Prostate International最新文献

To determine which method of radiotherapy proves more effective after prostatectomy: Adjuvant (ART) or early salvage (ESRT), we observed the pathologic and adverse risk factors of patients and their results from both treatments, looking specifically at biochemical-free survival rates, metastasis-free survival rates, and overall survival rates. Peer review articles containing their own data collected between 1986 and 2022 were reviewed. We reviewed 67 peer review articles and included 33 that met criteria. Studies focused on the adverse risk factors and the results of patients either before/after receiving adjuvant or early salvage/salvage radiotherapy were included in the analysis. Patient characteristics had an effect on what treatment a patient would receive; if a patient had more than one adverse risk factor such as a high Gleason score, prostate-specific antigen (PSA) level, T-stage, or positive margins, they would receive immediate radiation after prostatectomy, which would classify as ART. If the patient had no adverse risk factors after surgery, they would be placed in an observation period to follow their PSA and overall health, and only if necessary, undergo ESRT. Of the 33 studies, ART was proven to be only slightly more beneficial when relating to biochemical recurrence-free survival while ART and ESRT results were similar in metastasis-free survival and overall survival. ART and ESRT are overall comparable in their patient outcomes, despite their own unique pros and cons. The use of ESRT reduces overtreatment in men who may not experience biochemical recurrence. However, in those with very high-risk pathologic features, a multi-disciplinary approach should be utilized to best determine which mode of radiation therapy after surgery is recommended.

Purpose

Approximately 7% of patients with newly diagnosed prostate cancer (PCa) in the US will have have metastatic disease. The dogma that there is no role for surgery in this population has been questioned recently. Here we report long-term outcomes of a phase 1 clinical trial on cytoreductive radical prostatectomy.

Materials and methods

This is a multicenter phase 1 trial. The major inclusion criterion was biopsy proven N1M0 or NxM1a/b PCa. Primary end point was the Clavien-Dindo-based major complication rate. Secondary outcomes were biochemical progression and overall survival. RNA-seq correlative study was conducted in nine select cases as a pilot study.

Results

Final accrual was 32 patients of which 25 and 7 were cNxM1 and cN1M0, respectively. With the median follow-up of 46 months (interquartile range 31.7 - 52.7 months), 25 out of the 32 patients (75%) were alive at the time of last contact. There were three disparate groups based on the oncologic outcome: favorable, intermediate, and poor. In seven men with favorable response, androgen deprivation therapy was switched to intermittent approach and five remain free of any evidence of disease after more than two years off all systemic therapy with the normalization of serum testosterone. Of these five patients, three had M1 disease. Long-term use of one pad or less per day was 80%. RNA-seq analysis revealed an enriched downregulation of tumor necrosis factor (TNF)-α signature in the favorable group.

Conclusion

Overall long-term oncologic outcome of cytoreductive radical prostatectomy was significantly higher than historical results. Importantly, the combination of surgery with systemic therapy may result in a long durable response in a minority of men who present with metastatic PCa.

Background

Prostate-specific antigen (PSA) is used for diagnosing prostate cancer, but does not reflect the characteristics of prostate cancer cells to allow assessment of cancer progression. PSA mRNA and circulating tumor cells (CTCs) could be potential biomarkers. However, the relationship between serum PSA levels and PSA mRNA in CTCs is unclear, and this study aimed to investigate this relationship.

Methods

Healthy donors (HD, n = 9), and patients with local non-metastatic stage prostate cancer (n = 30), metastatic hormone–sensitive prostate cancer (mHSPC, n = 10), and metastatic castration–resistant prostate cancer (mCRPC, n = 75), were included. The expression of PSA mRNA in CTCs was measured by droplet digital PCR. Serum PSA (ng/mL) levels and PSA mRNA (copies/μL) in CTCs were then compared using Spearman correlation coefficients.

Results

PSA mRNA expression in CTCs was observed in 30% (9/30) of patients with localized cancer, 60.0% (6/10) among patients with mHSPC, 65.3% (49/75) among patients with mCRPC, and 0% among patients with HD, indicating that the detection rate of PSA mRNA increased with cancer stage. PSA mRNA expression in CTCs also increased from localized to metastatic stages. PSA mRNA levels rapidly increased in the mHSPC and mCRPC stages. Interestingly, PSA mRNA expression in CTCs was not correlated with serum PSA levels at the localized stage (R = 0.064, P = 0.512). However, there were significant correlations between serum PSA levels and PSA mRNA expression in mHSPC (R = 0.532, P = 0.041) and mCRPC (R = 0.566, P = 0.025). The number of CTCs isolated from mHSPC and mCRPC was not proportional to serum PSA and PSA mRNA levels.

Conclusion

CTC PSA mRNA has the potential to be used as a biomarker to complement serum PSA protein analysis or replace serum PSA in metastatic stages of prostate cancer.

Background

Up- and/or downgrading rates in single intermediate-risk positive biopsy core are unknown.

Methods

We identified single intermediate-risk (Gleason grade group (GGG) 2/GGG3) positive biopsy core prostate cancer patients (≤ cT2c and PSA ≤ 20 ng/mL) within the Surveillance, Epidemiology, and End Results (SEER) database (2010–2015). Subsequently, separate uni- and multivariable logistic regression models tested for independent predictors of up- and downgrading.

Results

Of 1,328 assessable patients with single core positive intermediate-risk prostate cancer at biopsy, 972 (73%) harbored GGG2 versus 356 (27%) harbored GGG3. Median PSA (5.5 vs 5.7; p = 0.3), median age (62 vs 63 years; p = 0.07) and cT1-stage (77 vs 75%; p = 0.3) did not differ between GGG2 and GGG3 patients. Of individuals with single GGG2 positive biopsy core, 191 (20%) showed downgrading to GGG1 versus 35 (4%) upgrading to GGG4 or GGG5 at RP. Of individuals with single GGG3 positive biopsy core, 36 (10%) showed downgrading to GGG1 versus 42 (12%) significant upgrading to GGG4 or GGG5 at RP. In multivariable logistic regression models, elevated PSA (10–20 ng/mL) was an independent predictor of upgrading to GGG4/GGG5 in single GGG3 positive biopsy core patients (OR:2.89; 95%-CI: 1.31–6.11; p = 0.007).

Conclusion

In single GGG2 positive biopsy core patients, downgrading was four times more often recorded compared to upgrading. Conversely, in single GGG3 positive biopsy core patients, up- and downgrading rates were comparable and should be expected in one out of ten patients.

Introduction and objectives

This study aimed to assess the incidence of urinary tract infections (UTIs) after transperineal prostate biopsy (TP-PB) comparing patients who underwent antibiotic prophylaxis (AP) with patients who had no prophylaxis.

Materials and methods

This prospective, double-center trial was conducted between August and December 2020. Patient candidates to PB were included with 1:1 allocation to case (Group A-no AP) and control group (Group B-standard AP). All TP-PBs were performed in an outpatient setting under local anesthesia. Data collected 2 weeks after the procedure included incidence of UTIs or bacteriuria, evaluated with a urine culture (UC), main symptoms, and complications related to TP-PBs.

Results

A total of 200 patients were included (100 patients in each group). The mean age was 66.2 ± 7.7 in Group A and 67.4 ± 8 years in Group B (P = 0.134). Mean prostate volume was 65.5 ± 26.7 vs. 51 ± 24.6 cc (P < 0.001), number of biopsy cores was 17.8 ± 2.4 vs. 14.9 ± 0.8 (P < 0.001), and PSA value was 15.9 ± 28.1 vs. 13.3 ± 22.3 ng/ml (P = 0.017). Overall PCa detection rate was 55% vs. 59% (P = 0.567). Postoperative UTI occurred in one patient in Group A vs. zero in Group B. Asymptomatic bacteriuria was present in 3 vs. 5 patients (P = 0.470) and was not treated with antibiotics. Postoperative hematuria was observed in 13 patients vs. 29 (P < 0.05), and acute urinary retention was observed in one patient in each group.

Conclusions

The incidence of bacteriuria and UTIs in TP-PBs is not related to AP. Therefore, AP could be discontinued in TP-PB candidates without the risk of increasing UTI-related complications.

The expansion of the indication to use androgen deprivation therapy (ADT) to treat patients with advanced or metastatic prostate cancer has dramatically increased over the recent decades, resulting in the progress of patients’ survival. However, chronic health implications can become more apparent as the number of long-term cancer survivors is expected to be increased along with the adverse effect of ADT. In particular, interest in investigating ADT, especially luteinizing hormone-releasing hormone (LHRH) agonist association with cognitive dysfunction has been growing. Previous studies in animals and humans suggest that the level of androgen decreases with age and that cognitive decline occurs with decreases in androgen. Correspondingly, some of the extensive studies using common neurocognitive tests have shown that LHRH agonists may affect specific domains of cognitive function (e.g., visuospatial abilities and executive function). However, the results from these studies have not consistently demonstrated the association because of its intrinsic limitations. Large-scale studies based on electronic databases have also failed to show consistent results to make decisive conclusions because of its heterogeneity, complexity of covariates, and possible risk of biases. Thus, this review article summarizes key findings and discusses the results of several studies investigating the ADT association with cognitive dysfunction and risk of dementia from various perspectives.

Background

Prostate-specific antigen (PSA) is a marker of prostate cancer (PCa), although its efficacy as a diagnostic marker remains controversial. A high false-positive rate leads to repeat biopsy in approximately 70% of patients, which may not be necessary. Epigenetic biomarkers of field cancerization have been investigated widely as promising tools for the diagnosis of patients with suspected tumors. In the current study, we examined the diagnostic value of two microRNA (miRNA) candidates, hsv1-miR-H18 and hsv2-miR-H9, using formalin-fixed paraffin-embedded (FFPE) tissues from patients with PCa or benign prostate hyperplasia (BPH) (as controls) to determine the usefulness of these markers for detecting the presence of cancer.

Methods

Expression of hsv1-miR-H18 and hsv2-miR-H9 in 201 FFPE tissues, including 52 primary tumors, 73 surrounding noncancerous tissues, and 90 BPH nontumor controls was examined by real-time PCR.

Results

Expression of hsv1-miR-H18 and hsv2-miR-H9 was significantly higher in primary tumors from PCa patients than in BPH controls (P < 0.0001). In patients within the PSA gray zone, the two viral miRNAs could distinguish PCa from controls with appropriate sensitivity and specificity. Expression of the two miRNAs did not differ between primary tumors and noncancerous surrounding tissues.

Conclusions

The viral miRNAs hsv1-miR-H18 and hsv2-miR-H9 may be associated with field cancerization of PCa and could be promising supplemental biomarkers to the PSA assay to decrease the rate of unnecessary biopsy, particularly in patients within the PSA gray zone.

Objectives

To evaluate the detection rate of clinically significant prostate cancer (csPCa) in Magnetic resonance imaging and ultrasonography (MRI/US) fusion biopsy in patients with biopsy-naïve men for varying prostate-specific antigen (PSA) levels. Since MRI can efficiently detect csPCa compared to standard transrectal ultrasound (TRUS) guided biopsy; however, the optimal PSA threshold for its use is unclear.

Materials and methods

We retrospectively reviewed those who underwent MRI/US-fusion and standard biopsy from January 2016 to June 2018. Patients were divided into three groups: PSA <4, 4–10, >10 ng/mL. Propensity scoring was performed to balance the characteristics of the different biopsy groups, and the detection rate of csPCa was compared.

Results

Data from a total of 670 males were included in the analysis (standard TRUS, n = 333; MRI/US fusion, n = 337). Prior to matching, patients who received MRI/US-fusion biopsy had lower prostate volume. Propensity score matching balanced this characteristic and generated a cohort comprising 195 patients from each group. In the matched cohort, patients with PSA 4–10 ng/mL had a significantly increased risk of csPCa by MRI/US-fusion vs. standard biopsy (35.0% vs. 26.6%, P = 0.033). However, patients with PSA <4 ng/mL had csPCa found by MRI/US-fusion versus standard biopsy (12.0% vs. 16.0%, P = 0.342), whereas, patients with PSA >10 ng/mL had csPCa found by MRI/US-fusion versus standard biopsy (78.0% vs. 80.0%, P = 0.596). In multivariate logistic analysis among patients with PSA 4-10 ng/mL, MRI/US-fusion biopsy (odds ratio: 2.46, 95% confidence interval = 1.31–4.60, P = 0.005) were significantly associated with a detection of csPCa.

Conclusions

Detection of csPCa by MRI/US-fusion biopsy is more efficient in patients with biopsy-naïve men with PSA 4–10 ng/mL. However, standard TRUS biopsy may identify csPCa in patients with PSA <4 ng/mL and ≥10 ng/mL, emphasizing the importance of performing a standard biopsy in conjunction with MRI/US-fusion biopsy in such populations.

Background

We investigated the necessity of multiple core biopsies when performing transperineal template-guided mapping biopsy (TTMB) for patients with large prostates and no suspicious lesions on multiparametric magnetic resonance imaging (mpMRI).

Materials and methods

We retrospectively analyzed 304 patients on active surveillance (AS), 212 patients with previously negative transrectal ultrasound-guided biopsy (TRUS-Bx) and 67 biopsy naïve patients who underwent TTMB between May 2017 and December 2020. The number of core biopsies and acute urinary retention (AUR) rates were analyzed in relation to the prostate volume (PV). Cancer detection rate according to the prostate volume and Prostate Imaging-Reporting and Data System (PI-RADS) scores were compared using the Pearson Chi-square test.

Results

AUR occurred more frequently in patients with PV over 39 cc (5.5% vs. 24.4%, P < 0.001). In addition, incidence of AUR was more in patients with PV over 39 cc and PI-RADS score of 1–2 on mpMRI (3.7% vs. 22.2%, P < 0.001). There was no significant difference in the detection rates of any prostate cancer or clinically significant prostate cancer (csPCA) between the patients on AS with PV < 39 cc and PV ≥ 39 cc and PI-RADS score 1–2 (57.4% vs. 50%, P = 0.507; 17% vs. 8.8%, P = 0.412, respectively). Additionally, no significant difference was found in the detection rates of any prostate cancer or csPCA between the patients with PV < 39 cc and PV ≥ 39 cc and PI-RADS score 1–2 who either had a previously negative TRUS-Bx or were biopsy naïve (27.9% vs. 16.2%, P = 0.101, 8.2% vs. 4.1%, P = 0.31, respectively).

Conclusion

Increasing the number of core biopsies of prostates measuring ≥39 cc with PI-RADS 1–2 on mpMRI does not significantly increase the detection rates of any prostate cancer or csPCA.

Objectives

To efficiently implement artificial intelligence (AI) software for medical applications, it is crucial to understand the acceptance, expected effects, expected performance, and concerns of software users. In this study, we examine the acceptance and expectation of the Dr. Answer AI software for prostate cancer.

Methods

We conducted an online survey for urologists from August 13 to September 18, 2020. The target software is an AI-based clinical software called Dr. Answer AI software, used for prostate cancer diagnosis. We collected data from 86 urologists and conducted a basic statistical and multiple regression analysis using the R package.

Results

The compatibility was significantly associated with the intention to use the Dr. Answer AI software. The expected average accuracy for the software ranges from 86.91% to 87.51%, and the urologists perceived that the cloud method is suitable to introduce the software. The most desirable function of the software for the specialists is predicting the occurrence of extracapsular extension, seminal vesicle invasion, and lymph node metastasis after radical prostatectomy. Finally, the primary concerns involved the cost, compatibility with existing systems, and obtaining accurate information from the software.

Conclusions

Our results present an understanding of the acceptance, expected effects, expected performance, and concerns of software users. The results provide a guide to help AI software be properly developed and implemented in medical applications.