External validation of a nomogram for identification of pathologically favorable disease in intermediate risk prostate cancer patients.

OBJECTIVE: To establish an external validation of the new nomogram from Gandaglia et al which provides estimates of the probability of pathological favorable disease in pre-operatively defined intermediate-risk PCa. PATIENTS AND METHODS: Overall, 2928 intermediate-risk PCa patients according to the D'Amico classification undergoing RP and bilateral lymph node dissection in seven academic centres between 2000 and 2011. Pathologically favorable PCa was defined as low-grade organ-confined disease. The Receiver Operating Characteristic (ROC) curve was obtained to quantify the overall accuracy (Area Under the Curve, AUC) of the model to predict specimen-confined (SC) disease. Calibration curve was then constructed to illustrate the relationship between the risk-estimates obtained by the model and the observed proportion of SC disease. Kaplan-Meier method was used for PSA recurrence-free survival (PSA-RFS) assessment. RESULTS: Median age was 68 years. 10.6% patients finally presented pathologically favorable disease characteristics at RP. A higher PSAD (OR = 0.01; 95%CI = 0.00-0.04; P < 0.0001) and percentage of positive cores (OR = 0.97; 95%CI = 0.96-0.98; P < 0.0001) were associated with a reduced probability of favorable disease at RP in multivariate analysis. ROC curve analysis showed strongest accuracy of the model (AUC = 0.82; 95%CI = 0.79-0.84). Favorable PCa had a significantly better PSA recurrence-free survival rates as compared to unfavorable PCa after RP (94.2% vs 74.4% at 4 years, P < 0.0001). CONCLUSIONS: This external validation of the Gandaglia nomogram shows relevant accuracy with one out of ten patients in this intermediate risk PCa group with pathologically proven organ-confined disease. This validated risk calculator can help physician to distinguish favorable intermediate risk PCa that can be treated by conservative approach or safer nerve-sparing surgery.

Quantified analysis of histological components and architectural patterns of gleason grades in apparent diffusion coefficient restricted areas upon diffusion weighted MRI for peripheral or transition zone cancer locations.

PURPOSE: To quantify and compare the histological components and architectural patterns of Gleason grades in cancerous areas with restriction on apparent diffusion coefficient (ADC) maps. MATERIALS AND METHODS: Twelve consecutive cases with 14 separate ADC restriction areas, positive for cancer in the peripheral zone (PZ) and transition zone (TZ) were included. All had 3 Tesla MRI and radical prostatectomy. Ten regions of interest (ROIs) within and outside the 14 ADC restriction areas positive for cancer were selected. For each ROI, we performed quantitative analysis of (a) prostate benign and malignant histological component surface ratios, including stroma, glands, epithelium, lumen, cellular nuclei; (b) percent of Gleason grades and measures of ADC values. Means of histological components according to ADC restriction for cancerous area were compared with analyses of variance with repeated measures. RESULTS: Independent predictors of the probability of cancer were median epithelium/ROI ratio (P = 0.001) and nuclei/ROI ratio (P = 0.03). Independent predictors of the probability of ADC restriction were malignant glands/ROI and luminal space/ROI (P < 0.0001). Effect of malignant glands/ROI area was different according to the localization of the ROI (P = 0.03). We observed an overall difference between the means for all of the histological components for the comparison of true positive and false negative (P < 0.0001), except for the percent of Gleason grade 4 (P = 0.18). In TZ cancers, a predominant grade 3 pattern was associated with low ADC values. In PZ cancers, a predominant grade 4 pattern was associated with low ADC values. CONCLUSION: Determinants of low ADC were high ratio of malignant glands/ROI area which may be seen in Gleason grades 3 or 4 cancers. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2017;46:1786-1796.

Robot-assisted partial prostatectomy for anterior prostate cancer: a step-by-step guide.

OBJECTIVE: To describe a step-by-step guide to robot-assisted anterior partial prostatectomy (RA-APP) for isolated magnetic resonance imaging (MRI)-detected anterior prostate cancer (APC). PATIENTS AND METHODS: After Institutional Review Board approval, over an 8-year period (2008-2015), 17 consenting patients were enrolled in a prospective, single-arm, single-centre, Idea, Development, Evaluation, Assessment and Long-term evaluation of innovative surgery (IDEAL) phase 2a study. The inclusion criteria comprised pre-urethral, low-intermediate risk APC diagnosed by MRI and targeted biopsies. Patient position and port placement were identical to the transperitoneal RA radical prostatectomy procedure. Three steps of dissection were identified in the following order: (i) retrograde apical, after dorsal venous plexus division, transition zone (TZ) enucleation, and distal peripheral zone (PZ) sectioning; (ii) antegrade, at the bladder neck (BN) after anterior BN sectioning, TZ enucleation up to the verumontanum; and (iii) lateral dissections, including anterolateral PZ sectioning without incision of the endopelvic fascia. We report the incidence of perioperative complications. The RA completion of prostatectomy in four cases with cancer recurrence was performed at 0.3, 2.5, 2 and 2 years, respectively. RESULTS: The RA-APP comprised en bloc excision of the anterior part of the prostate comprising of the anterior fibromuscular stroma, BN, prostate adenoma (TZ and median lobe) along with the proximal prostate urethra, PZ apical anterior horns, anterior aspect of the distal (sub-montanal) urethra, and anterior BN. The posterolateral parts of the PZ and distal (sub-montanal) urethra and peri-prostatic tissues were preserved intact. The bladder opening was sutured to the anterior sphincteric urethra wall and PZ lateral edges. The technique was feasible in all cases with no conversion to an open procedure. Perioperative complications were only Clavien-Dindo grade II. RA completion of prostatectomy was feasible in the four cases with cancer recurrence. CONCLUSION: PZ prostate-sparing RA-APP for isolated APC is feasible and safe, and represents an option for highly selected men with APCs as an alternative to other focal ablative therapy.

Improved decision making in intermediate-risk prostate cancer: a multicenter study on pathologic and oncologic outcomes after radical prostatectomy.

BACKGROUND: Prognoses for intermediate-risk prostate cancer (PCa) remain heterogeneous. Improved substratification could optimize treatment and monitoring strategies. The objective was to validate this subclassification in a radical prostatectomy (RP) series. METHODS: Between 2000 and 2011, 4038 patients who underwent RP for intermediate-risk PCa in seven French academic centers were included. Unfavorable intermediate-risk (UIR) PCa was defined as having a primary Gleason score of 4, ≥50% positive biopsy cores (PPBC), or more than one D'Amico intermediate-risk factor (i.e., cT2b, PSA 10-20, or Gleason score 7). Remaining PCa cases were classified as favorable. Main endpoints were pathologic results (pT stage, final Gleason score, surgical margin status), and oncologic outcomes were assessed according to PSA recurrence-free survival (PSA-RFS). Univariate and multivariate analyses were performed using the log-rank test and the Cox proportional hazards model. RESULTS: Median follow-up was 48 months (95% CI = [45-49]). Patients with UIR had worse PSA-RFS (68.17 vs. 81.98% at 4 years, HR = 1.97, 95% CI = [1.71; 2.27], p < 0.0001) compared to those with a favorable disease. The need for adjuvant therapy was significantly greater for UIR patients (43.5 vs. 29.2%, p < 0.0001). In multivariate analysis, primary Gleason score of 4 (HR = 1.81, 95% CI = [1.55; 2.12], p < 0.0001) and PPBC ≥ 50% (HR = 1.26, 95% CI = [1.02; 1.56], p = 0.0286) were significant preoperative predictors for worse PSA-RFS. CONCLUSIONS: This study highlights the heterogeneity of NCCN intermediate-risk patients and validates (in a large RP cohort) the previously proposed subclassification for this group. This classification can significantly predict both pathologic and oncologic outcomes. This easy-to-use stratification could help physicians' decision making. Prospective study and new tools as genomic tests and novel molecular-based approaches can improve this stratification in the future for patient counseling.

Focal therapy as primary treatment for localized prostate cancer: definition, needs and future.

Focal therapy (FT) may offer a promising treatment option in the field of low to intermediate risk localized prostate cancer. The aim of this concept is to combine minimal morbidity with cancer control as well as maintain the possibility of retreatment. Recent advances in MRI and targeted biopsy has improved the diagnostic pathway of prostate cancer and increased the interest in FT. However, before implementation of FT in routine clinical practice, several challenges are still to overcome including patient selection, treatment planning, post-therapy monitoring and definition of oncologic outcome surrogates. In this article, relevant questions regarding the key steps of FT are critically discussed and the main available energy modalities are analyzed taking into account their advantages and unmet needs.

Impact of arterial input function selection on the accuracy of dynamic contrast-enhanced MRI quantitative analysis for the diagnosis of clinically significant prostate cancer.

PURPOSE: Using a limited temporal resolution dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) dataset to assess the impact of the arterial input function (AIF) choice on the transfer constant (K(trans) ) to distinguish prostate carcinoma (PCa) from benign tissue. MATERIALS AND METHODS: Thirty-eight patients with clinically important peripheral PCa (≥0.5 cc) were retrospectively studied. These patients underwent 1.5T multiparametric prostate MR with PCa and benign regions of interest (ROIs) selected using a visual registration with morphometric reconstruction obtained from radical prostatectomy. Using three pharmacokinetic (PK) analysis software programs, the mean K(trans) of ROIs was computed using three AIFs: an individual AIF (Ind-AIF) and two literature population average AIFs of Weinmann (W-AIF) and of Fritz-Hansen (FH-AIF). A pairwise comparison of the area under the receiver operating characteristic curves (AUROCC) obtained with different AIFs was performed. RESULTS: AUROCCs obtained with W-AIF (ranging from 0.801 to 0.843) were significantly higher than FH-AIF (ranging from 0.698 to 0.780, 0.002 ≤ P ≤ 0.045) and similar to or higher than Ind-AIF (ranging from 0.591 to 0.839, 0.014 ≤ P ≤ 0.9). Ind-AIF and FH-AIF provided similar AUROCC (0.34 ≤ P ≤ 0.81). The pairwise correlation of K(trans) values was moderate to very strong when comparing W-AIF with FH-AIF (the Spearman's correlation coefficients [SCCs] ranged from 0.55 to 0.93) and very weak to moderate when comparing W-AIF with Ind-AIF (the SCCs ranged from 0.018 to 0.59) or FH-AIF with Ind-AIF (the SCCs ranged from 0.30 to 0.51). CONCLUSION: W-AIF yielded a higher performance than FH-AIF and a similar or higher performance than Ind-AIF in distinguishing PCa from benign tissue.

Magnetic Resonance Imaging Targeted Biopsy Improves Selection of Patients Considered for Active Surveillance for Clinically Low Risk Prostate Cancer Based on Systematic Biopsies.

PURPOSE: Current selection criteria for active surveillance based on systematic biopsy underestimate prostate cancer volume and grade. We investigated the role of additional magnetic resonance imaging targeted biopsy in reclassifying patients eligible for active surveillance based on systematic biopsy. MATERIALS AND METHODS: We performed a study at 2 institutions in a total of 281 men with increased prostate specific antigen. All men met certain criteria, including 1) prebiopsy magnetic resonance imaging, 12-core transrectal systematic biopsy and 2 additional magnetic resonance imaging targeted biopsies of lesions suspicious for cancer during the same sequence as systematic biopsy, and 2) eligibility for active surveillance based on systematic biopsy results. Criteria for active surveillance were prostate specific antigen less than 10 ng/ml, no Gleason grade 4/5, 5 mm or less involvement of any biopsy core and 2 or fewer positive systematic biopsy cores. Patient characteristics were compared between reclassified and nonreclassified groups based on magnetic resonance imaging targeted biopsy results. RESULTS: On magnetic resonance imaging 58% of the 281 patients had suspicious lesions. Magnetic resonance imaging targeted biopsy was positive for cancer in 81 of 163 patients (50%). Of 281 patients 28 (10%) were reclassified by magnetic resonance imaging targeted biopsy as ineligible for active surveillance based on Gleason score in 8, cancer length in 20 and Gleason score plus cancer length in 9. Suspicious areas on magnetic resonance imaging were in the anterior part of the prostate in 15 of the 28 men (54%). Reclassified patients had a smaller prostate volume (37 vs 52 cc) and were older (66.5 vs 63 years) than those who were not reclassified (p < 0.05). CONCLUSIONS: Magnetic resonance imaging targeted biopsy reclassified 10% of patients who were eligible for active surveillance based on systematic biopsy. Its incorporation into the active surveillance eligibility criteria may decrease the risk of reclassification to higher stages during followup.

Influence of preoperative factors on the oncologic outcome for upper urinary tract urothelial carcinoma after radical nephroureterectomy.

PURPOSE: To evaluate the influence of preoperative factors on the survival of patients diagnosed with upper tract urothelial carcinoma (UTUC) who underwent a radical nephroureterectomy (RNU). METHODS: A multicentre retrospective study was performed on all patients with UTUC who underwent a RNU. Multiple preoperative criteria were tested as prognostic factors for cancer-specific survival (CSS) using univariate and multivariable Cox regression analyses. RESULTS: Overall, 476 patients with a median age of 69.2 (IQR 60.8-76.5) years were included. The median follow-up was 27.8 months (IQR 10.5-49.3). At the time of diagnosis, 400 (84.1 %) patients presented with symptoms and 76 patients (15.9 %) were asymptomatic. Renal failure, altered general health, a preoperative locally advanced tumour and multifocal disease appeared to be preoperative prognostic factors for CSS (p = 0.01, 0.03, 0.001 and 0.03, respectively) in the univariate analysis. Only renal failure (p = 0.03), a preoperative locally advanced tumour (0.004), and multifocal locations (p = 0.01) were confirmed as independent factors of CSS in the multivariate analysis. The independent prognosticators of definitive muscle-invasive stage and non-organ-confined disease were preoperative renal failure (p = 0.02, 0.027, respectively), locally advanced stage (p < 0.001, <0.001, respectively) and positive cytology (p = 0.006, 0.003 respectively). Female gender was independent factor only for prediction of final non-organ-confined disease (p = 0.007). The addition of these parameters in our preoperative complex model permitted the prediction of muscle-invasive or locally advanced disease in 65.3 and 67.2 % of patients, respectively. CONCLUSIONS: Patients with preoperative impaired renal function, locally advanced stage and multifocal tumours before RNU had worse survival outcomes compared to other patients.

Understanding the pathological implications of MRI: application to focal therapy planning.

PURPOSE OF REVIEW: The current challenge in prostate cancer (PCa) focal therapy indication and planning is how to accurately estimate tumor parameters such as volume, extent and grade. In addition to biopsy results, MRI provides an estimation of PCa contour, volume and histopathological characteristics such as presence of high Gleason grade. Among MRI sequences, diffusion-weighted imaging with apparent diffusion coefficient map is the sequence that showed the best results for cancer aggressiveness characterization. RECENT FINDINGS: It was shown that the higher the Gleason score, the lower the apparent diffusion coefficient value. However, accuracy is not sufficient for peripheral zone cancers to be validated for clinical decision and it was not enough investigated for transition zone cancers. Analysis of tumor extent showed a significant underestimation of tumor volume by imaging and this finding should be taken into consideration when planning focal therapy procedures. SUMMARY: Pathological implications of MRI for focal therapy planning are significant but not mature enough to be validated. Future research should aim to quantify cellularity and architectural patterns of PCa Gleason system in correlation with signal abnormalities for better assessment of tumor aggressiveness and extent, and to compare the boundaries of tumors between MRI and histopathological evaluation in order to define an optimal treatment margin.

How are we going to train a generation of radiologists (and urologists) to read prostate MRI?

PURPOSE OF REVIEW: Multiparametric MRI has gained tremendous importance in the daily practice for patients at risk or diagnosed with prostate cancer. Interpretation of multiparametric-MRI is a complex task, supposedly restricted to experienced radiologists. The purpose of this review is to analyze fundamentals of multiparametric-MRI interpretation and to describe how multiparametric-MRI training could be organized. RECENT FINDINGS: Recently, professional guidelines have been published to provide technical and interpretation frameworks and harmonize multiparametric-MRI practice, but the question of physicians training in prostate multiparametric-MRI reading is still pending. What kind of education, practice, and training makes a radiologist able to reliably interpret a prostate multiparametric-MRI? How can findings be reported to be easily understood? How much experience is needed? How can we train urologists and other physicians to review the examinations they request? Is double-reading necessary? SUMMARY: An institutional-based competency certification process for prostate multiparametric-MRI interpretation may encourage nonspecialized radiologists to qualify for prostate imaging in a standardized and reproducible way, exactly as urologists need it.

International Prostate Symptom Score is a predictive factor of lower urinary tract symptoms after radical prostatectomy.

OBJECTIVE: To evaluate the impact of radical prostatectomy on lower urinary tract symptoms by using the International Prostate Symptom Score and International Prostate Symptom Score quality of life. METHODS: The present prospective study comprised 804 patients having localized prostate cancer who underwent radical prostatectomy. International Prostate Symptom Score and International Prostate Symptom Score quality of life were recorded preoperatively, and at 1, 3, 6, 12 and 24 months. Two study groups were considered: group 1 included patients with International Prostate Symptom Score ≤7 (mild) and group 2 included patients with International Prostate Symptom Score ≥8 (moderate to severe). Student's t-test and logistic regression were carried out to detect a predictive factor of International Prostate Symptom Score ≤7 at 24 months. RESULTS: The mean International Prostate Symptom Score was 5.58 ± 6.6, 11.12 ± 7.1 and 7.62 ± 6 at baseline, 1 month and 3 months, respectively (P <0.0001). The mean quality of life score showed the same evolution with a significant difference at 1 and 3 months. The mean International Prostate Symptom Score was initially 1.57 ± 1.9 in group 1 and 13.51 ± 5.5 in group 2 (P <0.0001), evolving to 3.41 ± 3.1 and 7.69 ± 5.8 at 24 months (P <0.0001), respectively. The mean quality of life score was significantly different between the groups initially, and at 6 and 12 months with P <0.0001, P = 0.005 and P = 0.02, respectively. The multivariate logistic regression showed that age, prostate volume and preoperative International Prostate Symptom Score were independent predictive factors of International Prostate Symptom Score ≤7 at 24 months (P <0.0001). In group 2, 47 patients (17%) had an International Prostate Symptom Score ≥8 at 24 months, 15 of them (32%) having a QoL score ≥3. CONCLUSIONS: The present study shows the beneficial impact of radical prostatectomy on lower urinary tract symptoms. However, a proportion of patients with a baseline International Prostate Symptom Score ≥8 maintain the same score at 24 months, with worsening in quality of life score in one-third of them.

Positive surgical margins after minimally invasive radical prostatectomy in patients with pT2 and pT3a disease could be considered pathological upstaging.

OBJECTIVE: To assess the prognostic significance of positive surgical margins (PSMs) after minimally invasive radical prostatectomy (MIRP) in interaction with other established prognosis factors. PATIENTS AND METHODS: We retrospectively analysed data prospectively collected between 1998 and 2010 for 4628 consecutive patients who underwent MIRP for clinically localized prostate cancer. The impact of PSM on biochemical recurrence (BCR), defined as prostate-specific antigen (PSA) >0.2 ng/mL, was evaluated using multivariable Cox proportional hazards regression. Estimates of BCR-free survival were generated using the Kaplan-Meier method and compared among groups using the log-rank test. RESULTS: The median follow-up was 55 months. On multivariable analysis, PSM was an independent prognostic factor for BCR (adjusted hazard ratio: 2.14 for PSMs vs negative surgical margins (NSMs); 95% confidence interval [CI]: 1.86-2.45; P < 0.001). Other independent predictors for BCR were preoperative PSA, date of surgery, pT stage, Gleason score and lymph node involvement (all P < 0.001). The 5-year BCR-free probability was 80.6% (95% CI: 79-82.2) for NSMs vs 51% (95% CI: 47-55) for PSMs (log-rank P < 0.001). Patients with pT2 and pT3a PSMs had a similar prognosis to those with pT3a and pT3b NSMs, respectively (log-rank P ≥ 0.05). CONCLUSION: A PSM after MIRP is associated with 2.14-fold increased risk of BCR. In patients with pT2 and pT3a disease, a PSM could be considered a pathological upstaging.

Hereditary-like urothelial carcinomas of the upper urinary tract benefit more from adjuvant cisplatin-based chemotherapy after radical nephroureterectomy than do sporadic tumours.

OBJECTIVE: To evaluate the impact of 'hereditary-like' status in upper tract urothelial carcinoma (UTUC) on the survival of patients who have undergone radical nephroureterectomy (RNU) and adjuvant chemotherapy. PATIENTS AND METHODS: A multicentre retrospective study was performed on all patients with high-risk UTUC who underwent RNU and adjuvant cisplatin-based chemotherapy. Using a patient risk identification tool, we distinguished tumours suspected to be hereditary from sporadic tumours and compared survival rates. RESULTS: A total of 112 patients with a median age of 67 years were included. Hereditary-like tumour status was detected in 35 patients (31.3%), while 77 patients (68.7%) had sporadic tumours. The median age was significantly younger in the hereditary-like tumour group (56.0 vs 69.8 years, P < 0.001). Overall survival (OS) after chemotherapy was significantly better in the group with hereditary-like tumours than in the group with sporadic tumours (5-year OS: 48.2 vs 32%; P = 0.008). The cancer-specific survival (CSS) rate was significantly better in the group with 'hereditary-like' tumours than in the group with sporadic tumours (5-year CSS: 58 vs 35%; P = 0.006). Although there was a trend in favour of the hereditary-like tumours, we observed no significant difference regarding progression-free survival (PFS) between the two groups (5-year PFS: 71 vs 52%; P = 0.07). CONCLUSION: Adjuvant chemotherapy after RNU improves survival outcomes in patients with hereditary-like UTUC compared with those with sporadic tumours.

The role of MRI-targeted and confirmatory biopsies for cancer upstaging at selection in patients considered for active surveillance for clinically low-risk prostate cancer.

PURPOSE: The purpose of this study was to assess the roles of MRI-targeted biopsies (TB) and confirmatory biopsies for cancer upstaging at selection in patients considered for active surveillance (AS) for low-risk prostate cancer (PCa) based on the first systematic biopsy (SB) series in another centre. METHODS: From 2009 to 2012, 41 patients with PCa diagnosed within the last 4 months and eligible for AS [clinical stage ≤T2a, prostate-specific antigen (PSA) <10 ng/ml, ≤2 positive biopsy cores with no Gleason pattern 4 or 5 and ≤5 mm involvement of any biopsy core] underwent pre-biopsy MRI, confirmatory transrectal ultrasound 12-core SB and MRI-TB of suspicious lesions. A contingency table assessed the accuracy of MRI to predict cancer upstaging. RESULTS: Median age and PSA were 63.5 years and 5.3 ng/ml, respectively. Overall, 24 patients (59 %) were upstaged. This upstaging was obtained at a confirmatory SB in 16 patients (39 %) based on the Gleason score (9), on cancer length (8) or both (7) and at MRI-TB in 17 patients (41 %) based on the Gleason score (14), cancer length (9) or both (6). Nine patients were upstaged at both SB and TB (22 %). The added value of MRI-TB was 20 % (8/41). The positive and negative predictive values of MRI for predicting cancer upstaging were 79 and 70.5 %, respectively. CONCLUSION: MRI-TB and confirmatory SB upstaged 59 % of cases, improving the selection of patients considered for AS at the first series of SB. Variation in histologic grade assignation between centres and better cancer sampling may explain this high upstaging rate.

Oncologic outcomes after minimally invasive radical prostatectomy in patients with seminal vesicle invasion (pT3b) without adjuvant therapy.

PURPOSE: To evaluate the long-term outcomes of patients with prostate cancer who have pathological pT3b N0-Nx, with postoperative PSA < 0.1 ng/ml and no systematic adjuvant treatment. MATERIALS AND METHODS: Using a monocentric prospectively maintained database, we identified among 2,142 men who underwent minimally invasive radical prostatectomy, 104 pT3b N0-Nx patients, with postoperative PSA < 0.1 ng/ml and at least 5 years of follow-up. Patients were considered for salvage treatment at biochemical recurrence (PSA ≥ 0.2 ng/ml). RESULTS: The median time of follow-up was 83.5 months (interquartile range [IQR]: 69-99). Overall, 102 patients (98 %) had T2 clinical stage or less. Specimen Gleason score was 7 in 71 patients (68 %) and <7 in 15 (14 %). Thirty-eight patients (37 %) were upgraded for Gleason score after radical prostatectomy. The overall 5-year probability of freedom from biochemical recurrence for the entire cohort was 55.8 % (95 % CI 45.8-65.8) and 73.3 % for patients who had specimen Gleason score <7 (p = 0.005). In univariate analysis, specimen Gleason score and surgical margin status were significant predictors for biochemical failure after radical prostatectomy (p = 0.05 and 0.007, respectively). In multivariate analysis, only specimen Gleason score >7 was significantly associated with biochemical failure (p = 0.009). CONCLUSION: SVI is an adverse prognostic factor, but it is not associated with a uniformly poor prognosis. Specimen Gleason score and surgical margin status are significant predictors of recurrence after radical prostatectomy in patients with prostate cancer and SVI.

Risk stratification of metastatic recurrence in invasive upper urinary tract carcinoma after radical nephroureterectomy without lymphadenectomy.

PURPOSE: To assess the risk factors of metastasis relapse in pT2-3 upper tract urothelial carcinomas (UTUCs) treated by radical nephroureterectomy (RNU) without lymphadenectomy (LN). METHODS: A multicentric retrospective study was performed for pT2-3 pNx UTUCs treated by RNU between 1995 and 2010. The following criteria were retrieved: age, gender, American Society of Anaesthesiologists physical status, surgical approach, preoperative hydronephrosis, stage, grade, tumor location, surgical margin, lymphovascular invasion (LVI) status and outcomes. Metastasis-free survival (MFS) was measured by Kaplan-Meier method with the log-rank test. RESULTS: Overall, 151 patients were included. The median follow-up was 18.5 months (IQR 9.5-37.9). The 2- and 5-year MFS were 69 % ± 4.5 and 54.1 % ± 5.8, respectively. In univariate analysis, ureteral location, pT3 stage, positive LVI status and positive surgical margin were significantly associated with worse MFS (p = 0.03; 0.02; 0.01 and 0.006, respectively). In the multivariate analysis of ureteral location and pT3 stage were independent prognostic factors (p = 0.03 and 0.03, respectively). Based on the results of the univariate analysis, we proposed a risk model predicting MFS, which classifies patients into 3 categories with different overall survival (p < 0.001). CONCLUSION: In view of our data, tumor location, T stage, LVI and surgical margin status are mandatory to predict survival in case of RN without LN. Contingent upon external validation, our risk model based on these variables could be useful to provide relevant information concerning metastasis relapse probability and necessity of close follow-up for these patients.

Clinical outcomes after salvage radiotherapy without androgen deprivation therapy in patients with persistently detectable PSA after radical prostatectomy: results from a national multicentre study.

PURPOSE: To assess oncologic outcomes after salvage radiotherapy (SRT) without androgen deprivation therapy (ADT) in patients with persistently detectable PSA after radical prostatectomy (RT). METHODS: Two hundred and one patients who failed to achieve an undetectable PSA received SRT without ADT. The primary endpoint was failure to SRT that was defined by clinical progression or use of second-line ADT. Clinicopathological parameters, 6-week PSA level, PSAV and pre-SRT PSA levels were assessed using time-dependent analyses. RESULTS: Median postoperative 6-week PSA and pre-SRT PSA levels were 0.25 and 0.48 ng/mL, respectively. Median time between surgery and SRT was 7 months. Failure to SRT was reported in 42.8 % of cases with the need for second-line ADT in 26.9 % of cases. Pre-SRT PSA was strongly correlated with postoperative 6-week PSA (p < 0.001) but not with PSAV. The risk of SRT failure was increased by threefold in case of Gleason score 8-10 (p = 0.036) or pT3b cancer (p = 0.006). Risk group classification based on these prognostic factors improved SRT failure prediction. Survival curves confirmed that 5-year ADT-free survival rates were significantly influenced by PSAV (p = 0.002) and pre-SRT PSA (p = 0.030). CONCLUSIONS: In patients with persistently detectable PSA after RP and selected for local salvage treatment, SRT offers good oncologic clinical outcomes. The most powerful pathologic predictive factors of SRT failure include a pT3b stage, a Gleason score 8 or more cancer and high PSAV and pre-SRT PSA levels. Patients having a high PSAV >0.04 ng/mL/mo would be potentially better candidates for a systemic therapy due to a high SRT failure rate.

How accurately can MRI detect indolent disease?

PURPOSE OF REVIEW: The current challenge in prostate cancer diagnosis is how to accurately measure the risk of disease progression and guide the treatment decision process between effective intervention for potentially harmful tumors and active surveillance for indolent disease. The issue is how to better identify patients harboring insignificant disease using the current diagnosis pathway based on 12-core systematic biopsy, which misclassifies tumor volume and/or grade in up to 30% of cases. Integrating MRI into the diagnosis process may help to better determine if the cancer is at very low risk of disease progression, i.e. clinically indolent or insignificant. RECENT FINDINGS: Recent advances in prostate imaging techniques suggest that multiparametric MRI has a high negative predictive value (up to 95%) in ruling out clinically significant prostate cancer and may potentially have clinical use in diagnostic pathways in men at risk for prostate cancer. Prospective studies should be performed to examine the rate of reclassification using MRI-targeted biopsy in patients potentially eligible for active surveillance based on current tests (12-cores systematics biopsies). SUMMARY: Patients with nonsuspicious multiparametric MRI represent a special very low-risk group of men with either no disease or clinically insignificant disease, allowing them to be managed conservatively.

Prostate cancer diagnosis: multiparametric MR-targeted biopsy with cognitive and transrectal US-MR fusion guidance versus systematic biopsy--prospective multicenter study.

PURPOSE: To compare biopsy performance of two approaches for multiparametric magnetic resonance (MR)-targeted biopsy (TB) with that of extended systematic biopsy (SB) in prostate cancer (PCa) detection. MATERIALS AND METHODS: This institutional review board-approved multicenter prospective study (May 2009 to January 2011) included 95 patients with informed consent who were suspected of having PCa, with a suspicious abnormality (target) at prebiopsy MR. Patients underwent 12-core SB and four-core TB with transrectal ultrasonographic (US) guidance, with two cores aimed visually (cognitive TB [TB-COG]) and two cores aimed using transrectal US-MR fusion software (fusion-guided TB [TB-FUS]). SB and TB positivity for cancer and sampling quality (mean longest core cancer length, Gleason score) were compared. Clinically significant PCa was any 3 mm or greater core cancer length or any greater than 3 Gleason pattern for SB or any cancer length for TB. Statistical analysis included t test, paired χ(2) test, and κ statistic. Primary end point (core cancer length) was calculated (paired t test). RESULTS: Among 95 patients (median age, 65 years; mean prostate-specific antigen level, 10.05 ng/mL [10.05 µg/L]), positivity rate for PCa was 59% (n = 56) for SB and 69% (n = 66) for TB (P = .033); rate for clinically significant PCa was 52% (n = 49) for SB and 67% (n = 64) for TB (P = .0011). Cancer was diagnosed through TB in 16 patients (17%) with negative SB results. Mean longest core cancer lengths were 4.6 mm for SB and 7.3 mm for TB (P < .0001). In 12 of 51 (24%) MR imaging targets with positive SB and TB results, TB led to Gleason score upgrading. In 79 MR imaging targets, positivity for cancer was 47% (n = 37) with TB-COG and 53% (n = 42) with TB-FUS (P = .16). Neither technique was superior for Gleason score assessment. CONCLUSION: Prebiopsy MR imaging combined with transrectal US-guided TB increases biopsy performance in detecting PCa, especially clinically significant PCa. No significant difference was observed between TB-FUS and TB-COG for TB guidance.