Current Clinical Aspects of Androgen Deprivation Therapy for Locally Advanced and Metastatic Prostate Cancer: A Scoping Review for Urologists and Medical Providers.

Prostate cancer (PCa) currently stands as the most common malignancy and the second most common cause of death in men worldwide. Dr. C. Huggins revolutionized the field of PCa treatment through his work investigating the therapeutic effects of androgen deprivation. These early surgical castration methods were expanded upon by integrating reversible pharmacologic castration via biologic agonists. Following this, intermittent ADT (iADT) became a medical substitute for its continuous counterpart. This data synthesis aims to highlight and assess the pertinent adverse effects of ADT, to compare mortality for PCa treatment plans, and consequently provide direction for clinicians in choosing the suitable systemic ADT approach. We performed a thorough systematic search across the PubMed database to identify prospective randomized clinical trials (RCTs) comparing continuous and intermittent androgen deprivation therapy (cADT and iADT). Our qualitative analysis aimed to evaluate the potential of iADT as an alternative treatment approach, emphasizing recent clinical outcomes. The analysis of randomized control trials in the literature revealed no discernable statistical difference in PCa-specific mortality in comparison of iADT and cADT treatments. Further, in the analysis of mortality due to non-PCa causes, iADT patients fared more favorably compared to cADT. Due to iADT's characteristics of being more cost-efficient and less likely to cause undesirable side effects, urologic healthcare professionals should be made aware of these findings when counseling patients on the optimal form of ADT and consulting for future treatment guidelines.

Computerized metric assessment of glandular tissue volume within the peripheral zone of the prostate using combined magnetic resonance imaging and histopathology: Possible pathophysiological implications on prostate cancer development.

PURPOSE: Benign prostatic hyperplasia (BPH) and prostate cancer (PCa) are prevalent urological ailments in elderly males. Numerous clinical studies have revealed an invert association between BPH/prostate size and PCa growth. This study investigates the association between prostate size and total glandular tissue volume of the peripheral zone (GVPZ) using a unique blend of magnetic resonance imaging (MRI) and histo-anatomical imaging technique. MATERIALS AND METHODS: Patients were selected who underwent both radical prostatectomy and preoperative MRI scans. MRI scans provided quantitative measurements of prostatic zone dimensions, while histo-anatomical slides yielded quantitative data on glandular density of the peripheral zone (PZ) using imaging software. Integration of MRI and histopathology enabled the assessment of the GVPZ. Statistical analysis identified relationships between total prostate volume (TPV) and GVPZ. RESULTS: Seventy-two patients were selected and 40 cc was determined to be the optimal cutoff for small-to-moderate versus large prostates. Once the two subgroups in TPV were formed, the relationship between TPV and GVPZ was found to be highly significant (p<0.001). CONCLUSIONS: The combination of MRI and histopathology offers a novel approach for precise quantification of glandular tissue within the prostatic PZ. This study corroborates the hypothesis of PZ compression via an enlarging transition zone in larger BPH prostates, resulting in PZ glandular atrophy. Given that most PCa originates in the PZ, these results shed light on the potential protective role of larger BPH prostates against PCa growth.

Novel clinical risk calculator for improving cancer predictability of mpMRI fusion biopsy in prostates.

PURPOSE: Prostate Imaging-Reporting and Data System (PI-RADS) assists in evaluating lesions on multiparametric magnetic resonance imaging (mpMRI), but there are still ongoing efforts in improving the predictive value for the presence of clinically significant PCa (csPCa) with a Gleason grade group ≥ 2 on Fusion-Biopsy. This pilot study intends to propose an easily implementable method for augmenting predictability of csPCa for PI-RADS. METHODS: A cohort of 151 consecutive patients underwent mpMRI Fusion and random US Biopsy as a result of having at least one PI-RADS lesion grade 3-5 between January 1, 2019 and December 31, 2022. A single radiologist reads all films in this study applying PI-RADS V2. RESULTS: Of the 151 consecutive patients, 49 had a highest lesion of PI-RADS 3, 82 had a highest lesion of PI-RADS 4, and 20 had a highest lesion of PI-RADS 5. For each respective group, 12, 42, and 18 patients had proven csPCa. Two predictive models for csPCa were created by employing a logistical regression with parameters readily available to providers. The models had an AUC of 0.8133 and 0.8206, indicating promising effective models. CONCLUSION: PI-RADS classification has relevant predictability problems for grades 3 and 4. By applying the presented risk calculators, patients with PI-RADS 3 and 4 are better stratified, and thus, a significant number of patients can be spared biopsies with potential complications, such as infection and bleeding. The presented predictive models may be a valuable diagnostic tool, adding additional information in the clinical decision-making process for biopsies.

Comparison of Intermittent and Continuous Androgen Deprivation Therapy in Prostate Cancer Patients: An Up-to-Date Meta-analysis for Urologists and Medical Providers.

INTRODUCTION: Androgen deprivation therapy first became the treatment of choice for advanced prostate cancer in the 1940s with Charles Huggins' discoveries. Eight decades later, androgen deprivation therapy has significantly evolved, and yet is still utilized in various ways to treat certain forms of prostate cancer. For local recurrence after failed primary treatment and for locally advanced and metastatic disease, continuous androgen deprivation therapy has been standard of treatment. However, intermittent androgen deprivation therapy has emerged as a therapeutic alternative to continuous androgen deprivation therapy. The purpose of this meta-analysis is to provide an update on mortality, specifically prostate cancer-specific and nonprostate cancer causes, in order to offer some guidance when selecting the appropriate form of systemic androgen deprivation therapy. METHODS: The PubMed database was searched for prospective randomized clinical trials. Inclusion and exclusion criteria were defined. Using statistical software, we analyzed random-effects models with the assumption that the data were randomly sampled, estimated the pooled log risk ratio, assessed heterogeneity, and created funnel plots to evaluate publication bias. RESULTS: A total of 12 randomized clinical trials met all inclusion criteria for final analysis. There was no statistically significant difference in prostate cancer-specific mortality between intermittent androgen deprivation therapy and continuous androgen deprivation therapy (RR=1.10 [0.85-1.42]). The analysis of nonprostate cancer mortality favored intermittent androgen deprivation therapy over continuous androgen deprivation therapy, but the difference was statistically insignificant (RR=0.94 [0.76-1.17]). CONCLUSIONS: These 2 treatment modalities can be considered as equivalent in long-term treatment outcomes. As intermittent androgen deprivation therapy is more cost-efficient and less likely to yield adverse side effects, future treatment guidelines should consider these advantages over continuous androgen deprivation therapy.

Association between prostate size and glandular tissue volume of the peripheral zone via novel combined MRI and histopathology: possible pathophysiological implications on prostate cancer development.

PURPOSE: Benign prostatic hyperplasia (BPH) and prostate cancer (PCa) are the two most prevalent urologic diseases affecting elderly men. An inverse relationship between BPH/prostate size and PCa incidence is well documented in the current literature, but the precise mechanism is poorly understood. This study aims to investigate the effect of total prostate volume on total glandular tissue volume of the peripheral zone via a novel combination of magnetic resonance imaging (MRI) and histo-anatomical imaging. METHODS: 42 male patients between ages 53-79 years underwent both radical prostatectomy and pre-operative MRI scans. Prostate sizes ranged from 14.8-133.3cc. Quantitative measurements of surgical capsule thickness and glandular epithelial cell density within the peripheral zone (PZ) were obtained on histo-anatomical slides using computer-based imaging software. Quantitative prostatic zonal measurements were obtained from MRI scans. Combining MRI- and histopathology-obtained parameters allowed measurement of the total glandular tissue volume of the PZ (GVPZ). Statistical analysis was performed to identify associations between total prostate volume (TPV) and GVPZ. RESULTS: The Mann-Whitney U-test showed significant decreases in GVPZ in larger prostates when compared to smaller prostates. CONCLUSIONS: Combined MRI and histopathology techniques provide a novel method for accurate measuring of glandular tissue content within the prostatic PZ. The findings of this pilot study support the hypothesis of PZ compression by an expanding transition zone in large BPH prostates, leading to atrophy of PZ glandular tissue. As the majority of PCa originates in the PZ, this dynamic process may explain the protective effect of large BPH prostates against PCa development.

MRI determined prostate volume and the incidence of prostate cancer on MRI-fusion biopsy: a systemic review of reported data for the last 20 years.

PURPOSE: Magnetic resonance imaging (MRI) is a precise, systemic and advantageous imaging technique when compared to transrectal ultrasound (TRUS) which is very operator dependent. The negative correlation between prostate volume and the incidence of prostate cancer (PCa) obtained by TRUS biopsy has been well documented in the literature. The purpose of this systemic review is analyzing the reported MRI-fusion study results on prostate biopsies regarding any correlation between prostate volume and the incidence of PCa. METHODS: After defining the inclusion and exclusion criteria an in-depth review were performed between 01.01.2000 and 02.08.2022 using the PubMed database and applying the "PRISMA" guidelines. RESULTS: Twelve studies qualified, and all showed an inverse/negative relationship between prostate volume and incidence of PCa. Sample sizes ranged from 33 to 2767 patients in single and multi-institutional studies. All studies showed a statistically significant inverse relationship with a p value < 0.05. The graph summarizing all of studies and using Fisher's method revealed a highly significant combined p level of 0.00001. Additionally, not one single study was found showing the contrary (a positive correlation between prostate size and the incidence of PCa). CONCLUSION: To our knowledge, this is the first systemic review of reported MRI-Fusion data on the incidence of PCa in correlation with prostate volume. This MRI review confirms previous TRUS-biopsy studies which demonstrated an inverse relationship between prostate volume and the incidence of PCa, and thus further supports the hypothesis that large prostates size may be protective against PCa when compared to smaller prostates.

Association Between Prostate Size and MRI Determined Quantitative Prostate Zonal Measurements.

Purpose: Benign prostatic hyperplasia (BPH) and prostate cancer (PCa) are the two most prevalent and common urologic diseases impacting elderly men. The current literature has well documented an inverse relationship between prostate/BPH-size and incidence of PCa, but the exact interaction between these two disease entities is not well understood. The purpose of this study is to analyze prostatic zonal measurements with magnetic resonance imaging (MRI) in order to investigate the dynamic changes of the transition zone (TZ) and peripheral zone (PZ) in response to prostate/BPH growth. Methods: Multiparametric magnetic resonance imaging (mpMRI) scans of 430 consecutive male patients aged 18-89 years were obtained to measure the different zonal areas of the prostate. The data were statistically analyzed to identify specific associations between the different measurement parameters and total prostate volume (TPV). Results: The Mann-Whitney U-test showed a significant decline of the average peripheral zone thickness (PZT) (z = -4.5665, p < 0.0001) in larger prostates when compared to smaller prostates. The Spearman correlation between TPV and PZT demonstrated a significant negative correlation (-0.20, p < 0.0001). Conclusion: The data revealed that PZT was significantly smaller in the subgroup of patients with higher TPV. This supports the hypothesis of PZ compression and thinning caused by the growing and expanding TZ in BPH prostates. This dynamic growth-related process in the different prostatic zones may explain the protective effect of BPH against PCa.

Evolution of Androgen Deprivation Therapy (ADT) and Its New Emerging Modalities in Prostate Cancer: An Update for Practicing Urologists, Clinicians and Medical Providers.

Androgen deprivation therapy (ADT) has been the main management strategy for prostate cancer for more than eight decades, nowadays achieved commonly by administration of luteinizing hormone-releasing hormone agonists. ADT markedly suppresses androgen hormones with the long-term risks of adverse events such as muscle weakness, impairment of glucose and lipid metabolism, impotence, osteoporosis, and secondary fractures. Extensive research has provided significantly better insight into the dynamics of ADT including identification of the benefits of sequential and combination therapies. This has led to the development of new pharmaceutical ADT modalities. This review provides a general overview of the evolution of ADT in the context of the new emerging pharmaceutical ADT modalities so that clinicians and medical providers have a better understanding of personalizing the available ADT options with their different risk-benefit profiles.

Any Correlation Between Prostate Volume and Incidence of Prostate Cancer: A Review of Reported Data for the Last Thirty Years.

PURPOSE: Prostate cancer (PCa) is the most common non-skin cancer in men worldwide and more than 80% of men with PCa also have histo-anatomical findings of benign prostate hyperplasia (BPH). It is well documented that BPH develops in the transition zone (TZ), whereas 80-85% of PCa originates in the peripheral zone (PZ) of the prostate. Possible causal links between both disease entities are controversially discussed in the current literature. Some studies have reported that larger prostates have a decreased incidence of PCa compared to smaller prostates. The purpose of this systematic review is to comprehensively summarize studies analyzing any association between prostate gland volume and incidence of PCa. METHODS: A thorough literature review was performed between 01.01.1990 through 02.28.2020 using PubMed and applying the "PRISMA" guidelines. Inclusion and exclusion criteria were defined. RESULTS: Our systematic review found 41 articles reporting an inverse (negative) relationship between prostate gland volume and incidence of prostate cancer. Sample sizes ranged from 114 to 6692 patients in these single institutional and multi-institutional studies. Thirty-nine (95%) of the 41 articles showed a statistically significant inverse relationship. In our search, no study was found showing a positive correlation between BPH size and the incidence of PCa. CONCLUSION: To our knowledge, this is the first systematic review on the important clinical question of interaction between prostate size and the incidence of PCa. The results are demonstrating an inverse relationship, and therefore reveal strong evidence that large prostates may be protective of PCa when compared to smaller prostates.

Possible clinical implications of prostate capsule thickness and glandular epithelial cell density in benign prostate hyperplasia.

PURPOSE: The negative correlation between BPH-size and incidence of prostate cancer (PCa) is well-documented in the literature, however the exact mechanism is not well-understood. The present study uses histo-anatomical imaging to study prostate volume in correlation to prostate capsule thickness, and glandular epithelial cell density within the peripheral zone (PZ). MATERIALS AND METHODS: Specimens were selected from radical prostatectomies ranging from 20 to 160 mL based on ease of anatomical reconstruction by the slides. A total of 60 patients were selected and underwent quantitative measurements of prostate capsule thickness and glandular epithelial density within the PZ using computer-based imaging software. Pearson's correlation and a stepwise multiple linear regression analysis was conducted to determine the relationship between these measured parameters and the clinical characteristic of these patients. RESULTS: Pearson's correlation analysis revealed a strongly significant, negative correlation between prostate volume and glandular epithelial cell density (r(58)=-0.554, p<0.001), and a strongly significant, positive correlation between prostate volume and average capsule thickness (r(58)=0.462, p<0.001). Results of multiple regression analysis showed that average glandular epithelial cell density added statistically to this prediction (p<0.05). CONCLUSIONS: The results suggest that growth of the transition zone in BPH causes increased fibrosis of the PZ, leading to atrophy and fibrosis of glandular cells. As 80% of PCa originates from the glandular epithelium within the PZ, this observed phenomenon may explain the inverse correlation between BPH and PCa that is well-documented in the literature.

Association between prostate size and the incidence of prostate cancer: a meta-analysis and review for urologists and clinicians.

PURPOSE: To review the literature regarding any clinically significant association between prostate size and the incidence of prostate cancer (PCa). No previous review or meta-analysis has reported this clinical question. METHODS: A thorough literature review was performed using PubMed and applying the 'PRISMA' guidelines. Inclusion and exclusion criteria were defined. RESULTS: A total of 30 articles met the search criteria. Of these 30 articles, 27 reported an inverse correlation between prostate volume (PV) and incidence of biopsy-proven PCa. The remaining three articles provided no clear statistically significant results, and there was no study showing a direct or positive correlation between PV and the incidence of PCa. CONCLUSION: This review and meta-analysis is the first report summarizing the literature on the clinical question of whether prostate size affects the incidence of PCa. Ninety percent of studies (27/30) show significant evidence supporting the hypothesis that prostate size may be protective of PCa. This review and the outlined discussion should encourage other clinical investigators to explore the relationship between PV and the incidence and aggressiveness of PCa. If future studies should confirm the hypothesis of the dynamic interactions between the different prostatic zones in a growing prostate, it will have relevant clinical implications on the management of BPH and PCa.

Quantitative measurements of prostatic zones by MRI and their dependence on prostate size: possible clinical implications in prostate cancer.

AIM: Many studies support an inverse relationship between benign prostate hypertrophy (BPH) size and incidence of prostate cancer (PCa), but the causal link between these conditions is poorly understood. Recent studies suggest that a growing transition zone (TZ) in the prostate may induce pressure on the outer peripheral zone (PZ), leading to atrophy of the glandular tissue where PCa often originates, providing a possible explanation for this interaction. To further investigate this phenomenon, our pilot study uses magnetic resonance imaging (MRI) to examine quantitative zonal changes in a consecutive cohort of prostates. METHODS: MRI scans of male patients [n = 204, 61.57 ± 13.90 years, average body mass index (BMI) 29.05 kg/m2] with various prostate sizes were analyzed statistically to identify possible associations between prostate parameters, such as total prostate volume (TPV) and peripheral zone thickness (PZT). RESULTS: TPV and PZT demonstrated a weak, inverse correlation (r = -0.21, p = 0.002). However, when examining the plotted data, the relationship between TPV and PZT was significantly different when the cohort was divided into two groups; lower TPV: ⩽87.5 ml (n = 188, TPV x- = 36.01 ± 18.18 ml), and higher TPV: >87.5 ml (n = 17, TPV x- = 125.69 ± 41.13 ml). Average PZT differed significantly between these groups (z = -3.5554, p = 0.0004). CONCLUSIONS: PZT was significantly different for patients with lower versus higher TPVs, suggesting that, above a certain point of BPH growth, the PZ is unable to withstand pressure from an expanding TZ, supporting the notion that growing BPH causes compression of the PZ glandular tissue, and, therefore, BPH may be protective against PCa.

Quantitative measurements of prostate capsule and gland density and their correlation to prostate size: possible clinical implications in prostate cancer.

PURPOSE: To study histo-anatomical imaging features and possible association between prostate volume, capsule thickness and glandular density within the peripheral zone (PZ) of prostates of different sizes. METHODS: Patients were selected who had undergone radical prostatectomy. Specimen selection was based on two factors: first, easy reconstruction of prostate anatomy by the histological slides; and second, based on prostate size. Specimens were chosen with small (< 35 cc) and also with large size (> 80 cc). A total of 20 patients were selected. None of these patients had undergone previous treatment. Computer-based imaging for quantitative measurements of capsule thickness and glandular density within the PZ were performed. Multiple regression analysis was performed to determine the relationship between these measured parameters and the clinical characteristics of these patients. RESULTS: Multiple regression analysis revealed a strong, positive association between prostate size and average capsule thickness; on the contrary, we found a negative correlation between prostate volume and average glandular density. Fibrotic thickness of the capsule was associated with gland atrophy and decreased gland density within the PZ. CONCLUSIONS: The results suggest that BPH may be associated with the development of fibrosis and gland atrophy within the peripheral zone. As 80% of prostate cancer originates from the glandular epithelium within the peripheral zone, this observed phenomenon may explain the inverse relationship between BPH and incidence of prostate cancer well documented in the literature.

Possible clinical implications of peripheral zone changes depending on prostate size.

PURPOSE: Although numerous studies have observed an inverse relationship between the size of benign prostate hypertrophy (BPH) and the incidence of prostate cancer (PCa), few studies have explored specific mechanisms by which BPH and PCa may influence one another. In a recent study, one possibility has been brought up that growth in the transition zone due to BPH may cause pressure-induced fibrotic changes in the peripheral zone, an area where 80% of cancer occurs, leading to gland atrophy and the thickening of the prostatic capsule. To shed more light on this phenomenon, we conducted a pilot study examining the quantitative and qualitative histo-anatomical changes that occur in the peripheral zone associated with BPH. METHODS: Thirty-nine prostate specimens of various sizes were selected from patients who had undergone radical prostatectomies. Each prostate was evaluated in six different locations along the dorsal aspect of the peripheral zone by measuring the thickness of the peripheral fibrotic zone (prostate capsule) and its association with gland atrophy. Multiple regression analysis was performed to determine the relationship between prostate size and the average thickness of the prostate capsule. RESULTS: Multiple regression analysis revealed a strong, positive relationship between prostate size and average capsule thickness with a Pearson coefficient of 0.707 (p < 0.05). Fibrotic histo-anatomical changes were spatially associated with gland atrophy: glands found within the peripheral fibrotic zone appeared elongated and atrophic. CONCLUSION: The results suggest that BPH may be associated with the development of fibrotic material and atrophy of glands within the peripheral zone. Because this atrophy involves glands where 80% of prostate cancer originates, this potentially explains the inverse relationship between PCa and BPH.

Histological changes of the peripheral zone in small and large prostates and possible clinical implications.

INTRODUCTION: It is well documented in literature that most prostate carcinomas (PCa) arise in the peripheral zone (PZ). Additionally, an inverse relationship between prostate size and the incidence of PCa has been demonstrated in recent studies. However, little is known about gland distribution in the peripheral zone of larger prostates compared to smaller prostates. In this study, we examined the histo-anatomical gland distribution within the peripheral zone in small and large prostates and discuss possible clinical implications. METHODS: A semi-quantitative analysis of gland density and capsule thickness was performed using light microscopy on 10 large (≥80 g) prostate specimens and 10 small (<30 g) prostate specimens from patients who underwent radical prostatectomy at Texas Tech University Health Sciences Center between the years 2010 and 2016. Samples from radical prostatectomies were used to ensure a whole, preserved prostate with an intact surgical capsule. Gland counts were performed on five random fields under 100 × magnification, while capsule thickness was measured on three random fields per case; thus, a total 50 fields and 30 fields were analyzed for each of the two groups for gland counts and capsule thickness measurements, respectively. Microscopy was standardized to the posterior aspect of the prostate, between 4 o'clock and 6 o'clock along the equatorial region between the apex and base. RESULTS: Large prostates possessed a significantly lower mean gland count per field compared to small prostates (10.34±4.15, n=50 vs 18.00±5.41, n=50; t=8.16, df=49, P<0.001). Additionally, large prostates showed a significantly higher average capsule thickness in millimeters compared to small prostates (1.80 mm, ±1.12 mm, n=30 vs 0.90 mm, ±0.56, n=30; t=8.16, df=49, P<0.001). CONCLUSION: The results demonstrate that prostate hypertrophy leads to both decreased gland density in the peripheral zone and increased capsule thickness, suggesting that growth-induced expansion of the prostate against its capsule leads to compression-induced atrophy and fibrosis of glandular tissue within the peripheral zone (PZ). A decrease in gland density within the PZ may have clinical implications shedding light, for instance, on the reduction in PCa incidence in patients with large prostates as compared to smaller prostates, a phenomenon well documented in the literature.

Implications on clinical management of the small renal mass in patients 80 years of age and older based on a retrospective review of the SEER database.

PURPOSE: Incidental detection of small renal masses has increased in recent years with increased use of various imaging modalities, and a substantial number of diagnoses are made in the elderly population. Minimally invasive surgical procedures have previously been established as options with excellent long-term oncological results, but surveillance strategies have more recently been introduced as alternatives for surgical intervention. This study reviews the outcomes for elderly patients treated with observation or surgery for small renal masses in order to better elucidate optimal management strategies. METHODS: A total of 4647 patients from the SEER database met criteria for inclusion in this study. Cumulative incidences of RCC-specific mortality and non-RCC-related mortality were estimated, and frequency distributions by tumor size and surgical status were calculated. RESULTS: No difference in RCC-related mortality was observed among all treatment groups, including surveillance, for tumors 1-30 mm in size. RCC-related mortality was significantly lower for surgically treated patients for all other tumor size groups. Mortality unrelated to RCC was significantly higher in patients undergoing surveillance compared to those undergoing surgical intervention for tumor sizes 1-30 or 1-40 mm. CONCLUSIONS: A small renal mass in patients of 80+ years of age is best defined as up to 3 cm in size. For these patients, observation appears be a valid, if not preferential strategy. Patients 80+ years of age with renal masses greater than 3 cm still appear to benefit from surgical intervention.