Prostate Cancer Post Radical Prostatectomy Research Articles

Factors associated with biochemical recurrence of prostate cancer post radical prostatectomy

Factors associated with biochemical recurrence of prostate cancer post radical prostatectomy

Pelvic Floor Muscle Exercise pada Pasien Post Radikal Prostatektomi dalam Menurunkan Inkontinensia Urine dan Kualitas Hidup

This study aims to determine the effect of Pelvic Floor Muscle Exercise (PMFE) on urinary incontinence and quality of life (QOL) in post-radical prostatectomy prostate cancer patients. This research method is a systematic review by searching literature through several indexed electronic databases (Scopus, Science Direct, CINAHL, PubMed, ProQuest, SAGE, Springer Link). The study results were obtained from 10 articles on pelvic floor muscle exercise (PFME) modality therapy. Eight pieces explained that PFME without a combination effectively reduced urinary incontinence and improved the quality of life (QOL) of post-RP patients; one article explained the effectiveness of the variety of PFME with electrical stimulation in reducing incontinence urine in post-RP patients. One article describes the combination of PFME with the WeChat application reducing urine leakage and improving urinary continence. In conclusion, Pelvic Floor Muscle Exercise (PFME) is a therapy that is effective for urinary incontinence and men's quality of life after radical prostatectomy (RP).
 
 Keywords: Urinary Incontinence, Pelvic Floor Muscle Exercise, Radical Prostatectomy

PSMA PET/CT guided intensification of therapy in patients at risk of advanced prostate cancer (PATRON): a pragmatic phase III randomized controlled trial

BackgroundPositron emission tomography targeting the prostate specific membrane antigen (PSMA PET/CT) has demonstrated unparalleled performance as a staging examination for prostate cancer resulting in substantial changes in management. However, the impact of altered management on patient outcomes is largely unknown. This study aims to assess the impact of intensified radiotherapy or surgery guided by PSMA PET/CT in patients at risk of advanced prostate cancer.MethodsThis pan-Canadian phase III randomized controlled trial will enroll 776 men with either untreated high risk prostate cancer (CAPRA score 6–10 or stage cN1) or biochemically recurrent prostate cancer post radical prostatectomy (PSA > 0.1 ng/mL). Patients will be randomized 1:1 to either receive conventional imaging or conventional plus PSMA PET imaging, with intensification of radiotherapy or surgery to newly identified disease sites. The primary endpoint is failure free survival at 5 years. Secondary endpoints include rates of adverse events, time to next-line therapy, as well as impact on health-related quality of life and cost effectiveness as measured by incremental cost per Quality Adjusted Life Years gained.DiscussionThis study will help create level 1 evidence needed to demonstrate whether or not intensification of radiotherapy or surgery based on PSMA PET findings improves outcomes of patients at risk of advanced prostate cancer in a manner that is cost-effective.Trial registrationThis trial was prospectively registered in ClinicalTrials.gov as NCT04557501 on September 21, 2020.

Outcomes of Salvage Lymph Node Dissection in Oligorecurrent Prostate Cancer Post Radical Prostatectomy: Experience of an Oncologic Center in Spain

Introduction and ObjectivesWe report our experience with salvage lymph node dissection (sLND) in oligorecurrent prostate cancer (PCa) post radical prostatectomy (RP).Material and MethodsWe retrospectively analyzed data of 24 patients who underwent sLND for biochemical recurrence (BCR) post RP, from July 2012 to February 2018. sLND was performed following an extended bilateral template. Clinical and pathological characteristics of primary RP and sLND were reported. Biochemical response and initiation of additional therapy post sLND were analyzed. Survival analysis was performed using KaplanMeier curves.Results24 sLND were performed. RP specimens showed 58.3% of Gleason score 7 and 50% of locally advanced disease. Median time to BCR post RP was 24 months with a median PSA value of 1.4 ng/ml pre sLND. 75% of patients underwent imaging prior to sLND. sLND showed oligometastasis on the final pathology report in 54.2% of patients. Metastatic lymph nodes were mainly identified in the iliac artery territory (61.5%). Complete biochemical response (PSA < 0.2 ng/ml) was maintained throughout the first 12 months of follow-up in 20.83% of patients and 8.33% of patients at the end of the study (median follow-up 70 months). Survival rates free of additional therapy (ADT/RT) were 45.83% at one year and 25% at 5 years.ConclusionsWe observed a biochemical response post sLND in 20.83% of our patients, lasting throughout the first year of follow up, with survival rates free of ADT and/or RT of 45.83% at one year and 25% at 5 years.

18F]DCFPyL PET/CT in detection and localization of recurrent prostate cancer following prostatectomy including low PSA < 0.5ng/mL.

The primary aim of this retrospective multicenter analysis was to assess the performance of PSMA PET/CT using [18F]DCFPyL in the detection and localization of recurrent prostate cancer post radical prostatectomy (RP). Particular reference is given to low PSA groups < 0.5ng/mL to aid discussion around the inclusion of this group in PSMA guidelines and funding pathways. Retrospective analysis of combined PSMA database patients from centers in Australia and New Zealand. Two hundred twenty-two patients presenting with recurrence post RP were stratified into five PSA groups (ng/mL): 0-0.19, 0.2-0.49, 0.5-0.99, 1-1.99, and ≥ 2. Lesions detected by [18F]DCFPyL PET/CT were recorded as local recurrence, locoregional nodes, and metastases. Of 222 patients, 155 (69.8%) had evidence of abnormal uptake suggestive of recurrent prostate cancer. The detection efficacies for [18F]DCFPyL PET/CT were 91.7% (44/48) for PSA levels ≥ 2ng/mL, 82.1% (23/28) for PSA levels 1-1.99ng/mL, 62.8% (27/43) for PSA levels 0.5-0.99ng/mL, 58.7% (54/92) for PSA levels 0.2-0.49ng/mL, and 63.6% (7/11) for PSA levels ≤ 0.2ng/mL. In those with PSA < 0.5ng/mL, 47.6% (49/103) had detectable lesions, 71.4% (35/49) had disease confined to the pelvis, 22.4% (11/49) had prostate bedrecurrence, 49.0% (24/49) had pelvic lymph nodes, and 28.6% (14/49) had extra pelvic disease. [18F]DCFPyL PET/CT has a high detection rate in recurrence following RP even at low PSA levels with similar detection levels in the PSA subgroups < 0.5ng/mL. Employing rigid PSA thresholds when constructing guidelines for PSMA PET/CT funding eligibility may result in a significant number of patients below such thresholds having delayed or inappropriate treatment.

Correlation of integrated ERG/PTEN assessment with biochemical recurrence in prostate cancer

IntroductionProstate cancer is a heterogeneous disease, with a complex molecular landscape that evolves throughout disease progression. Common alterations in genes such as ERG and PTEN have been attributed to worse prognosis. This study aimed to further examine the clinical relevance of PTEN and ERG expression in a cohort of patients with prostate cancer post radical prostatectomy. MethodsTissue microarrays were constructed from 132 patients with prostate cancer from the Irish Prostate Cancer Research Consortium and University Hospital of Orebro, Sweden. Patients were divided into three groups – Group 1: biochemical recurrence, Group 2: no biochemical recurrence and Group 3: immediate progression after surgery. PTEN and ERG immunohistochemical analysis was performed and the association between expression levels and clinical parameters were compared. ResultsPathological stage pT3 tumours were more common at borderline significantly higher levels amongst patients who biochemically recurred when compared to patients who did not recur after radical prostatectomy (p = 0.05). ERG and PTEN expression levels were compared separately and concurrently across all three patient groups. Lack of ERG expression was strongly associated with immediate progression after surgery (p = 0.029). Loss of/low PTEN trended towards an association with immediate progression, however this was not statistically significant (p = 0.066). ConclusionIn this study, negative ERG expression was strongly associated with immediate biochemical progression after radical prostatectomy. Moreover, a trend towards a relationship between aberrant PTEN expression and progression was observed. Additional studies with long-term follow up data may provide further clinical insight into the genomic heterogeneity in this population.

Diagnostic performance of F-18 fluciclovine PET/CT in post-radical prostatectomy prostate cancer patients with rising prostate-specific antigen level ≤0.5 ng/mL.

The aim of the study was to assess the diagnostic performance of fluciclovine positron emission tomography (PET)/computerized tomography (CT) in post-radical prostatectomy prostate cancer patients with rising prostate-specific antigen (PSA) ≤0.5 ng/mL, and identify the associated predictive factors of positive studies. From 30 June 2017 to 9 August 2019, patients with post-radical prostatectomy prostate cancer who underwent F-18 fluciclovine PET/CT and had PSA level within 2-week interval (PSAPET) ≤0.5 ng/mL were enrolled into this single-institution retrospective study. Data on tumor characteristics, including Gleason scores, extra-prostatic extension, seminal vesicle invasion, surgical margin and nodal metastasis, PSA after radical prostatectomy, previous hormonal therapy, PSA doubling time (PSADT), scanner type, PSAPET and site of recurrence were collected. Comparison of these factors between groups of positive and negative fluciclovine PET/CT was done by using Mann-Whitney U-test and Fisher's exact test. Of 94 eligible patients with post-radical prostatectomy prostate cancer, 10 patients had positive studies (10.6%). Detection rate at PSAPET 0.1, 0.2, 0.3, 0.4 and 0.5 ng/mL were 0% (0/11), 0% (0/15), 20% (6/30), 4% (1/25) and 23.1% (3/13), respectively. Upon multivariate analysis of clinical factors, only a PSADT <3 months (P = 0.023) was shown to have a statistically significant correlation with a positive study. In post-radical prostatectomy prostate cancer patients with rising PSA 0.1-0.5 ng/mL, the sensitivity of F-18 fluciclovine PET/CT for identifying tumor recurrence/metastases is poor with an overall detection rate of 10.6%. Larger prospective studies are required to validate these findings.

Overall survival outcomes with the use of adjuvant chemotherapy, radiation therapy and hormone therapy in high-risk, very-high-risk and node-positive prostate cancer post radical prostatectomy: A NCDB analysis.

118 Background: Phase III trials have not consistently demonstrated overall survival (OS) advantage of adjuvant radiation therapy (ART) in prostate cancer (PC) with high risk/very high risk features after radical prostatectomy (RP). Adjuvant hormone therapy (AHT) in PC after RP improved OS in patients with positive lymph nodes (pLNs). We report an observational study on the impact of AHT to ART in NCCN defined high-risk/very high risk (Group 1), and adjuvant chemotherapy (ACT) to AHT in pLNs (group 2) post RP on OS. Methods: We conducted a retrospective study of PC patients (group 1 and group 2) who underwent RP and/or pelvic lymph node dissection. OS was calculated using Kaplan Meier analysis. Group 1 compared ART+AHT vs ART and Group 2 AHT+ ACT vs AHT within 16 weeks of RP. Multivariate analysis was performed with Cox proportional hazard regression model to adjust for different variables. Results: Out of 1,390,357 PC patients reported in NCDB (2004-2015) 182,653 and 11,972 met our inclusion criteria for Group 1 and Group 2 respectively. 3.37% of Group 1 received ART and/or AHT. 19.81% of Group 2 received AHT and/or ACT. Patients who received ART + AHT were more likely to be older, Non-Hispanic white, more likely to have pT4, and have higher prostate specific antigen (PSA) and Gleason scores (GS). Patients who received AHT+ACT were more likely to be younger, with private insurance, and lower Charlson-Deyo Score (CDCC) score. Five and seven year OS with adjusted hazard ratio (aHR) among Group 1 and Group 2 are depicted in table. Conclusions: No statistically significant difference in OS was seen among respective treatment groups. Limitations that exist with this registry based study include lack of randomization, differences in surgical and radiation techniques, duration and choices of ACT and AHT.[Table: see text]

Adjuvant androgen deprivation (AD) +/- mitoxantrone + prednisone (MP) in patients with high-risk prostate cancer (PC) post radical prostatectomy (RP): Phase III intergroup trial S9921.

5019 Background: Patients (pts) with high-risk PC post RP are at risk of systemic relapse with related morbidity/mortality. Adjuvant AD can reduce this risk. In 1999, based on available data, we hypothesized that adjuvant MP + 2 years (ys) of AD can further reduce mortality. Methods: Eligible pts had cT1-T3, N0 PC with post RP &gt; = 1 high risk factors defined as Gleason sum (GS) ≥ 8, pT3b, pT4, pN+, GS 7 + positive margin or any of these preoperative findings (in pts with neoadjuvant AD): preoperative PSA of &gt; 15 ng/ml, bx GS score &gt; 7, or PSA of &gt; 10 ng/ml + bx GS &gt; 6. Pts had to have post RP PSA = &lt; 0.2 ng/ml, were stratified by T, N, GS, and adjuvant radiation plan and randomized: Arm 1 AD (bicalutamide + goserelin for 2 ys) or Arm 2 AD + 6 cycles m 12 mg/m2 + P 5mg BID. Primary endpoint: overall survival (OS). Median OS was estimated to be 10 ys in AD arm requiring 680 pts/arm to detect a hazard ratio (HR) of 1.30 with 92% power and one-sided α = 0.05. Results: 983 pts (961 eligible intent to treat) with median age 60 ys and median PSA 7.6 ng/ml were randomized to AD or AD + MP from 10/99 -1/07 when the DSMC recommended stopping accrual due to higher leukemia rate in Arm 2. 16% had N1 (Group “Gr” 1), 61% GS ≥8 or pT3b (Gr 2),23% other risk factors (Gr 3). Median time to testosterone recovery was 9.5 months. Median follow-up (f/u) 11.2 ys. Conclusions: OS was higher than anticipated in both arms; MP did not improve OS and increased other malignancy risk. These data illustrate that systemic therapy benefit cannot be extrapolated from different disease stages and the importance of adequate f/u in adjuvant PCa trials. The remarkable DFS and 10 y OS, irrespective of risk extent, may be result of risk definition, and/or 2 ys AD. Pending definitive data 2 ys adjuvant AD for high-risk PCa post RP is a reasonable option to consider. Clinical trial information: NCT00004124. [Table: see text]

Magnetic Resonance Imaging-guided Cryoablation of Recurrent Prostate Cancer After Radical Prostatectomy: Initial Single Institution Experience

To establish the feasibility of magnetic resonance imaging (MRI)-guided cryoablation in patients with previous radical prostatectomy and MRI visualized biopsy-proven local recurrence of prostate adenocarcinoma. Eighteen postprostatectomy patients (mean 67, 57-78 years) were treated with MRI-guided cryoablation for recurrent prostate carcinoma. Patients were found to have a hyperenhancing nodule using multiparametric MRI with endorectal coil followed by a positive transrectal ultrasound-guided biopsy. Of 18 postsurgical patients, 6 had additional salvage external beam radiation with subsequent recurrence. Under general anesthesia and MRI guidance (wide-bore 1.5T MRI), 2-5 cryotherapy probes were placed in or around the recurrence by transperineal approach and cryoablation performed. The patients were stratified into 2 groups: the initial 9 consecutive patients had cryoprobes placed 1 cm apart with 2 freeze-thaw cycles (group 1), and the subsequent 9 patients had cryoprobes placed 0.5 cm apart with 3 freeze-thaw cycles (group 2). In group I, the average preprocedure prostate-specific antigen (PSA) was 1.21 ± 1.12 ng/mL, and 1-3 months postprocedure PSA was 0.14 ± 0.11 ng/mL (P<.01). Sixty-seven percent of patients had PSA≤0.2 ng/mL at 1-3 months follow-up, but only 25% at 4-6 months. No change in impotence or incontinence occurred. In group II, average preprocedure PSA was 2.24 ± 2.71 ng/mL, and 1-3 month postprocedure PSA was 0.08 ± 0.10 ng/mL (P<.05). Eighty-nine percent of patients had PSA≤0.2 ng/mL at 1-3 months follow-up and at 4-6 months. Complications in group 2 included worsening incontinence in 3 patients. MRI-guided salvage cryoablation of postradical prostatectomy prostate cancer recurrence is safe and feasible. Both techniques produce early PSA decrease with more lasting PSA results in the more aggressive group II methodology.

The role of advanced genetic testing in the management of prostate cancer post radical prostatectomy.

5089 Background: The genomic classifier (Decipher, GC) is a prospectively validated assay that predicts clinical metastasis post radical prostatectomy (RP) more accurately than standard clinicopathologic factors. While over 70% of high risk patients tested in a previous validation had low GC scores and good prognosis, patients with high GC scores had a cumulative incidence of metastasis over 25% over the study duration. Among men diagnosed with localized prostate cancer, these most at risk patients may derive the greatest benefit from novel therapies. We thus examined differential expression (DE) of druggable genes that may be targeted in this group. Methods: High-density microarray expression profiles of primary FFPE tumor specimens from 764 men treated with RP at the Mayo Clinic (1987-2006) were evaluated. A subset of 323 patients was flagged as high risk of clinical metastasis (mets) by virtue of having GC score ≥ 0.4. Enrichment and identification of DE genes as druggable targets were pursued using DAVID and DrugBank. Results: Median follow-up of patients was 15.1 years. Among the 323 patients with high GC scores, 62% had mets during follow-up.We identified 2,262 genes DE between mets and non-mets, 230 of which are associated with 331 approved pharmaceuticals and 547 experimental agents. These agents included multiple established anti-neoplastic therapies not currently used to treat prostate cancer such as bortezomib, capecitabine, dasatinib, etoposide, gemcitabine, imatinib, irinotecan, pemetrexed and vinblastine. The two most enriched pathways, spliceosome and ubiquitin-mediated proteolysis, have been proposed previously as therapeutic targets in cancer. Conclusions: Advanced genomic testing that includes validated molecular risk scores as well as transcriptome profiling from a single assay may better enable application of directed, multimodal therapy for individual patients with high risk prostate cancer.

Multicenter Clinical Validation of PITX2 Methylation as a Prostate Specific Antigen Recurrence Predictor in Patients With Post-Radical Prostatectomy Prostate Cancer

Radical prostatectomy is potentially curative in patients with clinically localized prostate cancer. However, biochemical recurrence affects 15% to 30% of men who undergo radical prostatectomy. We previously reported the prognostic potential of PITX2 gene promoter methylation using conventional assays. In the current study we validated PITX2 methylation status as a biochemical recurrence predictor after radical prostatectomy using a novel microarray based platform in a multi-institutional setting. PITX2 methylation status was assessed in formalin fixed, paraffin embedded prostatectomy tumor tissue samples from 476 patients from a total of 4 institutions on customized EpiChip PITX2 microarrays. Associations between PITX2 methylation and biochemical recurrence were assessed using the log rank test and Cox regression controlling for prostate cancer features. On multivariate analysis men with high methylation status were at significantly higher risk for biochemical recurrence than those with low methylation status (HR 3.0, 95% CI 2.0-4.5, p <10(-5)). The biochemical recurrence-free survival rate 5 years after surgery was 85% and 61% in the low and high methylation groups, respectively. In men with pathological Gleason 7 tumors the relative risk of biochemical recurrence was twice as high for high than for low PITX2 methylation (HR 2.0, 95% CI 1.2-3.3, p = 0.005). PITX2 methylation status assessed by EpiChip PITX2 identifies patients with prostate cancer who are most likely to have biochemical recurrence. This test independently adds to the prognostic information provided by standard clinicopathological analysis, improving prostatectomy case stratification into those at high and low risk for biochemical recurrence. This new clinical tool would be of particular benefit to assess intermediate risk cases (Gleason 7) in which risk stratification remains a challenge.

Clinical outcome of Taiwanese men with clinically localized prostate cancer post-radical prostatectomy: a comparison with other ethnic groups

Background. Prostate cancer incidence varies significantly among different ethnic groups. However, the report concerning the clinical outcome after radical prostatectomy (RP) in the low incidence Asian population is still limited. We aimed to compare the clinical outcome in patient treated with RP among different ethnic groups and to identify significant prognostic factors in Taiwanese patients.Methods. A total of 341 patients with clinical localized prostate cancer undergoing curative RP in three medical centers in Taiwan were included in this study. Ethnic group comparison was performed using the CaPSURE, SEARCH databases from United States (US) and one large European series. The Kaplan–Meier analysis and Cox proportional hazard model were used to identify significant predictors for prostate-specific antigen (PSA) recurrence.Results. Compared to the Caucasian white population in the US and Europe studies, the Taiwanese population have higher age at surgery and higher pre-operative PSA level. With mean and median follow-up of 39.1 months and 31.0 months (range 5–120 months), 127 men (37.2%) had PSA recurrence which was significant higher than the Western series. Significant predictors for PSA recurrence identified in the post-operative overall model were PSA level, pathological Gleason Score, pathological tumor stage and lymph node metastasis.Conclusions. The clinical outcome of Taiwanese male with prostate cancer post-RP appears inferior to the Western country, which is largely due to delay surgery at higher PSA level. Earlier diagnosis and treatment may improve the cancer control of RP.

PITX2 methylation and biochemical recurrence in postradical prostatectomy prostate cancer patients

5124 Background: PITX2 is a bicoid-related transcription factor induced by the Wnt pathway and required for effective cell-type-specific proliferation during development. We previously reported prognostic potential of PITX2 gene promoter methylation for outcome prediction in breast and prostate cancer (PC) patients. Radical prostatectomy (RP) is potentially curative in patients with clinically localized PC. However, biochemical recurrence (BCR) affects 15–30% of patients undergoing RP. In the current study, we validate PITX2 methylation status as a predictor of BCR following RP. Methods: PITX2 methylation status was assessed in formalin-fixed paraffin-embedded RP tumor tissue samples from 476 patients from four different institutions in USA and Europe using customized microarrays. Associations between PITX2 methylation and BCR were assessed using log-rank test and Cox regression controlling for PC features. Results: In multivariate analysis, patients with a high methylation status were at significantly higher risk for BCR compared to patients with low methylation status (HR = 3.0; 95%CI = 2.0–4.5; p &lt; 10-5). BCR-free survival at five years after surgery was 85% and 61% for patients in the low and high methylation group, respectively. In patients with pathological Gleason 7 tumors, the relative risk of suffering BCR was twice as high for a patient with high PITX2 methylation relative to patients with low PITX2 methylation (HR = 2.0; 95%CI = 1.2–3.3; p = 0.005). Moreover, PITX2 methylation status was significant in the group of patients with tumor involvement of the surgical margins in the prostatectomy specimen. (HR = 3.36, 95% CI: 2.24–5.06, p = 0.001). Conclusions: PITX2 methylation status identifies PC patients most likely to experience BCR. This test independently adds to prognostic information provided by standard clinico-pathological analyses improving stratification of RP patients into high- or low-risk for BCR. This new clinical tool would be of particular benefit in assessment of intermediate-risk patients (Gleason 7) or patients with positive surgical margins wherein risk stratification remains a challenge. [Table: see text]