A nomogram to predict the absence of clinically significant prostate cancer in males with negative MRI

PURPOSE: To create a nomogram to predict the absence of clinically significant prostate cancer (CSPCa) in males with non-suspicion multiparametric magnetic resonance imaging (mpMRI) undergoing prostate biopsy (PBx). MATERIALS AND METHODS: We identified consecutive patients who underwent 3T mpMRI followed by PBx for suspicion of PCa or surveillance follow-up. All patients had Prostate Imaging Reporting and Data System score 1-2 (negative mpMRI). CSPCa was defined as Grade Group ≥2. Multivariate logistic regression analysis was performed via backward elimination. Discrimination was evaluated with area under the receiver operating characteristic (AUROC). Internal validation with 1,000x bootstrapping for estimating the optimism corrected AUROC. RESULTS: Total 327 patients met inclusion criteria. The median (IQR) age and PSA density (PSAD) were 64 years (58-70) and 0.10 ng/mL2 (0.07-0.15), respectively. Biopsy history was as follows: 117 (36%) males were PBx-naive, 130 (40%) had previous negative PBx and 80 (24%) had previous positive PBx. The majority were White (65%); 6% of males self-reported Black. Overall, 44 (13%) patients were diagnosed with CSPCa on PBx. Black race, history of previous negative PBx and PSAD ≥0.15ng/mL2 were independent predictors for CSPCa on PBx and were included in the nomogram. The AUROC of the nomogram was 0.78 and the optimism corrected AUROC was 0.75. CONCLUSIONS: Our nomogram facilitates evaluating individual probability of CSPCa on PBx in males with PIRADS 1-2 mpMRI and may be used to identify those in whom PBx may be safely avoided. Black males have increased risk of CSPCa on PBx, even in the setting of PIRADS 1-2 mpMRI.

Systematic Biopsy of the Prostate can Be Omitted in Men with PI-RADS™ 5 and Prostate Specific Antigen Density Greater than 15.

PURPOSE: We evaluated the prostate cancer and clinically significant prostate cancer detection on systematic biopsy (SB), target biopsy (TB) alone and combined SB and TB in men with Prostate Imaging Reporting and Data System™ (PI-RADS™) 5 lesion. MATERIALS AND METHODS: From a prospectively maintained prostate biopsy database, we identified consecutive patients with PI-RADS 5 lesion on multiparametric magnetic resonance imaging. The patients underwent multiparametric magnetic resonance imaging followed by transrectal TB of PI-RADS 5 lesion and 12-core SB. The prostate cancer and clinically significant prostate cancer (Grade Group, GG ≥2) detection on SB, TB and SB+TB were determined for all men and accordingly to prostate specific antigen density. Statistic significant was set a p <0.05. RESULTS: Overall, 112 patients met inclusion criteria. The detection rate of prostate cancer for SB, TB and SB+TB was 89%, 93% and 95%, respectively, and for clinically significant prostate cancer it was 72%, 81% and 85%, respectively. SB added 2% prostate cancer and 4% clinically significant prostate cancer detection to TB. A total of 78 patients had prostate specific antigen density >0.15 ng/ml2, and the detection rate of PCa for SB, TB and SB+TB was 92%, 97% and 97%, respectively, and for clinically significant prostate cancer it was 79%, 91% and 95%, respectively. In this population, if SB was omitted, 0 prostate cancer and only 4% (3) of clinically significant prostate cancer would be missed. The clinically significant prostate cancer detection rate improved with increased prostate specific antigen density for SB (p=0.01), TB (p <0.0001) and combined SB+TB (p=0.002). CONCLUSIONS: In patients with PI-RADS 5 on multiparametric magnetic resonance imaging and prostate specific antigen density >0.15 ng/ml2, SB marginally increases clinically significant prostate cancer detection, but not overall prostate cancer detection in comparison to TB alone. Systematic biopsy did not affect patients' management and can be omitted on this population.

Multiparametric magnetic resonance imaging facilitates reclassification during active surveillance for prostate cancer.

OBJECTIVE: To investigate the utility of multiparametric magnetic resonance imaging (mpMRI) in the reassessment and monitoring of patients on active surveillance (AS) for Grade Group (GG) 1 prostate cancer (PCa). PATIENTS AND METHODS: We identified, from our prospectively maintained institutional review board-approved database, 181 consecutive men enrolled on AS for GG 1 PCa who underwent at least one surveillance mpMRI followed by MRI/prostate biopsy (PBx). A subset analysis was performed among 68 patients who underwent serial (at least two) mpMRI/PBx during AS. Pathological progression (PP) was defined as upgrade to GG ≥2 on follow up biopsy. RESULTS: Baseline MRI was performed in 34 patients (19%). At a median follow-up of 2.2 years for the overall cohort, the PP was 12% (6/49) for Prostate Imaging Reporting and Data System (PI-RADS) 1-2 lesions and 37% (48/129) for the PI-RADS ≥3 lesions. The 2-year PP-free survival rate was 84%. Surveillance prostate-specific antigen density (P < 0.001) and surveillance PI-RADS ≥3 (P = 0.002) were independent predictors of PP on reassessment MRI/PBx. In the serial MRI cohort, the 2-year PP-free survival was 95% for the No-MRI-progression group vs 85% for the MRI-progression group (P = 0.02). MRI progression was significantly higher in the PP (62%) than in the No-PP (31%) group (P = 0.04). If serial MRI were used for PCa surveillance and biopsy were triggered based only on MRI progression, 63% of PBx might be postponed at the cost of missing 12% of GG ≥2 PCa in those with stable MRI. Conversely, this strategy would miss 38% of those with upgrading to GG ≥2 PCa on biopsy. Stable serial mpMRI correlates with no reclassification to GG ≥3 PCa during AS. CONCLUSION: On surveillance mpMRI, PI-RADS ≥3 was associated with increased risk of PCa reclassification. Surveillance biopsy based only on MRI progression may avoid a large number of biopsies at the cost of missing many PCa reclassifications.

Current state of image-guided focal therapy for prostate cancer.

PURPOSE: To review the current evidence regarding protocols and outcomes of image-guided focal therapy (FT) for prostate cancer (PCa). METHODS: A literature search of the latest published studies assessing primary FT for PCa was carried out in Medline and Cochrane library databases followed by a critical review. FT modalities, follow-up strategies, and oncological and toxicity outcomes were summarized and discussed in this review. RESULTS: Twenty-four studies with six different sources of energy met the inclusion criteria. A heterogeneity of patient selection, energy sources, treatment templates, and definitions of failure was found among the studies. While a third of patients may be found to have additional cancer burden over 3-5 years following FT, most patients will remain free of a radical procedure. The vast majority of patients maintain urinary continence and good erectile function after FT. Acute urinary retention is the most common complication, whilst severe complications remain rare. CONCLUSION: An increasing number of prospective studies with longer follow-up have been recently published. Acceptable cancer control and low treatment toxicity after FT have been consistently reported. Follow-up imaging and routine biopsy must be encouraged post-FT. While there is no reliable PSA threshold to predict failure after FT, reporting post-FT positive biopsies and retreatment rates appear to be standard when assessing treatment efficacy.

Five-alpha reductase inhibitors in men undergoing active surveillance for prostate cancer: impact on treatment and reclassification after 6 years follow-up.

OBJECTIVES: To evaluate the impact of 5-alpha reductase inhibitors (5-ARIs) on definitive treatment (DT) and pathological progression (PP) in patients on active surveillance (AS) for prostate cancer. METHODS: We identified 361 consecutive patients, from an IRB-approved database, on AS for prostate cancer with minimum 2 years follow-up. Patients were grouped into two cohorts, those using 5-ARIs (5-ARI; n = 119) or not using 5-ARIs (no 5-ARI; n = 242). Primary and secondary endpoints were treatment-free survival (TFS) and PP-free survival (PPFS), which were evaluated by Kaplan-Meier analysis. Univariate and multivariable cox regression analysis were used to identify predictors for PP and DT. A p value < 0.05 was considered statistically significant. RESULTS: Baseline characteristics and the prostate biopsy rate were similar between the two groups. Median (range) follow-up was 5.7 (2.0-17.2) years. Five-year and 10-year TFS was 92% and 59% for the 5-ARI group versus 80% and 51% for the no 5-ARI group (p = 0.005), respectively. Five-year and 10-year PPFS was 77% and 41% for the 5-ARI group versus 70% and 32% for the no 5-ARI group (p = 0.04), respectively. Independent predictors for treatment and PP were not taking 5-ARIs (p = 0.005; p = 0.02), entry PSA > 2.5 ng/mL (p = 0.03; p = 0.01) and Gleason pattern 4 on initial biopsy (p < 0.001; p < 0.001), respectively. The main limitation is the retrospective study design. CONCLUSIONS: 5-ARIs reduces reclassification and cross-over to treatment in men on active surveillance for prostate cancer. Further, taking 5-ARIs was an independent predictor for prostate cancer progression and definitive treatment.

Techniques and Outcomes of MRI-TRUS Fusion Prostate Biopsy.

PURPOSE OF REVIEW: The goal of this study is to review recent findings and evaluate the utility of MRI transrectal ultrasound fusion biopsy (FBx) techniques and discuss future directions. RECENT FINDINGS: FBx detects significantly higher rates of clinically significant prostate cancer (csPCa) than ultrasound-guided systematic prostate biopsy (SBx), particularly in repeat biopsy settings. FBx has also been shown to detect significantly lower rates of clinically insignificant prostate cancer. In addition, a dedicated prostate MRI can assist in more accurately predicting the Gleason score and provide further information regarding the index cancer location, prostate volume, and clinical stage. The ability to accurately evaluate specific lesions is vital to both focal therapy and active surveillance, for treatment selection, planning, and adequate follow-up. FBx has been demonstrated in multiple high-quality studies to have improved performance in diagnosis of csPCa compared to SBx. The combination of FBx with novel technologies including radiomics, prostate-specific membrane antigen positron emission tomography (PSMA PET), and high-resolution micro-ultrasound may have the potential to further enhance this performance.

High Intensity Focused Ultrasound Hemigland Ablation for Prostate Cancer: Initial Outcomes of a United States Series.

PURPOSE: We report outcomes of hemigland high intensity focused ultrasound ablation as primary treatment for localized prostate cancer in the United States. MATERIALS AND METHODS: A total of 100 consecutive men underwent hemigland high intensity focused ultrasound (December 2015 to December 2019). Primary end point was treatment failure, defined as Grade Group 2 or greater on followup prostate biopsy, radical treatment, systemic therapy, metastases or prostate cancer specific mortality. IIEF (International Index of Erectile Function), I-PSS (International Prostate Symptom Score) and 90-day complications were reported. RESULTS: At study entry patients had very low (8%), low (20%), intermediate favorable (50%), intermediate unfavorable (17%) and high (5%) risk prostate cancer. Median followup was 20 months. The 2-year survival free from treatment failure, Grade Group 2 or greater recurrence, repeat focal high intensity focused ultrasound and radical treatment was 73%, 76%, 90% and 91%, respectively. Bilateral prostate cancer at diagnosis was the sole predictor for Grade Group 2 or greater recurrence (p=0.03). Of men who underwent posttreatment biopsy (58), 10 had in-field and 8 out-of-field Grade Group 2 or greater positive biopsy. Continence (zero pad) was maintained in 100% of patients. Median IIEF-5 and I-PSS scores before vs after hemigland high intensity focused ultrasound were 22 vs 21 (p=0.99) and 9 vs 6 (p=0.005), respectively. Minor and major complications occurred in 13% and 0% of patients. No patient had rectal fistula or died. CONCLUSIONS: Short-term results of focal high intensity focused ultrasound indicate safety, excellent potency and continence preservation, and adequate short-term prostate cancer control. Radical treatment was avoided in 91% of men at 2 years. Men with bilateral prostate cancer at diagnosis have increased risk for Grade Group 2 or greater recurrence. To our knowledge, this is the initial and largest United States series of focal high intensity focused ultrasound as primary treatment for prostate cancer.

Hemigland Cryoablation of Localized Low, Intermediate and High Risk Prostate Cancer: Oncologic and Functional Outcomes at 5 Years.

PURPOSE: We evaluated 5-year oncologic and functional outcomes of hemigland cryoablation of localized prostate cancer. MATERIALS AND METHODS: We reviewed the records of 160 consecutive men who underwent hemigland cryoablation of localized prostate cancer. Recurrent and/or residual clinically significant prostate cancer was defined as Grade Group 2 or greater on followup biopsy. A prostate specific antigen nadir plus 2 ng/ml according to the Phoenix criteria was used to define biochemical failure. Radical treatment was defined as any whole gland therapy. Treatment failure was defined as any radical and/or whole gland treatment, systemic therapy initiation, metastasis or prostate cancer specific mortality. The study primary end point was treatment failure-free survival. The secondary end points were survival free of biochemical failure, clinically significant prostate cancer and radical treatment. Followup biopsy and functional outcomes were also evaluated. Statistical analysis included the Kaplan-Meier method, and univariate and multivariable Cox and logistic regression with significance considered at p <0.05. RESULTS: Median patient age was 67 years, baseline prostate specific antigen was 6.3 ng/ml and followup was 40 months. A total of 131 patients (82%) had D'Amico intermediate (66%) or high risk (16%) prostate cancer. At 5 years the treatment failure-free survival rate was 85%, the biochemical failure-free survival rate was 62% and the survival rate free of clinically significant prostate cancer was 89%. Higher baseline prostate specific antigen independently predicted treatment failure (p <0.001), biochemical failure (p=0.048), recurrence and radical treatment (p <0.01). Grade Group 3 or greater independently predicted treatment failure (p=0.04). The metastasis-free survival rate was 100% at 5 years. Pad-free continence and potency (erections sufficient for intercourse) were retained in 97% and 73% of patients, respectively. There was no rectal fistula or mortality. CONCLUSIONS: Hemigland cryoablation of localized prostate cancer provides effective midterm oncologic outcomes with good continence and potency. Patients with higher baseline prostate specific antigen are at increased risk for biochemical failure, recurrent cancer and treatment failure.

Diagnostic accuracy of a five-point Likert scoring system for magnetic resonance imaging (MRI) evaluated according to results of MRI/ultrasonography image-fusion targeted biopsy of the prostate.

OBJECTIVE: To evaluate the accuracy of a magnetic resonance imaging (MRI)-based Likert scoring system in the detection of clinically significant prostate cancer (CSPC), using MRI/ultrasonography (US) image-fusion targeted biopsy (FTB) as a reference standard. PATIENTS AND METHODS: We retrospectively reviewed 1218 MRI-detected lesions in 629 patients who underwent subsequent MRI/US FTB between October 2012 and August 2015. 3-Tesla MRI was independently reported by one of eight radiologists with varying levels of experience and scored on a five-point Likert scale. All lesions with Likert scores 1-5 were prospectively defined as targets for MRI/US FTB. CSPC was defined as Gleason score ≥7. RESULTS: The median patient age was 64 years, PSA level 6.97 ng/mL and estimated prostate volume 52.2 mL. Of 1218 lesions, 48% (n = 581) were rated as Likert 1-2, 35% (n = 428) were Likert 3 and 17% (n = 209) were Likert 4-5. For Likert scores 1-5, the overall cancer detection rates were 12%, 13%, 22%, 50% and 59%, respectively, and the CSPC detection rates were 4%, 4%, 12%, 33% and 48%, respectively. Grading using the five-point scale showed strong positive correlation with overall cancer detection rate (r = 0.949, P = 0.05) and CSPC detection rate (r = 0.944, P = 0.05). By comparison, in Likert 4-5 lesions, significant differences were noted in overall cancer detection rate (63% vs 35%; P = 0.001) and CSPC detection rate (47% vs 29%; P = 0.027) for the more experienced vs the less experienced radiologists. CONCLUSIONS: The detection rates of overall cancer and CSPC strongly correlated with the five-point grading of the Likert scale. Among radiologists with different levels of experience, there were significant differences in these cancer detection rates.

Focal therapy for prostate cancer: concepts and future directions.

PURPOSE OF REVIEW: To present a perspective on the current status and future directions of focal therapy for prostate cancer (PCa). RECENT FINDINGS: Focal therapy for localized PCa is a rapidly evolving field. Various recent concepts - the index lesion driving prognosis, the enhanced detection of clinically significant PCa using multiparametric MRI and targeted biopsy, improved risk-stratification using novel blood/tissue biomarkers, the recognition that reducing radical treatment-related morbidity (along with reducing pathologic progression) is a clinically meaningful end-point - have all led to a growing interest in focal therapy. Novel focal therapy modalities are being investigated, mostly in phase 1 and 2 studies. Recently, level I prospective randomized data comparing partial gland ablation with a standard-of-care treatment became available from one study. Recent developments in imaging, including 7-T MRI, functional imaging, radiomics and contrast-enhanced ultrasound show early promise. We also discuss emerging concepts in patient selection for focal therapy. SUMMARY: PCa focal therapy has evolved considerably in the recent few years. Overall, these novel focal therapy treatments demonstrate safety and feasibility, low treatment-related toxicity and acceptable short-term and in some cases medium-term oncologic outcomes. As imaging techniques evolve, patient selection, detection of clinically significant PCa and noninvasive assessment of therapeutic efficacy will be further optimized. The aspirational goal of achieving oncologic control while reducing radical treatment-related morbidity will drive further innovation in the field.

Robotic Intracorporeal Continent Cutaneous Diversion.

PURPOSE: Robotic intracorporeal urinary diversion has mostly been done for ileal conduit or orthotopic neobladder diversion. We present what is to our knowledge the initial series, detailed technique and outcomes of the robotic intracorporeal Indiana pouch with a minimum 1-year followup. MATERIALS AND METHODS: Ten patients underwent robotic radical cystectomy, pelvic lymphadenectomy and intracorporeal Indiana pouch urinary diversion for cancer in 9 and benign disease in 1. Data were collected prospectively. Baseline demographics, pathology data, and 1-year complication rates and functional outcomes were assessed. RESULTS: All 10 cases were successfully completed intracorporeally without open conversion. Median total operative time was 6 hours, including 3.5 hours for pouch creation. Median blood loss was 200 cc and median hospital stay was 10 days. Four Clavien grade 1-2 and 3 Clavien 3-5 complications occurred. None of the patients had a bowel leak. One noncompliant patient requested undiversion to an ileal conduit. The remaining 9 patients successfully catheterized the ileal channel and were completely continent at the last followup at a median of 13.7 months (range 12.3 to 15.2). Study limitations include small sample size and short followup. CONCLUSIONS: We present what is to our knowledge the initial series of robotic completely intracorporeal Indiana pouch diversion. Early perioperative data indicate acceptable operative efficiency and complication rates. Longer followup is required to assess the functional outcomes of this less commonly performed diversion.

Evolution of robot-assisted orthotopic ileal neobladder formation: a step-by-step update to the University of Southern California (USC) technique.

OBJECTIVE: To describe our, step-by-step, technique for robotic intracorporeal neobladder formation. PATIENTS AND METHODS: The main surgical steps to forming the intracorporeal orthotopic ileal neobladder are: isolation of 65 cm of small bowel; small bowel anastomosis; bowel detubularisation; suture of the posterior wall of the neobladder; neobladder-urethral anastomosis and cross folding of the pouch; and uretero-enteral anastomosis. Improvements have been made to these steps to enhance time efficiency without compromising neobladder configuration. RESULTS: Our technical improvements have resulted in an improvement in operative time from 450 to 360 min. CONCLUSION: We describe an updated step-by-step technique of robot-assisted intracorporeal orthotopic ileal neobladder formation.

Detection of prostate cancer using magnetic resonance imaging/ultrasonography image-fusion targeted biopsy in African-American men.

OBJECTIVE: To assess the diagnostic yield of targeted prostate biopsy in African-American (A-A) men using image fusion of multi-parametric magnetic resonance imaging (mpMRI) with real-time transrectal ultrasonography (US). PATIENTS AND METHODS: We retrospectively analysed 661 patients (117 A-A and 544 Caucasian) who had mpMRI before biopsy and then underwent MRI/US image-fusion targeted biopsy (FTB) between October 2012 and August 2015. The mpMRIs were reported on a 5-point Likert scale of suspicion. Clinically significant prostate cancer (CSPC) was defined as biopsy Gleason score ≥7. RESULTS: After controlling for age, prostate-specific antigen level and prostate volume, there were no significant differences between A-A and Caucasian men in the detection rate of overall cancer (35.0% vs 34.2%, P = 0.9) and CSPC (18.8% vs 21.7%, P = 0.3) with MRI/US FTB. There were no significant differences between the races in the location of dominant lesions on mpMRI, and in the proportion of 5-point Likert scoring. In A-A men, MRI/US FTB from the grade 4-5 lesions outperformed random biopsy in the detection rate of overall cancer (70.6% vs 37.2%, P = 0.003) and CSPC (52.9% vs 12.4%, P < 0.001). MRI/US FTB outperformed random biopsy in cancer core length (5.0 vs 2.4 mm, P = 0.001), in cancer rate per core (24.9% vs 6.8%, P < 0.001), and in efficiency for detecting one patient with CSPC (mean number of cores needed 13.3 vs 81.9, P < 0.001), respectively. CONCLUSIONS: Our key finding confirms a lack of racial difference in the detection rate of overall prostate cancers and CSPC with MRI/US FTB between A-A and Caucasian men. MRI/US FTB detected more CSPC using fewer cores compared with random biopsy.

Morphometric analysis of prostate zonal anatomy using magnetic resonance imaging: impact on age-related changes in patients in Japan and the USA.

OBJECTIVES: To evaluate the impact of morphometric magnetic resonance imaging (MRI) analysis of the prostate zonal anatomy on aging, prostatic hypertrophy and lower urinary tract symptoms in patients from Japan and the USA. SUBJECTS AND METHODS: A retrospective analysis of 307 men, including 156 men from Japan and 151 from the USA, who consecutively underwent 3-Tesla MRI and International Prostate Symptom Score (IPSS) assessment because of elevated PSA levels. Using Synapse-Vincent (Fujifilm), the prostatic zones were segmented in each axial step-section of the T2-weighted MRI to reconstruct a three-dimensional model of the prostate, which was used to calculate: zonal volumes (whole-gland prostate, transition zone and peripheral zone volumes); the presumed circle area ratio (PCAR); and PZ thickness. Bivariate associations were quantified using Spearman's rank correlation coefficients. RESULTS: The USA subgroup had a greater prostate volume (49 vs 42 mL; P = 0.003) and TZ volume (26 vs 20 mL; P < 0.001) than the Japan subgroup, with no difference in PZ volume (19 vs 20 mL; P = 0.2). There was no age-related increase in PZ volume in either of the subgroups or in the entire cohort (P = 0.9, P = 0.2, P = 0.3, respectively). PZ thickness had a significant negative correlation with PCAR (P < 0.001) and TZ volume (P < 0.001). The greater the increase in the TZ volume with the increase in PCAR, which probably correlates with obstructive pressure, the thinner the PZ became. PCAR had a significant positive correlation with IPSS (P = 0.003) and obstructive symptoms (P = 0.007), while PZ thickness had a significant negative correlation (P = 0.018). CONCLUSIONS: No age-related increases and no differences between the Japanese and the US subgroups were found with regard to PZ volume. The more TZ volume increased, the higher the obstructive pressure and the thinner the PZ became; these changes were associated with increased obstructive symptoms. MRI analysis of prostate zonal anatomy enhanced our understanding of age-related changes in morphology and urinary symptoms.

Does Computed Tomography Still Have Limitations to Distinguish Benign from Malignant Renal Tumors for Radiologists?

OBJECTIVES: To evaluate the current accuracy of CT for diagnosing benign renal tumors. MATERIALS AND METHODS: We retrospectively reviewed 905 patients who underwent preoperative CT followed by surgical resection. The final pathology was benign in 156 patients (17%). After exclusions, 140 patients with 163 benign tumors were included and 3 sets of the CT interpretations by radiologists with varying levels of experience were analyzed. RESULTS: The histological breakdown was as follows: oncocytomas (54.6%), angiomyolipomas (AMLs; 30.7%), renal cysts (8.0%), other miscellaneous benign tumors (6.7%). The sensitivities of diagnosing oncocytomas were 3.4, 9.0, and 13.5% in primary radiological reports, second blinded reviews, and third non-blinded reviews, respectively (p = 0.055). The sensitivities of diagnosing AMLs were 46.0, 58.0, and 62.0% in the 3-sets of CT interpretations, respectively (p = 0.246). As for renal cysts, the sensitivities were 69.2, 92.3, and 100% in the 3-sets of CT interpretations, respectively (p = 0.051). In primary reports, the positive predictive values were 95.8% in lipid poor (lp)-AMLs, 60.0% in oncocytomas, 69.2% in renal cysts, respectively (p < 0.05). CONCLUSIONS: Current conventional CT imaging still has limitations in differentiating oncocytomas and lp-AMLs from renal cell carcinomas, even when images were re-examined by experienced radiologists.