Prostate Health Index and multiparametric magnetic resonance imaging to predict prostate cancer grade reclassification in active surveillance.

OBJECTIVE: To identify the value of combining the Prostate Health Index (PHI) and multiparametric magnetic resonance imaging (mpMRI), tools which have previously been shown to be independently predictive of prostate cancer (PCa) grade reclassification (GR; Gleason score >6), for the purpose of predicting GR at the next surveillance biopsy to reduce unnecessary prostate biopsies for men in PCa active surveillance (AS). PATIENTS AND METHODS: Between 2014 and 2019, we retrospectively identified 253 consecutive men in the Johns Hopkins AS programme who had mpMRI and PHI followed by a systematic ± targeted biopsy. PHI and PHI density (PHID) were evaluated across Prostate Imaging-Reporting and Data System version 2.0 (PI-RADSv2) scores and compared to those with and without GR. Next, the negative predictive value (NPV) and area under the receiver operating curve (AUC) were calculated to compare the diagnostic value of PI-RADSv2 score combined with PHI, PHID, or prostate-specific antigen density (PSAD) for GR using their respective first quartile as a cut-off. RESULTS: Of the 253 men, 38 men (15%) had GR. Men with GR had higher PHI values (40.7 vs 32.0, P = 0.001), PHID (0.83 vs 0.57, P = 0.007), and PSAD (0.12 vs 0.10, P = 0.037). A PI-RADSv2 ≤3 alone had a NPV of 91.6% for GR (AUC 0.67). Using a PHI cut-off of 25.6 in addition to PI-RADSv2 ≤3, the NPV and AUC were both increased to 98% and 0.70, respectively. Using a PSAD cut-off of 0.07 ng/mL/mL with PI-RADSv2 had an AUC of 0.69 and NPV of 95.4%. PHI and PI-RADSv2 together could have avoided 20% of biopsies at the cost of missing 2.6% of GRs. CONCLUSIONS: The combination of PHI and mpMRI can aid in the prediction of GR in men on AS and may be useful for decreasing the burden of surveillance prostate biopsies.

Older Age Predicts Biopsy and Radical Prostatectomy Grade Reclassification to Aggressive Prostate Cancer in Men on Active Surveillance.

PURPOSE: Age at prostate cancer diagnosis has been positively associated with prostate cancer specific mortality and in men on active surveillance with a higher risk of biopsy grade reclassification to Gleason score 3 + 4 or greater (Grade Group 2 or greater). However, to our knowledge the association between age and biopsy grade reclassification to an aggressive phenotype (Gleason score 4 + 3 or greater [Grade Group 3 or greater]) has not been explored. MATERIALS AND METHODS: From 1995 to 2016 we followed 1,625 men 41 to 81 years old with NCCN® (National Comprehensive Cancer Network®) very low (68%) or low (32%) risk prostate cancer on active surveillance. We determined the rate of biopsy grade reclassification to Grade Group 3 or greater. Competing risk analysis was applied to evaluate the association between age at enrollment and the risk of biopsy grade reclassification. Additionally, in men who underwent radical prostatectomy after biopsy grade reclassification we assessed the rate of radical prostatectomy grade reclassification (ie radical prostatectomy Grade Group greater than biopsy Grade Group). RESULTS: The 5-year incidence of biopsy grade reclassification to Grade Group 3 or greater was 4%, 7% and 14% in men younger than 60, 60 to 69 and 70 years old or older, respectively (p <0.001). On univariate analysis older age was associated with biopsy grade reclassification to Grade Group 3 or greater (per 10-year increase HR 2.43, p <0.001). On multivariable analysis adjusting for year of diagnosis, race, prostate specific antigen density and cancer volume at diagnosis older age remained associated with biopsy grade reclassification to Grade Group 3 or greater (per 10-year increase HR 2.19, p <0.001). In men who underwent radical prostatectomy after biopsy grade reclassification those who were older had a higher rate of radical prostatectomy grade reclassification (p <0.05). CONCLUSIONS: In men on active surveillance older age at diagnosis was positively associated with biopsy grade reclassification to Grade Group 3 or greater and radical prostatectomy grade reclassification. These observations imply that for many older men, active surveillance as opposed to watchful waiting remains a more appropriate management strategy.

MR Imaging for Prostate Cancer Screening and Active Surveillance.

The current prostate cancer management paradigm has been criticized in recent years for contributing to the overdiagnosis and overtreatment of the disease. Active surveillance is an avenue by which to reduce overtreatment, but patient selection and monitoring remain a challenge. The use of prostate MR imaging has been growing in recent years and has been incorporated into prostate cancer screening and patient selection and monitoring for active surveillance. This review article discusses the current evidence for the use of MR imaging in each of those settings.

Combining Prostate Health Index density, magnetic resonance imaging and prior negative biopsy status to improve the detection of clinically significant prostate cancer.

OBJECTIVES: To determine the performance of Prostate Health Index (PHI) density (PHID) combined with MRI and prior negative biopsy (PNB) status for the diagnosis of clinically significant prostate cancer (PCa). PATIENTS AND METHODS: Patients without a prior diagnosis of PCa, with elevated prostate-specific antigen and a normal digital rectal examination who underwent PHI testing prospectively prior to prostate biopsy were included in this study. PHID was calculated retrospectively using prostate volume derived from transrectal ultrasonography at biopsy. Univariable and multivariable logistic regression modelling, along with receiver-operating characteristic (ROC) curve analysis, was used to determine the ability of serum biomarkers to predict clinically significant PCa (defined as either grade group [GG] ≥2 disease or GG1 PCa detected in >2 cores or >50% of any one core) on biopsy. Age, PNB status and Prostate Imaging Reporting and Data System (PI-RADS) score were incorporated into the regression models. RESULTS: Of the 241 men who qualified for the study, 91 (37.8%) had clinically significant PCa on biopsy. The median (interquartile range) PHID was 0.74 (0.44-1.24); it was 1.18 (0.77-1.83) and 0.55 (0.38-0.89) in those with and without clinically significant PCa on biopsy, respectively (P < 0.001). On univariable logistic regression, age and PNB status were associated with clinically significant cancer. Of the tested biomarkers, PHID demonstrated the highest discriminative ability for clinically significant disease (area under the ROC curve [AUC] 0.78 for the univariable model). That continued to be the case in multivariable logistic regression models incorporating age and PNB status (AUC 0.82). At a threshold of 0.44, representing the 25th percentile of PHID in the cohort, PHID was 92.3% sensitive and 35.3% specific for clinically significant PCa; the sensitivity and specificity were 93.0% and 32.4% and 97.4% and 29.1% for GG ≥2 and GG ≥3 disease, respectively. In the 104 men who underwent MRI, PI-RADS score was complementary to PHID, with a PI-RADS score ≥3 or, if PI-RADS score ≤2, a PHID ≥0.44, detecting 100% of clinically significant disease. For that subgroup, of the biomarkers tested, PHID (AUC 0.90) demonstrated the highest discriminative ability for clinically significant disease on multivariable logistic regression incorporating age, PNB status and PI-RADS score. CONCLUSIONS: In this contemporary cohort of men undergoing prostate biopsy for the diagnosis of PCa, PHID outperformed PHI and other PSA derivatives in the diagnosis of clinically significant cancer. Incorporating age, PNB status and PI-RADS score led to even further gains in the diagnostic performance of PHID. Furthermore, PI-RADS score was found to be complementary to PHID. Using 0.44 as a threshold for PHID, 35.3% of unnecessary biopsies could have been avoided at the cost of missing 7.7% of clinically significant cancers. Despite these encouraging results, prospective validation is needed.

Dynamic Contrast Enhanced Magnetic Resonance Imaging Improves Classification of Prostate Lesions: A Study of Pathological Outcomes on Targeted Prostate Biopsy.

PURPOSE: PI-RADS™, version 2 stipulates that dynamic contrast enhanced imaging should be used to classify diffusion-weighted imaging score 3 peripheral zone lesions as PI-RADS score 3 (dynamic contrast enhanced imaging negative or nonenhancing) or 4 (dynamic contrast enhanced imaging positive or enhancing). However, to our knowledge it is unknown whether dynamic contrast enhanced imaging separates lesions into clinically meaningful pathological groups. We examined whether dynamic contrast enhanced imaging would improve the detection of clinically significant cancer. MATERIALS AND METHODS: We identified patients without a prior diagnosis of prostate cancer who underwent multiparametric magnetic resonance imaging-transrectal ultrasound fusion targeted biopsy of peripheral zone lesions with a diffusion-weighted imaging score of 3 or 4. Each lesion was grouped into 1 of 3 classifications, including group 1-diffusion-weighted imaging score 3/nonenhancing/PI-RADS score 3, group 2-diffusion-weighted imaging score 3/enhancing/PI-RADS score 4 or group 3-diffusion-weighted imaging score 4/PI-RADS score 4. We measured the rate of grade group 2 or greater pathology detected for each lesion group with subgroup analyses in patients with vs without prior negative systematic biopsy. RESULTS: We identified a total of 389 peripheral zone diffusion-weighted imaging score 3 or 4 lesions in 290 patients. The rate of grade group 2 or greater cancer on biopsy for group 1, 2 and 3 lesions was 8.9%, 21% and 36.5%, respectively (p <0.03). The rate of grade group 2 or greater pathology was higher in group 2 than group 1 lesions in patients with prior negative systematic prostate biopsy (28% vs 5.0%, p <0.001) but not in those without such a biopsy (16% vs 12%, p = 0.5). Group 3 lesions had a higher rate of grade group 2 or greater cancer than group 2 lesions in the biopsy naïve subgroup (46% vs 16%, p = 0.001). However, the rates were similar in patients with prior negative systematic prostate biopsy (27% vs 28%, p = 0.9). CONCLUSIONS: Diffusion-weighted imaging score 3 peripheral zone lesions were more likely to be clinically significant cancer (grade group 2 or greater) if they were dynamic contrast enhanced T1-weighted imaging positive. That was most apparent in patients with a prior negative systematic prostate biopsy. In such patients including a dynamic contrast enhanced sequence in multiparametric magnetic resonance imaging allowed for optimal lesion risk stratification.

Prostate MRI prior to radical prostatectomy: effects on nerve sparing and pathological margin status.

OBJECTIVES: The aim of this study was to assess the positive surgical margin (PSM) and nerve sparing (NS) rates in patients who underwent prostate MRI (pMRI) prior to radical prostatectomy (RP) and compare them with matched, nonimaged control RP patients. METHODS: We identified 204 men who underwent preoperative pelvic MRI (pelMRI), of whom 176 (86.3%) underwent pMRIs, within 60 days of RP, and compared them (1:1) with a nonim-aged control group matched by surgeon, age, race, body mass index (BMI), prostate-specific antigen (PSA), pathological Gleason score, prostate specimen weight, and RP year. RESULTS: The rates of nonfocal extracapsular extension (nfECE) on RP pathology in the MRI and control groups were similar. PSM rates were lower in the MRI group (13.7% vs 19.3%; P=0.14), but the difference did not meet statistical significance; this was also the case in patients with nfECE on RP pathology (27.7% vs 39.5%; P=0.3). NS rates were similar between groups. In the MRI group, 54 (26.5%) patients had an MRI suspicious for nfECE; their PSM rate (20.4%) was higher than that of patients with an MRI not suspicious for nfECE (11.3%; P=0.11), but the difference lacked statistical significance; the former group had significantly lower rates of NS. Limitations of the study include sample power and nonuniform heeding of MRI results by each surgeon. CONCLUSION: MRI did not significantly decrease the rates of PSM, including in the subset of patients with nfECE on final pathology. Even wider resection may be necessary in patients with MRIs suggesting locally-advanced disease. Studies with greater power are needed.

Urinary continence recovery after radical prostatectomy - anatomical/reconstructive and nerve-sparing techniques to improve outcomes.

In an editorial board-moderated debate format, two experts in prostate cancer surgery are challenged with presenting the key strategies in radical prostatectomy that improve urinary functional outcomes. Dr Bernardo Rocco was tasked with arguing the facts that support the anatomical preservation and reconstruction steps that improve urinary continence. Drs Christian Pavlovich and Sasha Druskin were tasked with arguing the facts supporting neurovascular bundle and high anterior release surgical planes that improve urinary continence. Associate Editor John Davis moderates the debate, and outlines the current status of validated patient questionnaires that can be used to evaluate urinary continence, and recent work that allows measuring what constitutes a 'clinically significant' difference that either or both of these surgical techniques could influence. A review of raw data from a publication from Dr Pavlovich's team demonstrates how clinically relevant differences in patient-reported outcomes can be correlated to technique. A visual atlas is presented from both presenting teams, and Dr Davis demonstrates further reproducibility of technique. A linked video on this concept is available as a supplementary file.

Prostate Health Index density improves detection of clinically significant prostate cancer.

OBJECTIVES: To explore the utility of Prostate Health Index (PHI) density for the detection of clinically significant prostate cancer (PCa) in a contemporary cohort of men presenting for diagnostic evaluation of PCa. PATIENTS AND METHODS: The study cohort included patients with elevated prostate-specific antigen (PSA; >2 ng/mL) and negative digital rectal examination who underwent PHI testing and prostate biopsy at our institution in 2015. Serum markers were prospectively measured per standard clinical pathway. PHI was calculated as ([{-2}proPSA/free PSA] × [PSA]½ ), and density calculations were performed using prostate volume as determined by transrectal ultrasonography. Logistic regression was used to assess the ability of serum markers to predict clinically significant PCa, defined as any Gleason score ≥7 cancer or Gleason score 6 cancer in >2 cores or >50% of any positive core. RESULTS: Of 118 men with PHI testing who underwent biopsy, 47 (39.8%) were found to have clinically significant PCa on biopsy. The median (interquartile range [IQR]) PHI density was 0.70 (0.43-1.21), and was 0.53 (0.36-0.75) in men with negative biopsy or clinically insignificant PCa and 1.21 (0.74-1.88) in men with clinically significant PCa (P < 0.001). Clinically significant PCa was detected in 3.6% of men in the first quartile of PHI density (<0.43), 36.7% of men in the IQR of PHI density (0.43-1.21), and 80.0% of men with PHI density >1.21 (P < 0.001). Using a threshold of 0.43, PHI density was 97.9% sensitive and 38.0% specific for clinically significant PCa, and 100% sensitive for Gleason score ≥7 disease. Compared with PSA (area under the curve [AUC] 0.52), PSA density (AUC 0.70), %free PSA (AUC 0.75), the product of %free PSA and prostate volume (AUC 0.79), and PHI (AUC 0.76), PHI density had the highest discriminative ability for clinically significant PCa (AUC 0.84). CONCLUSIONS: Based on the present prospective single-centre experience, PHI density could be used to avoid 38% of unnecessary biopsies, while failing to detect only 2% of clinically significant cancers.

Surgical histopathology for suspected oncocytoma on renal mass biopsy: a systematic review and meta-analysis.

To estimate the proportion of oncocytic renal neoplasms diagnosed on renal mass biopsy (RMB) confirmed on surgical pathology, a systematic review of MEDLINE, Embase, and the Cochrane databases (1997 to 1 July 2016) was conducted quantifying all cases of reported oncocytic renal neoplasms on RMB suggestive of an oncocytoma. In addition, institutional data was assessed to identify additional cases. Concordance with surgical histopathology (positive predictive value [PPV]) was evaluated for patients undergoing surgery by performing a meta-analysis. In all, 10 RMB series, including institutional data, were included in the meta-analysis with 205 RMBs identifying oncocytic renal neoplasms and 46 (22.4%) proceeding to surgery. One additional study identified two neoplasms not captured by the primary RMB series for a total of 48 unique lesions included in the analysis. Surgical pathology showed oncocytoma (64.6%), chromophobe renal cell carcinoma (RCC; 12.5%), other RCC (12.5%), hybrid oncocytic/chromophobe tumour (6.3%), and other benign lesions (4.2%). PPV of oncocytoma on RMB was 67% (95% confidence interval 34-94%) with significant heterogeneity between studies (I2 = 71.8%, P < 0.01). Risk of bias was judged to be low for four of the 10 series. Confidently diagnosing a localised renal mass as a benign lesion, such as an oncocytoma, has implications for the ultimate management strategy a patient will undergo. RMB was found to be unreliable in confidently diagnosing a localised renal mass as an oncocytoma, with one in four found to be RCC on surgical pathology. Patients and physicians should be aware of the uncertainty in diagnosis when considering management strategies.

Minimally Invasive ("Mini") Percutaneous Nephrolithotomy: Classification, Indications, and Outcomes.

Minimally invasive endoscopic procedures are often employed for the surgical removal of kidney stones. Traditionally, large stones are removed by (standard) percutaneous nephrolithotomy (SPCNL). Although effective for the clearance of large stone burdens, SPCNL is associated with significant morbidity. Therefore, in an effort to reduce this morbidity, while preserving efficacy, mini-PCNL (MPCNL) with a smaller tract size (<20 French) was developed. Several studies suggest that MPCNL has a comparable stone-free rate to SPCNL. However, the question of lower morbidity with MPCNL remains unanswered. In this review, we describe the equipment, indications, and efficacy of MPCNL with particular attention to its value over traditional minimally invasive stone removal techniques.

Novel treatment of a failed quadriceps tendon repair in a diabetic patient using a patella-quadriceps tendon allograft.

Recurrent quadriceps tendon rupture is a debilitating condition that may be challenging to treat, especially in the presence of systemic disease such as diabetes mellitus (Bedi et al., J Shoulder Elbow Surg 19:978-988, 2010; Chbnou and Frenette, Am J Physiol Regul Integr Comp Physiol 5:R952-R957, 2004; Chen et al., J Shoulder Elbow Surg 5:416-421, 2003). Many surgical treatment protocols have been proposed (Azar, in Canale and Beatty, eds., Campbell's Operative Orthopedics, Mosby/Elsevier, Philadelphia, PA, 2008; Ilan et al., J Am Acad Orthop Surg 3:192-200, 2003; Rodeo and Izawa, in Garrett et al., eds., Principles and Practice of Orthopedic Sports Medicine, Lippincott Williams & Wilkins, Philadelphia, PA, 2000). We report the case of a diabetic male with multiple treatment failures. He ultimately sustained a good outcome following treatment with a novel surgical technique that utilized a patella quadriceps tendon allograft. Tendon allograft-to-native bone healing had previously failed in this patient, so we used a bone-tendon construct allograft to provide an allograft bone-to-native bone healing site. Now, 13 months postoperative, the patient has increased strength, minimal pain, 20 ° of extensor lag and 130 ° of flexion.