Advances in radiology and pathology of prostate cancer: a review for the pathologist.

Multiparametric magnetic resonance imaging (mpMRI) has improved systematic prostate biopsy procedures in the diagnosis of clinically significant prostate cancer (csPCa) by reducing the number of unnecessary biopsies; numerous level one evidence studies have confirmed the accuracy of MRI-targeted biopsy, but, still today, systematic prostate biopsy is recommended to reduce the 15-20% false negative rate of mpMRI. New advanced imaging has been proposed to detect suspicious lesions and perform targeted biopsies especially when mpMRI cannot be performed. Transrectal ultrasound (TRUS) modalities are emerging as methods with greater sensitivity and specificity for the detection of PCa compared to the traditional TRUS; these techniques include elastography and contrast-enhanced ultrasound, as well as improved B-mode and Doppler techniques. These modalities can be combined to define a novel ultrasound approach: multiparametric ultrasound (mpUS). More recently, micro-ultrasound (MicroUS) and prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) have demonstrated to be sensitive for the detection of primary prostatic lesions resulting highly correlated with the aggressiveness of the primary prostatic tumor. In parallel, artificial intelligence is advancing and is set out to deeply change both radiology and pathology. In this study we address the role, advantages and shortcomings of novel imaging techniques for Pca, and discuss future directions including the applications of artificial intelligence-based techniques to imaging as well as histology. The significance of these findings for the practicing pathologist is discussed.

Empiric antibiotics therapy for mildly elevated prostate specific antigen: Helpful to avoid unnecessary biopsies?

PURPOSE: The management of mildly elevated (4.0-10.0 ng/ml) prostate specific antigen (PSA) is uncertain. Immediate prostate biopsy, antibiotic treatment, or monitoring PSA level for 1-3 months is still in controversy. MATERIALS AND METHODS: We retrospectively analysed the effect of empiric antibiotics on an increased PSA in a mono-institutional study. We analysed the data of 100 patients with a PSA of 4-10 ng/ml and normal digital rectal examination undergoing their first prostate biopsy. Patients were divided in two different cohorts. One cohort was submitted to antibiotic therapy (Levoxacin 500 mg daily for 20 days) and both cohort had a re-dosing of PSA before the prostate biopsy. RESULTS: Average age of the whole group of patients was 66.48 ± 8.32 years and their average initial PSA level was 6.67 ± 1.57 ng/mL. In the treated group (N = 49) 29 patients had a decreasing PSA value from mean baseline PSA value of 6.6 ± 1.54 ng/ml to the re-dosed mean PSA level of 5.4 ± 1,61 ng/ml (p = 0.7); 20 patients didn't experience a decrease PSA value, with a mean PSA level of 6.9 ± 1.68 ng/ml. In the control group (N = 51), 30 patients had a decrease of PSA level from mean baseline PSA level of 6.5 ± 1,59 ng/ml to a re-dosed PSA level of 5.5 ± 1.57 ng/ml; 21 patients didn't experience a decrease of PSA value, with a mean PSA level of 6.7 ± 1.71 ng/ml. Multivariate analysis of age, PSA changes, antibiotics therapy and biopsy results (presence or absence of cancer) revealed no significant difference between the two cohorts. Sepsis after biopsy occurred in 3 patient in the antibiotics group (6%) and in one of the control group (2%). CONCLUSIONS: The study, even with some limitations, does not seem to show an advantage due to the administration of antibacterial therapy to reduce PSA values before prostate biopsy and subsequently to reduce unnecessary prostate biopsies.

Observational database serenoa repens (DOSSER): overview, analysis and results. A multicentric SIUrO (Italian Society of Oncological Urology) project.

OBJECTIVE: Men affected with Benign Prostate Hyperplasia (BPH) and Lower Urinary Tract Symptoms (LUTS) are demonstrating to require an increasing amount of attention from Urologists and Primary-care Physicians. Over the years, common urological medications were based on either alpha-blockers and/or 5alpha-reductase inhibitors. During the last decade the phytotherapeutic drugs are gaining a more often central role in the BPH and LUTS managements. In particular, clinical usage of the extract of the dried ripe fruit of serenoa repens with a dosage of 320 mg per day, has shown its clinical efficacy and its superiority. Purpose of this multicentric observational retrospective study was to evaluate all the urological aspects (clinical, biochemical, instrumental and pathological) of patients affected by BPH and LUTS, with a PSA < 10 ng/ml, a previous negative prostatic biopsy and in therapy with a daily dose of 320/640 mg of serenoa repens. PATIENTS AND METHODS: The study was conducted in 8 different centers throughout Italy from September 2010 to November 2011. Data and information of 298 men with an average of 63 years (mean PSA of 5.4 ng/ml and mean prostate gland volume of 57 cc), affected by non-acute urinary symptoms caused by BPH, a dosed PSA level inferior to 10 ng/ml, a previous negative prostate biopsy and in therapy with serenoa repens alone or associated to an alpha-blocker, were retrospectively inserted in an extensive on-line SIUrO Database. Comprehensive questionnaires were filled in for each patient at 3 and 6 months of follow-up. Each questionnaire contained various sections, each of them composed by several items: dosed PSA levels, uroflowmetry, International Prostate Symptoms Score (IPSS), International Index of Erectile Function (IIEF-5), trans-rectal ultrasound (TRUS) patterns, digital rectal examinations (DRE) aspects, previous prostate bioptical results (histology) and side effects. RESULTS: PSA levels weren't subjected to an increase, revealing a stabilizing or downward trend. Percentage of patients with PSA below the level of 4 ng/mL was lower at the end of the study. The overall changes in the uroflowmetry were similar and parallel both in the group with only serenoa repens intake and in the group with serenoa repens plus alpha-blocker. The mean medium flow and the mean maximum flow had a slightly increase along the observation time. There was a substantial decreasing in the amount of patients presenting severe prostatic symptoms. Patients reported through the IIEF-5 score a sexual activity substantially unchanged after 6 months of follow-up. The serenoa repens intake resulted in an improvement of the "inflammatory-like reports", in terms of ultrasound patterns, DRE and bioptical features. CONCLUSIONS: serenoa repens demonstrated its efficacy reducing dysuria with minimal side effects. Further prospective studies might confirm its stabilization or lowering role on PSA levels in this cohort of patients and its possible clinical anti-inflammatory action.

Blood donors: an ideal population to study the PSA value and the incidence of prostate cancer in healthy population.

Population screening for prostatic carcinoma (CP) is a debated topic, and its real utility is still unknown. Nowadays only surveys on little groups or clinical randomized studies are recommended. In this study the male population of blood donors of our hospital aged between 45 and 65 years underwent a complete evaluation for CP. The objectives of the study were: (a) early diagnosis of CEP (b) exclusion of carriers of neoplastic pathology from blood donations (theoretic risk of transmission of neoplastic cells in immunodepressed patients); (c) evaluation of the feasibility of a model to be exported to other Transfusion Centres if successful with an high adhesion rate to the screening. A total of 1387 PSA dosages were obtained on 605 patients. In the 45 to 49 years group PSA value ranged from 0.26 to 2.86 ng/mL (mean and median value were 0.85 and 0.68 respectively), in the 50-59 years group PSA range was 0.6 to 7.96 (mean and median value 1.21 and 0.87 respectively) and in the 60 to 69 years group PSA ranged from 0.7 to 293.67 (mean and median 3.6 and 1.29 respectively). A total of 32 biopsies for high PSA values and/or for suspect digital rectal finding were performed allowing diagnosis of prostate adenocarcinoma in 15 subjects (2.4%). Out of them, 14 underwent radical prostatectomy (9 pT2 - 5 pT3), and one was placed on hormonal therapy

Lessons from 52 patients with leydig cell tumor of the testis: the GUONE (North-Eastern Uro-Oncological Group, Italy) experience.

INTRODUCTION: The goal of the study was to define treatment rules for the uncommon, rarely (10%) malignant and chemorefractory Leydig cell tumors (LCT) of the testis. METHODS: The main clinical data of patients treated in centers affiliated to the GUONE (North-Eastern Uro-Oncological Group, Italy) were reviewed. We considered 52 patients (54 tumors, 2 bilateral) whose ages ranged from 13 to 70 years (mean 36). Of the treatments performed, 52 were orchiectomies and 2 were enucleations (unfavorable pathology in only 2 tumors). There were 5 lymphadenectomies (retroperitoneal lymph node dissections): 2 for suspected stage II disease and 1 each for unfavorable pathology, bilateral disease and associated Sertoli tumor (pathology: pN0 in all cases). The length of follow-up ranged from 15 to 249 months (mean 81). RESULTS: There was no relapse in 51 patients and 1 died as a result of metastatic disease (orchiectomy at the age of 70; unremarkable pathology). CONCLUSIONS: Malignant LCT seems to be, in our experience, less frequent than previously reported. Age and pathology are useful prognostic factors, but their predictive value should never be considered absolute. Enucleation seems justified in young patients with favorable pathology. In clinical stage I LCT, retroperitoneal lymph node dissection should be offered to older patients and/or to patients with unfavorable pathology. A prolonged follow-up is mandatory.

Renal cell carcinoma. 2002 TNM classification is still adequate?

The TNM classification should be a tool that allows the physician to make therapeutic decisions and gain even a prognostic scheme. Currently, the 2002 TNM classification for kidney cancer doesn't have these features. Really it doesn't make a distinction when performed a conservative therapy in the early stages: literature and the clinical experience suggest that the criteria for a partial resection of the kidney is the location of the tumour, rather than its size; for this reason, the division pT1 a-pT1b is rather outdated. Moreover, the T2 category, isto-pathologically restricted, receives less than 2% of all kidney cancers; into the T3 category, if there is also adrenal invasion, it makes a worse prognostic trend, similar to T4 category. The TNM classification, moreover, is inaccurate and unclear regarding the staging of lymph node involvement. For these reasons the TNM classification for parenchymal renal cell carcinoma is unreliable, so an appropriate review of the classification is needed.

Systematic development of clinical practice guidelines for prostate biopsies: a 3-year Italian project.

BACKGROUND: The only available method to detect prostate cancer is prostate biopsy; however, to our knowledge, no evidence-based clinical practice guidelines have been established on this topic. MATERIALS AND METHODS: A three-year project was elaborated in which experts in the field worked to define the controversies existing in clinical practice regarding prostatic biopsies and then to develop guidelines by means of a systematic search of all the English-language literature using online databases and a consensus conference. RESULTS AND CONCLUSION: The guidelines were formulated to help practitioners in making clinical decisions regarding the appropriate time the patient should undergo prostate biopsy, the type of antibiotic prophylaxis and anaesthesia, the biopsy approach, the method for processing and reporting prostatic needle cores, the biopsy technique, when to repeat a biopsy after a prior negative biopsy, radiotherapy or radical prostatectomy and the accuracy of biopsies in staging prostate cancer.

Italian Prostate Biopsies Group: 2016 Updated Guidelines Insights.

AIM: To present a summary of the updated guidelines of the Italian Prostate Biopsies Group following the best recent evidence of the literature. MATERIALS AND METHODS: A systematic review of the new data emerging from 2012-2015 was performed by a panel of 14 selected Italian experts in urology, pathology and radiology. The experts collected articles published in the English-language literature by performing a search using Medline, EMBASE and the Cochrane Library database. The articles were evaluated using a systematic weighting and grading of the level of the evidence according to the Grading of Recommendations Assessment, Development and Evaluation framework system. RESULTS: An initial prostate biopsy is strongly recommended when i) prostate specific antigen (PSA) >10 ng/ml, ii) digital rectal examination is abnormal, iii) multiparametric magnetic resonance imaging (mpMRI) has a Prostate Imaging Reporting and Data System (PIRADS) ≥4, even if it is not recommended. The use of mpMRI is strongly recommended only in patients with previous negative biopsy. At least 12 cores should be taken in each patient plus targeted (fusion or cognitive) biopsies of suspicious area (at mpMRI or transrectal ultrasound). Saturation biopsies are optional in all settings. The optimal strategy for reducing infection complications is still a controversial topic and the instruments to reduce them are actually weak. The adoption of Gleason grade groups in adjunction to the Gleason score when reporting prostate biopsy results is advisable. CONCLUSION: These updated guidelines and recommendations are intended to assist physicians and patients in the decision-making regarding when and how to perform a prostatic biopsy.

The effects of renal ischemia on kidney function in renal cancer conservative surgery.

Over the past ten years nephron sparing surgery for renal cancer has been compared to radical nephrectomy for what concern oncological results, even in elective situations but it is necessary to consider functional results (renal function) as well. Clamping renal artery, inducing a temporary renal ischemia that might represent the major known cause of permanent renal damage, is advised for both open and laparoscopic conservative approach. Data from literature show that before the clamping, the patient should be adequately hydrated and receive mannitol. Ischemia should last preferentially less than 30 minutes and kidney cooling should be advised in case of more prolonged ischemia. Artery reclamping should be avoided. Both in warm and cold ischemia, the renal tissue should be perfused by mannitol once the circulation is resumed.

Evaluating serum insulin-like growth factor 1 and insulin-like growth factor binding protein 3 as markers in prostate cancer diagnosis.

BACKGROUND: Prostate-specific antigen (PSA) lacks specificity and sensitivity in discriminating prostate cancer (PCa) from benign prostatic hyperplasia (BPH) when the total PSA (tPSA) level is between 4 and 10 ng/mL. It remains to be investigated if additional tumor-associated molecules may improve the PCa diagnostic accuracy. The aim of the present study was to investigate whether serum levels of insulin-like growth factor 1 (IGF1), insulin-like growth factor binding protein 3 (IGFBP3) and their combinations with PSA may enhance the diagnosis of PCa. METHODS: Serum tPSA and free PSA (fPSA) levels were measured using an automated chemiluminescence-based method. IGF1 and IGFBP3 levels were evaluated by radioimmunoassays in a prospectively and consecutively enrolled subset of 149 patients with tPSA ≤10 ng/mL made up of patients with benign prostatic hyperplasia (BPH; n = 113) and PCa (n = 36). RESULTS: IGF1 and IGFBP3 serum levels did not significantly differ between the PCa and BPH groups. No important correlation was found between the IGF molecules and PSA isoforms in both groups. Statistical analysis of the combination of markers indicated that only the free/total PSA ratio (f/tPSA%) was informative and independent in predicting the presence of PCa, considering that for high values of this percentage (17%) the probability of finding PCa decreased. Receiver operating characteristics areas under the curve (AUC) for IGF1 and IGFBP3 were not informative (AUC ~0.5 in both cases) contrary to the AUC for f/tPSA% (AUC = 0.689, p = 0.0002). CONCLUSIONS: The present study showed that neither IGF1 and IGFBP3 alone nor in combination with PSA enhance the diagnostic performance of PSA in PCa.

New experimental models for the in vitro reconstitution of human bladder mucosa.

This study describes two experimental models for the in vitro reconstitution of the human bladder mucosa (neo-bladder): human urothelial stabilized cell lines were cultured on three-dimensional matrices, collagen or platelet-fibrin gels, containing murine fibroblast 3T3-J2 cells. Low-density seeding (2x10(4) cells/ml) of both normal (TCA-48) and neoplastic cell lines (TCA-47) on collagen matrix gave rise to isolated papillar colonies, while high-density seeding (3.75x10(6) cells/ml) led to the formation of wide pluristratified epithelial sheets, resembling the normal transitional epithelium. In contrast, high-density seeding (5x10(5) cells/ml) on platelet-fibrin matrix did not allow the formation of epithelial sheets: only isolated voluminous colonies of normal TCA-48 cells, and sparse and small colonies of neoplastic TCA-47 could be observed. Growth assays and cytotoxicity reduction tests showed that the growth inhibitory effect of platelet-fibrin gel on urothelial cells was probably due to the aspecific activation of the complement contained in the plasmatic fraction, whose precipitation forms fibrin-glue. Collectively, these findings allow us to draw the following conclusions: i) neobladders obtained by culturing urothelial cells on collagen matrix reproduce normal bladder mucosa and could be utilized in pharmacological studies; and ii) platelet-fibrin gels, that specifically inhibit neoplastic urothelial cell growth, could be used as scaffolds in surgical bladder reconstitution.

[Response to a cognitive questionnaire on the guideline project of prostatic biopsy of the SIEUN--GUONE--SIUrO--SIBioC]. / Risposte ad un questionario conoscitivo nell'ambito del progetto linee guida sulla biopsia prostatica della SIEUN--GUONE--SIUrO--SIBioC.

Ultrasound guided systemic sextant needle biopsy of the prostate is the procedure of choice for the diagnosis of prostate cancer. During the past 50 years, the techniques, indications, and pathologic interpretation of prostate biopsies have evolved. Moreover, the indications for prostate biopsy have become more refined. This paper provides the results of an interactive questionnaire on ultrasound guided biopsy of the prostate. 14 questions have been selected. A range of 102-109 answers have been collected for every questions at Castrocaro (Fo) during the 14th National Congress of the Italian Society of Urological, Andrological and Nephrological Ultrasound on May 3rd 2002.

[Prostatic tumor: how many biopsies?]. / Tumore prostatico: quante biopsie?

INTRODUCTION: Ultrasound-guided prostatic biopsy is usually performed by sextants according to Hodge, but the authors feel that 6 biopsies are insufficient. It has been suggested that the number of prostatic biopsies be increased and the mapped areas extended, but this causes discomfort to patients and increases effective costs. The authors suggest repetition of biopsies in "risk" cases, routinely selecting patients taking into account the best cost-benefit ratio. MATERIALS AND METHODS: From January 2000 to December 2001, 682 first series biopsies were performed on as many patients. A Stamey modified sextant technique was used: 6 biopsies, 3 on each side carried out more posterolaterally than the original technique. The biopsy procedure was repeated within 4 months in 11 patients with high risk clinical parameters (PSA > 10 or high PSA and prostatic nodule). During the period of observation, 25 patients had over 0.75 ng/year increase in their PSA and so biopsies were repeated. RESULTS: After the first biopsy series, 277 were positive. Of the 11 repeated biopsies, 3 were positive. Of the 25 patients with altered PSA velocity, 9 were positive. DISCUSSION AND CONCLUSIONS: It has been shown that only 10-12% of biopsies are false negative in the sextant biopsy series when taken posterolaterally. The techniques that increase the number of biopsies have around 3-5% false negatives, but this involves more discomfort for the patient, local anaesthesia and a possible increase in complications. The procedure whereby biopsies were only repeated in patients with high risk clinical elements, saved 3852 biopsies from being carried out, with an economic saving (just on the histological exam that was not carried out) assessed at 59.681,80 Euro (115,560,000 Lire) for our Local Health Service.

Evidence-based guidelines for the treatment of lower urinary tract symptoms related to uncomplicated benign prostatic hyperplasia in Italy: updated summary from AURO.it.

BACKGROUND: The first Italian national guidelines were developed by the Italian Association of Urologists and published in 2007. Since then, a number of new drugs or classes of drugs have emerged for the treatment of lower urinary tract symptoms (LUTS) related to benign prostatic hyperplasia (BPH), new data have emerged on medical therapy (monotherapies and combination therapies), new surgical techniques have come into practice, and our understanding of disease pathogenesis has increased. Consequently, a new update of the guidelines has become necessary. METHODS: A structured literature review was conducted to identify relevant papers published between 1 August 2006 and 12 December 2010. Publications before or after this timeframe were considered only if they were recognised as important milestones in the field or if the literature search did not identify publications within this timeframe. The quality of evidence and strength of recommendations were determined according to the Grading of Recommendations Assessment, Development and Evaluation framework. MAIN FINDINGS: Decisions on therapeutic intervention should be based on the impact of symptoms on quality of life (QoL) rather than the severity of symptoms (International Prostate Symptom Score (IPSS) score). A threshold for intervention was therefore based on the IPSS Q8, with intervention recommended for patients with a score of at least 4. Several differences in clinical recommendations have emerged. For example, combination therapy with a 5α-reductase inhibitor plus α blocker is now the recommended option for the treatment of patients at risk of BPH progression. Other differences include the warning of potential worsening of cognitive disturbances with use of anticholinergics in older patients, the distinction between Serenoa repens preparations (according to the method of extraction), and the clearly defined threshold of prostate size for performing open surgery (>80 g). While the recommendations included in these guidelines are evidence based, clinical decisions should also be informed by patients' clinical and physical circumstances, as well as patients' preferences and actions. CONCLUSIONS: These guidelines are intended to assist physicians and patients in the decision-making process regarding the management of LUTS/BPH, and support the process of continuous improvement of the quality of care and services to patients.

Analysis of costs of transrectal prostate biopsy.

INTRODUCTION: Literature reports mortality and morbidity data from prostatic carcinoma which permit a better use of some routine diagnostic tools such as transrectal ultrasound-guided biopsy. The aim of this work is to quantify the overall cost of transrectal ultrasound biopsy of the prostate (TRUSB) and to assess the economic impact of current procedures for diagnosing prostatic carcinoma. MATERIALS AND METHODS: The total cost of TRUSB was calculated with reference to 247 procedures performed in 2008. The following cost factors were evaluated: personnel, materials, maintenance/depreciation of the equipment, energy consumption, and hospital overheads. A literature review was also carried out to check if our extrapolated costs corresponded to those of other authors worldwide, and to consider them in the wider framework of the economic effectiveness of strategies for early diagnosis of cancer of the prostate. RESULTS: The overall cost of TRUSB (8 samples) was EUR 249,000, obtained by adding together the costs of: personnel (EUR 160,000); materials (EUR 59,000); equipment maintenance and depreciation (EUR 12,400); energy consumption (EUR0,1); hospital overheads (EUR 17,500). With extended or saturation biopsies the cost increases for the more time needed by pathologists and can be calculated as EUR 300,000. The literature review points out TRUSB as an invasive tool for diagnosing prostatic carcinoma, clinically and economically controversial. Post-mortem data report the presence of cancer cells in the prostate of 50% of 70-year-old men, while extrapolations calculate a morbidity rate from prostatic carcinoma in 9.5% of 50-year-old men. It is therefore obvious that randomized prostatic biopsies, methods apart, have a good probability of being positive. This probability varies with the patient's age, the level of prostate specific antigen (PSA), the density of PSA/cm3 of prostate volume (PSAD), and the detection by digital exploration and/or positive transrectal ultrasound. CONCLUSIONS. Despite the severe application of all these criteria and the critical assessment of the patient's general conditions, TRUSB is indicated for 16% of the male population over 50 years of age, with obvious economic consequences. Quite recently the clinical utility of assays of PSA derivatives (such as Pro-2PSA) has gained more and more importance. The Pro-2PSA seems to reduce the use of TRUSB.

Nomogram predictive of pathological inguinal lymph node involvement in patients with squamous cell carcinoma of the penis.

PURPOSE: In penile cancer the therapeutic benefits of early inguinal lymphadenectomy must be counterbalanced by the high rates of morbidity, postoperative complications and mortality. A relevant aim is optimizing the selection of the patients who could really have the highest survival advantage from inguinal lymphadenectomy, limiting the cases in which this surgery might be considered over treatment with a risk of severe complications. We generated a nomogram estimating the risk of pathological inguinal lymph node involvement according to clinical lymph node stage and pathological findings of the primary tumor. MATERIALS AND METHODS: We retrospectively collected the clinical and pathological data of 175 patients who had undergone surgical therapy for squamous cell carcinoma of the penis from 1980 to 2002 at 11 urological centers in northeastern Italy. A logistic regression model was used to construct the nomogram. RESULTS: The presence of palpable groin lymph nodes and the histological findings of vascular and/or lymphatic embolization were important predictors of metastatic inguinal lymph node involvement. The nomogram predicting the risk of metastatic lymph node involvement showed a good concordance index (0.876) and good calibration. CONCLUSIONS: The clinical stage of groin lymph nodes and pathological findings of penectomy specimens allowed us to generate a nomogram to predict the probability of metastatic lymph node involvement in patients with squamous cell carcinoma of the penis. The statistical model showed an excellent ability to identify the patients with lymph node metastases and good calibration.

Nomogram predictive of cancer specific survival in patients undergoing partial or total amputation for squamous cell carcinoma of the penis.

PURPOSE: We created the first nomograms to predict cancer specific survival probabilities of patients with squamous cell carcinoma of the penis, clustering prognostic information from the most commonly used clinical and pathological variables. MATERIALS AND METHODS: We retrospectively collected clinical and pathological data from 175 patients who had undergone surgery for squamous cell carcinoma of the penis from 1980 to 2002 at 11 urological centers in northeastern Italy. A logistic regression model was used to construct the nomogram. RESULTS: At a median followup of 24 months, 101 patients (57.7%) were alive and disease-free while 74 (42.3%) died of penile cancer. According to multivariate analyses, 2 models predictive of cancer specific survival probability were generated. The first model was based on the pathological findings of the primary tumor after penectomy and on the clinical stage of groin lymph nodes, while the second model included the pathological data of the primary tumor and groin lymph nodes. The concordance index was 0.728 for the first model and 0.747 for the second. Calibration appeared to be good in both models. CONCLUSIONS: In this article we propose 2 models to predict the 5-year cancer specific survival probabilities of patients with squamous cell carcinoma of the penis. Both models showed good discriminating power and calibration in predicting patient 5-year cancer specific survival. These nomograms could improve the quality of prognostic data provided to patients and support physicians in planning treatment.

Lymphatic and vascular embolizations are independent predictive variables of inguinal lymph node involvement in patients with squamous cell carcinoma of the penis: Gruppo Uro-Oncologico del Nord Est (Northeast Uro-Oncological Group) Penile Cancer data base data.

BACKGROUND: The objective of the current study was to identify independent clinical and pathologic variables that were predictive of lymph node involvement in patients with squamous cell carcinoma of the penis in a multicenter series with the intent to select patients who were suitable to undergo immediate inguinal lymphadenectomy. METHODS: Data were analyzed from 175 patients who underwent surgery for penile carcinoma in 11 urologic centers participating in the Gruppo Uro-Oncologico del Nord-Est (Northeast Uro-Oncological Group) Penile Cancer Data Base. Pathologically positive lymph nodes were defined as the presence of histologically confirmed lymph node metastasis in patients who underwent either immediate or delayed inguinal and/or pelvic lymphadenectomy. Patients who had clinically positive lymph nodes with cytologically positive fine-needle aspiration results and who had not undergone lymphadenectomy were censored. RESULTS: Overall, lymph-node involvement was observed in 71 of 175 patients (40.6%) included in the analyses. After analyzing the whole group of patients, the following variables were identified as independent predictors of pathologic lymph node metastasis: clinical lymph node status, pathologic stage of the primary tumor, venous and lymphatic embolizations, and histologic grade. In the subgroup of patients with clinically negative lymph nodes, tumor thickness, histologic grade, lymphatic and venous embolizations, infiltration of both corpus spongiosum and urethra, and pathologic stage of the primary tumor (according to the 1997 TNM classification system) were predictive of lymph node involvement on univariate analysis. The generated logistic regression model showed that venous and/or lymphatic embolizations and infiltration of the corpus spongiosum and/or urethra were independent predictors of pathologic lymph node metastasis in patients with clinically negative lymph nodes. CONCLUSIONS: Venous and/or lymphatic embolizations played relevant roles as predictors of pathologic lymph node involvement in patients with penile neoplasia and should be considered important parameters in determining which patients with clinically negative lymph nodes should undergo immediate lymphadenectomy.