Current Urology

Flammia, Rocco Simone; Hoeh, Benedikt; Chierigo, Francesco; Hohenhorst, Lukas; Sorce, Gabriele; Tian, Zhen; Leonardo, Costantino; Graefen, Markus; Terrone, Carlo; Saad, Fred; Shariat, Shahrokh F.; Briganti, Alberto; Montorsi, Francesco; Chun, Felix K. H.; Gallucci, Michele; Karakiewicz, Pierre I.

2022 Current Urology

doi: 10.1097/cu9.0000000000000132pmid: 36714227

Abstract Background The National Comprehensive Cancer Network (NCCN) guidelines recommend pelvic lymph node dissection (PLND) in NCCN high- and intermediate-risk prostate cancer patients. We tested for PLND nonadherence (no-PLND) rates within the Surveillance Epidemiology and End Results (2010–2015). Materials and methods We identified all radical prostatectomy patients who fulfilled the NCCN PLND guideline criteria (n = 23,495). Nonadherence rates to PLND were tabulated and further stratified according to NCCN risk subgroups, race/ethnicity, geographic distribution, and year of diagnosis. Results Overall, the no-PLND rate was 26%; it was 41%, 25%, and 11% in the NCCN intermediate favorable, intermediate unfavorable, and high-risk prostate cancer patients, respectively (p < 0.001). Over time, the no-PLND rates declined in the overall cohort and within each NCCN risk subgroup. Georgia exhibited the highest no-PLND rate (49%), whereas New Jersey exhibited the lowest (15%). Finally, no-PLND race/ethnicity differences were recorded only in the NCCN intermediate unfavorable subgroup, where Asians exhibited the lowest no-PLND rate (20%) versus African Americans (27%) versus Whites (26%) versus Hispanic-Latinos (25%). Conclusions The lowest no-PLND rates were recorded in the NCCN high-risk patients followed by NCCN intermediate unfavorable and favorable risk in that order. Our findings suggest that unexpectedly elevated differences in no-PLND rates warrant further examination. In all the NCCN risk subgroups, the no-PLND rates decreased over time.

Tidd-Johnson, Atiyah; Sebastian, Sneha Annie; Co, Edzel Lorraine; Afaq, Munaza; Kochhar, Hansini; Sheikh, Mona; Mago, Arpit; Poudel, Sujan; Fernandez, John A.; Rodriguez, Ivan D.; Razdan, Sanjay

2022 Current Urology

doi: 10.1097/cu9.0000000000000145pmid: 36714234

Abstract Prostate cancer (PCa) screening remains one of the most controversial topics in clinical and public health. Despite being the second most common cancer in men worldwide, recommendations for screening using prostate-specific antigen (PSA) are unclear. Early detection and the resulting postscreening treatment lead to overdiagnosis and overtreatment of otherwise indolent cases. In addition, several unwanted harms are associated with PCa screening process. This literature review focuses on the limitations of PSA-specific PCa screening, reasons behind the screening controversy, and the novel biomarkers and advanced innovative methodologies that improve the limitations of traditional screening using PSA. With the verdict of whether or not to screen not yet unanimous, we hope to aid in resolution of the long-standing debate.

Sakellakis, Minas; Flores, Laura Jacqueline

2022 Current Urology

doi: 10.1097/cu9.0000000000000120pmid: 36714229

Abstract Mitochondria are more than just the cellular powerhouse. They also play key roles in vital functions such as apoptosis, metabolism regulation, and other intracellular interactions. The mitochondrial DNA (mtDNA) encodes for 12 subunits of the oxidative phosphorylation (OXPHOS) system. Depletion of mtDNA in androgen-dependent prostate cancer (PCa) cell lines renders them androgen-independent and more aggressive. Paradoxically, pharmaceutical inhibition of OXPHOS is lethal for subsets of PCa cells, whereas others become dependent on androgen receptor (AR) signaling for survival. Given that the AR-mitochondria interaction is critical for early PCa, it is crucial to understand the details of this interaction. Technical hurdles have made mitochondria traditionally difficult to study, with many techniques used for isolation masking the properties of given individual mitochondria. Although the isolation of mitochondria enables us to study OXPHOS, we miss the context in which mitochondria interact with the rest of the cell. Both AR signaling and mtDNA affect apoptosis, metabolism regulation, cellular calcium storage and homeostasis, intracellular calcium signaling, and redox homeostasis. In this review, we will attempt to understand how the crosstalk between AR-mtDNA-OXPHOS is responsible for “life or death” decisions inside the cells. Our aim is to point toward potential vulnerabilities that can lead to the discovery of novel therapeutic targets.

Patel, Parth U.; Bock, David; Hettinger, Christian A.

2022 Current Urology

doi: 10.1097/cu9.0000000000000140pmid: 36714236

Abstract Objectives To provide concise information to clinicians on how to better interpret multiparametric magnetic resonance imaging for prostate cancer risk stratification. Materials and methods We analyzed 2 separate cohorts. For patients receiving a Prostate Imaging Reporting and Data System version 2 (PI-RADSv2) score of 1 or 2, we reviewed the charts of 226 patients who underwent multiparametric magnetic resonance imaging of the prostate ordered from 2015 to 2017 to determine who developed clinically significant prostate cancer (csPCa) by August 27, 2020. For patients receiving PI-RADSv2 a score of 3, 4, or 5, we reviewed the results of 733 fusion biopsies on solitary lesions. Statistical analysis was used to further determine risk factors for csPCa. Results Ten percent of men with PI-RADSv2 a score of 1 eventually developed csPCa. Seven percent with a score of 2 were eventually diagnosed with csPCa. Only 1 of 226 with a score of 1 or 2 developed metastasis. For PI-RADSv2 scores of 3, 4, and 5, csPCa was detected in 16%, 45%, and 67% of fusion biopsies. Peripheral zone (PZ) PI-RADSv2 score of 4 or 5 and prostate-specific antigen density (PSA-D) were significant predictors of csPCa on multivariable analysis. Using a PSA-D × PI-RADSv2 score of ≤0.39, we identified 38% of men with a PI-RADSv2 score of 3 in the PZ or 3, 4, or 5 in the transition zone who could have avoided a benign biopsy. Conclusions The vast majority of patients with PI-RADSv2 scores 1 and 2 can be safely monitored with close surveillance. Lesions with PI-RADSv2 scores of 4 and 5 in the PZ should be biopsied. Peripheral zone lesions with a PI-RADSv2 score of 3 and transition zone lesions with 3, 4, or 5 can be risk-stratified using the PSA-D × PI-RADSv2 score to determine who may safely avoid a biopsy and who should proceed to fusion biopsy.

Cozzi, Salvatore; Bardoscia, Lilia; Najafi, Masoumeh; Igdem, Sefik; Triggiani, Luca; Magrini, Stefano Maria; Botti, Andrea; Guedea, Ferran; Melocchi, Laura; Ciammella, Patrizia; Iotti, Cinzia; Gutierrez, Cristina

2022 Current Urology

doi: 10.1097/cu9.0000000000000118pmid: 36714233

Abstract Objective The aim of the study is to evaluate clinical features and outcomes after different therapeutic strategies for ductal prostate adenocarcinoma (DPC), a rare but aggressive subtype of invasive prostate cancer (PCa) accounting for, in the pure and mixed form, 1% or less and 5% or less, respectively, of all the newly diagnosed PCa. Materials and methods Patients with a proven diagnosis of DPC undergoing surgery, radiotherapy, and androgen deprivation therapy, alone or in combination, were considered for this multicenter, retrospective study. The study assessed overall survival (OS), disease-free survival (DFS), and age-related disease-specific survival. Results Eighty-one patients met the study inclusion criteria. Pure DPC was found in 29 patients (36%) and mixed ductal-acinar-PCa in 52 patients (64%). After a median follow-up of 63 months (range, 3–206 months), 3- and 5-year OS rates were 84% and 67%, respectively, and 3- and 5-year DFS rates were 54% and 34%, respectively. There were no significant differences in OS or DFS between the pure and mixed DPC groups. Pure DPC was associated with a higher rate of metastatic disease at onset. Patients 74 years or younger had better disease-specific survival (p=0.0019). A subgroup analysis favored radiotherapy as the primary treatment for nonmetastatic, organ-confined DPC (3- and 5-year DFS of 80% and 50%, respectively, compared with 5-year DFS of 35% for surgical patients; p = 0.023). Conclusions Our study found DPC to be rarer, more aggressive, more likely to metastasize, and have a worse prognosis than the common acinar variant, especially in its pure form. Multicenter series are encouraged to obtain large data sets, or propensity score matching analyses with patients with conventional PCa are desirable to understand the best therapeutic approach and improve outcomes.

Nayak, Arvind; El-Taji, Omar; Sukumar, Sugeeta; Piedad, John; Ghose, Aruni; Hughes, Rob; Alonzi, Roberto; Ostler, Peter; Sharma, Anand; Lane, Tim; Adshead, Jim; Vasdev, Nikhil

2022 Current Urology

doi: 10.1097/cu9.0000000000000115pmid: 36714225

Abstract Background Pathological involvement of the seminal vesicle poses a treatment dilemma following robotic prostatectomy. Margin status plays an important role in deciding further management. A wide range of treatment options are available, including active monitoring, adjuvant radiotherapy, salvage radiotherapy, and occasionally androgen deprivation therapy. Patients undergoing postoperative radiotherapy tend to have higher risk of urinary and bowel morbidities. The recent RADICALS-RT concluded that adjuvant radiotherapy did not have any benefit compared with salvage radiotherapy. We aim to audit the incidence, margin status, and management of T3b cancer cases at our center. Materials and methods A retrospective analysis was conducted of all patients diagnosed with pathological T3b (pT3b) prostate cancer following robotic-assisted laparoscopic prostatectomy from January 2012 to July 2020. Preoperative parameters analyzed included prostate-specific antigen (PSA), T stage, and age. A chi-square test and 2-tailed t test were used to determine the relationship between categorical and continuous variables, respectively. Kaplan-Meier survival curves were generated to assess overall survival in patients with pT3b prostate cancer and used to compare unadjusted progression-free survival among those who underwent adjuvant and salvage radiotherapy. Results A total of 83 (5%) of 1665 patients who underwent robotic prostatectomy were diagnosed with pT3b prostate cancer between January 2012 and July 2020. Among these, 36 patients (44%) did not receive any radiotherapy during follow-up, compared with 26 patients (31%) who received adjuvant radiotherapy and 21 (25%) who received salvage radiotherapy. The median age of our cohort was 64 (SD, 6.4) years. Mean PSA at presentation was 12.7 μg/L. Positive margins were seen in 36 patients (43%); however, there was no statistically significant difference between treatment groups (p = 0.49). The median overall survival was 96%. There was no significant difference between the adjuvant and salvage groups in terms of biochemical progression-free survival (p = 0.66). Five-year biochemical progression-free survival was 94% for those in the adjuvant radiotherapy group and 97% for those in the salvage radiotherapy group. Conclusions Our audit corroborates with the recently concluded RADICALS-RT study, although we had fewer patients with positive margins. Radiotherapy can be avoided in patients with T3b prostate cancer, even if margin is positive, until there is definitive evidence of PSA recurrence. In keeping with the conclusion of RADICALS-RT, salvage radiotherapy may be preferable to adjuvant radiotherapy.

Tamhankar, Ashwin Sunil; Patil, Saurabh; Singh, Shanky; Carbin, Danny Darlington; Mokal, Smruti; Ahluwalia, Puneet; Gautam, Gagan

2022 Current Urology

doi: 10.1097/cu9.0000000000000129pmid: 36714232

Abstract Objective The aim of the study is to evaluate the effect of deferred androgen deprivation therapy on biochemical recurrence (BCR) and other survival parameters in node-positive prostate cancer patients after robot-assisted radical prostatectomy with bilateral extended pelvic lymph node dissection (RARP + EPLND). Materials and methods Of the 453 consecutive RARP procedures performed from 2011 to 2018, 100 patients with no prior use of androgen deprivation therapy were found to be lymph node (LN) positive and were observed, with initiation of salvage treatment at the time of BCR only. Patients were divided into 1 or 2 LNs (67)—and more than 2 LNs (33)—positive groups to assess survival outcomes. Results At a median follow-up of 21 months (1–70 months), the LN group (p < 0.000), preoperative prostate-specific antigen (PSA, p = 0.013), tumor volume (TV, p = 0.031), and LND (p = 0.004) were significantly associated with BCR. In multivariate analysis, only the LN group (p = 0.035) and PSA level (p = 0.026) were statistically significant. The estimated BCR-free survival rates in the 1/2 LN group were 37.6% (27%–52.2%), 26.5% (16.8%–41.7%), and 19.9% (9.6%–41.0%) at 1, 3, and 5 years, respectively, with a hazard of developing BCR of 0.462 (0.225–0.948) compared with the more than 2 LN-positive group. Estimated 5-year overall survival, cancer-specific, metastasis-free, and local recurrence-free survival rates were 88.4% (73.1%–100%), 89.5% (74%–100%), 65.1% (46.0%–92.1%), and 94.8% (87.2%–100.0%), respectively, for which none of the factors were significant. Based on cutoff values for PSA, TV, and LND of 30 ng/mL, 30%, and 10%, respectively, the 1/2 LN group was substratified, wherein the median BCR-free survival for the low- and intermediate-risk groups was 40 and 12 months, respectively. Conclusions Nearly one fourth and one fifth of 1/2 node-positive patients were BCR-free at 3 and 5 years after RARP + EPLND. Further substratification using PSA, TV, and LN density may help in providing individualized care regarding the initiation of adjuvant therapy.

Ambinder, David; Wang, Shu; Siddiqui, Mohummad Minhaj

2022 Current Urology

doi: 10.1097/cu9.0000000000000119pmid: 36714228

Abstract Objectives To determine the learning curve (LC) of total operative time and the discrete components of the robotic-assisted radical prostatectomy (RARP) for a recent robotic fellowship‐trained urologic surgeon. Materials and methods We performed a retrospective analysis of RARP procedures performed by a single new attending surgeon from August 2015 to April 2019. Patients' demographics and operative details were assessed. Total operative time was divided and prospectively recorded in 7 parts: (a) docking robot, (b) dissecting seminal vesicles (SVs) (c) dissecting endopelvic fascia (EPF), (d) incising bladder neck (BN), (e) completing the dissection, (f) lymph node dissection, and (g) urethrovesical anastomosis (UVA) and robot undocking. Cumulative sum analysis was used to ascertain the LC for total operative time and the 7 parts of the procedure. Results One hundred twenty consecutive RARPs were performed. The LC was overcome at 25 cases for total operative time, 13 cases for docking the robot, 33 cases for dissecting SVs, 31 cases for dissecting EPF, 46 cases for incising BN, 38 cases for prostate dissection, 25 cases for lymph node dissection, and 52 cases for UVA. Total operative time was decreased 22.8% (p < 0.0001) and time for robot docking, dissecting SVs, dissecting EPF, incising BN, completing prostate dissection, lymph node dissection, and UVA were decreased 16.7%, 30.5%, 29.5%, 36.2%, 37.3%, 32.2%, and 26.9%, respectively (all p < 0.05). Conclusions We observed a 25-case LC for a fellowship-trained urologist to achieve stable operative performance of RARP surgery. Procedural components demonstrated variable LCs including the UVA that required upward of 52 cases.

El-attar, Ahmed Z.; Hussein, Samia; Salama, Mariam F. A.; Ibrahim, Hanaa M.; AlKaramany, Amira S.; Elsawi, Mansour K.; Hemeda, Mohamed; Algazeery, Ahmed

2022 Current Urology

doi: 10.1097/cu9.0000000000000141pmid: 36714231

Abstract Background Prostatic epithelial cells synthesize the active form of vitamin D (1,25-dihydroxyvitamin D3), which participates in regulating prostate growth. Calcitriol, a synthetic form of vitamin D3, exhibits antiproliferative and prodifferentiation activities in prostate cancer. The function of 1,25-dihydroxyvitamin D3 is mediated by its binding to vitamin D receptor (VDR). VDR forms a heterodimer, typically with retinoid X receptor, to regulate vitamin D target genes. We evaluated the relationship between VDR polymorphism and clinical characteristics associated with prostate cancer risk and prognosis among Egyptian men. Materials and methods This case-control study included 2 groups of patients: group A, a control group of 50 subjects with benign prostate hyperplasia, and group B, 50 subjects newly diagnosed with prostate cancer. All participants performed complete blood count, liver and kidney function tests, prostate specific antigen measurement, histopathological analysis and immunohistochemistry for Dickkopf Homolog 3. Restriction fragment length polymorphism-polymerase chain reaction as performed to detect VDR polymorphism. Results Patients with prostate cancer and controls showed a significantly different CA genotype frequency (p = 0.007). Furthermore, prostate-specific antigen levels were significantly different in different genotypes in patients with prostate cancer (p < 0.001). Finally, T stage and the VDR ApaI C/A polymorphism were significantly associated (p < 0.041). Conclusion The VDR ApaI C/A polymorphism may be a diagnostic and prognostic marker for prostate cancer in Egyptian men.

Porcaro, Antonio Benito; Amigoni, Nelia; Rizzetto, Riccardo; Migliorini, Filippo; Tafuri, Alessandro; Piccoli, Pierluigi; Tiso, Leone; De Michele, Mario; Bianchi, Alberto; Gallina, Sebastian; Ornaghi, Paola Irene; Orlando, Rossella; Cianflone, Francesco; Gozzo, Alessandra; Antoniolli, Stefano Zecchini; Lacola, Vincenzo; Brunelli, Matteo; Cerruto, Maria Angela; Artibani, Walter; Antonelli, Alessandro

2022 Current Urology

doi: 10.1097/cu9.0000000000000146pmid: 36714226

Abstract Objectives To test hypothesized associations between the ABO blood group (ABO-bg) system and the pathological features of prostate cancer (PCa). Material and methods Between January 2013 and September 2019, 1173 patients underwent radical prostatectomy. Associations between ABO-bg levels and pathological features were evaluated using statistical methods. Results Overall, 1149 consecutive patients were evaluated using the ABO-bg system, which was represented by O-bg (42.8%) and A-bg (41.3%), followed by B-bg (11.1%) and AB-bg (4.8%). Only positive surgical margins (PSMs) was correlated with ABO-bg (Pearson correlation coefficient, r = 0.071; p = 0.017), and the risk was increased in group-O (odds ratio [OR], 1.497; 95% confidence interval, 1.149–1.950; p = 0.003) versus non–O-bg. In clinical and pathological models, O-bg was at increased risk of PSM after the adjustment for prostate-specific antigen, percentage of biopsy-positive cores, and high surgical volume (adjusted OR, 1.546; 95% confidence interval, 1.180–2.026; p = 0.002); however, the adjusted OR did not change after the adjustment for tumor load and stage as well as high surgical volume. Conclusions In clinical PCa, the risk of PSM was higher in O-bg versus non–O-bg patients after the adjustment for standard predictors. Confirmatory studies are needed to confirm the association between ABO-bg and unfavorable PCa features.

Paschou, Eleni; Betsikos, Achilleas; Zagkotsis, Georgios; Sabanis, Nikolaos

2022 Current Urology

doi: 10.1097/cu9.0000000000000153pmid: 36714235

Lee, Wai Gin

2022 Current Urology

doi: 10.1097/cu9.0000000000000139pmid: 36628403

Stemberger, Andrew; Zeffren, Marc; Birbe, Ruth; Tan, Wei Phin

2022 Current Urology

doi: 10.1097/cu9.0000000000000123pmid: 36714230