Preoperative Prostate-specific Antigen Research Articles

Overexpression of the TRIM24 E3 Ubiquitin Ligase is Linked to Genetic Instability and Predicts Unfavorable Prognosis in Prostate Cancer.

Tripartite motif containing 24 (TRIM24) is a multifunctional protein involved in p53 degradation, chromatin binding, and transcriptional modulation of nuclear receptors. Emerging research has revealed that upregulation of TRIM24 in numerous tumor types is linked to poor prognosis, attributing an important role to TRIM24 in tumor biology. In order to better understand the role of TRIM24 in prostate cancer, we analyzed its immunohistochemical expression on a tissue microarray containing >17,000 prostate cancer specimens. TRIM24 immunostaining was detectable in 61% of 15,321 interpretable cancers, including low expression in 46% and high expression in 15% of cases. TRIM24 upregulation was associated with high Gleason grade, advanced pathologic tumor stage, lymph node metastasis, higher preoperative prostate-specific antigen level, increased cell proliferation as well as increased genomic instability, and predicted prognosis independent of clinicopathologic parameters available at the time of the initial biopsy (all P<0.0001). TRIM24 upregulation provides additional prognostic information in prostate cancer, particularly in patients with low Gleason grade tumors who may be eligible for active surveillance strategies, suggesting promising potential for TRIM24 in the routine diagnostic work-up of these patients.

Impact of perioperative factors on nadir serum prostate-specific antigen levels after holmium laser enucleation of prostate.

ObjectiveTo investigate the relationship of preoperative prostate size, urinary retention, positive urine culture, and histopathological evidence of prostatitis or incidental prostate cancer on baseline and 3‐month nadir prostate‐specific antigen (PSA) value after Holmium laser enucleation of prostate (HoLEP).Patients and methodsData from 90 patients who underwent a HoLEP by En‐bloc technique were analyzed. PSA values at baseline and at 3‐month follow‐up, preoperative urinary retention and urine culture status, weight of resected tissue, and histopathological evidence of prostatitis or prostate cancer were recorded. We performed univariable and multivariable gamma‐regression analyses to determine the impact of the aforementioned perioperative variables on preoperative PSA, 3‐month postoperative PSA, and change in PSA.ResultsSerum PSA reduced significantly at 3 months from 6.3 ± 5.9 ng/mL to 0.6 ± 0.6 ng/mL. On both univariable and multivariable analysis, 3‐month nadir level was independent of all preoperative factors examined, except preoperative urinary retention status. Although patients with smaller prostate (resected tissue weight <40 g) had less percentile reduction in PSA when compared with those with larger prostate (resected tissue weight >80 g) (77.67% vs 89.06%; P < .001), patients from both these groups noted a similar PSA nadir level after 3 months (0.54 vs 0.56 ng/dL). The drop in PSA level after HoLEP remained stable up to 1‐year follow‐up.ConclusionsPSA nadir 3 months after HoLEP remains relatively consistent across patients, regardless of preoperative prostate size, PSA value, urine culture status, and histopathological evidence of prostatitis or incidental prostate cancer.

Circulating Vitamin D and Selenium Levels and Outcome in Prostate Cancer Patients: Lessons from the MARTINI-Lifestyle Cohort

BackgroundDietary agents, in particular vitamin D (Vit D) and selenium, are widely used by prostate cancer (PCa) patients to improve cancer outcomes. ObjectiveTo investigate whether plasma Vit D and selenium levels prior to radical prostatectomy (RP) are associated with worse pathologic tumor characteristics and increased risk of disease recurrence. Design, setting, and participantsA total of 3849 men with PCa scheduled for RP in the Martini-Klinik at the University Hospital Hamburg-Eppendorf, Hamburg, Germany, between January 2014 and December 2018 were included in this study. Outcome measurements and statistical analysisAge, and clinical and laboratory values were collected prior to RP. Biochemical recurrence (BCR) was defined as prostate-specific antigen (PSA) ≥0.2 μg/l and rising after RP. Kaplan-Meier plots depicted BCR-free survival. Cox regression models (adjusted for age, preoperative PSA, pT stage, pN stage, pGG, surgical margin status, and year of surgery) tested the relationship between oncologic outcomes and Vit D and selenium levels. Results and limitationsMedian plasma Vit D and selenium levels were 19.3 and 71 μg/l, respectively. Circulating Vit D and selenium levels correlated inversely with PSA values. Histologic grade, pT stage, and pN stage were not associated with Vit D and selenium levels at the time of RP. In the overall cohort, BCR-free survival at 3 yr of follow-up was 82.9%. When stratified according to median Vit D levels, BCR-free survival at 3 yr of follow-up was 82.7% and 83.0% (p ≤ 0.59). Upon stratification according to median selenium levels, BCR-free survival was 82.2% and 83.7% (p = 0.19). In a multivariable Cox regression model predicting BCR, lower Vit D and selenium levels were not independent predictors of BCR. ConclusionsPlasma Vit D and selenium levels prior to RP were not associated with BCR-free survival. Patient summaryThe results of the MARTINI-Lifestyle cohort could not show a correlation between the occurrence of biochemical recurrence of prostate cancer after radical prostatectomy and the serum levels of vitamin D and selenium. A recommendation should therefore be made to compensate for a potential deficiency and not with the expectation of a reduction in the risk of progression.

Evaluation of ERG Expression in Prostate Adenocarcinoma and Its Prognostic Impact in Patients Survival Rate.

Background & Objective:Some certain markers, including prostatic specific antigen (PSA), are being used to screen prostate cancer (PC), but none of them have sufficient sensitivity and specificity for evaluation of prognosis. Currently, genetic variants have found their place in the prognosis of PC. ETS-related gene (ERG) expression and its intensity have contradictory evidence regarding ERG expression with PC incidence or associating outcome. Our purpose was to survey the relationship of ERG expression and its intensity with PC and relative clinical outcome.Methods:We studied the immunohistochemichal (IHC) expression of ERG in 101 radical prostatectomy specimens with PC of different histologic grades. All samples were chosen from pathology department of Sina hospital in Tehran-Iran from 2011 to 2018. Positive ERG expression and its association with Gleason score, preoperative PSA, metastasis status, stage and grade of tumors was evaluated.Results:In total, ERG expression was observed in 42 cases (41.58%) and of these, 7 (16.66%) were categorized as weak, 13 (30.95%) moderate and 22(52.38%) as strong. There was no significant correlation between ERG expression and age, preoperative PSA, Gleason score, lymph node involvement, metastatic pattern, stage, and grade of the tumor (P>0.05). ERG expression frequency in the two groups of survived and expired patients was 42.85% and 0%, respectively; despite the noticeable difference, it was not statistically significance (P=0.264). Conclusion:Evaluation of ERG expression and its intensity may have no essential role as an acceptable prognostic factor in Iranian’s population for anticipating whether PC itself or the outcomes accompanied. This relation is vigorously under the influence of geographical/ethnical features.

Similar Recurrence Rate Between Gleason Score of Six at Positive Margin and Negative Margin After Radical Prostatectomy.

To investigate whether surgical margin (SM) status would affect the biochemical recurrence (BCR) after robot-associated RP (RARP). We evaluated BCR after RARP and the association between pre- and postoperative predictive factors and BCR. Positive SM (PSM) was observed in 97 out of 365 enrolled patients. On multivariate analysis, preoperative prostate specific antigen, biopsy Gleason score (GS), clinical stage, GS ≥7 at the PSM and pathological GS ≥7 were predictive factors for BCR. The 5-year BCR-free survival rate was 84.1% in the negative SM (NSM), 87.4% when GS=6 at the PSM, and 47.6% when GS ≥7 at the PSM. There was no statistically significant difference in BCR-free survival between the NSM group and GS=6 at the PSM group (p=0.966). It would be desirable to evaluate GS at PSM when PSM is present in a specimen removed by RP.

Prostate cancer: a presentation of clinicopathologic prognosticators among Filipino and American men at radical prostatectomy.

Lower incidence and mortality rates from prostate cancer (PCa) have been shown in Asian men in general compared to Westerners. This is the first study detailing the clinicopathologic features of resected prostate cancer in Filipino men living in the Philippines (PH). This study investigated the supposed “lower risk” Filipino and “higher risk” American PCa patients from the PH and the United States of America (USA), respectively. We examined 348 (176 from PH, 172 from USA) radical prostatectomy cases. The clinicopathologic features of both groups (age at time of diagnosis, preoperative prostate-specific antigen [pre-op PSA] level, Gleason score [GS], Grade groups [GG], margin involvement, extraprostatic extension [EPE], seminal vesicle invasion [SVI], and regional lymph node [RLN] metastasis) were compared. Six of seven prognosticators examined were more strongly associated with Filipinos than with Americans. Filipinos were older at diagnosis (PH: 64.32 ± 6.56 years vs USA: 58.98 ± 8.08 years) and had higher pre-op PSA levels (PH: 21.39 ± 46.40 ng ml−1 vs USA: 7.63 ± 9.19 ng ml−1). Filipino men had more advanced grade, GG 2 with minor pattern 5 (PH: 6.2% vs USA: 2.9%) and GG 5 (PH: 14.8% vs USA: 3.5%). Likewise, other adverse pathological features in margin positivity (PH: 52.3% vs USA: 23.8%), focal EPE (PH: 14.2% vs USA: 2.3%), and SVI (PH: 17.1% vs USA: 5.8%) were more commonly observed in Filipinos. This study reveals the prognostic disadvantage of Filipinos versus Americans and highlights an important difference of Filipinos from other studied Asian ethnicities that have repeatedly been shown to have lower-risk PCa. This study, the first on Filipino PCa patients with RP, suggests the need to modify Western-based risk stratification when employed in other countries like the PH.

Positive Surgical Margins (PSM) after Open Retropubic Radical Prostatectomy: Evaluation of Patient Survival

Background: Many patients who have had radical prostatectomy for prostate cancer may present with microscopic extraprostatic extension of the disease. Positive surgical margins are a common pathological finding in this subgroup of patients. To report the epidemiological, clinical and therapeutic aspects of PSM after radical prostatectomy (RP) and to evaluate the follow-up of patients. Patients and methods: A single-center retrospective descriptive study of patients who underwent radical prostatectomy between June 1, 2004 and December 31, 2019 was conducted. Patients who had radical prostatectomy with PSM on pathology report were included. The parameters studied were age, initial prostate specific antigen (PSA), Gleason and International Society of Uropathology (ISUP) scores, cTNM and pTNM stages, operative technique, PSA levels after surgery, adjuvant treatment and patient survival. Results: Eighty-six (86) radical prostatectomies were performed. PSM was found in 23 patients (26.7%). The mean age of the patients was 63.7 ± 6.1 years. The mean preoperative total PSA was 31.5 ng/mL (6.31 - 146 ng/mL). Prostate biopsy showed only prostatic adenocarcinoma. Thoracic-abdominopelvic CT was performed in all patients. Prostate cancers were found at the localized stage in 12 patients and locally advanced in 11 patients. A classification adjustment was obtained after pathological examination of the surgical specimen. The ISUP score 3 and 1 on the surgical specimen were in the majority with 9 and 7 patients respectively. After the recurrence, all patients who consented received hormone therapy, which was either medical with Goserelin and Triptorelin (7 patients) or surgical with testicular pulpectomy (1 patient). PSA was undetectable (<0.1 mg/mL) in 4 patients. The mean overall survival (OS) time was 28.1 months. Biological recurrence-free survival in the series was 25.7 months. Conclusion: RP with PSM is a fairly common condition that varies from less than 10% to more than 40% depending on the stage of the disease and the operators, and for which the main mean of treatment in our practice setting is hormone therapy.

The efficiency of prostate-specific antigen density measurement using three different methods on the prediction of biochemical recurrence

Background The aim of this study was to evaluate the efficiency of prostate-specific antigen (PSA) density (PSAD) calculated through prostate volume (PV) obtained via transrectal ultrasound (TRUS) and magnetic resonance imaging (MRI) and actual prostate weight (PW) methods obtained via pathological evaluation on the prediction of biochemical recurrence (BCR) in the follow-ups of patients who had undergone radical prostatectomy (RP). Methods A total of 335 clinically localized prostate cancer (PCa) patients who had received open RP between January 2015 and December 2018 were enrolled in the study. Pre and postoperative demographic data, clinical and pathological findings and BCR conditions were recorded. The PSAD was calculated using information obtained through preoperative TRUS examinations, MRI, and collected pathological specimens after RP by dividing the maximum preoperative PSA value and PV/PW. Results In a mean follow-up duration of 20.2 ± 8.5 months, recurrence was observed in 52 patients (24.4%) and progression was observed in 8 (3.8%) patients. The TRUS-PSAD, MRI-PSAD, and PW-PSAD values were statistically significantly higher in BCR patients compared to non-BCR patients. The International Society of Urologic Pathologists (ISUP) grade 5 and pT3b as a pathological stage were detected as independent variables in the prediction of BCR formation. Actual PW had a high prediction value compared to other PSAD measurements at <40 g prostate weights, but it had a low prediction value in prostates with an actual PW >60 g. Conclusions In this study, it was stated that PSAD acquired through different imaging methods does not affect the usability of PSAD in BCR prediction in clinical practice. The ISUP grade 5 and pT3b stage PCa were detected as independent markers in BCR prediction after RP.

Robotic assisted laparoscopic radical prostatectomy following open trans-vesical adenomectomy: A single centre experience and review of the literature.

Introduction:Robotic assisted laparoscopic radical prostatectomy (RALRP) following endoscopic resection of the prostate is known to be feasible with good outcomes. However, the literature evidence is limited on the feasibility and outcomes of RALRP following open prostatic surgery. In this study, our aim was to report our experience with RALRP in patients who had undergone trans-vesical adenomectomy of the prostate in the past.Patients and methods:We reviewed our prospectively maintained database of men treated with RALRP at our institution to identify patients with previous history of open suprapubic trans-vesical adenomectomy, between 2016 and 2020. Data were collected on demographic information, interventions, oncological outcomes and follow-up.Results:Out of 362 patients, four individuals were identified that had previous open suprapubic trans-vesical adenomectomy. The mean age was 71 years with a mean pre-operative prostate specific antigen (PSA) of 11.35 ng/ml, and an average of 10 years after their trans-vesical adenomectomy. The mean console time was 119 min with an average estimated blood loss of 137.5 ml and 75% underwent lymphadenectomy. Post-operatively, all patients were discharged after 1 day with their urinary catheters removed at 7 days post-op. For one of the patients, a urine leak was identified, and his pelvic drain was removed at 5 days instead of 1 day as for the other three patients. No other complications were noted within 30 days. The average prostate weight was 54.7 g with all specimens being T3a R0. At 6 weeks follow-up, PSA was undetectable, three patients reported full continence and 1 was using two pads/day.Conclusion:RALRP following previous open trans-vesical prostatectomy is feasible and safe with excellent oncological outcomes. They are, however, more challenging and cumbersome with increased console time.

Selecting Patients with Favorable Risk, Grade Group 2 Prostate Cancer for Active Surveillance-Does Magnetic Resonance Imaging Have a Role?

The National Comprehensive Cancer Network® recommends that selected men with grade group 2 prostate cancer be considered for active surveillance. However, selecting which patients with grade group 2 disease can be safely managed by active surveillance remains controversial. The aim of this study was to evaluate the association of multiparametric magnetic resonance imaging with adverse pathology in the radical prostatectomy specimen of men with favorable risk grade group 2 prostate cancer, which could help select patients for active surveillance. We retrospectively analyzed a cohort of patients with favorable grade group 2 disease who underwent radical prostatectomy between 2010 and 2019. Preoperative multiparametric magnetic resonance imaging was scored as negative (no identifiable lesion), positive (identifiable lesion) or equivocal. We defined a multivariable logistic regression model with multiparametric magnetic resonance imaging score as the predictor and adverse pathology (up staging to T3a/b disease, upgrading to ≥grade group 3 or lymph node invasion) as the outcome, adjusting for preoperative prostate specific antigen, biopsy Gleason grade, clinical stage, and number of negative and positive prostate biopsy cores. Secondary outcomes of biochemical recurrence, grade group upgrading alone and the added value of incorporating multiparametric magnetic resonance imaging data into the nomogram were also investigated. We identified 1,117 patients with favorable risk grade group 2 disease who underwent radical prostatectomy. Positive multiparametric magnetic resonance imaging was associated with higher rates of adverse pathology (OR 2.55, 95% CI 1.75-3.40, p <0.0001) and upgrading (OR 3.89, 95% CI 2.00-7.56, p <0.0001). However, as our study included only grade group 2 patients who underwent radical prostatectomy, our cohort may represent a higher risk group than grade group 2 patients as a whole. Adding multiparametric magnetic resonance imaging results to a standard prediction model led to higher net benefit on decision curve analysis. An identifiable lesion on multiparametric magnetic resonance imaging was associated with an increased risk of aggressive pathological features in the radical prostatectomy specimen of patients with favorable risk grade group 2 prostate cancer who were potential active surveillance candidates. This information could be used to inform biopsy strategy, counsel patients on treatment options and guide strategies for those on active surveillance. Combining multiple magnetic resonance imaging modalities (multiparametric magnetic resonance imaging) provides a more accurate prediction of the risk presented by prostate cancer than current prediction methods. In this study, positive magnetic resonance imaging results approximately doubled the chances that a patient with favorable risk prostate cancer would be found to have adverse pathology when their prostate was removed. Thus, multiparametric magnetic resonance imaging could help select patients with favorable risk cancer who may be good candidates for active surveillance, and help guide biopsy and surveillance strategies for such patients.

Pathologic response to neoadjuvant therapy of high risk prostate cancer

Background. The role of pathological response, which develops as a result of systemic therapy for localized and locally advanced high risk prostate cancer, is not still fully understood. There are no clear indications for neoadjuvant therapy and no data on the relationship between neoadjuvant therapy and median of overall or progression free survival. According to increasing interest for neoadjuvant chemohormonal therapy followed by radical prostatectomy, we evaluated the features of pathological response and its effects on overall and progression free survival rates.Objective. Estimating residual disease and pathologic response to neoadjuvant therapy of high risk prostate cancer and its relationship with oncological results.Materials and methods. This was a prospective randomized study: patients with prostate cancer of high and very high-risk groups (prostate specific antigen levels &gt;20 ng/ml and/or Gleason score ≥8 and/or clinical stage ≥T2c) were treated with neoadjuvant chemohormonal therapy followed by radical prostatectomy (n = 36). The neoadjuvant course included the intravenous administration of docetaxel once every 21 days (75 mg/m2 up to 6 cycles) and the antagonist of the gonadotropin releasing hormone degarelix according to the standard scheme (6subcutaneous injections every 28 days). The prostate tissue was evaluated for the residual disease, features of pathological response according to the ABC system. Additionally, the expression of IHC markers (p53, bcl-2, p16, Ki-67, androgen receptors, c-MYC, ERG, PTEN) was evaluated on postoperative material using tissue microarray.Results. A totally of 480 H&amp;Epostoperative and 775 H&amp;E biopsy slides were analyzed. Group A included 10 (32.3 %) cases, group B — 16 (51.6 %), and group C — 5 (16.1 %). The variance analysis revealed a significant difference in the frequency of more localized forms of prostate cancer in group B (43.7 %) (p = 0.028). During assessment we did not found any relationship ABC system assignment and preoperative prostate specific antigen level, the presence of a positive surgical margin, the pathological stage of diseases or regional lymph nodes involvement. However, the values of relapse-free survival vary sharply between groups: the highest median of relapse-free survival was found in group B — 23.02 ± 12.61 months, patients of groups A/C could not achieve the level of median relapse-free survival — 11.7 ± 6.43 and 16.19 ± 16.54 months respectively.Conclusion. The effectiveness of neoadjuvant chemohormonal therapy for high risk prostate cancer can be assessed by the features of pathologic response through ABC system which has demonstrated own versatility and reproducibility in presented material. Neoadjuvant therapy with docetaxel and degarelix can improve the treatment outcomes of prostate cancer patients at high and very high risk of disease progression. The data on changes in the prostate tissue can be helpful in predicting the duration of the effect after chemohormonal therapy with subsequent surgery.

The effect of peritoneal re-approximation on lymphocele formation in transperitoneal robot-assisted radical prostatectomy and extended pelvic lymphadenectomy.

The objective of the study was to evaluate the effect of peritoneal re-approximation at the end of the procedure in transperitoneal robot-assisted radical prostatectomy (tRARP) and extended pelvic lymphadenectomy (ePLND) on operative, oncologic, and symptomatic lymphocele rates. A total of 79 patients were included in the study who underwent tRARP and bilateral ePLND performed by two different experienced surgeons. One of the surgeons performed the peritoneal re-approximation (Group 1, n=41) and the other did not re-approximate the peritoneum (Group 2, n=38) at the end of the procedure in tRARP and ePLND. Operative parameters and symptomatic lymphocele rates were compared between the groups. There were no significant differences between the preoperative parameters age, body mass index, and preoperative prostate-specific antigen values (p>0.05). The perioperative parameters were as follows: the operation time and estimated blood loss (EBL) was less, and the number of removed lymph nodes was higher in Group 2. However, only the difference in the EBL was statistically significant (p=0.03). Hospitalization time, symptomatic lymphocele, intervention requiring lymphocele, and complication rates were found to be less in Group 2, but only hospitalization time was statistically significant (p=0.04). Pathological parameters were similar for both groups. There was a significant correlation between lymph node positivity and the presence of symptomatic lymphocele in the correlation analysis (p=0.05). It has been shown in this study that the re-approximation of the peritoneum does not provide any additional benefit in terms of complications. Considering that this process also increases the operation time and lymphocele formation, we think there is no need for re-approximation after robot-assisted radical prostatectomy and pelvic lymphadenectomy.

Multıparametric Prostate Magnetic Resonance Imaging Before Radical Prostatectomy: Can it Predict Histopathology?

We aimed to investigate the histopathological correlation of the suspected prostate malignancy detected in multiparametric prostate magnetic resonance imaging (mpMRI). The data of 93 patients underwent radical prostatectomy and had preoperative mpMRI were examined. Age and pre-operative Prostate-Specific Antigen value were retrospectively collected from patient files. The pathology specimens were examined again and post-operative ISUP grade group, other pathological findings (seminal vesicle invasion, lymph node involvement and extraprostatic extension), pre-operative mpMRI were re-examined and PIRADS score, extracapsular extension, seminal vesicle invasion, neurovascular bundle invasion, lymph node involvement and ADC values were recorded. 151 (92,07%) of 164 lesions detected in mpMRI were histopathologically correlated. 80% of patients with seminal vesicle invasion (P < 0.001), 28.8% of patients with extracapsular extension (P < 0.052) and 42.9% of patients with lymph node involvement (P = .001) in mpMRI were histopathologically correlated. A significant relationship was found between PIRADS scores and ISUP grade groups (P < 0.001). There was a negative correlation between ADC values and ISUP grade groups (P < 0.001). Our study showed that the lesions detected by mpMRI showed a high histopathological correlation.

Prostate cancer with cribriform pattern: Exclusion criterion for active surveillance?

Following the 2014 International Society of Urological Pathology meeting, a rapidly growing body of evidence by several researchers has been demonstrating a poor prognosis in association with cribriform morphology. The aim of our study was to describe the presence of cribriform foci in specimens of radical prostatectomies and to evaluate whether demographic and clinical characteristics are associated with the presence of cribriform pattern. This cohort study was based on 70 radical retropubic prostatectomies specimens collected between 2012 and 2016 and evaluated for the association of the cribriform pattern with age, prostate-specific antigen at surgery day, Gleason on biopsy, Gleason after radical prostatectomy, extracapsular extension, vesicles invasion, margins, multiparametric magnetic resonance imaging, and post-operative radiotherapy. Results; From the univariable analysis, biochemical prostatespecific antigen recurrence (p = 0.001), extracapsular extension (p = 0.003), pre-operative prostate-specific antigen (p = 0.017), vesicles invasion, (p = 0.038) and post-operative radiotherapy (p < 0.001) showed an association with the presence of cribriform pattern. There was also a significant difference of cribriform pattern and Gleason 7 in needle biopsy (p = 0.020) and cribriform pattern and Gleason 8 or 9 in radical prostatectomy specimen (p = 0.036). In our study, the increase in preoperative prostate-specific antigen had a high association with cribriform pattern. Further evidence is needed to discriminate preoperative prostate specific antigen values that might potentially be associated with the presence of cribriform pattern. Raising our knowledge about the cribriform pattern can be an excellent opportunity to correctly identify and treat patients who will eventually die from prostate cancer, sparing treatment in those who will not.

Timing of radiotherapy after radical prostatectomy (RADICALS-RT): a randomised, controlled phase 3 trial

The optimal timing of radiotherapy after radical prostatectomy for prostate cancer is uncertain. We aimed to compare the efficacy and safety of adjuvant radiotherapy versus an observation policy with salvage radiotherapy for prostate-specific antigen (PSA) biochemical progression. We did a randomised controlled trial enrolling patients with at least one risk factor (pathological T-stage 3 or 4, Gleason score of 7-10, positive margins, or preoperative PSA ≥10 ng/mL) for biochemical progression after radical prostatectomy (RADICALS-RT). The study took place in trial-accredited centres in Canada, Denmark, Ireland, and the UK. Patients were randomly assigned in a 1:1 ratio to adjuvant radiotherapy or an observation policy with salvage radiotherapy for PSA biochemical progression (PSA ≥0·1 ng/mL or three consecutive rises). Masking was not deemed feasible. Stratification factors were Gleason score, margin status, planned radiotherapy schedule (52·5 Gy in 20 fractions or 66 Gy in 33 fractions), and centre. The primary outcome measure was freedom from distant metastases, designed with 80% power to detect an improvement from 90% with salvage radiotherapy (control) to 95% at 10 years with adjuvant radiotherapy. We report on biochemical progression-free survival, freedom from non-protocol hormone therapy, safety, and patient-reported outcomes. Standard survival analysis methods were used. A hazard ratio (HR) of less than 1 favoured adjuvant radiotherapy. This study is registered with ClinicalTrials.gov, NCT00541047. Between Nov 22, 2007, and Dec 30, 2016, 1396 patients were randomly assigned, 699 (50%) to salvage radiotherapy and 697 (50%) to adjuvant radiotherapy. Allocated groups were balanced with a median age of 65 years (IQR 60-68). Median follow-up was 4·9 years (IQR 3·0-6·1). 649 (93%) of 697 participants in the adjuvant radiotherapy group reported radiotherapy within 6 months; 228 (33%) of 699 in the salvage radiotherapy group reported radiotherapy within 8 years after randomisation. With 169 events, 5-year biochemical progression-free survival was 85% for those in the adjuvant radiotherapy group and 88% for those in the salvage radiotherapy group (HR 1·10, 95% CI 0·81-1·49; p=0·56). Freedom from non-protocol hormone therapy at 5 years was 93% for those in the adjuvant radiotherapy group versus 92% for those in the salvage radiotherapy group (HR 0·88, 95% CI 0·58-1·33; p=0·53). Self-reported urinary incontinence was worse at 1 year for those in the adjuvant radiotherapy group (mean score 4·8 vs 4·0; p=0·0023). Grade 3-4 urethral stricture within 2 years was reported in 6% of individuals in the adjuvant radiotherapy group versus 4% in the salvage radiotherapy group (p=0·020). These initial results do not support routine administration of adjuvant radiotherapy after radical prostatectomy. Adjuvant radiotherapy increases the risk of urinary morbidity. An observation policy with salvage radiotherapy for PSA biochemical progression should be the current standard after radical prostatectomy. Cancer Research UK, MRC Clinical Trials Unit, and Canadian Cancer Society.

Change in Free To Total Prostate Specific Antigen Ratio Following Transurethral Resection of Prostate in Patient With Benign Prostatic Hyperplasia

Objective- To determine the changes in free to total serum prostate specific antigen (PSA) ratio level after transurethral resection of prostate (TURP) in BPH patients at different interval of time. Materials &amp; Methods- A total of 93 patients undergoing TURP for benign enlargement of prostate were included in the study. Serum total PSA and free PSA were assessed before operation and on the Ist and 7th postoperative day and at month 3 to determine the changes in total PSA, free PSA and free to total PSA ratio following TURP. Result- The preoperative mean total PSA, free PSA and free to total PSA ratio were 3.5 :L 1.7 ng/ml, 0.781 0.21 ng/ml and 0.28 + 0.07. In terms of IPSS, 75(80.7%) patients had severe lower urinary tract obstruction and 18(19.3%) moderate obstruction. Histopathological examination of the resected prostatic tissue revealed that all the 93 patients had benign prostatic lesion. Conclusion-The free and total PSA in first few days increases and thereafter it decreases in 3 months period following transurethral resection of prostate in men with BPH. As both these parameters decrease proportionately, the free to total PSA ratio remains consistent. If free to total PSA ratio decreases it raises suspicision about the early changes in malignancy. Bangladesh Journal of Urology, Vol. 18, No. 2, July 2015 p.83-87

Association between preoperative prostate-specific antigen levels and mortality in high- and intermediate-grade prostate cancer patients who received radical prostatectomy: Findings from the SEER database.

BackgroundThe degree of expression of prostate-specific antigen (PSA) has been applied for the purpose of screening and monitoring the progression of prostate cancer. The goal of this study was to evaluate the association between preoperative PSA levels and mortality outcomes in men with high- and intermediate-grade prostate cancer who received radical prostatectomy.MethodsThe 2004–2014 files of the Surveillance, Epidemiology, and End Result database were analyzed. A total of 97,357 patients with non-metastatic high- and intermediate-grade adenocarcinoma of the prostate who received radical prostatectomy were identified. Using Kaplan–Meier estimates and multivariable Cox proportional hazard models, the relationship between preoperative PSA values and cancer-specific mortality outcomes in men with high- and intermediate-grade prostate cancer who received radical prostatectomy was tested.ResultsOf 97,357 patients with high- and intermediate-grade prostate cancer who received radical prostatectomy from 2001 to 2014, there were 983 cancer-specific deaths, and the average follow-up time for the cohort was 85.0 (34.6) months. Preoperative PSA values > 10 ng/ml were associated with greater risk of cancer-specific mortality (hazard ratio 2.3, P < 0.0001) when compared to the referent/normal values for preoperative PSA (<4 ng/ml). Individuals with preoperative PSA values 4–10 ng/ml had lower risk of prostate cancer-specific mortality (hazard ratio 0.80, P = 0.03) when compared to individuals with normal preoperative PSA values.ConclusionsIndividuals with preoperative PSA values 4–10 ng/ml had 20% lower risk of prostate cancer-specific mortality when compared to individuals with preoperative PSA values of <4 ng/dl. The findings from this study suggest that low or normal preoperative PSA values may not always mean that prostate cancer is indolent, and more work needs to be done to better classify risk in men with prostate cancer.

Development of a novel nomogram incorporating platelet-to-lymphocyte ratio for the prediction of lymph node involvement in prostate carcinoma

ObjectiveThe available nomograms used to predict lymph node involvement (LNI) are not comprehensive. We sought to derive a novel nomogram incorporating the platelet to lymphocyte ratio (PLR) to predict LNI and compare its performance to validated preoperative risk nomograms in a cohort of men undergoing robotic-assisted radical prostatectomy at our institution. MethodsOur electronic health record was queried for patients who underwent robotic-assisted radical prostatectomy with bilateral pelvic lymphadenectomy between 2013 and 2019. A bootstrapped multivariate logistic regression model was constructed for the predictors of LNI while adjusting for other covariates. Then, we used the derived logistic regression formula to estimate each patient's risk (%) for LNI. Individualized risks were also calculated using the following verified nomograms: Briganti-2012, Cagiannos, Godoy, and Memorial Sloan Kettering Cancer Center. Subsequently, we plotted the risks for our nomogram and the 4 verified nomograms into receiver operating characteristics curves. We reported the area under the curve (AUC) for each of the 5 nomograms and the corresponding 95% confidence interval (CI). ResultsThe cohort included 173 patients, of which 13.9% demonstrated LNI. LNI was associated with higher preoperative prostate-specific antigen (PSA) ≥ 10 [odds ratio [OR] = 4.89; 95% confidence interval [CI] (1.42–16.83)], higher grade (WHO group ≥ 3)[19.21; (2.23–195.25)], and higher percentage of positive biopsy cores (≥60%) [3.38, (1.04–11.00)]. With every 30-unit increase in PLR the risk of LNI increased by 47%. The nomogram derived from our data had the highest AUC [(AUC 0.877; 95% CI (0.806–0.947)]. The Memorial Sloan Kettering Cancer Center and Briganti 2012 displayed almost congruent ability [0.836; 95% CI (0.758–0.915)] and [0.827; (0.752–0.902)] to identify patients with positive nodes in our cohort with perfect sensitivity and negative predictive value. ConclusionThe nomogram incorporating PLR demonstrated 94.7% sensitivity to predict LNI and avoided pelvic lymphadenectomy in half of the patients at a cut-off between 6.5% and 8.5%. A prospective study with a larger sample is needed to validate our findings.

Analysis of the expression and association of retinoblastoma binding protein 6 with the JNK signaling pathway in prostate cancers.

This study aims to investigate the expression of retinoblastoma binding protein 6 (RBBP6) in prostate cancer (PCa) and its association with the c-Jun N-terminal kinase (JNK) pathway. Immunohistochemistry was used to detect RBBP6 and JNK1/2 expression in PCa and benign prostatic hyperplasia tissues. RBBP6 expression in PCa cells (LNCap, PC3, and DU145) and noncancerous prostate epithelial cells (RWPE-1) was determined by quantitative real-time polymerase chain reaction and western blot analysis. PC3 and DU145 cells were transfected with RBBP6 small interfering RNAs (siRNAs) to examine the biological characteristics. Anisomycin (a JNK activator) with/without RBBP6 siRNA was used to treat PC3 cells for further investigating the ramification of the RBBP6-mediated JNK pathway in PCa. PCa tissues and cells showed higher RBBP6 and JNK1/2 expression. RBBP6 was positively correlated with JNK1/2 in PCa tissues. Besides, RBBP6 expression was correlated to clinical tumor stage, lymph node metastasis, Gleason grade, preoperative prostate-specific antigen level, as well as prognosis of PCa. RBBP6 siRNA reduced cell proliferation, arrested cells at G2/M, and promoted cell apoptosis, and suppressed JNK pathway. In addition, migration and invasion decreased after the RBBP6 siRNA transfection with downregulated matrix metallopeptidase-2 (MMP-2) and MMP-9. Anisomycin promoted the proliferation, invasion, and migration of PC3 cells and inhibited PC3 cell apoptosis, which could be reversed by RBBP6 siRNA. RBBP6 expression was upregulated in PCa tissues and positively correlated with expression level of JNK1/2. With inhibition of RBBP6 expression, the proliferation, invasion, and migration of PCa cells decreased dramatically, while PC3 cell apoptosis increased appreciably, accompanied by the suppression of the JNK pathway.

Quantification of perineural invasion focus after radical prostatectomy could improve predictive power of recurrence

Perineural invasion (PNI) after radical prostatectomy (RP) is a common feature of prostate cancer (PCa) and has been associated with unfavorable tumor characteristics. However, its prognostic relevance is controversial. In this study, we evaluated the impact of both PNI status (PNI+ versus PNI-) and quantified number of PNI focus on the long-term prognosis of biochemical recurrence (BCR) after RP. After reevaluating PNI of a total of 721 patients with localized PCa who underwent RP at our institution between 2000 and 2002, we examined associations between PNI status or PNI focus number and clinicopathological factors including tumor stage, Gleason score, margin status, tumor location, preoperative prostate specific antigen, age, prostate weight as well as BCR outcome. PNI was present in 530 of 721 cases (73.5%) of the RP specimens and was associated with more aggressive disease. BCR occurred in 19.4% of all patients within a median follow-up period of 8.5 years. PNI+ status was associated with poor BCR prognosis in univariate analysis but lost in multivariate analysis. Based on the number of PNI focus, PNI was further divided into 2 distinct group: PNI+ a (≤3) and PNI+ b (>3). In a multivariate Cox regression model, PNI+ b (>3) was identified as an independent BCR prognostic factor. Quantification of PNI focus number beside the dichotomized status recording will not only provide more detailed information but also be a novel prognostic indicator for risk stratification. Further external validation will be needed for an optimal cut-off value of the PNI focus number. Our findings will help further research on the relevance of PNI in the pretreatment setting and support ongoing efforts to understand its role of cancer progression.