Differences In Biochemical Recurrence-free Survival Research Articles

A non-invasive 25-Gene PLNM-Score urine test for detection of prostate cancer pelvic lymph node metastasis.

Prostate cancer patients with pelvic lymph node metastasis (PLNM) have poor prognosis. Based on EAU guidelines, patients with >5% risk of PLNM by nomograms often receive pelvic lymph node dissection (PLND) during prostatectomy. However, nomograms have limited accuracy, so large numbers of false positive patients receive unnecessary surgery with potentially serious side effects. It is important to accurately identify PLNM, yet current tests, including imaging tools are inaccurate. Therefore, we intended to develop a gene expression-based algorithm for detecting PLNM. An advanced random forest machine learning algorithm screening was conducted to develop a classifier for identifying PLNM using urine samples collected from a multi-center retrospective cohort (n = 413) as training set and validated in an independent multi-center prospective cohort (n = 243). Univariate and multivariate discriminant analyses were performed to measure the ability of the algorithm classifier to detect PLNM and compare it with the Memorial Sloan Kettering Cancer Center (MSKCC) nomogram score. An algorithm named 25 G PLNM-Score was developed and found to accurately distinguish PLNM and non-PLNM with AUC of 0.93 (95% CI: 0.85-1.01) and 0.93 (95% CI: 0.87-0.99) in the retrospective and prospective urine cohorts respectively. Kaplan-Meier plots showed large and significant difference in biochemical recurrence-free survival and distant metastasis-free survival in the patients stratified by the 25 G PLNM-Score (log rank P < 0.001 and P < 0.0001, respectively). It spared 96% and 80% of unnecessary PLND with only 0.51% and 1% of PLNM missing in the retrospective and prospective cohorts respectively. In contrast, the MSKCC score only spared 15% of PLND with 0% of PLNM missing. The novel 25 G PLNM-Score is the first highly accurate and non-invasive machine learning algorithm-based urine test to identify PLNM before PLND, with potential clinical benefits of avoiding unnecessary PLND and improving treatment decision-making.

The Negative Impact of Inflammation-Related Parameters in Prostate Cancer after Robot-Assisted Radical Prostatectomy: A Retrospective Multicenter Cohort Study in Japan (the MSUG94 Group).

Background and Objectives: We aimed to examine the relationship between the inflammation-related parameters, such as the neutrophil-to-lymphocyte ratio (NLR), and the pathological findings and biochemical recurrence (BCR) in patients with prostate cancer (PCa) undergoing robot-assisted radical prostatectomy (RARP). Materials and Methods: A retrospective multicenter cohort study of patients with PCa who underwent RARP at 10 institutes in Japan was conducted. This study enrolled 3195 patients. We focused on patients undergoing RARP who underwent the preoperative measurement of their inflammation-related parameters and who did not receive any neo- or adjuvant therapy. Data on the pre- and postoperative variables for the enrolled patients were obtained. The primary endpoint of this study was the association between BCR and the inflammation-related parameters after RARP. The secondary endpoint was the association between the inflammation-related parameters and the pathological diagnosis of PCa. Results: Data from 2429 patients with PCa who met the study's eligibility criteria were analyzed. The median follow-up period was 25.1 months. The inflammation-related parameters were divided into two groups, and cutoff values were determined based on the receiver operating characteristics. There were no statistically significant differences in biochemical recurrence-free survival for any of the parameters. In the univariate analysis, the NLR was predictive of pathological T3 and lymphovascular invasion; however, there were no significant differences in the multivariate analysis. Conclusions: The inflammation-related parameters did not significantly affect the incidence of BCR, at least among patients with PCa who underwent RARP.

Biochemical recurrence after chemohormonal therapy followed by robot-assisted radical prostatectomy in very-high-risk prostate cancer patients.

Robot-assisted radical prostatectomy (RARP) has become one of the standard radical treatments for prostate cancer (PCa). A retrospective single-center cohort study was conducted on patients with PCa who underwent RARP at Gifu University Hospital between September 2017 and September 2022. In this study, patients were classified into three groups based on the National Comprehensive Cancer Network risk classification: low/intermediate-risk, high-risk, and very-high-risk groups. Patients with high- and very-high-risk PCa who were registered in the study received neoadjuvant chemohormonal therapy prior to RARP. Biochemical recurrence-free survival (BRFS) after RARP in patients with PCa was the primary endpoint of this study. The secondary endpoint was the relationship between biochemical recurrence (BCR) and clinical covariates. We enrolled 230 patients with PCa in our study, with a median follow-up of 17.0months. When the time of follow-up was over, 19 patients (8.3%) had BCR, and the 2years BRFS rate for the enrolled patients was 90.9%. Although there was no significant difference in BRFS between the low- and intermediate-risk group and the high/very-high-risk group, the 2years BRFS rate was 100% in the high-risk group and 68.3% in the very-high-risk group (P = 0.0029). Multivariate analysis showed that positive surgical margins were a significant predictor of BCR in patients with PCa treated with RARP. Multimodal therapies may be necessary to improve the BCR in patients with very-high-risk PCa.

Effect of Adequate Local Radiation Dose on Oncological Outcomes in Localized Prostate Cancer Patients Treated With Low-dose-rate Brachytherapy.

We retrospectively investigated the effect of a biologically effective dose (BED) of Low-dose rate brachytherapy (LDR-BT) and its possible interaction with androgen deprivation therapy (ADT) during LDR-BT treatment for intermediate-risk prostate cancer (PCa). A total of 693 patients with localized, intermediate-risk PCa, who underwent LDR-BT with or without supplemental external beam radiotherapy, were included in this study. We stratified patients into two groups according to BED (<180 Gy2, lower BED group; ≥180 Gy2, higher BED group) and evaluated the effect of ADT duration on the oncological outcomes of each group. In total, 431 patients received BED ≥180 Gy2. Significant differences in biochemical recurrence-free survival (BCRFS) and clinical progression-free survival (CPFS) were observed among the non-ADT, ADT ≤3 months, and ADT >3 months subgroups of the lower BED group (p=0.005 and 0.049, respectively). However, no significant differences in BCRFS or CPFS were detected in the higher BED group (p=0.63 and 0.76, respectively). Multivariate analysis of BCR and CP in the lower BED group revealed a significant decreasing trend in the BCRFS (p for trend=0.001) and CPFS rates (p for trend=0.015) as ADT duration increased, which was associated with favorable outcomes. However, no significant trend was observed in the BCRFS or CPFS rate in the higher BED group. An adequate local radiation dose provides favorable oncological outcomes and could potentially reduce the need for long-term ADT.

Trends in the Use of Second-Generation Androgen Receptor Axis Inhibitors for Metastatic Hormone-Sensitive Prostate Cancer and Clinical Factors Predicting Biological Recurrence.

The advent of second-generation androgen receptor axis-targeted agents (ARATs) has revolutionized the treatment of metastatic hormone-sensitive prostate cancer (mHSPC). Biochemical recurrence-free survival (BRFS) was used to compare the efficacy of each ARAT. This multicenter retrospective study included 581 patients with newly diagnosed mHSPC who received first-line hormone therapy. The characteristics of patients treated with different ARATs were compared as well as changes in the usage of each drug over time. For BRFS, the apalutamide (Apa) and enzalutamide (Enza) groups, as well as the abiraterone acetate (Abi) and Apa/Enza groups, were compared. In addition, multivariate analysis was performed to determine predictive factors for biochemical recurrence (BCR). The use of second-generation ARATs tended to increase after May 2020. No significant difference in BRFS was found between patients receiving Apa and Enza (p = 0.490) and those receiving Abi or Apa/Enza (p = 0.906). Multivariate analysis revealed that the neutrophil-to-lymphocyte ratio (NLR) ≥ 2.76 and PSA ≥ 0.550 ng/mL were independent predictors of BCR. There were no significant differences in patient characteristics or BRFS in patients with mHSPC receiving different ARATs as first-line treatment. NLR and PSA may be prognostic factors following the first-line treatment of patients with mHSPC.

Radical prostatectomy versus external beam radiotherapy with androgen deprivation therapy for high-risk prostate cancer: a systematic review

BackgroundTo summarize recent evidence in terms of health-related quality of life (HRQoL), functional and oncological outcomes following radical prostatectomy (RP) compared to external beam radiotherapy (EBRT) and androgen deprivation therapy (ADT) for high-risk prostate cancer (PCa).MethodsWe searched Medline, Embase, Cochrane Database of Systematic Reviews, Cochrane Controlled Trial Register and the International Standard Randomized Controlled Trial Number registry on 29 march 2021. Comparative studies, published since 2016, that reported on treatment with RP versus dose-escalated EBRT and ADT for high-risk non-metastatic PCa were included. The Newcastle–Ottawa Scale was used to appraise quality and risk of bias. A qualitative synthesis was performed.ResultsNineteen studies, all non-randomized, met the inclusion criteria. Risk of bias assessment indicated low (n = 14) to moderate/high (n = 5) risk of bias. Only three studies reported functional outcomes and/or HRQoL using different measurement instruments and methods. A clinically meaningful difference in HRQoL was not observed. All studies reported oncological outcomes and survival was generally good (5-year survival rates > 90%). In the majority of studies, a statistically significant difference between both treatment groups was not observed, or only differences in biochemical recurrence-free survival were reported.ConclusionsEvidence clearly demonstrating superiority in terms of oncological outcomes of either RP or EBRT combined with ADT is lacking. Studies reporting functional outcomes and HRQoL are very scarce and the magnitude of the effect of RP versus dose-escalated EBRT with ADT on HRQoL and functional outcomes remains largely unknown.

Radiation technique and outcomes following moderately hypofractionated treatment of low risk prostate cancer: a secondary analysis of RTOG 0415.

While moderately hypofractionated radiotherapy (MHRT) for prostate cancer (PC) is commonly delivered by intensity modulated radiation therapy, IMRT has not been prospectively compared to three-dimensional conformal radiotherapy (3D-CRT) in this context. We conducted a secondary analysis of the phase III RTOG 0415 trial comparing survival and toxicity outcomes for low-risk PC following MHRT with IMRT versus 3D-CRT. RTOG 0415 was a phase III, non-inferiority trial randomizing low-risk PC patients to either MHRT or conventionally fractionated radiation with stratification by RT technique. A secondary analysis for differences in overall survival (OS), biochemical recurrence free survival (BRFS), or toxicity by EPIC scores and Common Terminology Criteria for Adverse Events (CTCAE) was performed. 1079 patients received the allocated intervention with a median follow up of 5.8 years. 79.1% of patients were treated with IMRT and radiation technique was balanced between arms. Across all patients, RT technique was not associated with significant differences in BRFS, OS, or rates of acute and late toxicities. For patients completing MHRT, there was a difference in the late GU toxicity distribution between 3D-CRT and IMRT but no difference in late grade 2 or greater GU or GI toxicity. Stratifying patients by RT technique and fractionation, no significant differences were observed in the minimal clinically important difference (MCID) in EPIC urinary and bowel scores following RT. RT technique did not impact clinical outcomes following MHRT for low-risk PC. Despite different late GU toxicity distributions in patients treated with MHRT by IMRT or 3D-CRT, there was no difference in late Grade 2 or greater GU or GI toxicity or patient reported toxicity. Increases in late GU and GI toxicity following MHRT compared to CFRT, as demonstrated in the initial publication of RTOG 0415, do not appear related to a 3D-CRT treatment technique.

Direct Comparison of Two Different Definitions with Biochemical Recurrence after Low-Dose-Rate Brachytherapy for Prostate Cancer

We aimed to determine whether biochemical recurrence-free survival (BRFS) of patients with prostate cancer (PCa) who received low-dose-rate brachytherapy (LDR-BT) differed according to the definition of biochemical recurrence (BCR) after radical prostatectomy (RP) and the definition given by the Japanese Prostate Cancer Outcome Study of Permanent Iodine-125 Seed Implantation (J-POPS). We reviewed the clinical records of 476 consecutive patients with PCa who received LDR-BT at the Gifu University Hospital. The primary endpoint of this study was the difference in BRFS between the two aforementioned definitions. When the follow-up period ended, 74 (15.5%) and 20 (4.2%) patients had BCR according to the RP and J-POPS definitions, respectively. The 5-year BRFS rates were 85.0% and 96.9% for the RP and J-POPS definitions, respectively (p < 0.005). According to the RP definition, the 5-year BRFS rates were 80.6% in the group aged <63 years and 86.6% in those aged ≥63 years (p = 0.050). According to the J-POPS definition, the 5-year BRFS rates were 94.1% and 97.8% in the groups aged <63 years and ≥63 years, respectively (p = 0.005). The definition of recurrence in LDR-BT may need to be reconsidered.

Effect of pelvic lymph node dissection and its extent on oncological outcomes in intermediate-risk prostate cancer patients: A multicenter study of the Turkish Uro-oncology Association.

Pelvic lymph node dissection (PLND) is the gold standard method for lymph node staging in prostate cancer. We aimed to evaluate the effect of PLND combined with radical prostatectomy (RP) on oncological outcomes in D'Amico intermediate-risk prostate cancer (IRPC) patients. Patients with D'Amico IRPC were included in the study. In the overall cohort and subgroups (biopsy International Society of Urological Pathology [ISUP]grade group 2 and 3), patients were divided into two groups as PLND and no-PLND. More extensive PLND, defined as a number of removed nodes (NRN) ≥ 75th percentile. After exclusion, a total of 631 patients were included: 351 (55.6%) had PLND and 280 (44.4%) had no-PLND. The mean age was 63.1 ± 3.60 years. The median NRN was 8.0 (1.0-40.0). The mean follow-up period was 47.7 ± 37.5 months. The lymph node involvement (LNI) rate was 5.7% in the overall cohort, 3.9% in ISUP grade 2, and 10.8% in ISUP grade 3. Patients with PLND were associated with more aggressive clinicopathologic characteristics but no significant difference in biochemical recurrence-free survival (BCRFS) was found between patients with PLND and no-PLND (p = 0.642). In the subgroup analysis for ISUP grades 2 and 3, no significant difference in BCRFS outcomes was found in patients with PLND and No-PLND (p = 0.680 and p = 0.922). Also, PLND extent had no effect on BCRFS (p = 0.569). The multivariable Cox regression model adjusted for preoperative tumor characteristics revealed that prostate specific antigen (PSA) (HR: 1.18, 95% CI: 1.01-1.25; p = 0.048) was an independent predictor of biochemical recurrence (BCR). The optimum cut-off value for PSA, which can predict BCRFS, was assigned to be 7.81 ng/ml, with an AUC of 0.63 (95% CI: 0.571-0.688). The highest sensitivity and specificity were 0.667 and 0.549. Overall and cancer-specific survival analyzes were not evaluated because not enough events were observed. Neither PLND nor its extent improved BCRFS outcomes in IRPC. The LNI rate is low in patients with biopsy ISUP grade 2 and the BCR rate is low in those with PSA < 7.81 ng/dl so PLND can be omitted in these IRPC patients.

Radiation technique and outcomes following moderately hypofractionated treatment of low risk prostate cancer: A secondary analysis of the NRG oncology RTOG 0415 randomized clinical trial.

243 Background: While intensity-modulated radiotherapy (IMRT) is commonly used to deliver moderately hypofractionated radiotherapy (MHRT) for prostate cancer (PC), IMRT has not been prospectively compared to three-dimensional conformal radiotherapy (3D-CRT) in the context of MHRT. This secondary analysis of the phase III RTOG 0415 trial compares survival outcomes and toxicity across RT technique between IMRT and 3D-CRT for low-risk PC. Methods: The phase III, non-inferiority trial RTOG 0415 randomized patients with low risk PC to either MHRT (70Gy at 2.5Gy/fraction) or conventionally fractionated radiation (CFRT; 73.8Gy at 1.8Gy/fraction) with stratification by RT technique. A secondary analysis for differences in overall (OS), biochemical recurrence free survival (BRFS), or toxicity by EPIC scores and Common Terminology Criteria for Adverse Events (CTCAE) was performed. For patient and tumor characteristics, continuous data were compared with Wilcoxon rank sum test and categorical data with Chi-squared test, as appropriate. Rates of BRFS and overall survival (OS) were calculated using the Kaplan-Meier method. Results: 1079 patients received the allocated intervention with a median follow up of 5.8 years. RT technique was balanced between treatment arms, with 79.1% of patients receiving IMRT. RT protocol compliance was &gt; 95% for both IMRT and 3D-CRT. There were no significant differences in BRFS between patients treated with 3D-CRT versus IMRT for all patients (p = 0.33), those randomized to CFRT (p = 0.78), or those randomized to MHRT (p = 0.24). Overall survival did not differ by RT technique as well. For all patients, there was no difference in acute and late GI and GU toxicity rates across RT technique. For patients treated with MHRT, late grade 2 GU toxicity was more common with IMRT than 3D-CRT (31.3% vs 23.4%; p = 0.004). On logistic regression analysis, only poor baseline urinary function, defined as an EPIC score of 90 or below, correlated with acute (p &lt; 0.001) or late (p &lt; 0.001) GU toxicity. Baseline bowel function did not correlate to GI toxicity. Conclusions: RT technique did not impact survival outcomes or toxicity rates following MHRT for low risk PC. Higher rates of late CTCAE grade 2+ GU and GI toxicity observed within the RTOG 0415 MHRT arm were not disproportionally observed following 3D-CRT than IMRT. These data highlight the need for careful consideration of target delineation and normal tissue constraints in the selection and delivery of appropriate RT technique.

Does Perioperative Testosterone Predict Post-Prostatectomy Genomic Risk Score?

The role of endogenous testosterone in de novo prostate cancer pathogenesis in humans remains unclear. The effect of testosterone on the tumor genome is not explored. We sought to explore the correlation between perioperative testosterone level and genomic risk score in a cohort of men who underwent radical prostatectomy. We included patients who underwent radical prostatectomy (2013-2018) and had adverse pathological features in their final surgical specimens (positive margin, and/or pT3a or higher). The outcome of interest was the genomic risk score: low (<0.45), intermediate (0.45-0.6) and high (>0.6). The associations between serum testosterone level and 188 gene expression-based signatures were examined. Secondary outcomes of interest included biochemical recurrence and receipt of secondary treatment. The median genomic risk score was lower in the low testosterone group compared to the intermediate and normal testosterone groups (0.38 vs 0.52 vs 0.53, respectively; p=0.049). There was no difference in biochemical recurrence-free survival between the 3 testosterone groups (p=0.9). Patients with low testosterone levels had higher odds of receiving secondary treatment (OR: 2.27; 95% CI: 1.14-4.50; p=0.02) than those with normal levels. A total of 43 (of 188) gene expression signatures were associated with testosterone level (p <0.05). In total, 33 signatures were positively associated with serum testosterone levels, including 12 signatures involved in DNA repair pathways. This is the first study to assess the correlation of preoperative testosterone level on the tumor transcriptome and showed no clinical correlation between pre-defined genomic risk score groups and testosterone groups. This study adds to the notion of the limited role of endogenous testosterone on the development of de novo high-risk localized prostate cancer.

A Multi-Institutional Analysis of Prostate Cancer Patients With or Without 68Ga-PSMA PET/CT Prior to Salvage Radiotherapy of the Prostatic Fossa.

Introduction68Ga-PSMA PET/CT is associated with unprecedented sensitivity for localization of biochemically recurrent prostate cancer at low PSA levels prior to radiotherapy. Aim of the present analysis is to examine whether patients undergoing postoperative, salvage radiotherapy (sRT) of the prostatic fossa with no known nodal or distant metastases on conventional imaging (CT and/or MRI) and on positron emission tomography/computed tomography (68Ga-PSMA PET/CT) will have an improved biochemical recurrence-free survival (BRFS) compared to patients with no known nodal or distant metastases on conventional imaging only.Material and MethodsThis retrospective analysis is based on 459 patients (95 with and 364 without 68Ga-PSMA PET/CT). BRFS (PSA < post-sRT Nadir + 0.2 ng/ml) was the primary study endpoint. This was first analysed by Kaplan-Meier and uni- and multivariate Cox regression analysis for the entire cohort and then again after matched-pair analysis using tumor stage, Gleason score, PSA at time of sRT and radiation dose as matching parameters.ResultsMedian follow-up was 77.5 months for patients without and 33 months for patients with 68Ga-PSMA PET/CT. For the entire cohort, tumor stage (pT2 vs. pT3-4; p= <0.001), Gleason score (GS ≤ 7 vs. GS8-10; p=0.003), pre-sRT PSA (<0.5 vs. ≥0.5ng/ml; p<0.001) and sRT dose (<70 vs. ≥70Gy; p<0.001) were the only factors significantly associated with improved BRFS. This was not seen for the use of 68Ga-PSMA PET/CT prior to sRT (p=0.789). Matched-pair analysis consisted of 95 pairs of PCa patients with or without PET/CT and no significant difference in BRFS based on the use of PET/CT was evident (p=0.884).ConclusionThis analysis did not show an improvement in BRFS using 68Ga-PSMA PET/CT prior to sRT neither for the entire cohort nor after matched-pair analysis after excluding patients with PET-positive lymph node or distant metastases a priori. As no improved BRFS resulted with implementation of 68Ga-PSMA PET in sRT planning, sRT should not be deferred until the best “diagnostic window” for 68Ga-PSMA PET/CT.

Identification of patients at risk for biochemical recurrence after radical prostatectomy with intra-operative frozen section.

To identify patients at risk for biochemical recurrence (BCR) of prostate cancer (PCa) after radical prostatectomy (RP) with intra-operative whole-mount frozen section (FS) of the prostate. We examined differences in BCR between patients with initial negative surgical margins at FS, patients with final negative surgical margins with initial positive margins at FS without residual PCa after secondary tumour resection, and patients with final negative surgical margins with initially positive margins at FS with residual PCa in the secondary tumour resection specimen. Institutional data of 883 consecutive patients undergoing RP were collected. Intra-operative whole-mount FS was routinely used to check for margin status and, if necessary, to resect more periprostatic tissue in order to achieve negative margins. Patients with lymph node-positive disease or final positive surgical margins were excluded from the analysis. Kaplan-Meier curves and multivariable Cox proportional hazards regression analyses adjusting for clinical covariates were employed to examine differences in biochemical recurrence-free survival (BRFS) according to the resection status mentioned above. The median follow-up was 22.4 months. The 1- and 2-year BRFS rates in patients with (81.0% and 72.9%, respectively; P = 0.001) and without residual PCa (90.3% and 82.3%, respectively; P = 0.033) after secondary tumour resection were significantly lower compared to patients with initial R0 status (93.4% and 90.9%, respectively). On multivariable Cox regression only residual PCa in the secondary tumour resection was associated with a higher risk of BCR compared to initial R0 status (hazard ratio 1.99, 95% confidence interval 1.01-3.92; P = 0.046). Despite being classified as having a negative surgical margin, patients with residual PCa in the secondary tumour resection specimen face a high risk of BCR. These findings warrant closer post-RP surveillance of this particular subgroup. Further research of this high-risk subset of patients should focus on examining whether these patients benefit from early salvage therapy and how resection status impacts oncological outcomes in the changing landscape of PCa treatment.

Transvesical Retzius-Sparing Versus Standard Robot-Assisted Radical Prostatectomy: A Retrospective Propensity Score-Adjusted Analysis.

ObjectivesTo estimate the safety and efficiency of transvesical Retzius-sparing robot-assisted radical prostatectomy (T-RARP) compared with standard robot-assisted radical prostatectomy (S-RARP) for localized prostate cancer (PCa).Materials and Methods174 patients bearing localized PCa and undergoing T-RARP or S-RARP between October 2017 and January 2020 were retrospectively enrolled in our analysis. All potential baseline confounders were strictly restrained with propensity-score matching (PM) method (1: 1). Within the matched setting, the perioperative and functional outcomes were compared between the T-RARP and S-RARP groups, while the oncological results and functional recovery of the two arms were presented with Kaplan-Meier curves.ResultsFinally, 114 and 60 eligible patients harbouring localized PCa were identified in the S-RARP and T-RARP group, respectively. No significant differences between the two groups were found in all baseline characteristics after PM. Within the matched cohort, no case was converted to open surgery in either group. The T-RARP group was significantly related to a higher mean operative time (p = 0.001) and shorter median hospital stay length (p < 0.001). There were not significant differences in the median estimated blood loss and specimen Gleason score between the two arms. The proportions of transfusion, pT3a disease, postoperative complication, and positive surgical margin in the T-RARP group were also comparable to that in the S-RARP group. The mean prostate-specific antigen and median erectile functional scores did not differ significantly between the two groups at postoperative 3 months and last follow-up. T-RARP vs. S-RARP had significantly improved urinary continence (UC) rates at the removal of catheter (p < 0.001) and postoperative 3 months (p < 0.001), but the significant difference between the two groups in UC recovery disappeared at last follow-up (p = 0.119). No significant difference in biochemical recurrence-free survival was observed following the two surgeries (p = 0.727).ConclusionsT-RARP by experienced hands was feasible for selected patients with clinically localized PCa, yielding significantly improved early return to UC and similar erectile functional preservation without compromising oncological control when compared with the standard approach.

Prostate-specific antigen kinetics and biochemical control following stereotactic body radiation therapy, high dose rate brachytherapy, and low dose rate brachytherapy: A multi-institutional analysis of 3502 patients

Background and purposeStereotactic body radiation therapy (SBRT), low dose rate brachytherapy (LDR-BT) and high dose rate brachytherapy (HDR-BT) are ablative-intent radiotherapy options for prostate cancer (PCa). These vary considerably in dose delivery, which may impact post-treatment prostate-specific antigen (PSA) patterns and biochemical control. We compared PSA kinetics between SBRT, HDR-BT, and LDR-BT, and assessed their relationships to biochemical recurrence-free survival (BCRFS). Methods and materialsRetrospective PSA data were analyzed for 3502 men with low-risk (n = 2223; 63.5%), favorable intermediate-risk (n = 869; 24.8%), and unfavorable intermediate-risk (n = 410; 11.7%) PCa treated with SBRT (n = 1716; 49.0%), HDR-BT (n = 512; 14.6%), or LDR-BT (n = 1274; 36.4%) without upfront androgen deprivation therapy at 10 institutions from 1990 to 2017. We compared nadir PSA (nPSA), time to nPSA, achievement of nPSA <0.2 ng/mL and <0.5 ng/mL, rates of nPSA <0.4 ng/mL at 4 years, and BCRFS. ResultsMedian follow-up was 72 months. Median nPSA and nPSA <0.2 ng/mL were stratified by risk group (interaction p ≤ 0.001). Median nPSA and time to nPSA were 0.2 ng/mL at 44 months after SBRT, 0.1–0.2 ng/mL at 37 months after HDR-BT, and 0.01–0.2 ng/mL at 51 months after LDR-BT (mean log nPSA p ≤ 0.009 for LDR-BT vs. SBRT or HDR-BT for low/favorable intermediate-risk). There were no differences in nPSA <0.4 ng/mL at 4 years (p ≥ 0.51). BCRFS was similar for all three modalities (p ≥ 0.27). Continued PSA decay beyond 4 years was predictive of durable biochemical control. ConclusionLDR-BT led to lower nPSAs with longer continued decay compared to SBRT and HDR-BT, but no differences in BCRFS.

Doublecortin Expression in Prostate Adenocarcinoma and Neuroendocrine Tumors

Recent work using prostate cancer mouse models implicated doublecortin (DCX)-expressing neural progenitor cells in prostate adenocarcinoma, reporting a strong association between DCX expression and histologic grade and clinical outcome. We sought to evaluate the relationship between DCX expression and these variables in human prostate cancer. DCX expression was measured in transcriptome-wide microarray data from 18,501 patients with localized prostate cancer and 290 patients with metastatic castration-resistant prostate cancer (mCRPC) and compared across disease states, histologic grades, and clinical outcomes. Biochemical recurrence-free survival (BRFS), metastasis-free survival (MFS), and overall survival (OS) were analyzed using Cox proportional hazards. DCX expression was not significantly different among normal prostate (n = 29), primary prostate cancer (n=131), and metastases (n = 19) and did not increase with grade in a large cohort of radical prostatectomy samples (n = 17,967). Those with DCX expression above and below the median did not have significant differences in BRFS (HR 1.15 [95% confidence interval, 0.88-1.49], P = .31), MFS (HR 1.2 [0.84-1.7], P = .3), or OS (HR 1.15 [0.7-1.84], P = .56). In a cohort with untreated prostate cancer, DCX expression was higher in neuroendocrine tumors (n = 10) compared with grade group 5 prostate adenocarcinoma (n = 110) (P = .007). Similarly, in 2 cohorts with mCRPC (n = 290), DCX expression was higher in lesions with neuroendocrine features compared with adenocarcinoma (P < .001). Contrary to recent data using mouse models, DCX expression did not differ by disease state or outcome and did not increase with grade in a large data set of patients with prostate adenocarcinoma. However, DCX expression appeared to correlate with neuroendocrine histology, a subgroup that can arise de novo or in the castrate-resistant setting. Further work is needed to define the role of DCX and its clinical significance in prostate cancer.

MP62-04 ONCOLOGICAL PROGNOSIS AND PATHOLOGICAL FEATURE AFTER RADICAL PROSTATECTOMY ACCORDING TO THE ZONAL ORIGIN OF HIGH GRADE PROSTATE CANCER

You have accessJournal of UrologyProstate Cancer: Staging I (MP62)1 Apr 2020MP62-04 ONCOLOGICAL PROGNOSIS AND PATHOLOGICAL FEATURE AFTER RADICAL PROSTATECTOMY ACCORDING TO THE ZONAL ORIGIN OF HIGH GRADE PROSTATE CANCER Jung Jun Kim*, Sung Kyu Hong, and Seok Soo Byun Jung Jun Kim*Jung Jun Kim* More articles by this author , Sung Kyu HongSung Kyu Hong More articles by this author , and Seok Soo ByunSeok Soo Byun More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000937.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: We assessed the impact of prostatic zone tumor origin on pathological prognostic features and subsequent biochemical outcomes after radical prostatectomy. METHODS: A total of 3,823 patients who underwent radical prostatectomy between 2003 and 2018 were divided into two grade group. A high grade group was defined as Gleason sum ≥ 4+3 and ISUP (International Society of Urological Pathology) groups 3 to 5. A low grade group was defined as Gleason sum ≤ 3+4, and ISUP groups 1/2. The patients was also classified according to the location of index lesion which is transition zone and peripheral zone. The Kaplan-Meier method was used to determine differences in biochemical recurrence-free survival. RESULTS: The presence of high grade index lesion at transition zone cancer was associated with significantly increased prostate specific antigen, tumor volume and incidence of positive surgical margins but a lower incidence of extraprostatic extension, seminal vesicle invasion, lymph node involvement and biochemical failure after radical prostatectomy compared with high grade peripheral zone cancer (Table 1&2). And the outcome was consisitent regardless of surgical margin (Figure). The zonal origin could not differ the recurrence of low grade cases(Table 2). however, the patients with low grade prostate cancer demonstrated good pathology and decent oncological prognosis regardless of tumor origin. CONCLUSIONS: Among high grade cancer, high grade transition zone index lesion independently impact better biochemical outcome in spite of some worse clinical and pathological prognostic factors. To predict prognosis of high grade cancer patients after prostatectomy, the location of index lesion is definitely one of the factor to consider. Source of Funding: None © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e946-e947 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jung Jun Kim* More articles by this author Sung Kyu Hong More articles by this author Seok Soo Byun More articles by this author Expand All Advertisement PDF downloadLoading ...

Impact of Cribriform Pattern 4 and Intraductal Carcinoma on Gleason 7 Prostate Cancer Treated with External Beam Radiotherapy

To assess the impact of cribriform pattern 4 (CP4) and/or intraductal carcinoma (IDC) on patients (pts) with Gleason 7 prostate cancer (PCa) treated with external beam radiotherapy (EBRT). We reviewed an institutional database of men with Gleason 7 (Grade Group 2 and 3) PCa treated with dose-escalated EBRT (standard- or hypo-fractionation) with or without androgen deprivation therapy (ADT). Dedicated genitourinary pathologists, blinded to patient outcomes, systematically reviewed prostate biopsies for the presence of CP4 and/or IDC. Immunohistochemical stains for p63 were used in cases where the distinction between CP4 and IDC could not be made reliably based on morphology alone. Endpoints were calculated from completion of EBRT to event, and included biochemical recurrence free survival (BRFS) per Phoenix criteria, distant metastasis free survival (DMFS), and disease specific survival (DSS). Cox proportional hazards model, backward elimination multivariable analysis (MVA), Fisher’s exact test, the Kaplan-Meier method, and log-rank test were utilized. P-values <0.05 were considered statistically significant. Of the 237 pts included, median follow up was 117 months (range 3-236) and median age was 70 years (range 52-85). 141 (59%) pts were White, and NCCN risk group was favorable intermediate risk in 58 (24%), unfavorable intermediate risk in 125 (53%), and high risk in 54 (23%) pts. CP4 without IDC was present in 86 (36%), CP4 with IDC in 30 (13%), IDC without CP4 in 0 (0%), and neither morphology in 121 (51%) pts. ADT was administered to 132 (56%) pts for a median duration of 6 months (range 3-48). On MVA, presence of CP4 with IDC (hazard ratio 4.22; 95% CI 2.08-8.53; p<0.0001), PSA 10-20 ng/ml (1.97; 1.03-3.79; p=0.04), and PSA >20 ng/ml (2.26; 1.21-4.23; p=0.01) were associated with worse BRFS. On MVA, only CP4 with IDC remained significantly associated with inferior DMFS (4.18; 1.43-12.28; p=0.01) and DSS (14.26; 2.75-74.04; p=0.0016). CP4 without IDC was not associated with BRFS, DMFS, or DSS (p>0.05 for each endpoint). Factors associated with having CP4 with or without IDC included Grade Group 3 (p<0.0001), NCCN high risk group (p=0.0003), and ≥50% positive biopsy cores (p=0.003). Stratified by neither morphology present, CP4 without IDC, and CP4 with IDC; 10-year BRFS rates were 75% (95% CI 66-86%), 59% (46-76%), and 39% (22-71%); 10-year DMFS rates were 92% (86-99%), 92% (84-100%), and 73% (56-96%); and 10-year DSS rates were 99% (96-100%), 98% (95-100%), and 73% (55-99%), respectively. Differences in BRFS (p=0.00042), DMFS (p=0.017), and DSS (p<0.0001) were statistically significant between the three groups. CP4 with IDC was associated with adverse outcomes among men with Gleason 7 PCa treated with ERBT with or without ADT, whereas CP4 without IDC was not. Future studies would benefit from dichotomizing these two histologic entities and utilizing them for additional risk stratification.

Outcome after PSMA PET/CT based salvage radiotherapy in patients with biochemical recurrence after radical prostatectomy: a bi-institutional retrospective analysis.

Prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) detects prostate cancer recurrence at low PSA levels. Radiotherapy with dose escalation to the former prostate bed has been associated with improved biochemical recurrence-free survival (BRFS). Thus, we hypothesized that PSMA PET/CT-guided salvage radiotherapy leads to improved BRFS. Methods: A total of 204 consecutive patients were referred for salvage radiotherapy following radical prostatectomy. PSMA PET/CT scans were performed and patients with PSA persistence (109 patients) or evidence of distant metastases (5 patients) were excluded from this analysis. Thus, the following analysis is based on a total of 90 patients who underwent PSMA PET/CT prior to radiotherapy due to biochemical recurrence and received salvage radiotherapy. In case of PET-positive findings, antiandrogen therapy was commenced before initiation of radiotherapy. BRFS (PSA ≤ 0.2 ng/ml) was defined as the study endpoint. Results: PET-positive lesions were detected in 42/90 (47%) patients: 24/42 (27%) fossa recurrence only, 12/42 (13%) pelvic lymph nodes only and 6/42 (7%) fossa and pelvic lymph node recurrence. Median PSA before radiotherapy was 0.44 (0.11 - 6.24). Cumulatively, a total dose of 70.0 Gy (67.2 - 72 Gy) was delivered to local macroscopic tumor, 66 Gy (59.4 - 70.2 Gy) to the prostatic fossa, 60.8 Gy (54 - 66 Gy) to PET-positive lymph nodes and 50.4 Gy (45 - 50.4 Gy) to the lymphatic pathways. After a median follow-up of 23 months, BRFS was 78%. Antiandrogen therapy was ongoing in 4 patients at last follow-up. No significant difference in BRFS between PET-positive (74%) vs. PET-negative patients (82%; p>0.05) was observed at last follow-up. Two patients had late genitourinary toxicity grade 3 and no patient had gastrointestinal toxicity ≥ 3 (NCI-CTCAE v4.03). Conclusion: PSMA PET/CT-guided salvage radiotherapy is an effective and safe local treatment option. No difference in BRFS between PET-positive and PET-negative patients was observed, indicating effective targeting of PET-positive lesions. PSMA PET/CT when readily available should be offered to patients with PSA recurrence for treatment individualization.

Pathological outcomes and biochemical recurrence-free survival after radical prostatectomy for high-risk prostate cancer in the Indian population.

Introduction:We analyzed the biochemical recurrence-free survival (BRFS) of patients with high-risk prostate cancer (HRCaP) as per the D’Amico classification undergoing radical prostatectomy (RP) at our center. We aimed to determine whether the number and type of risk factors (cT2c-T3b, prostate-specific antigen >20 ng/ml, Gleason score >7) are associated with biochemical recurrence (BCR) in HRCaP patients undergoing RP in the Indian population.Methods:Between 2006 and 2017, 192 patients underwent RP (open RP [ORP], laparoscopic RP [LRP], and robotic RP [RRP]) at our center, of which 109 had D’Amico HR disease. Preoperative, postoperative, and pathological outcome data were analyzed for patients with HR disease as per the D’Amico classification. Subgroups were formed to determine whether an increasing number of risk factors (1, 2, or 3) were associated with poorer oncological results and early BCR. The Kaplan–Meier method with log-rank test was used to test the difference in BRFS between the groups. Univariate and multivariate analyses were done to find significant variable against BCR.Results:According to the D’Amico criteria, 109 patients had HR, 63 patients had intermediate-risk, and 19 patients had low-risk disease. These 109 patients with HR disease were analyzed in our study (50 RRP, 33 ORP, and 26 LRP). A total of 59 (54.1%) patients had one HR factor (1HR), 44 (40%) had two HR factors (2HR), and 6 (5.5%) had three HR factors (3HR). The mean follow-up for our patient population was 21.5 ± 19 months (median 18 months; range, 0–108). Overall, the 2-year and 5-year BRFS was 45% and 35%, respectively (mean BRFS 46 ± 6 months). Two-year BRFS was 63%, 23%, and 22%, respectively, for 1HR, 2HR, and 3HR (logrank, P < 0.0001). The prognostic substratification based on the three risk factors was significantly predictive for adverse pathologic features and oncologic outcomes.Conclusion:Substratification based on the three well-defined criteria leads to a better identification of the more aggressive cancers and prediction of need for additional treatment modalities. Localized HRCaP includes a heterogeneous population of patients with variable oncological outcomes.