Radioisotope-Guided Sentinel Lymph Node Biopsy in Penile Cancer: A Long-Term Follow-Up Study.

Lymph node (LN) management is critical for survival in patients with penile cancer. However, radical inguinal lymphadenectomy carries a high risk of postoperative complications such as lymphedema, lymphocele, wound infection, and skin necrosis. The European Association of Urology guidelines therefore recommend invasive LN staging by modified inguinal lymphadenectomy or dynamic sentinel node biopsy (DSNB) in clinically node-negative patients (cN0) with intermediate- and high-risk tumors (≥ T1G2). However, the timing of DSNB (simultaneous vs. subsequent to partial or total penile resection) is controversial and the low incidence of penile cancer means that data on the long-term outcomes of DSNB are limited. The present study aimed to analyze the reliability and morbidity of DSNB in patients with penile cancer during long-term follow-up. This retrospective study included 41 patients (76 groins) who underwent radioisotope-guided DSNB simultaneously or secondarily after penile surgery from June 2004 to November 2018. In total, 193 sentinel LNs (SLNs) and 39 non-SLNs were removed. The median number of dissected LNs was 2.5 (interquartile range 2-4). Histopathological analysis showed that five of the 76 groins (6.6%) contained metastases. None of the non-SLNs were tumor-positive. In accordance with the guidelines, all inguinal regions with positive SLNs underwent secondary radical inguinal lymphadenectomy, which revealed three additional metastases in one groin. Regional LN recurrence was detected in three patients (four groins) during a median follow-up of 70 months, including two patients in whom DSNB had been performed secondarily after repetitive penile tumor resections. DSNB-related complications occurred in 15.8% of groins. Most complications were mild (Clavien-Dindo grade I; 50%) or moderate (II; 25%), and invasive intervention was only required in 3.9% of groins (IIIa: n = 1; IIIb: n = 2). In summary, this study suggests that the current radioisotope-guided DSNB procedure may reduce the complication rate of inguinal lymphadenectomy in patients with cN0 penile cancer. However, DSNB and penile surgery should be performed simultaneously to minimize the false-negative rate. Recent advances, such as new tracers and imaging techniques, may help to reduce the false-negative rate of DSNB further.

TGFB-induced factor homeobox 1 (TGIF) expression in breast cancer.

BACKGROUND: Breast cancer (BC) is the most frequent female cancer and preferentially metastasizes to bone. The transcription factor TGFB-induced factor homeobox 1 (TGIF) is involved in bone metabolism. However, it is not yet known whether TGIF is associated with BC bone metastasis or patient outcome and thus of potential interest. METHODS: TGIF expression was analyzed by immunohistochemistry in 1197 formalin-fixed, paraffin-embedded tissue samples from BC patients treated in the GAIN (German Adjuvant Intergroup Node-Positive) study with two adjuvant dose-dense schedules of chemotherapy with or without bisphosphonate ibandronate. TGIF expression was categorized into negative/low and moderate/strong staining. Endpoints were disease-free survival (DFS), overall survival (OS) and time to primary bone metastasis as first site of relapse (TTPBM). RESULTS: We found associations of higher TGIF protein expression with smaller tumor size (p = 0.015), well differentiated phenotype (p < 0.001) and estrogen receptor (ER)-positive BC (p < 0.001). Patients with higher TGIF expression levels showed a significantly longer disease-free (DFS: HR 0.75 [95%CI 0.59-0.95], log-rank p = 0.019) and overall survival (OS: HR 0.69 [95%CI 0.50-0.94], log-rank p = 0.019), but no association with TTPBM (HR 0.77 [95%CI 0.51-1.16]; p = 0.213). Univariate analysis in molecular subgroups emphasized that elevated TGIF expression was prognostic for both DFS and OS in ER-positive BC patients (DFS: HR 0.68 [95%CI 0.51-0.91]; log-rank p = 0.009, interaction p = 0.130; OS: HR 0.60 [95%CI 0.41-0.88], log-rank p = 0.008, interaction p = 0.107) and in the HER2-negative subgroup (DFS:HR 0.67 [95%CI 0.50-0.88], log-rank p = 0.004, interaction p = 0.034; OS: HR 0.57 [95%CI 0.40-0.81], log-rank p = 0.002, interaction p = 0.015). CONCLUSIONS: Our results suggest that moderate to high TGIF expression is a common feature of breast cancer cells and that this is not associated with bone metastases as first site of relapse. However, a reduced expression is linked to tumor progression, especially in HER2-negative breast cancer. TRIAL REGISTRATION: This clinical trial has been registered with ClinicalTrials.gov ; registration number: NCT00196872 .

Accuracy of Magnetometer-Guided Sentinel Lymphadenectomy after Intraprostatic Injection of Superparamagnetic Iron Oxide Nanoparticles in Prostate Cancer: The SentiMag Pro II Study.

Radioisotope-guided sentinel lymph node dissection (sLND) has shown high diagnostic reliability in prostate (PCa) and other cancers. To overcome the limitations of the radioactive tracers, magnetometer-guided sLND using superparamagnetic iron oxide nanoparticles (SPIONs) has been successfully used in PCa. This prospective study (SentiMag Pro II, DRKS00007671) determined the diagnostic accuracy of magnetometer-guided sLND in intermediate- and high-risk PCa. Fifty intermediate- or high-risk PCa patients (prostate-specific antigen (PSA) ≥ 10 ng/mL and/or Gleason score ≥ 7; median PSA 10.8 ng/mL, IQR 7.4-19.2 ng/mL) were enrolled. After the intraprostatic SPIONs injection a day earlier, patients underwent magnetometer-guided sLND and extended lymph node dissection (eLND, followed by radical prostatectomy. SLNs were detected in in vivo and in ex vivo samples. Diagnostic accuracy of sLND was assessed using eLND as the reference. SLNs were detected in all patients (detection rate 100%), with 447 sentinel lymph nodes SLNs (median 9, IQR 6-12) being identified and 966 LNs (median 18, IQR 15-23) being removed. Thirty-six percent (18/50) of patients had LN metastases (median 2, IQR 1-3). Magnetometer-guided sLND had 100% sensitivity, 97.0% specificity, 94.4% positive predictive value, 100% negative predictive value, 0.0% false negative rate, and 3.0% additional diagnostic value (LN metastases only in SLNs outside the eLND template). In vivo, one positive SLN/LN-positive patient was missed, resulting in a sensitivity of 94.4%. In conclusion, this new magnetic sentinel procedure has high accuracy for nodal staging in intermediate- and high-risk PCa. The reliability of intraoperative SLN detection using this magnetometer system requires verification in further multicentric studies.

Detection of CK19 mRNA Using One-step Nucleic Acid Amplification (OSNA) in Prostate Cancer: Preliminary Results.

Background: Accurate histopathological evaluation of lymph nodes (LNs) is essential for reliable staging in prostate cancer. In routine practice, conventional techniques only examine parts of the LN. Molecular nodal staging methods are limited by their high costs and extensive time requirement. One-step nucleic acid amplification (OSNA) determines the metastatic status of the complete LN and allows for rapid intraoperative detection of LN metastases. OSNA has been proposed for diagnosis of LN metastases from breast cancer by quantifying the CK19 mRNA copy number. To provide basic data for OSNA development for prostate cancer, we conducted an investigation of CK19 and OSNA in prostate cancer specimens. Methods: OSNA is based on a short homogenization step and subsequent automated amplification of CK19 mRNA directly from the sample lysate, with results available in 30-40 min. A total of 20 prostate cancer specimens from consecutive patients with intermediate or high-risk prostate cancer (Gleason-Score ≥7) were investigated by both OSNA and conventional histopathology (H&E staining, CK19 immunohistochemistry). OSNA was performed on frozen samples using a ready-to-use amplification kit in an automated real-time detection system. Samples were defined as 'negative' or 'positive' according to mRNA copy number: >5000 copies/µl (++), 250-5000 copies/µl (+), and <250 copies/µl (-). Results: Histopathological analysis confirmed prostate cancer in all samples: Gleason score 7 (n=11), Gleason score 8 (n=2), and Gleason score 9 (n=6). Gleason score could not be given for one patient who previously underwent hormonal treatment. OSNA analysis detected CK19 expression in 100% of the specimens and high numbers of CK19 mRNA copies in all cases (9 samples ++; 11 samples +). Immunohistochemistry confirmed CK19 expression in 19 of 20 cases. In the immunohistochemistry CK19-negative patient, a Gleason score 9 prostate cancer was diagnosed. Conclusions: This is the first study using OSNA to detect CK19 expression in prostate cancer. Initial data indicate that this rapid method for molecular LN staging reliably identifies CK19 mRNA in prostate cancer. These results suggest that the OSNA assay may be suitable to improve (intraoperative) LN staging in prostate cancer. For further verification, OSNA analysis of LN specimens from prostate cancer patients is required.

Updated Nomogram Incorporating Percentage of Positive Cores to Predict Probability of Lymph Node Invasion in Prostate Cancer Patients Undergoing Sentinel Lymph Node Dissection.

Objectives: To update the first sentinel nomogram predicting the presence of lymph node invasion (LNI) in prostate cancer patients undergoing sentinel lymph node dissection (sPLND), taking into account the percentage of positive cores. Patients and Methods: Analysis included 1,870 prostate cancer patients who underwent radioisotope-guided sPLND and retropubic radical prostatectomy. Prostate-specific antigen (PSA), clinical T category, primary and secondary biopsy Gleason grade, and percentage of positive cores were included in univariate and multivariate logistic regression models predicting LNI, and constituted the basis for the regression coefficient-based nomogram. Bootstrapping was applied to generate 95% confidence intervals for predicted probabilities. The area under the receiver operator characteristic curve (AUC) was obtained to quantify accuracy. Results: Median PSA was 7.68 ng/ml (interquartile range (IQR) 5.5-12.3). The number of lymph nodes removed was 10 (IQR 7-13). Overall, 352 patients (18.8%) had LNI. All preoperative prostate cancer characteristics differed significantly between LNI-positive and LNI-negative patients (P<0.001). In univariate accuracy analyses, the proportion of positive cores was the foremost predictor of LNI (AUC, 77%) followed by PSA (71.1%), clinical T category (69.9%), and primary and secondary Gleason grade (66.6% and 61.3%, respectively). For multivariate logistic regression models, all parameters were independent predictors of LNI (P<0.001). The nomogram exhibited a high predictive accuracy (AUC, 83.5%). Conclusion: The first update of the only available sentinel nomogram predicting LNI in prostate cancer patients demonstrates even better predictive accuracy and improved calibration. As an additional factor, the percentage of positive cores represents the leading predictor of LNI. This updated sentinel model should be externally validated and compared with results of extended PLND-based nomograms.

Reliability of radioisotope-guided sentinel lymph node biopsy in penile cancer: verification in consideration of the European guidelines.

BACKGROUND: Lymph node (LN) staging in penile cancer has strong prognostic implications. This contrasts with the high morbidity of extended inguinal LN dissection (LND) or over-treatment of many patients. Therefore, inguinal dynamic sentinel node biopsy (DSNB) or modified LND is recommended by the European Association of Urology (EAU) guidelines to evaluate the nodal status of patients with clinically node-negative penile cancer. This study analyzed the reliability and morbidity of radioguided DSNB in penile cancer under consideration of the current EAU recommendations in an experienced center with long-term follow-up. METHODS: Thirty-four patients who received primary surgery and had radioguided inguinal DSNB for penile cancer (≥ T1G2) were included (July 2004 to July 2013). Preoperative sentinel LN (SLN) mapping was performed using lymphoscintigraphy after peritumoral injection of (99m)Technetium nanocolloid on the day of surgery. During surgery, SLNs were detected using a gamma probe. According to the EAU guidelines, a secondary ipsilateral radical inguinal LND was performed in patients who had positive SLNs. The false-negative and complication rates of DSNB were assessed. RESULTS: A total of 32 patients were analyzed. Two patients were lost to follow-up. A total of 166 SLNs (median, 5; range, 1-15) were removed and 216 LNs (SLNs + non-SLNs; median, 6; range, 2-19) were dissected. LN metastases were found in five of the 32 (15.6 %) patients and nine of the 166 (5.4 %) SLNs were found to contain metastases. None of the remaining 50 non-SLNs contained metastases. In only one of the five SLN-positive patients, a singular further metastasis was detected by secondary radical inguinal LND. During follow-up (median, 30.5; range, 5-95 months) no inguinal nodal recurrence was detected. DSNB-related complications occurred in 11.1 % of explored groins. DISCUSSION AND CONCLUSIONS: Radioguided DSNB is a suitable procedure for LN staging in penile cancer considering the EAU recommendations and with the required experience. Under these circumstances, patients can be spared from higher morbidity without compromising the detection of LN metastases or therapeutic implications. Improvement of the methodology used to perform DSNB should be developed further to decrease the risk of missing LN metastases and to simplify the procedure.

First Nomogram Predicting the Probability of Lymph Node Involvement in Prostate Cancer Patients Undergoing Radioisotope Guided Sentinel Lymph Node Dissection.

INTRODUCTION: Existing nomograms predicting lymph node involvement (LNI) in prostate cancer (PCa) are based on conventional lymphadenectomy. The aim of the study was to develop the first nomogram for predicting LNI in PCa patients undergoing sentinel guided pelvic lymph node dissection (sPLND). MATERIALS AND METHODS: Analysis was performed on 1,296 patients with PCa who underwent radioisotope guided sPLND and retropubic radical prostatectomy (2005-2010). Median prostate specific antigen (PSA): 7.4 ng/ml (IQR 5.3-11.5 ng/ml). Clinical T-categories: T1: 54.8%, T2: 42.4%, T3: 2.8%. Biopsy Gleason sums: ≤ 6: 55.1%, 7: 39.5%, ≥ 8: 5.4%. Multivariate logistic regression models tested the association between all of the above predictors and LNI. Regression-based coefficients were used to develop a nomogram for predicting LNI. Accuracy was quantified using the area under the curve (AUC). RESULTS: The median number of LNs removed was 10 (IQR 7-13). Overall, 17.8% of patients (n = 231) had LNI. The nomogram had a high predictive accuracy (AUC of 82%). All the variables were statistically significant multivariate predictors of LNI (p = 0.001). Univariate predictive accuracy for PSA, Gleason sum and clinical stage was 69, 75 and 69%, respectively. CONCLUSIONS: The sentinel nomogram can predict LNI at a sPLND very accurately and, for the first time, aid clinicians and patients in making important decisions on the indication of a sPLND. The high rate of LN+ patients underscores the sensitivity of sPLND.

Targeted salvage lymphadenectomy in patients treated with radical prostatectomy with biochemical recurrence: complete biochemical response without adjuvant therapy in patients with low volume lymph node recurrence over a long-term follow-up.

BACKGROUND: Choline positron emission tomography/computed tomography (PET/CT) represents an option in restaging of prostate cancer patients with disease relapse after local treatment. The present study assess whether salvage resection of lymph node metastases detected on choline PET/CT imaging in prostate cancer patients with biochemical recurrence after radical prostatectomy can result in a long-term complete biochemical remission, without adjuvant therapy. METHODS: We analysed 13 patients with prostate specific antigen (PSA) recurrence (PSA median 1.64 ng/ml, range 0.5-9.55) after radical prostatectomy and suspicious lymph nodes (median 1; range 1-3) detected on [11C]choline and [18F]fluoroethylcholine PET/CT scans. An open salvage lymphadenectomy of positive lymph nodes in a PET/CT scan and nearby lymph nodes was carried out. We examined PSA outcome without adjuvant therapy; defined complete biochemical remission as PSA <0.01 ng/ml. Histological and PET/CT findings were compared. RESULTS: Ten of 11 patients with histologically confirmed lymph node metastases showed a PSA response. Three of ten patients with single lymph node metastases had a complete biochemical remission (median follow-up 72 months, range 31.0-83). In five cases with single lymph node metastasis PSA decreased <0.02 ng/ml. Histologically confirmed 13 of 16 metastasis suspicious lymph nodes. No lymph node metastases were detected in two patients. All of the additionally removed 30 lymph nodes were correctly negative. CONCLUSIONS: This is the first confirmation of a complete biochemical remission after PET/CT guided secondary resection of a single lymph node metastasis in prostate cancer patients with biochemical recurrence after radical prostatectomy, over the long-term (>6.5 years), without adjuvant therapy. In order to improve these promising results, longer-term studies with more patients are required.

Sentinel lymph node dissection in more than 1200 prostate cancer cases: rate and prediction of lymph node involvement depending on preoperative tumor characteristics.

OBJECTIVES: To stratify the rate and prediction of lymph node involvement in prostate cancer patients undergoing sentinel-lymphadenectomy depending on preoperative tumor characteristics, and to compare the outcome with the European Association of Urology Guideline indication for lymphadenectomy. METHODS: A total of 1229 patients (median age 66 years) were treated with open sentinel-lymphadenectomy and prostatectomy between 2005 and 2009. Median preoperative prostate-specific antigen was 7.4 ng/mL. The rate of lymph node involvement was analyzed for D'Amico risk groups. Multivariable logistic regression was used to estimate the probability of lymph node involvement. Predictor variables included preoperative prostate-specific antigen, clinical T-category and biopsy Gleason sum. Predictive accuracy has been quantified (area under the curve) and lymph node positive patients were verified under consideration of the recommended European threshold for lymphadenectomy (nomogram-predicted lymph node invasion risk of >7%). RESULTS: The median number of lymph nodes removed was 10 (interquartile range 7-13). Overall, 17.1% of patients had lymph node involvement; 3.2% in low-, 14.8% in intermediate- and 37.4% in high-risk disease. The predicted risk for lymph node involvement ranged from 2% (prostate-specific antigen ≤4 ng/mL, T1, Gleason sum ≤6) to 87% (prostate-specific antigen >20 ng/mL, T3, Gleason sum ≥8). The predictive accuracy was 82.1%. According to the European guidelines, 15.9% of all lymph node involved cases would not have been detected. CONCLUSIONS: The rate of lymph node involvement seems to be higher in the examined sentinel collective than expected according to the European Guideline nomogram. The first sentinel-based lymph node involvement prediction model can assist in deciding on the indication for sentinel-lymphadenectomy. The validation of a corresponding sentinel-based nomogram is still missing.

Complete PSA Remission without Adjuvant Therapy after Secondary Lymph Node Surgery in Selected Patients with Biochemical Relapse after Radical Prostatectomy and Pelvic Lymph Node Dissection.

Introduction. To evaluate whether secondary resection of lymph node (LN) metastases (LNMs) can result in PSA remission, we analysed the PSA outcome after resection of LNM detected on PET/CT in patients with biochemical failure. Materials and Methods. 11 patients with PSA relapse (mean 3.02 ng/mL, range 0.5-9.55 ng/mL) after radical prostatectomy without adjuvant therapy were included. Suspicious LN (1-3) detected on choline PET/CT and nearby LN were openly dissected (09/04-02/11). The PSA development was examined. Histological and PET/CT findings were compared. Results. 9 of 10 patients with histologically confirmed LNM showed a PSA response. 4 of 9 patients with single LNM had a complete permanent PSA remission (mean followup 31.8, range 1-48 months). Of metastasis-suspicious LNs (14) 12 could be histologically confirmed. The additionally removed 25 LNs were all correctly negative. Conclusions. The complete PSA remissions after secondary resection of single LNM argue for a feasible therapeutic benefit without adjuvant therapy. For this purpose the choline PET/CT is in spite of its limitations currently the most reliable routinely available diagnostic tool.

First results of [11C]choline PET/CT-guided secondary lymph node surgery in patients with PSA failure and single lymph node recurrence after radical retropubic prostatectomy.

INTRODUCTION: [(11)C]choline PET/CT provides the opportunity to detect small lymph node metastases (LNM) (>5 mm) in prostate cancer (PCa) with exact topographic allocation. PSA development after resection of single LN recurrence detected via [(11)C]choline PET/CT without adjuvant therapy is not yet analyzed. We wanted to evaluate the potential of [(11)C]choline PET/CT in the diagnosis of single LN recurrence after radical prostatectomy (RPE) and whether secondary resection can result in PSA remission. METHODS: We investigated 6 patients with biochemical recurrence (PSA: median 2.04, range 0.67-4.51 ng/ml) after RPE. A single suspicious LN was detected on PET/CT without suspicion of local relapse or distant metastasis. The suspicious and nearby LN were open dissected (09/2004-02/2008). Histological and PET/CT findings were compared and the postoperative PSA development was examined. RESULTS: All metastasis-suspicious LN could be confirmed histologically. The additionally removed 10 LN were all correctly negative for cancer. Three patients showed a complete permanent PSA remission (<0.01 (n = 2), <0.03 ng/ml (n = 1)) without adjuvant therapy (follow-up: median 24, range 21-35 months). CONCLUSIONS: In this small selected collective [(11)C]choline PET/CT achieved reliable results. After resection of single LNM in all patients the oncologic criteria of a remission were fulfilled. Three of 6 patients had a complete PSA remission without adjuvant therapy. Whether cure or a positive influence on the course of disease can be achieved in individual patients has to be shown in further studies.

Assessment of the enhancement in predictive accuracy provided by systematic biopsy in predicting outcome for clinically localized prostate cancer.

PURPOSE: Current localized prostate cancer treatment outcome nomograms rely on prostate specific antigen (PSA), tumor stage and grade. We investigated whether the addition of prostate biopsy features may enhance the accuracy of a nomogram predicting recurrence after radical prostatectomy (RP). MATERIALS AND METHODS: Clinical data from 1,152 patients who underwent RP were used and included PSA, clinical stage, biopsy Gleason grade and systematic biopsy information that quantified the amount of cancer and high grade cancer. Predictive accuracy for freedom from recurrence after RP was assessed with and without tumor quantification in the biopsy by the area under the receiver operating characteristics curve (AUC). RESULTS: Percentage and number of cores with cancer, and percentage and number of cores with high grade cancer were predictors of outcome when added to models that included PSA, Gleason grade and clinical stage (all p <0.0001). Nomogram accuracy with 3 traditional variables (AUC 0.790) was minimally enhanced with the addition of percentage or number of positive cores (AUC 0.804 and 0.800, respectively), or percentage or number of cores with high grade cancer (AUC 0.802 and 0.800, respectively). Maximum predictive accuracy of 0.811 was achieved after supplementing the traditional 3-variable nomogram with various combinations of additional pathological predictors. CONCLUSIONS: The information provided by systematic biopsies substantially improves the ability to predict outcome following RP. However, some incremental predictive accuracy was achieved by adding systematic biopsy features.

Assessment of clinical and pathologic characteristics predisposing to disease recurrence following radical prostatectomy in men with pathologically organ-confined prostate cancer.

OBJECTIVE: To identify risk factors for biochemical failure after radical prostatectomy (RP) in men with pathologically organ-confined (OC) prostate cancer (PCa). METHODS: Clinical and pathological characteristics of 331 consecutive men with pT2N0 PCa treated solely with RP were used in Cox proportional hazard models to identify independent predictors of prostate specific antigen (PSA) failure (PSA > or = 0.1 ng/ml). All pathologic specimens were step sectioned at 3 mm. RESULTS: Twelve patients (3.6%) failed at a median follow-up of 26 months (range 0.2-99.6 months) and 120 men remained at risk 3 years after RP. In univariate Cox models PSA (P < 0.001), percentage of high-grade cancer (P < 0.001) total and high-grade cancer volume (P = 0.001 and P < 0.0001, respectively) and RP Gleason sum (P = 0.003) represented significant predictors of PSA failure. Clinical stage (P = 0.4), surgical margin status (P = 0.3), age (P = 0.2), and pathologic evidence of unilateral versus bilateral PCa (P = 0.6) failed to reveal significance. In receiver operator curve (ROC) analyses, high-grade cancer volume achieved highest outcome predictive accuracy (area under the curve (AUC 0.93)), which was not exceeded by Cox regression-based nomogram combining serum PSA, RP Gleason sum, margin status and pathologic evidence of unilateral versus bilateral PCa (AUC 091). Predictive accuracy of this multivariate nomogram was not enhanced by adding total cancer volume (AUC 0.93), high-grade cancer volume (AUC 0.90), or percentage of high-grade cancer (AUC 0.90). CONCLUSIONS: In pT2N0 PCa high-grade cancer volume appears to represent the most important pathologic factor for prediction of outcome following RP. However, similar predictive accuracy may be achieved by combining routinely available tumor characteristics.

Prospective validation of an algorithm with systematic sextant biopsy to predict pelvic lymph node metastasis in patients with clinically localized prostatic carcinoma.

PURPOSE: We prospectively validate an algorithm to predict pelvic lymph node metastasis in patients with clinically localized prostatic carcinoma. MATERIAL AND METHODS: A total of 293 patients with prostatic cancer were identified before pelvic lymph node dissection according to an algorithm developed with the classification and regression tree analysis as high-greater than 3 sextant biopsies containing any Gleason grade 4 or 5 cancer, intermediate-at least 1 biopsy dominated by Gleason grade 4 or 5 cancer but not high risk and low risk-all other patients. Observed and predicted frequencies of pelvic lymph node metastasis were compared. RESULTS: The observed frequencies of lymph node metastasis were remarkably similar to the predicted frequencies, including 2.8% versus 2.2% in 85.7% of patients in the low risk group, 16.7% versus 19.4% in 10.2% intermediate and 41.7% versus 45.5% in 4.1% high, respectively. If patients in the low risk group were considered to have node negative disease the specificity and negative predictive value of the algorithm were 88.4% and 97.2%, respectively. CONCLUSIONS: Our algorithm is valid as a simple and accurate tool for the prediction of pelvic lymph node metastasis in patients with clinically localized prostatic cancer. Those 85.7% of patients classified by the algorithm to have a low risk of lymphatic spread should not undergo pelvic lymph node dissection before definitive local treatment.