had lymph node metastases of whom 22 (34.4%) had lymph node involvement above the bifurcation of the common iliac vessels outside the template of the standard lymph node dissection. The median number of retrieved lymph nodes was 27 (range 7 to 78) and in those with lymph node metastases 27 (range 11 to 49) included 8 (range 0 to 17) above the bifurcation and 18 (range 8 to 41) below the bifurcation of the common iliac vessels in the true pelvis. Lymph node involvement proved a significant adverse prognostic factor with a 5-year probability of survival of 39% vs 76%. The overall 5-year survival rates was similar in patients with lymph node involvement above the bifurcation of the common iliac vessels (37%) compared to the entire population with lymph node metastasis (41%) and to those with lymphatic metastases in the true pelvis below the bifurcation of the common iliac vessels (42%). The survival rate was significantly higher in patients with 5 or less involved lymph nodes (50% vs 13%, p <0.002) and in those with a lymph node density (number of lymph nodes involved/total number of lymph nodes removed) less than 20% (25% vs 47%, p <0.05), but it did not relate to the total number of retrieved lymph nodes. Overall 34% of our patients with lymph node metastases had nodal involvement in the common iliac, periaortic and presacral regions after radical cystectomy for bladder cancer. Survival was similar in this group of patients with lymphatic metastasis outside the boundaries of the standard pelvic lymph node dissection template compared to the entire population with lymph node metastasis. This finding underscores the contention that extended dissection not only provides the most accurate staging but also offers the patient the best chance of survival. Following radical cystectomy patients can be stratified into risk groups according to tumor stage, lymph node involvement, number of metastatic nodes and lymph node density. Our results support the idea that the benchmark for radical cystectomy should include extensive pelvic lymph node dissection with anatomical boundaries including the common iliac and presacral nodes.

Steven K ，Poulsen AL 《JOURNAL OF UROLOGY》