2024-06-01 2024, Volume 18 Issue 2

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  • research-article
    Awais Paracha, Zohair Siddiqui, Ali Abid, Ekamjit Deol, Fatima Waheed, Zachary Hamilton

    Between 2.6 and 3.8 million veterans served in Vietnam while the US military dispersed Agent Orange (AO), although the exact number of exposed individuals is unknown. Agent Orange, an herbicide, is a known risk factor for various cancers, including sarcoma and leukemia, but less is known about its link with prostate cancer (PC). Prostate cancer is the most commonly diagnosed malignancy in men and the fifth most common cause of cancer-related death in men worldwide. In 2023, approximately 288,300 patients will be given a diagnosis of PC, and an estimated 34,700 fatalities will occur in the United States. However, whether the pathologic characteristics of PC among those exposed to AO differ from those in the general population remains unclear. Our review synthesizes the literature regarding the impact of AO exposure on PC incidence and disease course. A comprehensive PubMed literature search of articles published beginning in 1950 was performed using the primary search terms “Agent Orange,” “TCDD,” and “tetrachlorodibenzodioxin” and the secondary search terms “prostate cancer” or “prostate neoplasm.” The search was limited to studies that focused on human participants and were published in English. Four authors thoroughly reviewed the retrieved articles for relevancy to the study aims: discussion of PC diagnosis, prognosis, or management among patients exposed to AO. Of 108 studies identified in our search, 13 were included in this systematic review. Findings within studies concerning AO exposure with relation to PC incidence, age at diagnosis or treatment initiation, and PC severity seemed to be mixed and generally conflicting. However, the literature seems to indicate that there are no significant differences in survivorship between exposed and unexposed veterans who are given a diagnosis of PC. Given these heterogeneous outcomes, the evidence does not encourage a significantly different approach to the diagnosis and management of PC for veterans exposed to AO. Clinicians should make case-by-case decisions regarding PC screening and potential treatment options for this patient group, weighing clinical suspicion against the harms of diagnostic workup and treatment.

  • research-article
    Ashish A. Kumar

    Prostate cancer (PC) is the most frequently diagnosed cancer and second leading cause of cancer-related deaths in men. It is heterogeneous, as is evident from the wide spectrum of therapeutic approaches. Most patients with PC are initially responsive to androgen deprivation therapy; however, the majority of cases are either hormone-sensitive PC or castration-resistant PC. Current therapeutic protocols follow the evolution of PC, a continuously progressive process involving a combination of widespread genomic alterations. These genomic alterations are either hereditary germline mutations, such as mutations in BRCA2, or specific only to tumor cells (somatic). Tumor-specific genomic spectra include genomic structural rearrangements, canonical androgen response genes, and many other specific genes such as TMPRSS2-ERG fusion, SPOP/FOXA1, TP53/RB1/PTEN, and BRCA2. New evidence indicates the involvement of signaling pathways including PI3K, WNT/β-catenin, SRC, and IL-6/STAT, which have been shown to promote epithelial-mesenchymal transition cancer stem cell-like features/stemness, and neuroendocrine differentiation in PC. Over the last decade, our understanding of the genotype-phenotype relationships has been enhanced considerably. The genetic background of PC related to canonical genetic alterations and signaling pathway activation genes has shed more insight into the molecular subtype and disease landscape, resulting in a more flexible role of individual therapies targeting diverse genotypes and phenotypes.

  • research-article
    Xiao Fang, Kong Ren, Yan Li, Qiao Meng, Mingyue Li, Miao Miao, Jing Zhan, Xia Wang, Fei Wu, Meixia Zhang

    Objectives: This study aims to not only investigate the prevalence of social alienation among elderly patients undergoing radical prostatectomy for prostate cancer but also identify the contributing factors.

    Materials and methods: A total of 245 elderly patients diagnosed with prostate cancer and undergoing radical prostatectomy at a tertiary care general hospital in Jinan were included in this study. To assess the patients, several questionnaires were used. These included the General Situation Questionnaire, General Alienation Scale, Social Impact Scale, Modified Memorial Anxiety Scale for Prostate Cancer, and Perceived Social Support Scale. Pearson correlation analysis was conducted to examine the relationships between variables, whereas multiple linear regression was used to identify the factors influencing social alienation among patients who underwent radical prostatectomy.

    Results: Patients who underwent radical prostatectomy had a mean total score of 44.13 ± 7.24 on the Social Alienation Scale. The results of the Pearson correlation analysis indicated that social alienation showed an inverse association with social support (r = −0.627, p < 0.05) and positive associations with age, disease stigma, and anxiety (r = 0.325, 0.575, 0.421, all p’s < 0.01) among patients who underwent radical prostatectomy. The findings from multiple linear regression analysis demonstrated that educational level, age, urinary incontinence, disease stigma, anxiety, and social support significantly influenced social alienation among elderly patients who underwent radical prostatectomy (p < 0.05).

    Conclusions: Elderly patients who undergo radical prostatectomy often experience social alienation. This study found that social alienation was associated with factors such as educational level, age, urinary incontinence, social support, anxiety, and disease stigma. Consequently, healthcare providers should actively monitor the degree of social alienation in elderly patients after radical prostatectomy and provide suitable psychological care to facilitate positive social reintegration and alleviate their feelings of social alienation.

  • research-article
    Jiten Jaipuria, Ishleen Kaur, Mohammad Najmud Doja, Tanvir Ahmad, Amitabh Singh, Sudhir Kumar Rawal, Vineet Talwar, Girish Sharma

    Background: The incidence of prostate cancer is increasing worldwide. A significant proportion of patients develop metastatic disease and are initially prescribed androgen deprivation therapy (ADT). However, subsequent sequences of treatments in real-world settings that may improve overall survival remain an area of active investigation.

    Materials and methods: Data were collected from 384 patients presenting with de novo metastatic prostate cancer from 2011 to 2015 at a tertiary cancer center. Patients were categorized into surviving (n = 232) and deceased (n = 152) groups at the end of 3 years. Modified sequence pattern mining techniques (Generalized Sequential Pattern Mining and Sequential Pattern Discovery using Equivalence Classes) were applied to determine the exact order of the most frequent sets of treatments in each group.

    Results: Degarelix, as the initial form of ADT, was uniquely in the surviving group. The sequence of ADT followed by abiraterone and docetaxel was uniquely associated with a higher 3-year overall survival. Orchiectomy followed by fosfestrol was found to have a unique niche among surviving patients with a long duration of response to the initial ADT. Patients who received chemotherapy followed by radiotherapy and those who received radiotherapy followed by chemotherapy were found more frequently in the deceased group.

    Conclusions: We identified unique treatment sequences among surviving and deceased patients at the end of 3 years. Degarelix should be the preferred form of ADT. Patients who received ADT followed by abiraterone and chemotherapy showed better results. Patients requiring palliative radiation and chemotherapy in any sequence were significantly more frequent in the deceased group, identifying the need to offer such patients the most efficacious agents and to target them in clinical trial design.

  • research-article
    Umberto Anceschi, Rocco Simone Flammia, Antonio Tufano, Michele Morelli, Antonio Galfano, Lorenzo Giuseppe Luciani, Leonardo Misuraca, Paolo Dell’Oglio, Gabriele Tuderti, Aldo Brassetti, Maria Consiglia Ferriero, Alfredo Maria Bove, Riccardo Mastroianni, Francesco Prata, Isabella Sperduti, Giovanni Petralia, Silvia Secco, Ettore Di Trapani, Daniele Mattevi, Tommaso Cai, Aldo Massimo Bocciardi, Giuseppe Simone

    Background: Recently, an innovative tool called “proficiency score” was introduced to assess the learning curve for robot-assisted radical prostatectomy (RARP). However, the initial study only focused on patients with low-risk prostate cancer for whom pelvic lymph node dissection (PLND) was not required. To address this issue, we aimed to validate proficiency scores of a contemporary multicenter cohort of patients with high-risk prostate cancer treated with RARP plus extended PLND by trainee surgeons.

    Material and methods: Between 2010 and 2020, 4 Italian institutional prostate-cancer datasets were merged and queried for “RARP” and “high-risk prostate cancer.” High-risk prostate cancer was defined according to the most recent European Association of Urology guidelines as follows: prostate-specific antigen >20 ng/mL, International Society of Urological Pathology ≥4, and/or clinical stage (cT) ≥ 2c on preoperative imaging. The selected cohort (n = 144) included clinical cases performed by trainee surgeons (n = 4) after completing their RARP learning curve (50 procedures for low-risk prostate cancer). The outcome of interest, the proficiency score, was defined as the coexistence of all the following criteria: a comparable operation time to the interquartile range of the mentor surgeon at each center, absence of any significant perioperative complications Clavien-Dindo Grade 3-5, no perioperative blood transfusions, and negative surgical margins. A logistic binary regression model was built to identify the predictors of 1-year trifecta achievement in the trainee cohort. For all statistical analyses, a 2-sided p < 0.05 was considered significant.

    Results: A proficiency score was achieved in 42.3% patients. At univariable level, proficiency score was associated with 1-year trifecta achievement (odds ratio, 8.77; 95% confidence interval, 2.42-31.7; p = 0.001). After multivariable adjustments for age, nerve-sparing, and surgical technique, the proficiency score independently predicted 1-year trifecta achievement (odds ratio, 9.58; 95% confidence interval, 1.83-50.1; p = 0.007).

    Conclusions: Our findings support the use of proficiency scores in patients and require extended PLND in addition to RARP.

  • research-article
    Lothar Weissbach, Andreas Schwarte, Edith A. Boedefeld, Jan Herden

    Background: We report here the long-term outcomes of patients with intermediate-risk prostate cancer (PCa) treated with active surveillance (AS) in a daily routine setting.

    Material and methods: HAROW (2008-2013) was a noninterventional, health service research study investigating the management of localized PCa in a community setting. A substantial proportion of the study centers were office-based urologists. A follow-up examination of all intermediate-risk patients with AS was conducted. Overall, cancer-specific, metastasis-free, and treatment-free survival rates, as well as reasons for discontinuation, were determined and discussed.

    Results: Of the 2957 patients enrolled, 52 with intermediate-risk PCa were managed with AS and were available for evaluation. The median follow-up was 6.8 years (interquartile range, 3.4-8.6 years). Seven patients (13.5%) died of causes unrelated to PCa, of whom 4 were under AS or under watchful waiting. Two patients (3.8%) developed metastasis. The estimated 8-year overall, cancer-specific, metastasis-free, and treatment-free survival rates were 85% (95% confidence interval [CI], 72%-96%), 100%, 93% (95% CI, 82%-100%), and 31% (95% CI, 17%-45%), respectively. On multivariable analysis, prostate-specific antigen density of ≥0.2 ng/mL2 was significantly predictive of receiving invasive treatment (hazard ratio, 3.29; p = 0.006). Reasons for discontinuation were more often due to patient's or physician's concerns (36%) than due to observed clinical progression.

    Conclusions: Although survival outcome data for intermediate-risk patients managed with AS in real-life health care conditions were promising, rates of discontinuation were high, and discontinuation was often a patient's decision, even when the signs of disease progression were absent. This might be an indication of higher levels of mental burden and anxiety in this specific subgroup of patients, which should be considered when making treatment decisions. From a psychological perspective, not all intermediate-risk patients are optimal candidates for AS.

  • research-article
    Yuki Kyoda, Kohei Hashimoto, Atsushi Takahashi, Takeshi Maehana, Kimihito Tachikawa, Takashi Muranaka, Shuichi Kato, Tomoyo Kurisu, Fumimasa Fukuta, Takahiro Kirisawa, Manabu Okada, Ko Kobayashi, Toshiaki Tanaka, Shiro Hinotsu, Naoya Masumori

    Background: We clarified the predictive factors for changes in the status of medications for lower urinary tract symptoms (LUTS) 2 years after local radiotherapy for nonmetastatic prostate cancer.

    Materials and methods: We retrospectively included patients who underwent local external radiotherapy for nonmetastatic prostate cancer in 8 institutions between April 2001 and March 2016. Patients were divided into the medication and no-medication group based on the use of drugs for LUTS before radiotherapy. We defined improvement of LUTS as when the patient did not require medication for LUTS at 24 months after radiotherapy in the medication group and as deterioration when medication was required in the no-medication group. Logistic regression analysis was used to evaluate predictive factors for changes in medication status.

    Results: Altogether, 505 patients were divided into a no-medication group (n = 352) and a medication group (n = 153). The number of patients with deterioration and improvement in LUTS was 49 (14%) and 36 (23%), respectively. In the multivariate analysis, the predictive variables for deterioration were the International Prostate Symptom Score (≥8; odds ratio [OR], 2.21; p = 0.014) and the biopsy Gleason score (≤3 + 4 = 7; OR, 2.430; p = 0.008) in the no-medication group, whereas those for improvement were age (<75 years old; OR, 5.81; p = 0.002), the quality of life score (<3; OR, 3.15; p = 0.028), and a positive biopsy core rate (≥50%; OR, 2.530; p = 0.027) in the medication group.

    Conclusions: These predictive factors for changes in the status of medications for LUTS at 2 years after external radiotherapy may help determine the definitive therapy for nonmetastatic prostate cancer.

  • research-article
    Francesco Chierigo, Rocco Simone Flammia, Gabriele Sorce, Benedikt Hoeh, Lukas Hohenhorst, Andrea Panunzio, Zhe Tian, Fred Saad, Marcus Graefen, Michele Gallucci, Alberto Briganti, Francesco Montorsi, Felix K.H. Chun, Shahrokh F. Shariat, Alessandro Antonelli, Giovanni Guano, Guglielmo Mantica, Marco Borghesi, Nazareno Suardi, Carlo Terrone, Pierre I. Karakiewicz

    Objectives: This study aimed to test the association between of type and number of D'Amico high-risk criteria (DHRCs) with cancer-specific mortality (CSM) in high-risk prostate cancer patients treated with radical prostatectomy.

    Materials and methods: In the Surveillance, Epidemiology, and End Results database (2004-2016), we identified 31,281 radical prostatectomy patients with at least 1 DHRC, namely, prostate-specific antigen (PSA) >20 ng/mL (hrPSA), biopsy Gleason Grade Group (hrGGG) score of 4 and 5, or clinical tumor stage ≥T3 (hrcT). Multivariable Cox regression models and competing risks regression models (adjusting for other cause mortality) tested the association between DHRCs and 5-year CSM.

    Results: Of 31,281 patients, 14,394 (67%) exclusively harbored hrGGG, 3189 (15%) harbored hrPSA, and 1781 (8.2%) harbored hrcT. Only 2132 patients (6.8%) harbored a combination of the 2 DHRCs, and 138 (0.6%) had all 3 DHRCs. Five-year CSM rates ranged from 0.9% to 3.0% when any individual DHRC was present (hrcT, hrPSA, and hrGGG, in that order), 1.6% to 5.9% when 2 DHRCs were present (hrPSA-hrcT, hrcT-hrGGG, and hrPSA-hrGGG, in that order), and 8.1% when all 3 DHRCs were present. Cox regression models and competing risks regression confirmed the independent predictor status of DHRCs for 5-year CSM that was observed in univariable analyses, with hazard ratios from 1.00 to 2.83 for 1 DHRC, 2.35 to 5.88 for combinations of 2 DHRCs, and 7.13 for all 3 DHRCs.

    Conclusions: Within individual DHRCs, hrcT and hrPSA exhibited weaker effects than hrGGG did. Moreover, a dose-response effect was identified according to the number of DHRCs. Accordingly, the type and number of DHRCs allow further risk stratification within the high-risk subgroup.

  • research-article
    Kevin Kunitsky, Abhishek Venkataramana, Katherine E. Fero, Jorge Ballon, Jacob Komberg, Robert Reiter, Wayne Brisbane

    Purpose: To evaluate the preliminary validity and acceptability of a low-cost low-fidelity robotic surgery dry lab for training and assessing residents’ technical proficiency with key robotic radical prostatectomy steps.

    Materials and methods: Three standardized inanimate tasks were created to simulate the radical prostatectomy steps of posterior dissection, neurovascular bundle release, and urethrovesical anastomosis. Urology trainees and faculty at a single institution completed and evaluated each dry lab task. Construct validity was evaluated by comparing task completion times and Global Evaluative Assessment of Robotic Skills scores across four participant cohorts: medical students (n = 5), junior residents (n = 5), senior residents (n = 5), and attending surgeons (n = 7). Content validity, face validity, and acceptability were evaluated through a posttask survey using a 5-point Likert scale.

    Results: There was a significant difference in the individual and composite task completion times and Global Evaluative Assessment of Robotic Skills scores across all participant cohorts (all p < 0.01). The model was rated favorably in terms of its content validity and acceptability for use in residency training. However, model realism, compared with human tissue, was poorly rated. The dry lab production cost was less than US $25.

    Conclusions: This low-cost procedure-specific dry lab demonstrated evidence of content validity, construct validity, and acceptability for simulating key robotic prostatectomy technical steps and can be used to augment robot-assisted laparoscopic prostatectomy surgical training.

  • research-article
    Shunsuke Sato, Toshiaki Tanaka, Takeshi Maehana, Kohei Hashimoto, Ko Kobayashi, Naoya Masumori

    Background: We retrospectively evaluated the postoperative renal function in patients who had undergone radical prostatectomy to compare the incidences of postoperative acute kidney injury (AKI) among the patients who had undergone robot-assisted radical prostatectomy (RARP), retropubic radical prostatectomy (RRP), and extraperitoneal laparoscopic radical prostatectomy (exLRP).

    Materials and methods: Patients with prostate cancer who had undergone radical prostatectomy at our institution between 2008 and 2014 were included. Robot-assisted radical prostatectomy was performed using an intraperitoneal approach in a 25-degree Trendelenburg position, whereas other procedures were performed with the patient in the supine position. We evaluated the serum creatinine levels and estimated glomerular filtration rates immediately after surgery and on postoperative day 1. We evaluated the incidence of AKI after prostatectomy using the Acute Kidney Injury Network criteria of the Kidney Disease: Improving Global Outcomes guidelines.

    Results: A total of 150 consecutive patients were included, with each of the 3 groups (RARP, RRP, and exLRP) comprising 50 patients. Postoperative AKI was observed in 15 (30.0%), 1 (2.0%), and 3 (6.0%) patients in the RARP, RRP, and exLRP groups, respectively. Stage 1 AKI was observed in all the patients except one. The incidence of AKI in RARP group was significantly higher than that in the other groups (p < 0.001). In the RARP group, the serum creatinine level was significantly elevated immediately after the surgery; however, it returned to baseline on postoperative day 1. Surgical procedures were the only independent factor associated with AKI incidence.

    Conclusions: This study suggest that compared with RRP and exLRP, RARP is associated with a higher incidence of postoperative AKI, although most patients recover rapidly. Intra-abdominal pneumoperitoneum may contribute to AKI onset.

  • research-article
    Mark D. Bevill, Justin N. Drobish, Kevin J. Flynn, Maheen Rajput, Catherine Metz, Chad R. Tracy, Paul T. Gellhaus

    Background: We aimed to evaluate whether large prostate size, small lesion volume, or long lesion distance from the ultrasound probe tip would decrease cancer detection in transrectal magnetic resonance imaging (MRI)-targeted biopsies.

    Materials and methods: Patients who underwent MRI-targeted biopsy at our institution between May 2017 and August 2019 were enrolled in a prospective database. Three to 5 cores were obtained from ≥2 prostate imaging reporting and data system v2 lesions. A multivariable model was created that included needle distance to the lesion, prostate specific antigen, prostate imaging reporting and data system, lesion volume, and prostate volume.

    Results: A total of 377 patients with 533 lesions underwent a biopsy during the study period. A total of 233 (44%) lesions were positive for prostate cancer, and 173 (32%) lesions had clinically significant prostate cancer. The mean needle distance to the lesion was 11.7 mm (interquartile range, 7.6-15.5 mm). The likelihood of obtaining a positive core on biopsy decreased as the distance from the ultrasound probe increased for all prostate cancers and clinically significant prostate cancer (p = 0.018 and p = 0.004, respectively). Every 10 mm from the rectum, there was an 8%-10% decrease in the rate of cancer detection. Similarly, as the prostate volume increased, the odds of obtaining a positive core also decreased (p = 0.039). There was no significant association between the lesion size and amount of cancer obtained on biopsy.

    Conclusions: Our data showed that transrectal MRI-targeted biopsy cancer detection modestly decreased the lesion from the ultrasound probe and with a large prostate volume but could not prove that lesion volume was a significant predictor of the amount of cancer detected.

  • research-article
    Yuya Iwahashi, Ryusuke Deguchi, Satoshi Muraoka, Takahito Wakamiya, Shimpei Yamashita, Kazuro Kikkawa, Yasuo Kohjimoto, Isao Hara

    Background: We investigated potential disparities in health-related quality of life, particularly concerning urinary function, between patients with preserved and those with impaired sexual function after robot-assisted radical prostatectomy (RARP).

    Materials and methods: Between December 2012 and April 2020, 704 men underwent RARP in our hospital. This study included 155 patients with a preoperative 5-item International Index of Erectile Function (IIEF-5) of ≥12 points and an assessable IIEF-5 at 12 months postoperatively. Health-related quality of life was assessed using the 8-item Short-Form Health Survey and Expanded Prostate Cancer Index Composite (EPIC) preoperatively and at 3, 6, and 12 months postoperatively. A logistic regression analysis and Wilcoxon rank sum tests were performed.

    Results: Patients were grouped according to the median IIEF-5 score 12 months after surgery: those with preserved sexual function (n = 71) and those with impaired sexual function (n = 84). The mental component summary of the 8-item Short-Form Health Survey was better in the group with preserved sexual function at 6 months postoperatively than in the group with impaired sexual function (p < 0.01). In the EPIC, the group with preserved sexual function performed better not only in the sexual domain but also in the urinary domain at all time points compared with the group with impaired sexual function (p < 0.01). In the comparison of the urinary subdomains of the EPIC, there were no significant differences in urinary function or incontinence, but there were significant differences in urinary distress and irritative/obstructive scores (p < 0.01).

    Conclusions: Patients with preserved postoperative sexual function after RARP showed better urinary function than those with impaired sexual function. Hence, preserved sexual function is closely associated with urinary function.

  • research-article
    Bakhman Guliev, Boris Komyakov, Maksim Shevnin, Murad Agagyulov, Ali Talyshinskii

    Urinary leak is one of the most significant complications after partial nephrectomy. In case of persistent urine leaks, placement of a ureteral stent is effective but not always sufficient. This study included 5 patients with persistent urinary leak after partial nephrectomy. The patients underwent flexible ureteroscopy wherein we identified the damaged calyx. Subsequently, we performed percutaneous puncture targeting the distal end of the endoscope at this calyx and installed a nephrostomy tube. Then, the endoscope was removed, and the ureter was drained with a stent. Ureteral stenting ensures elimination of urinary leak in most patients after partial nephrectomy. In patients with persistent urinary leak, retrograde endoscopic percutaneous drainage of the pelvicalyceal system is the method of choice because it allows for rapid and effective treatment of urinary fistulas.