Urinary bother, Urinalysis, and Two-Year Efficacy Follow-Up Results of Phase I Trial of Intravesical Bacillus Calmette-Guérin Combined with Intravenous Pembrolizumab in Recurrent or Persistent High-Grade Non-Muscle-Invasive Bladder Cancer after Previous Bacillus Calmette-Guérin Treatment.

OBJECTIVE: To report urinary bother, urinalysis changes, disease-free survival (DFS), and overall survival (OS) over 2 years for subjects enrolled in a phase I dose-escalation trial (NCT02324582) of intravesical Bacillus Calmette-Guérin (BCG) in combination with systemic pembrolizumab for recurrent or persistent high-grade non-muscle invasive bladder cancer (HGNMIBC). METHODS: Eighteen patients consented to the study. Five were screen failures. Clinical activity was determined using cystoscopy and cytology with a biopsy of suspicious lesions. Urinalysis and International Prostate symptom score were assessed at pre-treatment, Week 10 (during combined BCG and pembrolizumab treatment), and 3 and 6 months from treatment completion. IPSS was analyzed using a mixed-model repeated measures analysis. A Chi-square test was used to compare urinalysis results at each interval. RESULTS: The pathologic disease stage after restaging transurethral resection and before treatment was pTa in 6 (46.2%), CIS in 6 (46.2%), and pT1 in 1 (7.7%). There was no increase in reported urinary bother throughout treatment. Quality of life measurements demonstrated no change in subjective burden. On urinalysis, we did not observe significant differences at 3 months compared to baseline evaluation. At 12 months, the DFS and OS were 69.23% and 92.31%, respectively. At 24 months, the DFS and OS were 38.46% and 92.31%, respectively. CONCLUSIONS: Treatment with BCG combined with intravenous pembrolizumab is not showing increased urinary bother or adverse urinalysis changes. Two-year response data is promising and await confirmation in the phase III study (Keynote 676).

Association of request for opioid medications refill after hospital discharge with race in patients with prostate cancer treated with robotic-assisted laparoscopic radical prostatectomy.

BACKGROUND AND OBJECTIVE: Request for refills of opioids is one of the indicators of possible misuse. We aimed to investigate racial variations in request for refills of opioids after hospital discharge from robotic-assisted laparoscopic radical prostatectomy (RALP). METHODS: We conducted a retrospective study of a contemporary cohort of patients treated with RALP for prostate cancer and post-operative standardized pain control that employed nonopioid medications. Patients' request for refills of opioids (within 30 days) after discharge was examined, accounting for race, age, pain control after surgery, alcohol intake, marijuana consumption, pre-existing behavioral health diagnoses, and pre-existing chronic pain disorders using multivariate analysis. p-Value of < 0.05 was considered significant. RESULTS: We included a total of 282 adult patients in this study. African Americans (AA) patients comprised 24.5 percent of our post-prostatectomy individuals. Of the total cohort, 94.3 percent of patients reported adequate pain control in the hospital after surgery, and only 5.7 percent requested refills of opioid medications after discharge. No racial variations in request of refills were identified. Only pre-existing chronic pain disorders were found to be a significant predictor of requesting an opioid medication refill for pain control after discharge from the hospital. CONCLUSIONS: A combination of minimally invasive surgery and nonopioid heavy pain management leads to low level of post-hospital discharge request for refills of opioid medication in patients treated with RALP across racial groups. Awareness and better control of chronic pain perioperatively are needed to ensure better postdischarge pain control.

Machine learning-based prediction of upgrading on magnetic resonance imaging targeted biopsy in patients eligible for active surveillance.

OBJECTIVE: To examine the ability of machine learning methods to predict upgrading of Gleason score on confirmatory magnetic resonance imaging-guided targeted biopsy (MRI-TB) of the prostate in candidates for active surveillance. SUBJECTS AND METHODS: Our database included 592 patients who received prostate multiparametric magnetic resonance imaging in the evaluation for active surveillance. Upgrading to significant prostate cancer on MRI-TB was defined as upgrading to G 3+4 (definition 1 - DF1) and 4+3 (DF2). Machine learning classifiers were applied on both classification problems DF1 and DF2. RESULTS: Univariate analysis showed that older age and the number of positive cores on pre-MRI-TB were positively correlated with upgrading by DF1 (P-value ≤ 0.05). Upgrading by DF2 was positively correlated with age and the number of positive cores and negatively correlated with body mass index. For upgrading prediction, the AdaBoost model was highly predictive of upgrading by DF1 (AUC 0.952), while for prediction of upgrading by DF2, the Random Forest model had a lower but excellent prediction performance (AUC 0.947). CONCLUSION: We show that machine learning has the potential to be integrated in future diagnostic assessments for patients eligible for AS. Training our models on larger multi-institutional databases is needed to confirm our results and improve the accuracy of these models' prediction.

Utilizing lesion diameter and prostate specific antigen density to decide on magnetic resonance imaging guided confirmatory biopsy of prostate imaging reporting and data system score three lesions in African American prostate cancer patients managed with active surveillance.

OBJECTIVE: The objective of the study is to identify the rate of significant prostate cancer (PCa) detection in PI-RADS3 lesions in AA patients stratified by PSAD threshold of < 0.15 vs. ≥ 0.15 ng/ml2 and lesion diameter of < 1 cm vs ≥ 1 cm. METHODS: We analyzed our institutional database of MRI-TB to identify the rate of significant prostate cancer (PCa) detection in PI-RADS3 lesions in AA patients stratified by PSAD threshold of < 0.15 vs. ≥ 0.15 ng/ml2 and lesion diameter of < 1 cm vs ≥ 1 cm. Significant prostate cancer was defined as Gleason grade group 2 or higher on MRI-TB of the PI-RADS 3 lesion. RESULTS: Of 768 patients included in the database, 211 (27.5%) patients identified themselves as AAs. Mean age of AA patients was 63 years and mean PSAD was 0.21. Sixty nine (32.7%) AA patients were found to have PI-RADS 3 lesions. Mean PSAD of AA patients with PI-RADS 3 lesions was 0.21 ng/ml2 as well. Fifty percent of AA patients with PI-RADS 3 lesions had PSAD ≥ 0.15 ng/ml2. Significant PCa detection rate for AA patients with PI-RADS 3 lesions was 9% for PSAD of ≥ 0.15 vs. 0.03% percent for AA patients with PSAD < 0.15 ng/ml2 (OR 7.056, CI 1.017-167.9, P = 0.04). Stratification by lesion diameter (< 1 cm vs. > 1 cm) resulted in missing 0% of significant PCa when only AA patients with PSAD ≥ 0.15 ng/ml2 and lesion diameter ≥ 1 cm received MRI-TB. CONCLUSIONS: We report on the performance of a reported PSAD density threshold in detecting significant PCa in one of the largest series of AA patients receiving MRI-TB of the prostate. Our results have direct clinical implications when counseling AA patients with PI-RADS 3 lesion on whether they should undergo MRI-TB of such lesions.

Phase I trial of intravesical Bacillus Calmette-Guérin combined with intravenous pembrolizumab in recurrent or persistent high-grade non-muscle-invasive bladder cancer after previous Bacillus Calmette-Guérin treatment.

OBJECTIVES: We conducted the first phase I dose-escalation trial (NCT02324582) of intravesical Bacillus Calmette-Guérin (BCG) in combination with systemic pembrolizumab in patients with high-grade non-muscle-invasive bladder cancer (HGNMIBC) who had persistent or recurrent disease after prior intravesical therapy with BCG. The primary endpoint was the safety of this combination. The secondary endpoint was clinical activity at three months following BCG treatment. METHODS: Eighteen patients were consented for the study, five of which were screen failures. Six doses of pembrolizumab were administered every 3 weeks over 16 weeks concurrently with six weekly doses of BCG beginning at week 7. Patient safety was evaluated from the time of consent through 30 days following pembrolizumab treatment. Clinical activity was determined using cystoscopy and biopsy of suspicious lesions. RESULTS: Treatment-related adverse events included one grade 4 adverse event (AEs) (adrenal insufficiency). There were nine grade 3 AEs (chest discomfort, pulmonary embolism, arthritis, wrist edema, injection site reaction, bilateral wrist pain, cardiomyopathy, hypokalemia, urinary tract infection). There were 49 grade 1 and 30 grade 2 AEs (88% of AEs). Eleven patients finished the treatment, and two patients died during the study. Of 13 patients treated, nine patients (69%) had no evidence of disease at 3 months following BCG treatment. CONCLUSIONS: We report for the first time that combining BCG and pembrolizumab in treating HGNMIBC is safe allowing complete treatment of most patients. A phase III trial has opened to test the efficacy of this combination in HGNMIBC (KEYNOTE-676).

Prognostic significance of histomorphologic features of lymph node metastases in prostate cancer patients treated with radical prostatectomy: A single center study.

OBJECTIVE: We assessed the prognostic value of histomorphologic features of lymph node (LN) metastases in patients with prostate cancer treated with radical prostatectomy MATERIALS AND METHODS: We evaluated the effect of the features of LN metastasis on the risk of biochemical recurrence (BCR) in 280 LN-positive patients who underwent radical prostatectomy between 2006 to 2018. LN specific parameters recorded included number of metastatic LNs, size of the largest metastatic focus, Gleason Grade (GG) of the metastatic focus, and extranodal extension (ENE). RESULTS: A solitary positive LN was found in 166/280 (59%), 95/280 (34%) patients had 2-4 positive LNs, and 19/280 (7%) had 5 or more positive LNs. The size of the largest metastatic focus > 2 mm (macrometastasis) in 154/261 (59%). GG of the metastatic focus was as follows: GG 1-2: 29/224 (13%); GG 3: 27/224 (12%); and GG 4-5: 168/224 (75%). ENE was identified in 99/244 (41%). We found the number of LNs positive (2-4 vs. 1 Hazard ratio (HR) = 1.60; 95% CI: 1.02 to 2.5; P = 0.04) and GG of the metastatic focus (GG 4&5 vs. 1-3 HR = 1.90; 95% CI: 1.14-3.2; P= 0.014) to be independent predictors of the risk of BCR after surgery on multivariate analysis. CONCLUSIONS: Our study showed the number of LNs positive and GG of the LN metastatic focus to be significant independent predictors of BCR after radical prostatectomy. We recommend reporting histomorphologic parameters of LN metastasis as they may help in defining BCR risk categorization.

Post Prostatectomy Pathologic Findings of Patients With Clinically Significant Prostate Cancer and no Significant PI-RADS Lesions on Preoperative Magnetic Resonance Imaging.

OBJECTIVES: We present postprostatectomy pathology results from a series of prostate cancer (Pca) Gleason grade group ≥2 patients who did not have findings suggestive of cancer on preoperative pelvic magnetic resonance imaging (MRI). METHODS: We performed an institutional retrospective study of prostate magnetic resonance imaging (MRI) examinations done from October 2015 to February 2018. We identified patients who underwent prostatectomy for Pca Gleason ≥3 + 4 diagnosed on prostate biopsy with no associated MRI findings suggestive of malignancy and analyzed their postprostatectomy pathologic findings and MRI imaging results. RESULTS: At our institution, 850 men with Pca received MRI between 2015 and 2018, and 156/850 patients received robotic-assisted radical prostatectomy. Thirty-three patients (33/156 = 21%) had negative MRI for PIRAD 3 or greater but had a biopsy showing significant Pca. Their mean (range) age was 62.7 (50-86) years. Their median (interquartile range) PSA, and PSA density were, 4.6 (3.7) ng/mL and 0.12 (0.05) ng/mL/cm2, respectively; all not significantly different from patients with visible lesions on MRI who underwent surgery. On post prostatectomy pathology, 27/33 (82%) men had Pca Gleason score 7 or greater. The most common pattern was infiltrative growth with cancer glands intermingling between benign glands. CONCLUSION: We describe the pathologic and imaging findings in an extensive series of men with clinically significant Pca with no significant lesions on preoperative MRI. Our results support the importance of patient counseling on the risk of missing significant Pca on MRI in isolation from other clinical variables.

The effect of multiplicity of PI-RADS 3 lesions on cancer detection rate of confirmatory targeted biopsy in patients diagnosed with prostate cancer and managed with active surveillance.

BACKGROUND AND OBJECTIVE: To determine the effect of multiplicity of prostate imaging reporting and data system assessment category 3 (PI-RADS 3) lesions on cancer detection rate (CDR) of confirmatory targeted biopsy of such lesion in patients diagnosed with prostate cancer and managed with active surveillance. METHODS: This study was conducted at a single academic institution. There were 91 men with ≥ 1 PI-RADS 3 lesion detected through magnetic resonance imaging (MRI) after systematic prostate biopsy in the course of management of patients diagnosed with prostate cancer with active surveillance. We compared the CDRs based on targeted biopsy of PI-RADS 3 lesions that occurred (1) as solitary lesions, (2) as 1 of multiple PI-RADS 3 only lesions, or (3) with ≥ 1 higher grade lesion. RESULTS: Median age was 65.0 years (interquartile range 59.5-70.0), median prostate specific antigen was 5.95 ng/ml (interquartile range 4.30-8.83), and median prostate specific antigen density was 0.161 ng/ml2 (0.071-0.194). Forty-three men had solitary PI-RADS 3 lesions, 22 had multiple PI-RADS 3 only lesions, and 26 had multiple lesions with ≥ 1 higher grade lesion. The overall CDR (Gleason score ≥ 3 + 3) based on confirmatory MRI targeted biopsy in a given PI-RADS 3 lesion in each group was 23%, 45%, and 54%, respectively (P = 0.0274). The CDRs for clinically significant disease (Gleason score ≥ 3 + 4) were 16%, 32%, and 35%, respectively (P = 0.1701). CONCLUSIONS: Coexisting lesions increase the CDR of confirmatory MRI targeted biopsy of PI-RADS 3 lesions in patients managed with active surveillance. Risk stratification algorithms for PI-RADS 3 lesion to guide biopsy and management decisions may consider including multiplicity of lesions.

Using adaptive genetic algorithms combined with high sensitivity single cell-based technology to detect bladder cancer in urine and provide a potential noninvasive marker for response to anti-PD1 immunotherapy.

OBJECTIVE: To use adaptive genetic algorithms (AGA) in combination with single-cell flow cytometry technology to develop a noninvasive test to detect bladder cancer. MATERIALS AND METHODS: Fifty high grade, cystoscopy confirmed, superficial bladder cancer patients, and 15 healthy donor early morning urine samples were collected in an optimized urine collection media. These samples were then used to develop an assay to distinguish healthy from cancer patients' urine using AGA in combination with single-cell flow cytometry technology. Cell recovery and test performance were verified based on cystoscopy and histology for both bladder cancer determination and PD-L1 status. RESULTS: Bladder cancer patients had a significantly higher percentage of white blood cells with substantial PD-L1 expression (P< 0.0001), significantly increased post-G1 epithelial cells (P < 0.005) and a significantly higher DNA index above 1.05 (P < 0.05). AGA allowed parameter optimization to differentiate normal from malignant cells with high accuracy. The resulting prediction model showed 98% sensitivity and 87% specificity with a high area under the ROC value (90%). CONCLUSIONS: Using single-cell technology and machine learning; we developed a new assay to distinguish bladder cancer from healthy patients. Future studies are planned to validate this assay.

Combination of pembrolizumab and BCG treatment after endoscopic ablation of high-risk superficial upper urinary tract urothelial carcinoma in patients not candidates for radical nephroureterectomy: protocol for phase-II study.

INTRODUCTION: The treatment standard for high-risk upper urinary tract urothelial carcinoma (UUTUC) is radical nephroureterectomy. However, some patients may be unfit or unwilling, and in such patients the available alternatives are suboptimal. Therapies targeting the programmed death (PD) pathway have shown promise in urothelial carcinom (UC). We designed the current study to determine the safety and efficacy of administering MK-3475 (a monoclonal antibody targeting interaction between PD-1 and its ligand) in combination with bacillus Calmette-Guerin (BCG) in high-risk non-muscle invasive UUTUC patients. METHODS: This represents a single-centre phase-II efficacy study of MK-3475 therapy in combination with BCG for subjects, 18 years of age or older, with pathologically documented non-muscle invasive high-risk UUTUC unfit or unwilling to be treated with radical nephroureterectomy. Twenty subjects will be enrolled; patients will receive treatment with 200 mg of MK-3475 every 21 days, starting 2 weeks from the initial endoscopic resection and continuing for 6 weeks after the final dose of BCG. The primary objective is to determine the safety and efficacy of administering MK-3475 at a fixed dose of 200 mg every 3 weeks in conjunction with intrapelvic BCG. Secondary objectives include 19 week and the 3, 12 and 24-month post-treatment completion complete response and progression-free rate assessments. ETHICS AND DISSEMINATION: The study has been approved by the Institutional Review Board of the Henry Ford Hospital. The results of this study will be published in a peer-reviewed journal and presented at a scientific conference. TRIAL REGISTRATION NUMBER: NCT03345134.

Systematic Biopsy Does Not Contribute to Disease Upgrading in Patients Undergoing Targeted Biopsy for PI-RADS 5 Lesions Identified on Magnetic Resonance Imaging in the Course of Active Surveillance for Prostate Cancer.

OBJECTIVE: To compare the utility of the systematic 12-core prostate biopsy (SB) combined with magnetic resonance imaging (MRI)-targeted lesion biopsy (MRI-TB) vs MRI-TB alone in the diagnosis of high PI-RADS lesions. MATERIALS AND METHODS: Patients undergoing MRI-TB + SB for suspicious MRI lesions were retrospectively reviewed. These patients had a previous prostate biopsy and were evaluated with MRI to assess the need for a repeat biopsy. Pathologic findings of MRI-TB combined with a SB were compared to those of the patients' previous SB. An upgrade was defined as an increase in the Gleason Score of any prior biopsy. A no-upgrade (NU) MRI-TB was defined as a MRI-TB that did not lead to disease upgrading when compared to SB. RESULTS: A total of 148 patients were analyzed in this study. Of the 255 total lesions (247 lesions with PI-RADS ≥3), 141 were upgraded from the previous biopsy (55.3%). Of these, 104 were upgraded by the MRI-TB (40.8%), and 87 lesions were upgraded by the SB (34.1%). The MRI-TB had a NU rate of 26.2% for all lesions. On subanalysis, the NU rates of PI-RADS 3, 4, and 5 MRI-TBs were 39.3%, 21.2%, and 3.4%, respectively. CONCLUSION: The NU rate for the MRI-TB in a PIRADS-5 lesion is meager. Men with a PI-RADS 5 lesion may be safely managed with the MRI-TB alone without combining with SB. Men with PI-RADS 3 and 4 lesions should benefit from SB in addition to MRI-TB for accurate management of their disease.

Protocol for phase I study of pembrolizumab in combination with Bacillus Calmette-Guérin for patients with high-risk non-muscle invasive bladder cancer.

INTRODUCTION: The initial treatment for high-risk non-muscle invasive bladder cancer (NMIBC) is endoscopic resection of the tumour followed by BCG therapy. In those who develop recurrence, the standard treatment is radical cystectomy. Despite the advancement in surgical technique and postoperative care, the degree of morbidity associated with radical cystectomy remains high, therefore less invasive treatment modalities are desirable. Therapies targeting the programmed death (PD) pathway have shown promise in urothelial carcinoma. We undertook the current study to determine the safety and efficacy of administering pembrolizumab (a monoclonal antibody targeting the interaction between PD-1 and its ligand) in combination with BCG in high-risk NMIBC. METHODS: This is a single-centre phase I safety and efficacy study of pembrolizumab used in combination with intravesicular BCG treatment for subjects with pathologically documented high-risk NMIBC despite having received two courses of induction therapy or BCG treatment followed by maintenance BCG. Fifteen subjects will be enrolled, patients will receive treatment with 200 mg of pembrolizumab every 21 days, starting 2 weeks from the initial endoscopic resection and continuing for 6 weeks after the final dose of BCG. The primary objective is to determine the safety of administering pembrolizumab at a fixed dose of 200 mg every 3 weeks in conjunction with intravesicular BCG treatment in patients with high-risk NMIBC who have failed previous treatment. Secondary objectives are to determine the 19 weeks and the 3, 12 and 24 months post-treatment completion complete response rate with combined pembrolizumab and intravesicular BCG therapy in the aforementioned patients. ETHICS AND DISSEMINATION: The study has been approved by the Institutional Review Board of the Henry Ford Hospital. The results of this study will be published in a peer-reviewed journal and presented at a scientific conference. TRIAL REGISTRATION NUMBER: NCT02324582.

Prostate volume measured by magnetic resonance imaging is not a predictor of lower urinary tract symptoms.

PURPOSE: Prostate volume is frequently utilized to counsel patients presenting to family medicine physicians with voiding complaints. We evaluated the relation between International Prostate Symptom Score (IPSS) and prostate volume measured by phased-array surface coil magnetic resonance imaging (MRI). METHODS: We performed an institutional review board (IRB)-approved retrospective study of all patients who received a prostate MRI between 2015 and 2017. Correlation between the overall IPSS, IPSS components, prostate volume stratified by prostate specific antigen (PSA) (<1.4 vs. ≥1.4 g/dL), and race (black vs. white) was examined. RESULTS: In all, 592 patients had prostate MRIs performed between 2015 and 2017. Two hundred and twenty-nine of these patients had IPSS and prostate volume information available in their medical records. The mean age of the cohort was 64.67 (SD = ±7.82) and mean PSA was 7.75 (SD = ±8.3). The mean IPSS was 9.77 (SD ± 7.2), and mean prostate volume was 55.88 cubic cm (SD = ±38.9). The correlation coefficient between prostate volume and IPSS was 0.12789 (P = 0.05). The correlation between prostate volume and IPSS was also not significant in 128 men with prostate volume above 40 cubic cm. Stratifying analysis by race and PSA showed no significant correlation between volume and IPSS. Analysis of the correlation between the different dimension of prostate volume and IPSS revealed significant but weak associations. CONCLUSIONS: Even with more precise estimation with MRI, prostate volume does not predict obstruction complaints. This finding is of importance when treating males presenting with voiding dysfunction to primary care.

Barriers to obtaining prostate multi-parametric magnetic resonance imaging in African-American men on active surveillance for prostate cancer.

PURPOSE: Magnetic resonance imaging is playing an ever-bigger role in the management of prostate cancer. This study investigated barriers to obtaining multi-parametric MRI (mpMRI) in African-American men on active surveillance for prostate cancer in comparison to white men affected by the same type of cancer. MATERIALS AND METHODS: Retrospective review of prostate mpMRI orders from August 2015 to October 2017 at a single health organization treating a diverse population was performed. Data was extracted from the electronic medical records and cancellations were examined based on the documented reason for mpMRI cancellation, race, median zip code household income, and distance from healthcare facility. RESULTS: Out of 793 prostate mpMRI orders, 201 (25%) went unscanned. Access to care issues accounted for 46% of unscanned orders. Patient cancellations were the most common, followed by difficulty contacting patients, and insurance denials. African-American patients disproportionately went unscanned because institution staff were unable to contact patients (29% vs 10% in white men, P = 0.0015). Median zip code household income was significantly different between racial groups but did not vary between indication for cancellation. CONCLUSIONS: African-American prostate cancer patients' access to mpMRI is hindered more by barriers to care than White patients. Urology providers must consider these issues before using prostate mpMRI within their active surveillance pathways.

A propensity score matched analysis of the effects of African American race on the characteristics of regions of interests detected by magnetic resonance imaging of the prostate.

OBJECTIVES: To evaluate the effects of African American (AA) race on the number, location, Prostate Imaging Reporting and Data System (PI-RADS) score, cancer detection rate, and cancer upgrade rate of the regions of interest (ROI) discovered on mltiparametric magnetic resonance imaging (mp-MRI) of the prostate. METHODS: We performed an institutional retrospective study of 592 patients who received a prostate mp-MRI. Number of ROI (1-4), their location, and PI-RADS score v2 were evaluated in a matched cohort of Caucasian and AA males. Propensity score matching was performed using the variables of age, prostate specific antigen (PSA) level, and prostate volume. Comparisons utilized chi-square tests and P < 0.05 was considered significant. RESULTS: One hundred and twenty three AA patients were matched with an equal number of Caucasian men of similar characteristics. The AA population's median age was 63 years (57.3-69.3), median PSA 6.6 (4.6-12.1), and median prostate volume 55 ml (33-90.8). The Caucasian population's median age was 66.3 years (60.9-71.1), median PSA 5.4 (3.8-8), and median prostate volume 52.5 ml (33.2-83). The number of ROI was 2 or more in 24% of AA men and 12% of Caucasian men (P = 0.035), and 3 or more in 10% of AA and 2% of Caucasian men (P = 0.034). There was no significant difference in location, PI-RADS scores, cancer detection rate, and cancer upgrade rate of the ROI between the 2 groups. CONCLUSIONS: AA patients, as compared to Caucasian counterparts, have a higher number of ROI detected on prostate mp-MRI.

Prostate cancer with comedonecrosis is frequently, but not exclusively, intraductal carcinoma: a need for reappraisal of grading criteria.

AIMS: Comedonecrosis in prostate cancer has always been Gleason pattern 5. However, we aimed to evaluate how intraductal carcinoma (not graded) with comedonecrosis should be considered. METHODS AND RESULTS: From 52 radical prostatectomy patients, 40 were informative and evaluated with immunohistochemistry for basal cells. Clinical outcome was assessed for biochemical recurrence, metastatic disease and the need for adjuvant therapy. Comedonecrosis was predominantly located in intraductal carcinoma (24, 60%). However, nine (23%) had comedonecrosis within invasive cancer and seven (18%) within both invasive and intraductal carcinoma. Extraprostatic extension rarely showed comedonecrosis (5, 13%), but rather perineural invasion within cribriform glands. Tumours were largely high-stage (15, 38% pT3a and 19, 48% pT3b), with 15 (37%) having positive lymph nodes and four distant metastases. Most cases (25, 63%) had other patterns of Gleason pattern 5 (single cells, solid), although 10 were reclassified as containing no invasive pattern 5. Of these, most were pT3 (eight of 10), but none had positive lymph nodes. Lymph node metastases were more common in patients with invasive cancer containing comedonecrosis (P = 0.02), and the need for androgen deprivation was near significance (P = 0.07), but biochemical recurrence was not significantly different (P = 0.58). CONCLUSIONS: Prostate cancer with comedonecrosis is often intraductal; however, these tumours are largely high-stage, showing a higher rate of positive lymph nodes with invasive comedonecrosis. Immunohistochemistry may be considered when comedonecrosis may significantly change the tumour grade. However, it is not clear at present that excluding intraductal carcinoma from the grade is superior to including it in grading when it is associated with high-grade invasive cancer.

Effect of Lesion Location on Prostate Cancer Detection Rate with Magnetic Resonance Imaging Targeted Biopsy in African Americans.

PURPOSE: The updated PI-RADS™ (Prostate Imaging Reporting and Data System) version 2 defines different grading parameters for lesions located in the peripheral zone vs the transition zone. It has contributed to the implementation of magnetic resonance imaging targeted biopsy. In this study we evaluated the efficacy of magnetic resonance imaging targeted biopsy among African American patients with additional consideration for lesion location on magnetic resonance imaging. MATERIALS AND METHODS: We performed a retrospective review of magnetic resonance imaging targeted biopsy at a single institution where a racially diverse population is treated. A single radiology group read the prostate multiparametric magnetic resonance imaging scans and followed PI-RADS version 2 algorithms to categorize lesions. RESULTS: A total of 214 lesions from 125 men were included in the analysis, of which 162 (75.7%) were in the peripheral zone and 52 (24.3%) were in the transition zone. There were 64 lesions from African American patients and 150 from Caucasian patients with tumor location distributed proportionately. The 48 anterior lesions (22.4%) had a higher PI-RADS version 2 score and trended toward a larger size. The overall cancer detection rate was 50%, which did not differ significantly between prostate zones (p = 0.5468) or racial groups (p = 0.2294). The cancer upgrade rate was 41% and it also did not differ significantly between prostate zones (p = 0.5134) or racial groups (p = 0.2365). Anterior lesions had a higher cancer detection rate (p = 0.0117) and trended toward a higher cancer upgrade rate (p = 0.0781). CONCLUSIONS: This study provides evidence that magnetic resonance imaging targeted biopsy is equally effective in African American and Caucasian men, and does not preferentially identify prostate cancer in the peripheral zone or the transition zone.

Endocrine, Sexual Function, and Infertility Side Effects of Immune Checkpoint Inhibitor Therapy for Genitourinary Cancers.

PURPOSE OF REVIEW: Immune checkpoint therapy has grown in prominence in the last few decades and is being increasingly utilized in treatment of advanced cancers. Although information on toxicities of these drugs is forthcoming, not much is known regarding the toxicity profile of these drugs from a sexual function standpoint. We undertook the current review to appraise the literature for endocrine/sexual side effects of anti-PD-1/PD-L1 and anti-CTLA-4 therapy. RECENT FINDINGS: Our review included 32 articles and focused primarily on the programmed death (PD) pathway. We found that endocrine side effects after anti-PD-1/PD-L1 therapy are relatively rare, with hypothyroidism (range < 1 to 40%) and hypophysitis (range < 1 to 10%) being the two most common. None of the studies specifically commented on the infertility or sexual side effects of these drugs. However, two studies evaluating biochemical profiles of patients undergoing therapy with ipilimumab (a CTLA-4 inhibitor) or combination therapy (CTLA-4 + PD-1/PD-L1 inhibitors) noted that about < 1 to ~ 60% of the patients developed hypogonadotropic hypogonadism. None of the studies provided information regarding clinically meaningful sexual health endpoints such as libido, erectile function assessments, or sexual function-related quality of life. Endocrine side effects, although uncommon, are important and unique side effects of immune checkpoint therapy because they are often complex and can be life threatening. While side effects on sexual health may not be life threatening, they are lifestyle limiting. Thus, long-term follow-up, post-marketing surveillance, and future studies will need to elucidate the true rates of endocrine/sexual side effects and the mechanisms underlying them. This will aid in better counseling of the patients, as more of them undergo these novel immune checkpoint inhibitor therapies.