Updated nomogram predicting lymph node invasion in patients with prostate cancer undergoing extended pelvic lymph node dissection: the essential importance of percentage of positive cores

Background

Few predictive models aimed at predicting the presence of lymph node invasion (LNI) in patients with prostate cancer (PCa) treated with extended pelvic lymph node dissection (ePLND) are available to date.

Objective

Update a nomogram predicting the presence of LNI in patients treated with ePLND at the time of radical prostatectomy (RP).

Design, setting, and participants

The study included 588 patients with clinically localised PCa treated between September 2006 and October 2010 at a single tertiary referral centre.

Intervention

All patients underwent RP and ePLND invariably including removal of obturator, external iliac, and hypogastric nodes.

Measurements

Prostate-specific antigen, clinical stage, and primary and secondary biopsy Gleason grade as well as percentage of positive cores were included in univariable (UVA) and multivariable (MVA) logistic regression models predicting LNI and formed the basis for the regression coefficient-based nomogram. The area under the curve (AUC) method was used to quantify the predictive accuracy (PA) of the model.

Results and limitations

The mean number of lymph nodes removed and examined was 20.8 (median: 19; range: 10-52). LNI was found in 49 of 588 patients (8.3%). All preoperative PCa characteristics differed significantly between LNI-positive and LNI-negative patients (all p < 0.001). In UVA predictive accuracy analyses, percentage of positive cores was the most accurate predictor of LNI (AUC: 79.5%). At MVA, clinical stage, primary biopsy Gleason grade, and percentage of positive cores were independent predictors of LNI (all p ≤ 0.006). The updated nomogram demonstrated a bootstrap-corrected PA of 87.6%. Using a 5% nomogram cut-off, 385 of 588 patients (65.5%) would be spared ePLND. and LNI would be missed in only 6 patients (1.5%). The sensitivity, specificity, and negative predictive value associated with the 5% cut-off were 87.8%, 70.3%, and 98.4%, respectively. The relatively low number of patients included as well as the lack of an external validation represent the main limitations of our study.

Conclusions

We report the first update of a nomogram predicting the presence of LNI in patients treated with ePLND. The nomogram maintained high accuracy, even in more contemporary patients (87.6%). Because percentage of positive cores represents the foremost predictor of LNI, its inclusion should be mandatory in any LNI prediction model. Based on our model, those patients with a LNI risk < 5% might be safely spared ePLND.     

Impact of surgical volume on the rate of lymph node metastases in patients undergoing radical prostatectomy and extended pelvic lymph node dissection for clinically localized prostate cancer

BACKGROUND: Previous trials have shown that the number of procedures done by a single surgeon, that is, surgical volume (SV), is associated with several outcomes after radical prostatectomy (RP). OBJECTIVE: To test the association between SV and the detection of lymph node metastases during extended pelvic lymph node dissection (ePLND). DESIGN, SETTING, AND PARTICIPANTS: The study cohort consisted of 1020 men surgically treated for clinically localized prostate cancer. INTERVENTION: All patients underwent RP and ePLND by a group of six surgeons who were trained by the surgeon with the highest SV. All surgeons performed an anatomically extended PLND, including removal of obturator, external iliac, and hypogastric nodes. MEASUREMENTS: Univariable and multivariable logistic regression models tested the association between SV (either continuously coded or dichotomized according to the most informative cut-off, namely >144 vs /=0.06). Conversely, the surgeon with the highest SV removed more nodes and found more nodal metastases compared with the other surgeons (21.1 vs 17.9 mean number of nodes removed; p<0.001, and 15 vs 9.8% of LNI; p=0.01, respectively). At univariable logistic regression analysis, either continuously coded or dichotomized SV was a significant predictor of LNI (p=0.007 and p<0.001, respectively). In multivariable models, continuously coded as well as dichotomized SV maintained a significant association with the rate of LNI, after accounting for preoperative (p=0.04 and p=0.009, respectively) as well as for postoperative variables (p=0.03 and p=0.002, respectively). CONCLUSIONS: After adjusting for clinical and pathologic case-mix differences, patients treated by the highest-volume surgeons (>144 ePLNDs) were more likely to have LNI than those treated by low-volume surgeons, even though all surgeons used a similar extended template for node removal.     

Increasing rate of lymph node invasion in patients with prostate cancer treated with radical prostatectomy and lymph node dissection

Objectives

To investigate lymph node invasion (LNI) rates in prostate cancer (PCa) patients. Recent studies demonstrated an inverse stage migration in PCa patients toward more advanced and unfavorable diseases. We hypothesized that this trend is also evident in LNI rates, in PCa patients treated with radical prostatectomy (RP) and pelvic lymph node dissection (PLND).

Performance characteristics of computed tomography in detecting lymph node metastases in contemporary patients with prostate cancer treated with extended pelvic lymph node dissection

Background

Computed tomography (CT) is a commonly used noninvasive procedure for prostate cancer (PCa) staging. All previous studies addressing the ability of CT scan to predict lymph node invasion (LNI) were based on historical patients treated with limited pelvic lymph node dissection (PLND).

Objective

Assess the value of CT in predicting LNI in contemporary PCa patients treated with extended PLND (ePLND).

Design, setting, and participants

We evaluated 1541 patients undergoing radical prostatectomy and ePLND between 2003 and 2010 at a single center. All patients were preoperatively staged using abdominopelvic CT scan. All lymph nodes with a short axis diameter ≥10 mm were considered suspicious for metastatic involvement.

Intervention

All patients underwent preoperative CT scan, radical retropubic prostatectomy, and ePLND, regardless of PCa features at diagnosis.

Measurements

The performance characteristics of CT scan were tested in the overall patient population, as well as according to the National Comprehensive Cancer Network (NCCN) classification and according to the risk of LNI derived from a nomogram developed on an ePLND series. Logistic regression models tested the relationship between CT scan findings and LNI. Discrimination accuracy was quantified with the area under the curve.

Results and limitations

Overall, a CT scan that suggested LNI was found in 73 patients (4.7%). Of them, only 24 patients (32.8%) had histologically proven LNI at ePLND. Overall, sensitivity, specificity, and accuracy of CT scan were 13%, 96.0%, and 54.6%, respectively. In patients with low-, intermediate-, or high-risk PCa according to NCCN classification, sensitivity was 8.3%, 96.3%, and 52.3%, respectively; specificity was 3.6%, 97.3%, and 50.5%, respectively; and accuracy was 17.9%, 94.3%, and 56.1%, respectively. Similarly, in patients with a nomogram-derived LNI risk ≥50%, sensitivity, specificity, and accuracy were only 23.9%, 94.7%, and 59.3%, respectively. At multivariable analyses, inclusion of CT scan findings did not improve the accuracy of LNI prediction (81.4% compared with 81.3%; p = 0.8). Lack of a central scan review represents the main limitation of our study.

Conclusions

In contemporary patients with PCa, the accuracy of CT scan as a preoperative nodal-staging procedure is poor, even in patients with high LNI risk. Therefore, the need for and the extent of PLND should not be based on the results obtained by CT scan.     

Percentage of positive biopsy cores can improve the ability to predict lymph node invasion in patients undergoing radical prostatectomy and extended pelvic lymph node dissection

OBJECTIVE: We hypothesized that the information stemming from biopsy cores can enhance the ability to predict the rate of lymph node invasion (LNI) at radical retropubic prostatectomy (RRP) in men subjected to extended pelvic lymphadenectomy (ePLND). MATERIALS AND METHODS: A cohort of 278 consecutive patients (mean age: 66.2 yr) underwent a RRP and an ePLND, in which 10 or more nodes were removed and examined. The median PSA was 7.5 ng/ml. Clinical stage was mostly T1c (59.4%) and T2 (37.8%). Biopsy Gleason sum was 2-5 in 26.6%, 6 in 39.2%, 7 in 27%, and 8-10 in 7.2%. The number of positive cores was 1-19 (median: 4), whilst percentage of positive cores was 7.1-100% (median: 37.5%). Logistic regression models tested the association between the above predictors and LNI. Testing of PSA was coded as either a continuous variable (CV) or a cubic spline (CS). Individual variables and combined accuracy were tested in regression-based nomograms, which were subjected to 10,000 bootstrap resamples to reduce overfit bias. RESULTS: Mean number of lymph nodes examined was 17.5 (range: 10-38); 29 patients (10.4%) had LNI. Percentage of positive cores (78.5%) and biopsy Gleason sum (78.4%) were the most informative predictors of LNI. A nomogram based on clinical stage, PSA (CV), and biopsy Gleason sum was 79.7% accurate versus 83% (3.3% gain, p<0.001) when percentage of positive cores was added. A 2.7% gain (83.7% vs. 81%; p<0.001) was recorded after the addition of the percentage of positive cores when PSA was coded as a CS. CONCLUSIONS: Percentage of positive biopsy cores should be considered in prediction of LNI at ePLND, because it significantly improves the combined accuracy of established clinical predictors such as PSA, clinical stage, and biopsy Gleason sum.     

Adherence to pelvic lymph node dissection recommendations according to the National Comprehensive Cancer Network pelvic lymph node dissection guideline and the D'Amico lymph node invasion risk stratification

Purpose

To assess adherence rates to pelvic lymph node dissection (PLND) according to National Comprehensive Cancer Network (NCCN) PLND guideline (2% or higher risk) and D’Amico lymph node invasion (LNI) risk stratification (intermediate/high risk) in contemporary North American patients with prostate cancer treated with radical prostatectomy (RP).

Validation of a nomogram predicting the probability of lymph node invasion among patients undergoing radical prostatectomy and an extended pelvic lymphadenectomy

INTRODUCTION: Our goal was to develop and internally validate a nomogram for prediction of lymph node invasion (LNI) in patients with clinically localized prostate cancer undergoing extended pelvic lymphadenectomy (ePLND). METHODS: 602 consecutive patients (mean age 65.8 years) underwent an ePLND, where 10 or more nodes were removed. PSA was 1.1-49.9 (median 7.2). Clinical stages were: T1c in 55.6%, T2 in 41.4% and T3 in 3%. Biopsy Gleason sums were: 6 or less in 66%, 7 in 25.4%, 8-10 in 8.6%. Multivariate logistic regression models tested the association between all of the above predictors and LNI. Regression-based coefficients were used to develop a nomogram predicting LNI and 200 bootstrap resamples were used for internal validation. RESULTS: Mean number of lymph nodes removed was 17.1 (range 10-40). LNI was detected in 66 patients (11.0%). Univariate predictive accuracy for total PSA, clinical stage and biopsy Gleason sum was 63%, 58% and 73%, respectively. A nomogram based on clinical stage, PSA and Biopsy Gleason sum demonstrated bootstrap-corrected predictive accuracy of 76%. CONCLUSIONS: A nomogram based on pre-treatment PSA, clinical stage and biopsy Gleason sum can highly accurately predict LNI at ePLND.     

A nomogram is more accurate than a regression tree in predicting lymph node invasion in prostate cancer

OBJECTIVE

To compare the performance and discriminant properties of two instruments (a tree‐structured regression model and a logistic regression‐based nomogram), recently developed to predict lymph node invasion (LNI) at radical prostatectomy (RP), in a contemporary cohort of European patients.

PATIENTS AND METHODS

The cohort comprised 1525 consecutive men treated with RP and bilateral pelvic LN dissection (PLND) in two tertiary academic centres in Europe. Clinical stage, pretreatment prostate‐specific antigen (PSA) level and biopsy Gleason sum were used to test the ability of the regression tree and the nomogram to predict LNI. Accuracy was quantified by the area under the receiver operating characteristic curve (AUC). All analyses were repeated for each participating institution.

RESULTS

The AUC for the nomogram was 81%, vs 77% for the regression tree (P = 0.007). When data were stratified according to institution, the nomogram invariably had a higher AUC than the regression tree (Hamburg cohort: nomogram 82.1% vs regression tree 77.0%, P = 0.002; Milan cohort: 82.4% vs 75.9%, respectively; P = 0.03).

CONCLUSIONS

Nomogram‐based predictions of LNI were more accurate than those derived from a regression tree; therefore, we recommend the use of nomogram‐derived predictions.     

A Novel Nomogram to Identify Candidates for Extended Pelvic Lymph Node Dissection Among Patients with Clinically Localized Prostate Cancer Diagnosed with Magnetic Resonance Imaging-targeted and Systematic Biopsies

Background

Available models for predicting lymph node invasion (LNI) in prostate cancer (PCa) patients undergoing radical prostatectomy (RP) might not be applicable to men diagnosed via magnetic resonance imaging (MRI)-targeted biopsies.

Validation of a nomogram predicting the probability of lymph node invasion based on the extent of pelvic lymphadenectomy in patients with clinically localized prostate cancer

OBJECTIVE: To develop a multivariate nomogram to predict the rate of lymph node invasion (LNI) in patients with clinically localized prostate cancer according to the extent of extended pelvic lymphadenectomy (PLND), which is associated with significantly higher rate of LNI. PATIENTS AND METHODS: The study comprised 781 consecutive patients (median age 66.6 years, range 45-85) treated with PLND and radical retropubic prostatectomy (RRP) for clinically localized prostate cancer. Their median (range) prostate-specific antigen (PSA) level was 7 (1.03-49.91) ng/mL, and their clinical stages were T1c in 433 (55.4%), T2 in 328 (42%) and T3 in 20 (2.6%). Biopsy Gleason sums were 相似文献   

Low endogenous testosterone levels are associated with the extend of lymphnodal invasion at radical prostatectomy and extended pelvic lymph node dissection

Objective

To investigate clinical factors associated to lymphnodal metastasis load in patients who underwent to radical prostatectomy (RP) and extended pelvic lymph node dissection (ePLND).

Materials and methods

Between November 2014 and December 2019, ET was measured in 617 consecutive patients not under androgen deprivation therapy who underwent RP and ePLND. Lymphnode invasion (LNI) was codified as not present (N?=?0) or with one (N?=?1) or more than one metastatic node (N?>?1). The risk of multiple pelvic lymph node metastasis (N?>?1, mPLNM) was assessed by comparing it to the other two groups (N?>?1 vs. N?=?0 and N?>?1 vs. N?=?1). Then, we assessed the association between ET and lymphnode invasion for standard predictors, such as PSA, percentage of biopsy positive cores (BPC), tumor stage greater than 1 (cT?>?1) and tumor grade group greater than two (ISUP?>?2).

Results

Overall, LNI was detected in 70 patients (11.3%) of whom 39 (6.3%) with N?=?1 and 31 (5%) with N?>?1. On multivariate analysis, ET was inversely associated with the risk of N?>?1 when compared to both N?=?0 (odds ratio, OR 0.997; CI 0.994–1; p?=?0.027) as well as with N?=?1 cases (OR 0.994; 95% CI 0.989–1.000; p?=?0.015).

Conclusions

In clinical PCa, the risk of mPLNM was increased by low ET levels. As ET decreased, patients had an increased likelihood of mPLNM. Because of the inverse association between ET and mPLNM, higher ET levels were protective against aggressive disease. The influence of locally advanced PCa with high metastatic load on ET levels needs to be explored by controlled trials.

     

Current status of pelvic lymph node dissection in prostate cancer

Pelvic lymph node dissection (PLND) is presently considered the gold standard for the detection of lymph node invasion in prostate cancer (PCa) patients. Controversy exists over the adequate extent of PLND for patients at different stages of PCa and over the therapeutic value of the procedure. The most recent consensus advocates extended PLND (ePLND) in a patient with Gleason score ≥7 and serum prostate-specific antigen >10 ng/ml who is undergoing radical prostatectomy. Critics claim more aggressive dissection is associated with an increase in complications, hospitalization time, and cost. The present review examines the debate of limited versus ePLND, and discusses the potential value of the latter for patients with PCa. Furthermore, it examines the utility of robotic-assisted surgery in performing PLNDs with both comparable oncological outcomes and comparable complication rates. The literature has reported promising results that support both diagnostic and therapeutic benefits of ePLND. However, prospective, multi-center, long-term studies are necessary to alleviate criticism of the increased risk of complications and costs of performing PLND.     

Obesity and lymphatic mapping with sentinel lymph node biopsy in breast cancer

BACKGROUND: With increasing sentinel lymph node experience, patient subsets associated with lower success rates are being identified. Obesity may be one such subset. METHODS: A retrospective review was conducted of breast cancer patients who underwent sentinel lymph node biopsy from March 1997 to September 2002. Factors examined included demographics, body mass index (BMI), breast size, tumor characteristics, lymphoscintigraphy drainage, and success of mapping. Chi-square and exact P values were used for statistical analysis. RESULTS: One hundred seventy-four breast cancer patients had sentinel lymph node biopsy. Sixty-seven patients were normal weight (BMI <25.1); 56 patients were overweight (BMI 25.1 to 29.9); and 51 patients were obese (BMI >29.9). Failure to identify a sentinel lymph node and the false negative rate were not statistically different (P = 0.7783 and P = 0.9290, respectively) among the three groups. CONCLUSIONS: Obesity has no significant effect on sentinel node identification rate or false negative rate.     

Pelvic Lymph Node Dissection in Prostate Cancer

Context

Pelvic lymph node dissection (PLND) is considered the most reliable procedure for the detection of lymph node metastases in prostate cancer (PCa); however, the therapeutic benefit of PLND in PCa management is currently under debate.

Objective

To systematically review the available literature concerning the role of PLND and its extent in PCa staging and outcome. All of the existing recommendations and staging tools determining the need for PLND were also assessed. Moreover, a systematic review was performed of the long-term outcome of node-positive patients stratified according to the extent of nodal invasion.

Evidence acquisition

A Medline search was conducted to identify original and review articles as well as editorials addressing the significance of PLND in PCa. Keywords included prostate cancer, pelvic lymph node dissection, radical prostatectomy, imaging, and complications. Data from the selected studies focussing on the role of PLND in PCa staging and outcome were reviewed and discussed by all of the contributing authors.

Evidence synthesis

Despite recent advances in imaging techniques, PLND remains the most accurate staging procedure for the detection of lymph node invasion (LNI) in PCa. The rate of LNI increases with the extent of PLND. Extended PLND (ePLND; ie, removal of obturator, external iliac, hypogastric with or without presacral and common iliac nodes) significantly improves the detection of lymph node metastases compared with limited PLND (lPLND; ie, removal of obturator with or without external iliac nodes), which is associated with poor staging accuracy. Because not all patients with PCa are at the same risk of harbouring nodal metastases, several nomograms and tables have been developed and validated to identify candidates for PLND. These tools, however, are based mostly on findings derived from lPLND dissections performed in older patient series. According to these prediction models, a staging PLND might be omitted in low-risk PCa patients because of the low rate of lymph node metastases found, even after extended dissections (<8%). The outcome for patients with positive nodes is not necessarily poor. Indeed, patients with low-volume nodal metastases experience excellent survival rates, regardless of adjuvant treatment. But despite few retrospective studies reporting an association between PLND and PCa progression and survival, the exact impact of PLND on patient outcomes has not yet been clearly proven because of the lack of prospective randomised trials.

Conclusions

On the basis of current data, we suggest that if a PLND is indicated, then it should be extended. Conversely, in view of the low rate of LNI among patients with low-risk PCa, a staging ePLND might be spared in this patient category. Whether this approach is also safe from oncologic perspectives is still unknown. Patients with low-volume nodal metastases have a good long-term prognosis; to what extent this prognosis is the result of a positive impact of PLND on PCa outcomes is still to be determined.     

Optimizing the risk threshold of lymph node involvement for performing extended pelvic lymph node dissection in prostate cancer patients: a cost-effectiveness analysis

BackgroundExtended pelvic lymph node dissection (ePLND) may be omitted in prostate cancer (CaP) patients with a low predicted risk of lymph node involvement (LNI). The aim of the current study was to quantify the cost-effectiveness of using different risk thresholds for predicted LNI in CaP patients to inform decision making on omitting ePLND.MethodsFive different thresholds (2%, 5%, 10%, 20%, and 100%) used in practice for performing ePLND were compared using a decision analytic cohort model with the 100% threshold (i.e., no ePLND) as reference. Compared outcomes consisted of quality-adjusted life years (QALYs) and costs. Baseline characteristics for the hypothetical cohort were based on an actual Dutch patient cohort containing 925 patients who underwent ePLND with risks of LNI predicted by the Memorial Sloan Kettering Cancer Center web-calculator. The best strategy was selected based on the incremental cost effectiveness ratio when applying a willingness to pay (WTP) threshold of €20,000 per QALY gained. Probabilistic sensitivity analysis was performed with Monte Carlo simulation to assess the robustness of the results.ResultsCosts and health outcomes were lowest (€4,858 and 6.04 QALYs) for the 100% threshold, and highest (€10,939 and 6.21 QALYs) for the 2% threshold, respectively. The incremental cost effectiveness ratio for the 2%, 5%, 10%, and 20% threshold compared with the first threshold above (i.e., 5%, 10%, 20%, and 100%) were €189,222/QALY, €130,689/QALY, €51,920/QALY, and €23,187/QALY respectively. Applying a WTP threshold of €20.000 the probabilities for the 2%, 5%, 10%, 20%, and 100% threshold strategies being cost-effective were 0.0%, 0.3%, 4.9%, 30.3%, and 64.5% respectively.ConclusionApplying a WTP threshold of €20.000, completely omitting ePLND in CaP patients is cost-effective compared to other risk-based strategies. However, applying a 20% threshold for probable LNI to the Briganti 2012 nomogram or the Memorial Sloan Kettering Cancer Center web-calculator, may be a feasible alternative, in particular when higher WTP values are considered.     

Differences in the rate of lymph node invasion in men with clinically localized prostate cancer might be related to the continent of origin

OBJECTIVE: To test whether the rate of lymph node invasion (LNI) differs between patients treated with radical prostatectomy (RP) at a European or a North American centre. PATIENTS AND METHODS: In all, 1385 men had RP with bilateral lymphadenectomy for clinically localized prostate cancer (587 from Dallas, Texas and 798 from Milan, Italy). Univariate and multivariate analyses focused on the association between the continent of origin and the rate of LNI, after controlling for prostate-specific antigen (PSA) level, clinical stage, biopsy Gleason sum and the number of examined and removed lymph nodes. RESULTS: European men had higher PSA levels (9.1 vs 7.8 ng/mL), a higher proportion of palpable cancers (44.5 vs 32.8%), more nodes removed (mean 14.9 vs 7.8) and a higher rate of LNI (9.0% vs 1.2%; all differences P < 0.001). In multivariate analyses that controlled for PSA level and clinical variables, European men had an 8.9-fold higher risk of LNI (P < 0.001) than their counterparts from the USA. Among preoperative variables, the continent of origin was the third most informative predictor of LNI (67.5%), after biopsy Gleason sum (74.3%) and the number of examined lymph nodes (71.0%), and improved the ability to predict LNI by 4.7%. CONCLUSION: Men treated at a European centre had a 7.3-8.9-fold higher rate of LNI, despite adjusting for all clinical and pathological variables. It remains to be shown what predisposes European men to a higher rate of LNI.     

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.

     

Radical prostatectomy improves progression-free and cancer-specific survival in men with lymph node positive prostate cancer in the prostate-specific antigen era: a confirmatory study

Study Type – Therapy (outcomes research)
Level of Evidence 2b What’s known on the subject? and What does the study add? Historically, surgeons were reluctant to perform radical prostatectomy (RP) in LN positive disease. Nowadays, a shift towards multimodal treatment strategies in such patients, comprising RP with extended lymph node dissection followed by radiation and/or hormonal therapy can be detected. However, this change of paradigm is not supported by evidence derived from treatment guidelines. Retrospective studies on this topic, comprising small numbers of patients from the pre‐PSA era in the US suggest a survival advantage, if RP is performed. Our analyses of cancer control rates between patients with discontinued vs. completed prostatectomy revealed a superior clinical progression free‐ and cancer specific‐survival rate in those patients with completed prostatectomy. These results add knowledge on treatment outcome of a current patient population since previous retrospective studies include patients from the pre‐PSA era.

OBJECTIVE

? To assess the prognostic role of radical prostatectomy (RP) in lymph node (LN) positive patients with prostate cancer (PCa) in a contemporary RP cohort.

PATIENTS AND METHODS

? Between 1992 and 2004, 158 consecutive patients with clinically localized PCa and regional LN metastasis were identified. Fifty patients underwent LN dissection and discontinued RP, combined with early hormonal therapy (HT) (RP?), whereas, in 108 patients, RP was completed followed by adjunctive HT (RP+). ? Clinical progression‐free‐ (CPFS) and cancer‐specific survival (CSS) were studied using Kaplan–Meier analysis. ? Disease characteristics and the impact of RP on CPFS and CSS were further assessed using Cox proportional hazard models. ? A matched pair analysis between RP? and RP+ patients was performed based on clinical and pathological factors.

RESULTS

? Median follow‐up was 98 months (interquartile range, 88–113). Five‐ and 10‐year CPFS was 77% and 61% for RP+ patients vs 61% and 31%, for RP? patients (P= 0.005), respectively. ? A similar trend was observed for CSS (84% and 76% for RP+ vs 81% and 46% for RP?; P= 0.001). ? Type of treatment (RP? vs RP+) and number of positive LN were multivariate predictors of CPFS and CSS (all P≤ 0.05). ? In the matched pair analyses, RP+ patients showed superior CPFS and CSS (P < 0.005).

CONCLUSIONS

? RP had a beneficial impact, resulting in the superior survival of patients with LN positive PCa after controlling for LN tumour burden in a contemporary RP series. ? The findings obtained in the present study support the role of RP as an important component of multimodal strategies of LN positive PCa.     

A novel nomogram predicting lymph node invasion among patients with prostate cancer: The importance of extracapsular extension at multiparametric magnetic resonance imaging

PurposeTo develop a novel risk tool that allows the prediction of lymph node invasion (LNI) among patients with prostate cancer (PCa) treated with robot-assisted radical prostatectomy (RARP) and extended pelvic lymph node dissection (ePLND).MethodsWe retrospectively identified 742 patients treated with RARP + ePLND at a single center between 2012 and 2018. All patients underwent multiparametric magnetic resonance imaging (mpMRI) and were diagnosed with targeted biopsies. First, the nomogram published by Briganti et al. was validated in our cohort. Second, three novel multivariable logistic regression models predicting LNI were developed: (1) a complete model fitted with PSA, ISUP grade groups, percentage of positive cores (PCP), extracapsular extension (ECE), and Prostate Imaging Reporting and Data System (PI-RADS) score; (2) a simplified model where ECE score was not included (model 1); and (3) a simplified model where PI-RADS score was not included (model 2). The predictive accuracy of the models was assessed with the receiver operating characteristic-derived area under the curve (AUC). Calibration plots and decision curve analyses were used.ResultsOverall, 149 patients (20%) had LNI. In multivariable logistic regression models, PSA (OR: 1.03; P= 0.001), ISUP grade groups (OR: 1.33; P= 0.001), PCP (OR: 1.01; P= 0.01), and ECE score (ECE 4 vs. 3 OR: 2.99; ECE 5 vs. 3 OR: 6.97; P< 0.001) were associated with higher rates of LNI. The AUC of the Briganti et al. model was 74%. Conversely, the AUC of model 1 vs. model 2 vs. complete model was, respectively, 78% vs. 81% vs. 81%. Simplified model 1 (ECE score only) was then chosen as the best performing model. A nomogram to calculate the individual probability of LNI, based on model 1 was created. Setting our cut-off at 5% we missed only 2.6% of LNI patients.ConclusionsWe developed a novel nomogram that combines PSA, ISUP grade groups, PCP, and mpMRI-derived ECE score to predict the probability of LNI at final pathology in RARP candidates. The application of a nomogram derived cut-off of 5% allows to avoid a consistent number of ePLND procedures, missing only 2.6% of LNI patients. External validation of our model is needed.     

Extent of pelvic lymph node dissection and the impact of standard template dissection on nomogram prediction of lymph node involvement

Background

Our current lymph node involvement (LNI) nomogram was created using patients receiving both limited and standard lymph node dissection (LND). Over time, refinements in technique could affect the diagnostic yield from LND.

Objective

Our aim was to validate our existing LNI nomogram or develop a new nomogram with updated prediction coefficients that reflect the current standard LND template during radical prostatectomy (RP). We hypothesized that the existing nomogram would demonstrate good discrimination but poor calibration in a contemporary series of standard LND.

Design, setting, and participants

A retrospective analysis of 4176 consecutive primary RP patients was performed, including open procedures (3097 patients from 2000 to 2008) and laparoscopic procedures (1079 patients from 2005 to 2008). After excluding 127 patients (3%) with limited LND, 10 (0.2%) with pretreatment prostate-specific antigen (PSA) >50 ng/ml, and 318 (8%) with incomplete data, the final cohort totaled 3721 patients. The nomograms were evaluated using receiver operating characteristic analysis, calibration plots, and decision-curve analysis.

Interventions

Patients received open or laparoscopic (conventional and robot-assisted) RP and standard LND in our center.

Measurements

Assessments were obtained using preoperative PSA, biopsy Gleason score, and clinical stage.

Results and limitations

The median number of nodes removed was 11, with ∼60% of patients having at least 10 nodes removed (n = 2224). Overall, 5.2% of patients (n = 194) had positive lymph nodes. The new nomogram had very high discriminative accuracy (area under the curve: 0.862). The decision-curve analysis showed that the new nomogram had the highest clinical net benefit for all reasonable threshold probabilities.

Conclusions

The new nomogram shows improved calibration when predicting lymph node invasion in a contemporary cohort of patients with prostate cancer exclusively treated with RP and standard LND. This nomogram will be used as the preferred predictive model for counseling patients and developing studies at our institution.