Does increasing the nodal yield improve outcomes in contemporary patients without nodal metastasis undergoing radical prostatectomy?

ObjectivesTo determine if the number of lymph nodes (LNs) removed is an independent predictor of biochemical recurrence (BCR) in patients without LN metastases undergoing radical prostatectomy (RP).Material and methodsRetrospective analysis of 7,310 patients treated at 7 centers with RP and pelvic LN dissection for clinically localized prostate cancer between 2000 and 2011. Patients with LN metastases (n = 398) and other reasons (stated later in the article) (n = 372) were excluded, which left 6,540 patients for the final analyses.ResultsOverall, median biopsy and RP Gleason score were both 7; median prostate specific antigen level was 6 ng/ml (interquartile range [IQR]: 5); and median number of LNs removed was 6 (IQR: 8). A total of 3,698 (57%), 2,064 (32%), and 508 (8%) patients had ≥6, ≥10, and ≥20 LNs removed, respectively. Patients with more LNs removed were older, had a higher prostate specific antigen level, had higher clinical and pathologic T stage, and had higher RP Gleason score (all P<0.002). Within a median follow-up of 21 (IQR: 16) months, more LNs removed was associated with an increased risk of BCR (continuous: P = 0.021; categorical: P = 0.014). In multivariable analyses that adjusted for the effects of standard clinicopathologic factors, none of the nodal stratifications predicted BCR.ConclusionsThe number of LNs did not have any prognostic significance in our contemporary cohort of patients with LN-negative prostate cancer. This suggests that the risk of missed clinically significant micrometastasis may be minimal in patients currently treated with RP and having a lower LN yield.     

Selecting lymph node–positive patients for adjuvant therapy after radical prostatectomy and extended pelvic lymphadenectomy: An outcome analysis of 100 node-positive patients managed without adjuvant therapy

ObjectiveThe aim of the study is to evaluate the effect of deferred androgen deprivation therapy on biochemical recurrence (BCR) and other survival parameters in node-positive prostate cancer patients after robot-assisted radical prostatectomy with bilateral extended pelvic lymph node dissection (RARP + EPLND).Materials and methodsOf the 453 consecutive RARP procedures performed from 2011 to 2018, 100 patients with no prior use of androgen deprivation therapy were found to be lymph node (LN) positive and were observed, with initiation of salvage treatment at the time of BCR only. Patients were divided into 1 or 2 LNs (67)—and more than 2 LNs (33)—positive groups to assess survival outcomes.ResultsAt a median follow-up of 21 months (1–70 months), the LN group (p < 0.000), preoperative prostate-specific antigen (PSA, p = 0.013), tumor volume (TV, p = 0.031), and LND (p = 0.004) were significantly associated with BCR. In multivariate analysis, only the LN group (p = 0.035) and PSA level (p = 0.026) were statistically significant. The estimated BCR-free survival rates in the 1/2 LN group were 37.6% (27%–52.2%), 26.5% (16.8%–41.7%), and 19.9% (9.6%–41.0%) at 1, 3, and 5 years, respectively, with a hazard of developing BCR of 0.462 (0.225–0.948) compared with the more than 2 LN-positive group. Estimated 5-year overall survival, cancer-specific, metastasis-free, and local recurrence-free survival rates were 88.4% (73.1%–100%), 89.5% (74%–100%), 65.1% (46.0%–92.1%), and 94.8% (87.2%–100.0%), respectively, for which none of the factors were significant. Based on cutoff values for PSA, TV, and LND of 30 ng/mL, 30%, and 10%, respectively, the 1/2 LN group was substratified, wherein the median BCR-free survival for the low- and intermediate-risk groups was 40 and 12 months, respectively.ConclusionsNearly one fourth and one fifth of 1/2 node-positive patients were BCR-free at 3 and 5 years after RARP + EPLND. Further substratification using PSA, TV, and LN density may help in providing individualized care regarding the initiation of adjuvant therapy.     

Definition of high-risk prostate cancer impacts oncological outcomes after radical prostatectomy

BackgroundTo examine the impact of different pretreatment definitions on biochemical recurrence (BCR)-free survival, metastasis-free survival, and cancer-specific survival after radical prostatectomy.MethodsOverall, 26,364 patients with clinically localized disease who underwent radical prostatectomy at a single institution (1992–2017) were retrospectively analyzed. Seven pretreatment definitions of high-risk CaP (prostate-specific antigen [PSA] ≥20 ng/ml, clinical stage ≥T2c, clinical stage T3 [cT3], biopsy Gleason score [GS] 8–10 [Grade Group {GG} IV–V], biopsy GS 9 to 10 [GG V], D'Amico risk definition, National Comprehensive Cancer Network risk definition) were evaluated. Kaplan-Meier, as well as multivariable Cox regression analyses were used.ResultsDepending on the definition, patients with high-risk CaP comprised between 0.9% (cT3) and 20.3% (D'Amico high-risk) of the population. Ten-year BCR-free survival rates varied from 36.0% (≥cT2c) to 47.4% (National Comprehensive Cancer Network high-risk). Ten-year metastasis-free survival rates varied from 56.6% (GS 9–10/GG V) to 77.5% (PSA ≥ 20 ng/ml). Ten-year cancer-specific survival rates varied from 86.6% (cT3) to 94.5% (PSA ≥ 20 ng/ml). In multivariable analysis, all high-risk definitions were associated with significantly higher risk of BCR (hazard ratio [HR]: 3.4–3.9), metastatic progression (HR: 3.9–8.8), and cancer-specific mortality (HR: 2.8-11.2).ConclusionsVariety in outcomes exists, depending on the pretreatment definition of high-risk CaP. Among the tested, GS 9 to 10 (GG V), cT2c, and cT3 were the strongest predictor for higher BCR risk, cT3 was the strongest predictor for higher metastatic progression risk and GS 9 to 10 (GG V) was the strongest predictor for higher cancer-specific mortality risk in multivariable analyses.     

Utility of [11C]choline PET/CT in guiding lesion-targeted salvage therapies in patients with prostate cancer recurrence localized to a single lymph node at imaging: Results from a pathologically validated series

ObjectivePositron emission tomography (PET)/computed tomography (CT) has been shown to be a valid tool in detecting lymph node (LN) metastases in men with biochemical recurrence after radical prostatectomy. We assessed its validity in detecting a single positive LN at pathologic examination in regard to an increasing interest in lesion-targeted salvage therapies.Methods and materialsWe included 46 patients with biochemical recurrence after radical prostatectomy and a single positive spot at [¹¹C]choline PET/CT who underwent pelvic or pelvic and retroperitoneal LN dissection. The ability of [¹¹C]choline PET/CT in identifying the exact positive LN was assessed with the positive predictive value (PPV) in the overall population and according to androgen deprivation therapy, prostate-specific antigen value, and site of PET/CT positivity.ResultsOverall, 30 patients (65%) had positive LNs at pathologic examination. Of these, only 16 (35%) had pathologically confirmed metastases in the same lymphatic region and 11 (24%) had involvement of 1 single LN. Conversely, 28 patients had positive LNs in other areas and 8 had no evidence of metastases. The overall PPV of PET/CT was 34.8% and 23.9% when exact concordance was defined according to the lymphatic landing site and single positive LN, respectively. The PPV ranged from 33.3% to 44.4% and from 17.9% to 28.6%, in men with and without androgen deprivation therapy, respectively.ConclusionsThe PPV [¹¹C]choline of PET/CT in correctly identifying patients with a single positive LN at salvage LN dissection is poor (24%). Therefore, extensive salvage treatment approaches are needed to maximize the chance of cure.     

Extranodal Extension Is a Powerful Prognostic Factor in Bladder Cancer Patients with Lymph Node Metastasis

Background

Lymph node metastasis (LNM) is the most powerful pathologic predictor of disease recurrence after radical cystectomy (RC). However, the outcomes of patients with LNM are highly variable.

Objective

To assess the prognostic value of extranodal extension (ENE) and other lymph node (LN) parameters.

Design, setting, and participants

A retrospective analysis of 748 patients with urothelial carcinoma of the bladder and LNM treated with RC and lymphadenectomy without neoadjuvant therapy at 10 European and North American centers (median follow-up: 27 mo).

Intervention

All subjects underwent RC and bilateral pelvic lymphadenectomy.

Outcome measurements and statistical analysis

Each LNM was microscopically evaluated for the presence of ENE. The number of LNs removed, number of positive LNs, and LN density were recorded and calculated. Univariable and multivariable analyses addressed time to disease recurrence and cancer-specific mortality after RC.

Results and limitations

A total of 375 patients (50.1%) had ENE. The median number of LNs removed, number of positive LNs, and LN density were 15, 2, and 15, respectively. The rate of ENE increased with advancing pT stage (p < 0.001). In multivariable Cox regression analyses that adjusted for the effects of established clinicopathologic features and LN parameters, ENE was associated with disease recurrence (hazard ratio [HR]: 1.89; 95% confidence interval [CI], 1.55–2.31; p < 0.001) and cancer-specific mortality (HR: 1.90; 95% CI, 1.52–2.37; p < 0.001). The addition of ENE to a multivariable model that included pT stage, tumor grade, age, gender, lymphovascular invasion, surgical margin status, LN density, number of LNs removed, number of positive LNs, and adjuvant chemotherapy improved predictive accuracy for disease recurrence and cancer-specific mortality from 70.3% to 77.8% (p < 0.001) and from 71.8% to 77.8% (p = 0.007), respectively. The main limitation of the study is its retrospective nature.

Conclusions

ENE is an independent predictor of both cancer recurrence and cancer-specific mortality in RC patients with LNM. Knowledge of ENE status could help with patient counseling, clinical decision making regarding inclusion in clinical trials of adjuvant therapy, and tailored follow-up scheduling after RC.     

How accurate is 68Gallium-prostate specific membrane antigen positron emission tomography / computed tomography (68Ga-PSMA PET/CT) on primary lymph node staging before radical prostatectomy in intermediate and high risk prostate cancer? A study of patient- and lymph node- based analyses

Background and aimGallium-68 (68Ga)-Prostate Membrane Specific Antigen Positron Emission Tomography/Computed Tomography (68Ga-PSMA PET/CT) is an emerging diagnostic modality which is gaining importance in individualized prostate cancer (PCa) management era. This study aimed to investigate the diagnostic accuracy of ⁶⁸Ga-PSMA PET/CT on primary LN staging before radical prostatectomy (RP) in intermediate and high risk PCa.Materials and MethodsThe retrospectively documented 49 patients with intermediate and high risk non-metastatic PCa who had ⁶⁸Ga-PSMA PET/CT before RP were enrolled into this study. The histopathology of dissected LNs was used as reference standard to evaluate the accuracy of ⁶⁸Ga-PSMA PET/CT on primary LN staging, both in per-patient (n = 49) and in per-node (n = 454) analyses. The diagnostic accuracy was investigated using sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV), and by area under the curve (AUC) provided using receiver operating curve (ROC) analysis.ResultsMedian age was 64 (48-79) years and, median and mean PSA values were 10 (1.31–138) ng/ml and 16.2 (±19.8) ng/ml, respectively. 22 (44.9%) and 27 (55.1%) of patients had intermediate and high risk PCa, respectively. A total of 5 (10.2%) patients had histopathologically proven LN metastasis and 3 (60%) of them was detected in ⁶⁸Ga-PSMA PET/CT. In per patient analysis, the sensitivity, specifity, PPV and NPV of ⁶⁸Ga-PSMA PET/CT on primary LN staging were 0.60, 0.96, 0.60 and 0.96, respectively. Among overall 454 LNs, 16 (3.5 %) of them were reported as metastatic in histopathology and, 13 (2.9%) of these metastatic LNs were detected in ⁶⁸Ga-PSMA PET/CT. In per-node analysis, the sensitivity, specificity, PPV and NPV of ⁶⁸Ga-PSMA PET/CT on primary LN staging were 0.82, 0.99, 0.87 and 0.99, respectively. The ROC analyses found AUCs for primary LN staging as 0.777 (95%CI:0.508–1.0) in per patient analysis and, as 0.904 (95%CI:0.790 – 1.0) in per node analysis, respectively.ConclusionThe use of ⁶⁸Ga-PSMA PET/CT has promising diagnostic accuracy on primary LN staging before RP in intermediate and high risk PCa. However, the efforts should be taken to increase sensitivity of ⁶⁸Ga-PSMA PET/CT in individualized treatment era.     

The association between total and positive lymph node counts, and disease progression in clinically localized prostate cancer

PURPOSE: We examined the association between the number of LNs removed, the number of positive LNs and disease progression in patients undergoing pelvic lymph node dissection and radical retropubic prostatectomy for clinically localized prostate cancer. MATERIALS AND METHODS: We analyzed 5,038 consecutive patients who underwent radical retropubic prostatectomy between 1983 and 2003. Clinicopathological parameters, including the administration of neoadjuvant hormonal therapy, preoperative prostate specific antigen, specimen Gleason score, surgeon and pathological stage, were collected prospectively in our prostate cancer database. We excluded men treated with radiation or chemotherapy before surgery. BCR was defined as 2 postoperative prostate specific antigen increases greater than 0.2 ng/ml. Cox models were used to determine whether the number of nodes removed or the number of positive nodes predicted freedom from BCR after adjustment for prognostic covariates. RESULTS: The 4,611 eligible patients had a median of 9 LNs (IQR 5 to 13) removed. Positive nodes were found in 175 patients (3.8%). Overall the number of LNs removed did not predict freedom from BCR (HR per additional 10 nodes removed 1.02, 95% CI 0.92 to 1.13, p = 0.7). Results were similar in patients receiving and not receiving neoadjuvant hormonal therapy. Finding any LN involvement was associated with a BCR HR of 5.2 (95% CI 4.2 to 6.4, p <0.0005). However, in men without nodal involvement an increased number of nodes removed correlated significantly with freedom from BCR (p = 0.01). CONCLUSIONS: Nodal disease increased the risk of progression. Extensive lymphadenectomy enhances the accuracy of surgical staging. However, we were unable to determine that removing more nodes improves freedom from BCR uniformly. Since the proportion of patients with prostate cancer with positive nodes is low, the value of extensive lymphadenectomy requires a multi-institutional, randomized clinical trial.     

Oncological outcomes of pathologically organ-confined,lymph node-positive prostate cancer after radical prostatectomy

BackgroundThe aim of this study was to investigate the impact of lymph-node involvement on oncological outcomes in patients with pathologically organ-confined prostate cancer (pT2 CaP) after radical prostatectomy (RP).MethodsWe retrospectively analyzed 9,631 pT2 CaP patients who underwent RP at a single institution between 1998 and 2018. Kaplan-Meier plots and Cox regression models (CRMs) assessed biochemical recurrence (BCR)-free survival and metastasis-free survival (MFS) according to N-stage. In subgroup analyses of N1 patients, Kaplan-Meier plots and CRMs were stratified according to adjuvant treatment.ResultsOf 9,631 pT2 staged patients, 241 (2.5%) harbored lymph-node metastases after RP (pN1). The median follow-up was 60.8 months. No pT2 N1-staged patient died due to CaP. The 5-year BCR-free survival rates were 54.7 vs. 88.4% in pT2 N1 vs. pT2 N0 patients, respectively (P < 0.001). The 5-year MFS rates were 92.5 vs. 98.9% in pT2 N1 vs. pT2 N0 patients, respectively (P < 0.001). Within pT2 N1 patients, presence of ≥3 positive lymph nodes was an independent risk factor for BCR (hazard ratio [HR] 3.4, P < 0.001) and for metastatic progression (HR 1.7, P = 0.04). Finally, 3-year BCR-free survival was improved in pT2 N1 patients treated with adjuvant radiation therapy (87.1% vs. 63.7% for patients who received other treatment options [P < 0.001]).ConclusionPatients with pathologically organ-confined but lymph node-positive CaP exhibited favorable oncological outcomes after RP. Presence of ≥3 positive LNs predicted higher rates of BCR and metastatic progression. In consequence, in pT2 N1 patients treated with RP with ≥3 positive LNs, adjuvant treatment may be considered.9     

Prognostic significance of the degree of extranoda extension in patients with penile carcinoma

This study sought to assess the prognostic significance of the degree of extranodal extension （ENE） and several other risk factors in pathological ENE penile carcinoma. We analyzed prospectively collected data on a consecutive series of 31 chemotherapy-naive patients with proven ENE who underwent therapeutic regional lymphadenectomy. Postoperative external radiotherapy was then performed. We studied the extent of ENE utilizing a novel grading system and correlated patient grades with their outcome measures. ENE was graded as 1 - if the capsule of the lymph node （LN） was ruptured less than one-third of its circumference or 2 - if the capsule was disrupted more than one-third of its circumference or the entire LN was disrupted. We estimated overall survival （OS） using the Kaplan-Meier method. Multivariate analysis was performed according to the Cox proportional hazards model using factors that were identified as statistically significant in univariate analysis. The incidence rate of ENE was 51.8% in patients with pathological node-positive carcinoma of the penis. The median OS and 5-year survival were 18 months （95% confidence interval （CI）, 14.4-21.6） and 23%, respectively. Prognostic variables on univariate analysis were ENE grade 2, ≥3 LNs with ENE, maximal LN ≥ 35 mm, 〉5 positive LNs and pelvic LN involvement. On multivariate analysis, only ENE grade 2 remained associated with decreased OS （hazard ratio （HR）： 6.50）. In conclusion, patients with ENE have a poor outcome, and ENE grade 2 is an independent predictive factor of poor OS in patients with pathological ENE penile carcinoma.     

One-Step Nucleic Acid Amplification (OSNA) for the Application of Sentinel Node Concept in Gastric Cancer

Purpose

This study was designed to apply safely the sentinel node navigation surgery (SNNS) to the malignancies, an accurate and prompt intraoperative diagnosis of SN is essential, and micrometastasis has been frequently missed by conventional frozen sections. Recently, a novel molecular-based rapid diagnosis for the lymph node (LN) metastases has been developed using (OSNA) in breast cancer, which takes approximately 30 min to obtain a final result. We evaluated the efficacy of OSNA in terms of the intraoperative diagnosis of LN metastasis in patients with gastric cancer.

Methods

A total of 162 LNs dissected from 32 patients with gastric cancer was included in this study; 45 LNs were pathologically diagnosed as metastatic LNs and 117 LNs were negative. The LNs were bisected; halves were examined with H&;E stain, and the opposite halves were subjected to OSNA analyses of CK19 mRNA. The CK19 mRNA expression was examined in the positive or negative metastatic LNs, and the correlation between the tumor volume and CK19 mRNA expression in the metastatic LNs was examined.

Results

The CK19 mRNA expressions in the positive metastatic LNs were significantly higher than those of negative LNs. When 250 copies/μl was set as a cutoff value, the concordance rate was 94.4%, the sensitivity was 88.9%, and the specificity was 96.6%. The OSNA expression was significantly correlated with the estimated tumor volumes in the metastatic LNs.

Conclusions

The OSNA method is feasible and acceptable for detecting LN metastases in patients with gastric cancer. This should be applied for the intraoperative diagnosis in the SN-navigation surgery in gastric cancer.

     

The extent of pelvic lymph node dissection correlates with the biochemical recurrence rate in patients with intermediate- and high-risk prostate cancer

Study Type – Therapy (case series) Level of Evidence 4 What’s known on the subject? and What does the study add? Pelvic lymph‐node dissection during radical prostatectomy for prostate cancer is certainly a fundamental staging procedure but its therapeutic role is yet under debate. This retrospective study suggests that, in patients with intermediate‐ and high‐risk of prostate cancer, the greater the number of lymph‐nodes removed, the lower the risk of biochemical relapse, even in the presence of 1 or 2 lymph‐node metastasis. However, the Will Rogers phenomenon must be considered due to the retrospective nature of the present study.

OBJECTIVE

• ? To assess the impact of pelvic lymph node dissection (PLND) and of the number of lymph nodes (LNs) retrieved during radical prostatectomy (RP) on biochemical relapse (BCR) in pNX/0/1 patients with prostate cancer according to the clinical risk of lymph node invasion (LNI).

PATIENTS AND METHODS

• ? We evaluated 872 pT2‐4 NX/0/1 consecutive patients submitted to RP between October 1995 and June 2009, with the following inclusion criteria: (i) a follow‐up period ≥12 months; (ii) the avoidance of neoadjuvant hormonal therapy or adjuvant hormonal and/or adjuvant radiotherapy; (iii) the availability of complete follow‐up data; (iv) no pathological T0 disease; (v) complete data regarding the clinical stage and Gleason score (Gs), the preoperative prostate‐specific antigen (PSA) level and the pathological stage.
• ? The patients were stratified as having low risk (cT1a‐T2a and cGs ≤6 and PSA level < 10 ng/mL), intermediate risk (cT2b‐T2c or cGs = 7 or PSA level = 10–19.9) or high risk of LNI (cT3 or cGs = 8–10 or PSA level ≥ 20).
• ? The 872 patients were divided into two LN groups according to the number of LNs retrieved: group 1 had no LN or one to nine LNs removed; group 2 had 10 or more LNs.
• ? The variables analysed were LN group, age, PSA level, clinical and pathological stage and Gs, surgical margin status, LN status and number of LN metastases; the primary endpoint was the BCR‐free survival.

RESULTS

• ? The mean follow‐up was 55.8 months.
• ? Of all the patients, 305 (35%) were pNx and 567 (65.0%) were pN0/1.
• ? Of the 567 patients submitted to PLND, the mean number of LNs obtained was 10.9, and 49 (8.6%) were pN1.
• ? In the 402 patients at low risk of LNI, LN group was not a significant predictor of BCR at univariate analysis, while in the 470 patients at intermediate and high risk of LNI, patients with ≥10 LNs removed had a significantly lower BCR‐free survival at univariate and multivariate analysis.

CONCLUSION

• ? In our study population, a more extensive PLND positively affects the BCR‐free survival regardless of the nodal status in intermediate‐ and high‐risk prostate cancer.

     

Prognostic Value of Perinodal Lymphovascular Invasion Following Radical Cystectomy for Lymph Node–positive Urothelial Carcinoma

Background

Metastasis of urothelial carcinoma of the bladder (UCB) into regional lymph nodes (LNs) is a key prognosticator for cancer-specific survival (CSS) after radical cystectomy (RC). Perinodal lymphovascular invasion (pnLVI) has not yet been defined.

Objective

To assess the prognostic value of histopathologic prognostic factors, especially pnLVI, on survival.

Design, setting, and participants

A total of 598 patients were included in a prospective multicentre study after RC for UCB without distant metastasis and neoadjuvant and/or adjuvant chemotherapy. En bloc resection and histopathologic evaluation of regional LNs were performed based on a prospective protocol. The final study group comprised 158 patients with positive LNs (26.4%).

Intervention

Histopathologic analysis was performed based on prospectively defined morphologic criteria of LN metastases.

Outcome measurements and statistical analysis

Multivariable Cox proportional hazard regression models determined prognostic impact of clinical and histopathologic variables (age, gender, tumour stage, surgical margin status, pN, diameter of LN metastasis, LN density [LND], extranodal extension [ENE], pnLVI) on CSS. The median follow-up was 20 mo (interquartile range: 11–38).

Results and limitations

Thirty-one percent of patients were staged pN1, and 69% were staged pN2/3. ENE and pnLVI was present in 52% and 39%, respectively. CSS rates after 1 yr, 3 yr, and 5 yr were 77%, 44%, and 27%, respectively. Five-year CSS rates in patients with and without pnLVI were 16% and 34% (p < 0.001), respectively. PN stage, maximum diameter of LN metastasis, LND, and ENE had no independent influence on CSS. In the multivariable Cox model, the only parameters that were significant for CSS were pnLVI (hazard ratio: 2.47; p = 0.003) and pT stage. However, pnLVI demonstrated only a minimal gain in predictive accuracy (0.1%; p = 0.856), and the incremental accuracy of prediction is of uncertain clinical value.

Conclusions

We present the first explorative study on the prognostic impact of pnLVI. In contrast to other parameters that show the extent of LN metastasis, pnLVI is an independent prognosticator for CSS.     

Significance of Lymph Node Retrieval From the Terminal Ileum for Patients With Cecal and Ascending Colonic Cancers

Background

For patients with cecal and ascending colonic cancers, the significance of regional lymph node (LN) metastasis at the terminal ileum has not been elucidated. We analyzed its metastatic patterns and significance.

Methods

The records of patients with cecal and ascending colonic cancers receiving standard radical right hemicolectomy with D3 LN dissection between 2000 and 2010 were collected. The regional LNs were grouped according to the Japanese Classification of Colorectal Carcinoma. The regional LNs supplied by ileocolic vessels were further divided into 201-A (terminal ileal side) and 201-B (colonic side). The clinicopathologic characteristics of all cases showing positive for metastasis in 201-A LN were analyzed.

Results

Forty-seven cases of cecal and 56 cases of ascending colonic cancer were included. Seven cases had 201-A-positive LNs: five (10.6%) in cecal cancers and two (3.6%) in ascending colonic cancers. They all had distant metastases (P < 0.001), and the incidences were significantly correlated with the numbers of metastatic LNs (P < 0.05). There was no 201-A-positive LN noted among patients with stage I to III disease. Poor prognosis was noted for patients with a 201-A-positive LN.

Conclusions

Both cecal and ascending colonic cancers have a potential for LN metastasis at the terminal ileum. These cases are exclusively stage IV and have poor prognosis.     

Reassessing the current TNM lymph node staging for renal cell carcinoma

OBJECTIVE: The most commonly used staging system for renal cell carcinoma (RCC) is the tumor-node-metastasis (TNM) system. In the most recent TNM edition, lymph node (LN) involvement is defined as pN0, pN1, or pN2, depending on the number of metastatic LNs (none, 1, or >1). This study evaluated the prognostic value of this classification and tried to improve its clinical impact by considering an additional parameter, that is, LN density (ratio between number of positive LNs and total number of LNs retrieved). METHODS: All pathologic reports of radical nephrectomies performed for RCC in two urologic centers between November 1983 and December 1999 were reviewed. For each patient, complete clinical and pathologic data, number of LNs removed, location and number of positive LNs, and LN density were recorded. The Kaplan-Meyer method and the log-rank test were used to calculate cause-specific survival rates and to compare survival curves, respectively. RESULTS: A total of 735 patients underwent radical nephrectomy. Lymphadenectomy was performed in 618 cases, and the rate of positive LNs was 14.2%. The 5-yr cause-specific survival rate of pN+ patients was 18%, with no statistically significant difference between pN1 and pN2. The average number of LNs removed was 13 (range, 1-35). The median number of LNs involved was 3 (range, 1-18). LN density ranged between 3.7% and 100% (median, 22.9%). The number of LNs removed had no impact on survival in pN+ patients. The only significant unfavorable prognostic factors were >4 LNs involved (p = 0.02) and LN density >60% (p = 0.01). CONCLUSION: The results show that in RCC the current TNM stratification of positive LNs is not significantly correlated with prognosis. From our data it appears that classification as < or =4 or >4 LNs involved, supported by LN density, better reflects the impact of the disease on survival.     

Presence of positive surgical margin in patients with organ-confined prostate cancer equals to extracapsular extension negative surgical margin. A plea for TNM staging system reclassification

BackgroundTo test the hypothesis that patients with pT2 and positive surgical margins (SM) have a similar biochemical-recurrence (BCR) risk to patients with pT3a, and negative SM. Moreover, we examined the effect of incorporating positive SM as a higher stage on the discrimination accuracy of the current TNM staging system.Materials and methodsWe evaluated 1,503 prostate cancer patients treated with radical prostatectomy, between 1998 and 2010. Only individuals with pT2N0 or pT3aN0, without neoadjuvant and/or adjuvant therapy, were included. Cox regression analyses tested the relationship between SM status (negative [R0] vs. positive [R1]) and BCR rate, after stratification according to T stage. Predictive accuracy of the current T stage and of a novel T stage, which consider positive SM as a higher stage, was quantified with Harrell's concordance index.ResultsPositive SM rate was 20.3%. The 5-year BCR rates were 96%, 82%, 78%, and 62% for patients with, respectively, pT2R0, pT2R1, pT3aR0, and pT3a1 (all P ≤ 0.03). In multivariable analyses, the BCR rate was 3.6-, 2.5-, and 6.0-fold higher (all P < 0.001) in patients with, respectively, pT2R1, pT3aR0, and pT3aR1 stage relative to patients with pT2R0 stage. The maximum univariable (14.1%) and multivariable (6.9%) discrimination accuracy gains were observed, when tumor stage was stratified into pT2R0 vs. pT2R1/pT3R0 vs. pT3R1.ConclusionsThe presence of positive SM at radical prostatectomy (RP) specimen substantially increases the BCR risk. Patients with pT2R1 have similar BCR risk to patients with pT3aR0. Considering these patients as 1 category substantially improves the discrimination accuracy of the current TNM staging system.     

Surgical margin length and location affect recurrence rates after robotic prostatectomy

BackgroundRobotic-assisted laparoscopic radical prostatectomy is a current standard treatment for localized prostate cancer, with treatment failure defined by biochemical recurrence (BCR). Open radical prostatectomy series have identified the presence of a positive surgical margin (PSM) as a predictor of long-term recurrence, a measure that is affected by the surgeon׳s skill. We evaluate the effect of PSM parameters on BCR rates from robotic-assisted laparoscopic radical prostatectomy, across 3 high-volume institutions.MethodsDe-identifiable clinicopathological and histopathological data were prospectively collected for 4,001 patients with at least 3 years of follow-up. Kaplan-Meier plots and 3 statistical models were used to evaluate the effect of margin parameters on BCR, via crude rates, traditional multivariable Cox regression, and a propensity-adjusted Cox regression model.ResultsOverall, 37% of men with a PSM developed BCR compared with 10% of men with negative margins (hazard ratio [HR] = 1.81, 95% CI: 1.47–2.22). Length ≥3 mm or a multifocal positive margin was associated with a higher risk of BCR compared with negative margin cases. On multivariable Cox regression analysis of the positive margin cohort, only apical margins significantly predicted BCR relative to basal margins (HR = 2.03, 95% CI: 1.01–4.09), whereas there was no significant difference in BCR rates for posterolateral margins relative to basal margins (HR = 1.62, 95% CI: 0.84–3.11). Propensity-adjusted modeling confirmed a greater effect of apical compared with posterolateral PSM.ConclusionsA PSM length ≥3 mm is predictive of BCR, as is to a lesser extent multiple positive margins. In contrast to open prostatectomy series, posterolateral margins carry a smaller risk of BCR compared with apical margins.     

La densidad de los ganglios linfáticos en la linfadenectomía retroperitoneal como marcador novel para predecir la recurrencia en pacientes con cáncer testicular de células germinales: estudio de casos y controles y experiencia clínica a largo plazo de un hospital de referencia terciario

Introduction and objectivesIn this retrospective study, we aimed to evaluate lymph node (LN) density in retroperitoneal lymph node dissection (RPLND) to analyze whether residual mass after chemotherapy might behave as predicting factor for recurrence in patients with germ cell testicular cancer (GCTC).Materials and methodsThe data of 185 patients that were operated between 12/2004 and 02/2017 because of GCTC were reviewed retrospectively. LN density was calculated. The patients were compared statistically in terms of demographic features, tumor characteristics, serum tumor marker levels, treatment strategies, and pathological results according to GCTC subtypes. Correlation analysis was performed to determine the parameters related to recurrent disease.ResultsThe median follow-up was 79 (31-179) months and the median age of the patients was 23 (16-71). The median tumor size was 4 (1-18) cm. Five (2.7%) patients had metastatic disease at initial diagnosis. Seminoma, non-seminomatous-GCT and mix type-GCTC was detected in 62 (33.5%), 60 (32.4%) and 63 (34.1%) patients, respectively. Following inguinal orchiectomy, 48 (25.9%) patients underwent follow-up, 126 (68.1%) patients underwent chemotherapy and 11 (5.9%) patients underwent radiotherapy. A total of 21 (11.4%) patients underwent post-chemotherapy RPLND. Early and late recurrence was seen in 3 (1.6%) and 2 (1.1%) of the patients, respectively. A mild to moderate, negative, but significant correlation was found between the recurrence and the number of LNs containing metastatic deposits and LN density (r= –0.490, P=.024 and r= –0.450, P=.041, respectively).ConclusionsThere was a negative correlation between the number of LNs containing metastatic deposits and LN density and recurrent disease.     

Critical analysis of the 2010 TNM classification in patients with lymph node–positive bladder cancer: Influence of lymph node disease burden

ObjectivesIn 2010, a new TNM staging system was published by American Joint Committee on Cancer, changing the nodal classification to include the presence of common iliac lymph node (LN) involvement as N3 category. The objective of this study was to define the capability of the current TNM nodal classification to separate patients with different prognostic stages and to evaluate the effect of LN disease burden.Methods and materialsA total of 93 patients with metastatic LNs after radical cystectomy and extended LN dissection for urothelial carcinoma of the bladder between 1999 and 2012 were included. The median follow-up was 21.5 months. The correlation between N3 and indicators of LN disease burden was analyzed using the Spearman correlation coefficient. Recurrence-free survival (RFS) and overall survival (OS) analysis was performed using the Kaplan-Meier and Cox proportional hazards methods.ResultsThe presence of N3 disease was associated with higher number of metastatic LNs (7 vs. 2, P<0.01); however, this was highly variable and correlation coefficients between common iliac metastatic LNs and other lymphatic disease burden indicators demonstrated weak association (0.39–0.63). Patients with N1 lesions were found to have a distinct RFS and OS (P<0.01 and P = 0.01, respectively). A trend toward worse RFS (P = 0.07) and OS (P = 0.08) was observed in patients with N3 lesions. However, no difference in RFS or OS was found between patients with N2 and N3 lesions (P = 0.83 and 0.50, respectively).ConclusionsThe N3 category in the current TNM classification defines a group of patients with high but heterogeneous disease burden. This may be the explanation for its lack of prognostic stratification when compared with N2 category bladder cancer.