Persistent Prostate-specific Antigen Research Articles

Cribriform pattern 4/intraductal carcinoma of the prostate and persistent prostate‐specific antigen after radical prostatectomy

AbstractObjectivesThe objective of this study is to identify the effect of cribriform pattern 4 carcinoma/intraductal carcinoma of the prostate (CC/IDCP) on persistent prostate‐specific antigen (PSA) levels after robot‐assisted radical prostatectomy (RARP) in patients with localized prostate cancer (PCa).Patients and MethodsThis retrospective study included 730 consecutive patients with localized PCa who underwent RARP at Mie University (n = 392) and Aichi Medical University (n = 338) between 2015 and 2021. Patients with clinically metastatic PCa (cN1 and cM1) and those who received neoadjuvant and/or adjuvant therapy before biochemical recurrence were excluded. We evaluated the effects of CC/IDCP on persistent PSA levels after RARP. Persistent PSA was defined as PSA level ≥0.2 ng/mL at 1 month postoperatively and consecutively thereafter. Using factors from logistic regression analysis, models were developed to predict persistent PSA levels.ResultsApproximately 6.3% (n = 46) of the patients had persistent PSA levels. Patients with biopsy CC/IDCP (bCC/IDCP) and pathological CC/IDCP (pCC/IDCP) based on RARP specimens were 11.6% (85/730) and 36.5% (267/730), respectively. Multivariate analysis of the prediction of persistent PSA levels using preoperative factors revealed that PSA density, percentage of positive cancer cores, biopsy grade group and bCC/IDCP were independent prognostic factors. Furthermore, multivariate analysis of the prediction of persistent PSA levels using postoperative factors, excluding pN1, revealed that pathological grade group, pCC/IDCP, seminal vesicle invasion and lymphovascular invasion were independent prognostic factors. In the receiver operating characteristic curve analysis for predicting persistent PSA after RARP, areas under the receiver operating characteristic curve for the model with preoperative factors, postoperative factors, including pN1, and postoperative factors, excluding pN1, were 0.827, 0.833 and 0.834, respectively.ConclusionsbCC/IDCP predicted persistent PSA after RARP in the overall population, while pCC/IDCP predicted persistent PSA only when the pN1 population was excluded. This may be useful for predicting susceptible patients with worse outcomes.

Prognostication in Lymph Node-Positive Prostate Cancer with No PSA Persistence After Radical Prostatectomy.

This study aimed to create a prognostic model to predict disease recurrence among patients with lymph node involvement but no prostate-specific antigen (PSA) persistence and to explore its clinical utility. The study analyzed patients with lymph node involvement after pelvic lymph node dissection with radical prostatectomy in whom no PSA persistence was observed between 2006 and 2019 at 33 institutions. Prognostic factors for recurrence-free survival (RFS) were analyzed by the Cox proportional hazards model. Among 231 patients, 127 experienced disease recurrence. The factors prognostic for RFS were PSA level at diagnosis (≥ 20 vs. < 20ng/mL: hazard ratio [HR], 1.66; 95% confidence interval [CI], 1.09-2.52; P = 0.017), International Society of Urological Pathology grade group at radical prostatectomy (RP) specimen (group ≥ 4 vs. ≤ 3: HR, 1.63; 95% CI 1.12-2.37; P = 0.010), pathologic T-stage (pT3b/4 vs. pT2/3a: HR, 1.70; 95% CI 1.20-2.42; P = 0.0031), and surgical margin status (positive vs. negative: HR, 1.60; 95% CI 1.13-2.28; P = 0.0086). The prognostic model using four parameters were associated with RFS and metastasis-free survival. The prognostic model in combination with postoperative PSA value and number of lymph nodes is clinically useful for discussing treatment choice with patients.

Oncological outcomes in robot-assisted radical prostatectomy: the value of PSA density as a preoperative predictive factor

Background: Pretreatment assessment of patients diagnosed with localized prostate cancer (PCa) is essential for therapeutic decision-making. Currently available staging systems based on prostate-specific antigen (PSA), Gleason score, and clinical stage allow for determining the prognostic characteristics of these patients. Several studies have evaluated the preoperative use of prostate-specific antigen density (PSAD) as a prognostic factor for further risk stratification. To date, the role of PSAD in this setting is still an object of debate. Objectives: The present analysis aimed to assess the predictive potential of PSAD for adverse oncological outcomes after robot-assisted radical prostatectomy (RARP) and to compare its accuracy to preoperative PSA (pPSA). Design and methods: We retrospectively reviewed 427 patients diagnosed with localized PCa who underwent RARP at a single institution between January 2015 and January 2020. Generating receiver operator characteristic (ROC) curves, calculating areas under the curves (AUCs), and using a linear regression model, we analyzed the association of PSAD and pPSA with postoperative positive surgical margins (PSM), Gleason score ⩾ 7, persistent PSA, and biochemical recurrence (BCR), with a median follow-up of 47 months. Results: PSAD showed a significant association with PSM ( p &lt; 0.0001), PSA persistence ( p &lt; 0.0001), and Gleason ⩾ 7 ( p &lt; 0.0001), without being statistically significant in predicting BCR ( p = 0.098). The predictive value of PSAD was comparable to pPSA for outcomes of PSA persistence (AUC 0.727 versus 0.771) and Gleason ⩾ 7 (AUC 0.683 versus 0.649). Conclusion: PSAD is a predictive factor for postoperative oncological outcomes of PSM, Gleason score ⩾ 7, and persistence of PSA. Despite the need for further studies, PSAD could be useful as a prognostic parameter in conjunction with established staging systems.

Pretest Video Education Versus Genetic Counseling for Patients With Prostate Cancer: ProGen, A Multisite Randomized Controlled Trial.

Germline genetic testing (GT) is recommended for men with prostate cancer (PC), but testing through traditional models is limited. The ProGen study examined a novel model aimed at providing access to GT while promoting education and informed consent. Men with potentially lethal PC (metastatic, localized with a Gleason score of ≥8, persistent prostate-specific antigen after local therapy), diagnosis age ≤55 years, previous malignancy, and family history suggestive of a pathogenic variant (PV) and/or at oncologist's discretion were randomly assigned 3:1 to video education (VE) or in-person genetic counseling (GC). Participants had 67 genes analyzed (Ambry), with results disclosed via telephone by a genetic counselor. Outcomes included GT consent, GT completion, PV prevalence, and survey measures of satisfaction, psychological impact, genetics knowledge, and family communication. Two-sided Fisher's exact tests were used for between-arm comparisons. Over a 2-year period, 662 participants at three sites were randomly assigned and pretest VE (n = 498) or GC (n = 164) was completed by 604 participants (VE, 93.1%; GC, 88.8%), of whom 596 participants (VE, 98.9%; GC, 97.9%) consented to GT and 591 participants completed GT (VE, 99.3%; GC, 98.6%). These differences were not statistically significant although subtle differences in satisfaction and psychological impact were. Notably, 84 PVs were identified in 78 participants (13.2%), with BRCA1/2 PV comprising 32% of participants with a positive result (BRCA2 n = 21, BRCA1 n = 4). Both VE and traditional GC yielded high GT uptake without significant differences in outcome measures of completion, GT uptake, genetics knowledge, and family communication. The increased demand for GT with limited genetics resources supports consideration of pretest VE for patients with PC.

Which Patients with Prostate Cancer and Lymph Node Uptake at Preoperative Prostate-specific Membrane Antigen Positron Emission Tomography/Computerized Tomography Scan Are at a Higher Risk of Prostate-specific Antigen Persistence After Radical Prostatectomy? Identifying Indicators of Systemic Disease by Integrating Clinical, Magnetic Resonance Imaging, and Functional Imaging Parameters

BackgroundThe role of local therapies including radical prostatectomy (RP) in prostate cancer (PCa) patients with clinical lymphadenopathies on prostate-specific membrane antigen (PSMA) positron emission tomography/computerized tomography (PET/CT) has scarcely been explored. Limited data are available to identify men who would benefit from RP; on the contrary, those more likely to benefit already have systemic disease. ObjectiveWe aimed to assess the predictors of prostate-specific antigen (PSA) persistence in surgically managed PCa patients with lymphadenopathies on a PSMA PET/CT scan by integrating clinical, magnetic resonance imaging (MRI), and PSMA PET/CT parameters. Design, setting, and participantsWe identified 519 patients treated with RP and extended lymph node dissection, and who received preoperative PSMA PET between 2017 and 2022 in nine referral centers. Among them, we selected 88 patients with nodal uptake at preoperative PSMA PET (miTxN1M0). Outcome measurements and statistical analysisThe outcome was PSA persistence, defined as a PSA value of ≥0.1 ng/ml at the first measurement after surgery. Multivariable logistic regression models tested the predictors of PSA persistence. Covariates consisted of biopsy International Society of Urological Pathology (ISUP) grade group, clinical stage at MRI, and number of positive spots at a PET/CT scan. A regression tree analysis stratified patients into risk groups based on preoperative characteristics. Results and limitationsOverall, lymph node invasion (LNI) was detected in 63 patients (72%) and 32 (36%) experienced PSA persistence after RP. At multivariable analyses, having more than two lymph nodal positive findings at PSMA PET, seminal vesicle invasion (SVI) at MRI, and ISUP grade group >3 at biopsy were independent predictors of PSA persistence (all p < 0.05). At the regression tree analysis, patients were stratified in four risk groups according to biopsy ISUP grade, number of positive findings at PET/CT, and clinical stage at MRI. The model depicted good discrimination at internal validation (area under the curve 78%). ConclusionsOne out of three miN1M0 patients showed PSA persistence after surgery. Patients with ISUP grade 2–3, as well as patients with organ-confined disease at MRI and a single or two positive nodal findings at PET are those in whom RP may achieve the best oncological outcomes in the context of a multimodal approach. Conversely, patients with a high ISUP grade and extracapsular extension or SVI or more than two spots at PSMA PET should be considered as potentially affected by systemic disease upfront. Patient summaryOur novel and straightforward risk classification integrates currently available preoperative risk tools and should, therefore, assist physician in preoperative counseling of men candidates for radical treatment for prostate cancer with positive lymph node uptake at prostate-specific membrane antigen positron emission tomography.

Decipher Score predicts prostate specific antigen persistence after prostatectomy.

The aim of this study was to evaluate genomic risk of patients with persistent prostate specific antigen (PSA) using mRNA expression analysis and a validated prognostic genomic-risk classifier. Monocentric retrospective study including all patients who underwent radical prostatectomy (RP) by one surgeon and Decipher Test from October 2013 to December 2018. PSA persistent population was defined as all patients with two consecutive PSA>0.1 ng/mL at follow-up after the surgery. Neurovascular Structure-adjacent Frozen-section Examination (NeuroSAFE) was performed intraoperatively for research of positive surgical margins. Multivariate analysis was performed for persistent PSA (pPSA) predictors. A specific localized, organ-confined, and negative margins sub-population with PSA persistence was compared to a similar sub-population without PSA persistence for genomic differential expression analyses. A total of 564 patients were included and 61 of them had pPSA. Preoperative PSA was higher in the PSA persistent group (11.6 [6.4, 21.2] vs. 6.2 [4.7, 9.2] P=0.00010), as well as PSA density (PSAd) (0.3 [0.2, 0.5] vs. 0.2 [0.1, 0.3] P=0.0001). Postoperative characteristics, Gleason Score, and positive surgical margins were significantly higher in the PSA persistent population. 31 patients had pPSA in our specific subpopulation and were compared to 217 patients with no pPSA. On multivariate analysis, only Decipher Score (OR=5.64 [1.28; 24.89], P=0.022) and preoperative PSA (OR=1.06, [1.02; 1.09], P=0.001) were significant predictors for PSA persistence. We found two genes to be significantly upregulated with a 2.5-fold change in our specific subpopulation (SERPINB11 and PDE11A). We found unique genomic features of patients with pPSA, whilst confirming previous clinical findings that this condition behaves to a worse prognosis. Given this high genomic risk, further imaging studies should be performed to select patients for early treatment intensification.

Long-Term Prognosis and Treatment Strategy of Persistent PSA After Radical Prostatectomy.

Prostate-specific antigen (PSA) is thought to be undetectable (<0.1 ng/mL) after radical prostatectomy (RP), and persistent PSA (≥0.1 ng/mL) is considered a failure of curative treatment. The study population consisted of 135 patients, all of whom underwent RP for localized prostate cancer, and developed persistent PSA. We set the starting point at the timing of RP, and the endpoints were the development of castration-resistant prostate cancer (CRPC) and cancer-specific survival. Salvage radiation therapy (RT) and androgen deprivation therapy (ADT) were performed in 53 (39.3%) and 64 (47.4%) patients, respectively. Eighteen (13.3%) patients didn't receive any salvage treatment. During the median follow-up of 10.1 years, CRPC was observed in 23 patients, and 6 patients died due to prostate cancer. Kaplan-Meier curves demonstrated the 15-year CRPC-free and cancer-specific survivals were 79.5% and 92.7%, respectively. Cox multivariate analysis demonstrated that seminal vesicle invasion (SVI) (p = 0.007) and nadir PSA ≥1.0 ng/mL (p = 0.002) were independent risk factors for CRPC. Salvage RT demonstrated better cancer control (the 10-and 15-year CRPC-free survival was 94.1% and 94.1%) compared to ADT (75.9% and 58.5%, p = 0.017) after 1:1 propensity score matching. SVI and nadir PSA ≥1.0 ng/mL are independent risk factors for CRPC in patients with persistent PSA after RP. Salvage RT is considered to be the optimal treatment for this condition.

Risk factors for prostate-specific antigen persistence in pT3aN0 prostate cancer after robot-assisted laparoscopic radical prostatectomy: a retrospective study.

The aim of this study was to evaluate the risk factors for prostate-specific antigen (PSA) persistence in pathological stage T3aN0 prostate cancer (PCa) after robot-assisted laparoscopic radical prostatectomy (RALP). A retrospective study was performed on 326 patients with pT3aN0 PCa who underwent RALP between March 2020 and February 2022. PSA persistence was defined as nadir PSA of >0.1 ng/mL after RALP, and the risk factors for PSA persistence were evaluated using logistic regression analysis. Among 326 patients, 61 (18.71%) had PSA persistence and 265 (81.29%) had PSA of <0.1 ng/mL after RALP (successful radical prostatectomy [RP] group). In the PSA persistence group, 51 patients (83.61%) received adjuvant treatment. Biochemical recurrence occurred in 27 patients (10.19%) in the successful RP group during the mean follow-up period of 15.22 months. Multivariate analysis showed that the risk factors for PSA persistence were large prostate volume (hazard ratio [HR], 1.017; 95% confidence interval [CI], 1.002-1.036; p=0.046), lymphovascular invasion (LVI) (HR, 2.605; 95% CI, 1.022-6.643; p=0.045), and surgical margin involvement (HR, 2.220; 95% CI, 1.110-4.438; p=0.024). Adjuvant treatment may be needed for improved prognosis in patients with pT3aN0 PCa after RALP with a large prostate size, LVI, or surgical margin involvement.

Baseline PSMA-PET/CT as a predictor of PSA persistence following radical prostatectomy in high-risk nonmetastatic prostate cancer patients receiving neoadjuvant therapy.

The precise staging and proper management of high-risk prostate cancer (PCa) continues to be a challenge. We aimed to demonstrate the prognostic value of baseline prostate-specific membrane antigen-ligand positron emission tomography/computed tomography (PSMA-PET/CT) in high-risk, nonmetastatic PCa patients who received neoadjuvant hormonal or chemohormonal treatment followed by radical prostatectomy (RP). We performed retrospective analyses of 70 patients with high-risk, nonmetastatic PCa confirmed by biopsy between 2018 and 2021. All patients underwent neoadjuvant therapy followed by RP and pelvic lymph node dissection (PLND); PSMA-PET/CT was performed before initiation of neoadjuvant therapy. Acquired image information and clinical characteristics/outcomes were examined for possible associations. Among 70 high-risk PCa patients, median age was 69 years old and median prostate specific antigen (PSA) at presentation was 58.5 ng/mL. Thirty (42.9%) patients had uptake of the PSMA tracer only in the primary PCa lesions and 40 (57.1%) patients had PSMA-positive lesions in regional or distant sites. Sixteen (32%) localized PCa patients defined by pre-PET magnetic resonance imaging were found to have locally advanced PCa based on PSMA-PET/CT. Fifteen (30%) localized PCa patients and 7 (35%) locally advanced PCa patients were upstaged to metastatic PCa. The sensitivity and specificity of PSMA-PET/CT for the detection of lymph node involvement were 90.9% and 69.5%, respectively, with a positive prediction value of 35.7% and negative prediction value of 97.6%. The diagnostic accuracy was 72.9%. Univariate analysis showed upstaging, tumor stage, and metastasis location based on PSMA-PET/CT are predictors to PSA persistence after surgery, while multivariate logistic regression analysis showed only the tumor stage based on PSMA-PET/CT remained an independent predictor of the outcome. This study further highlights the accuracy and necessity of PSMA-PET/CT in newly diagnosed, high-risk, nonmetastatic PCa patients.

Corrigendum: The Impact of the Percent of Residual Prostate-Specific Antigen on Metastasis-Free Survival in Patients with Persistent Prostate-Specific Antigen after Radical Prostatectomy

Corrigendum: The Impact of the Percent of Residual Prostate-Specific Antigen on Metastasis-Free Survival in Patients with Persistent Prostate-Specific Antigen after Radical Prostatectomy

How has the COVID-19 pandemic influenced prostate cancer?—a tertiary single-centre analysis of oncological results, diagnosis and treatment times

The coronavirus disease 2019 (COVID-19) pandemic has affected care for diseases like cancer. The aim was to evaluate the impact of COVID-19 on waiting times for diagnosis and treatment of prostate cancer (PC), as well as the possible effect on the treatment results in PC patients undergoing radical prostatectomy. We compared the results of 497 patients who underwent biopsy prior to the COVID-19 pandemic (1 January-31 December 2019) with those of 290 patients biopsied during the COVID-19 pandemic (1 January-31 December 2020). Demographic data, tumour characteristics, type of treatment and diagnosis times were comparable. Prostate specific antigen (PSA) levels were recorded at consultation prior to biopsy and after treatment. Mann-Whitney and chi-square tests were used to compare continuous variables and percentages, respectively. In 2020, there were fewer urology consultations (35,160 vs. 40,225 in 2019). The median PSA in 2020 was significantly higher (14.3 vs. 9.9 ng/dL in 2019). In 2019, 53.1% (N=264) of the biopsies were positive for cancer vs. 47.2% (N=137) in 2020 (P=0.104). In 2020, more patients presented with metastatic disease (7.3% vs. 1.9%, P=0.009). Also, in 2020 there was a longer waiting time for prostate biopsy (42.1 vs. 35.3 days in 2019, P=0.019). A total of 132 patients underwent laparoscopic radical prostatectomy (LARP). The median time until surgery was similar in both years (71.9 vs. 58.29 days). During 2020, a higher percentage of patients had ISUP grade 4 in the surgical specimen (34.3% vs. 17.5%, P=0.07). Furthermore, a higher percentage of aggressive (pT3) tumours were diagnosed (37.2% vs. 27.2%, P=0.08), and the percentage of patients with involvement of surgical margins was also higher (48.6% vs. 29.3%, P=0.027). There were no differences between the groups in terms of biochemical recurrence or persistent PSA at one year (P=0.711). Delayed biopsy during the COVID-19 period did not appear to adversely impact biopsy results. Patients biopsied in 2020 had higher PSA, possibly due to proper triaging. A higher rate of adverse pathology outcomes was observed in patients undergoing radical prostatectomy during the pandemic, probably due to understaging of the biopsy. This study serves to raise awareness of the risk of deterioration of care of PC patients due to possible underdiagnosis.

Time to second biochemical recurrence as a prognostic indicator in postprostatectomy patients who undergo salvage radiation therapy: An RTOG 9601 based post hoc analysis.

The prognostic significance of a "second" biochemical recurrence (sBCR) after salvage radiation therapy (sRT) with/without hormonal therapy following primary radical prostatectomy in men with prostate cancer has not been examined. We hypothesized that a shorter time to sBCR will be associated with worse cancer control outcomes. The RTOG 9601 study included 760 patients with tumor stage pT2/T3, pN0, who had either persistently elevated prostate-specific antigen (PSA) postradical prostatectomy or developed subsequent biochemical recurrence with PSA levels between 0.2 and 4.0 ng/ml. All patients received sRT (with or without 2 years of Bicalutamide) from 1998 to 2015. For our study, we focused on 421 patients who had sBCR after sRT-which was defined as a PSA increase of at least 0.3 ng/ml over the first nadir. Patients were divided into two categories: early sBCR (n = 210) and late sBCR (n = 211) using median time to sBCR (3.51 years). All patients who experienced sBCR received salvage hormonal therapy. Competing-risk analysis was used to examine the impact of early versus late sBCR on prostate cancer specific mortality (CSM), after accounting for available covariates. The majority of patients were age 60 years or older (75.8%), had pT3 disease (74.8%), and Gleason score 7 (75.2%). Overall, 13.8% had persistent PSA initially after surgery. At 10 years, starting at the time of sBCR, CSM rate was 31.3% in the early sBCR group versus 20.0% in the late sBCR group. In competing-risk analysis, time to sBCR was an independent predictor of CSM, where patients with early sBCR had 1.7-fold higher CSM risk (p = 0.026) than their counterparts with late sBCR. Time to sBCR after sRT (with or without concomitant Bicalutamide) is a significant predictor of CSM following initial radical prostatectomy. This information can be used to guide subsequent treatments, and to counsel patients.

The Effect of Salvage Radiation Therapy on Survival, Functional Outcomes, and Quality of Life in Men with Persistent Prostate-specific Antigen After Robot-Assisted Radical Prostatectomy: Which Patient Benefits More?

PurposeThe aim of this study was to evaluate the effect of salvage radiation therapy (sRT) on survival, functional outcomes, and quality of life in men with persistent prostate-specific antigen (PSA >0.1 ng/mL) after a robot-assisted radical prostatectomy (RARP) and reveal subgroups that benefit more from sRT. Methods and MaterialsData of 3409 patients who underwent RARP was retrieved from a high-volume institute database, and 313 patients with persistent PSA were included in further analyses. Patients who received sRT and those who did not were compared after propensity score matching. Progression-free survival (PFS), metastasis-free survival (MFS), androgen deprivation therapy (ADT)-free, cancer-specific survival, and overall survival, as well as patient-reported outcomes were the endpoints. Multivariable Cox regression models were developed to reveal treatment effect sizes for the subgroups. ResultsThe overall persistent PSA rate was 9.2%, and the median follow-up time after RARP was 4.5 years (interquartile range, 2.7-7.9 years). The sRT was associated with improved PFS (hazard ratio [HR]: 0.29; P < .001), ADT-free survival (HR: 0.34; P < .001), MFS (HR: 0.39; P = .001), cancer-specific survival (HR: 0.34; P = .03), and overall survival (HR: 0.24; P = .001). Positive surgical margins (HR: 0.26; P < .001 for ADT-free survival), advanced pathological T stage (HR: 0.24; P < .001 for PFS) and positive lymph nodes (HR: 0.15; P = .001 for MFS), and lower Gleason score (HR: 0.15; P = .001 for PFS) were associated with marked survival benefits of sRT. Bowel symptoms were observed more frequently in patients who had sRT with or without ADT compared with patients with persistent PSA but no sRT (34.3% vs 19.2%; P = .01). Early sRT (<6 months after surgery) was associated with bothering incontinence (P < .001) and bowel symptoms (P = .03). ConclusionsPersistent PSA after a radical prostatectomy is still a common challenge in the robotic surgery era. sRT provides clear survival benefits for all endpoints, especially with unfavorable locoregional factors but a low Gleason score.

Validation of the Decipher genomic classifier in patients receiving salvage radiotherapy without hormone therapy after radical prostatectomy – an ancillary study of the SAKK 09/10 randomized clinical trial

The Decipher genomic classifier (GC) has shown to independently prognosticate outcomes in prostate cancer. The objective of this study was to validate the GC in a randomized phase III trial of dose-escalated salvage radiotherapy (SRT) after radical prostatectomy. A clinical-grade whole-transcriptome assay was carried out on radical prostatectomy samples obtained from patients enrolled in Swiss Group for Clinical Cancer Research (SAKK) 09/10, a phase III trial of 350 men with biochemical recurrence after radical prostatectomy randomized to 64 Gy versus 70 Gy without concurrent hormonal therapy or pelvic nodal RT. A prespecified statistical plan was developed to assess the impact of the GC on clinical outcomes. The primary endpoint was biochemical progression; secondary endpoints were clinical progression and time to hormone therapy. Multivariable analyses adjusted for age, T-category, Gleason score, postradical prostatectomy persistent prostate-specific antigen (PSA), PSA at randomization, and randomization arm were conducted, accounting for competing risks. The analytic cohort of 226 patients was representative of the overall trial, with a median follow-up of 6.3 years (interquartile range 6.1-7.2 years). The GC (high versus low-intermediate) was independently associated with biochemical progression [subdistribution hazard ratio (sHR) 2.26, 95% confidence interval (CI) 1.42-3.60; P < 0.001], clinical progression (HR 2.29, 95% CI 1.32-3.98; P= 0.003), and use of hormone therapy (sHR 2.99, 95% CI 1.55-5.76; P= 0.001). GC high patients had a 5-year freedom from biochemical progression of 45% versus 71% for GC low-intermediate. Dose escalation did not benefit the overall cohort, nor patients with lower versus higher GC scores. This study represents the first contemporary randomized controlled trial in patients treated with early SRT without concurrent hormone therapy or pelvic nodal RT that has validated the prognostic utility of the GC. Independent of standard clinicopathologic variables and RT dose, high-GC patients were more than twice as likely than lower-GC patients to experience biochemical and clinical progression and receive of salvage hormone therapy. These data confirm the clinical value of Decipher GC to personalize the use of concurrent systemic therapy in the postoperative salvage setting.

Radiotherapy plus androgen deprivation therapy for prostate-specific antigen persistence in lymph node-positive prostate cancer.

The treatment for lymph node involvement (LNI) after radical prostatectomy (RP) has not been established. This study aimed to reveal the outcomes of various management strategies among patients with LNI after RP. Retrospectively, 561 patients with LNI after pelvic lymph node dissection (PLND) with RP treated between 2006 and 2019 at 33 institutions participating in the Japanese Urological Oncology Group were investigated. Metastasis‐free survival (MFS) was the primary outcome. Patients were stratified by prostate‐specific antigen (PSA) persistence after RP. Cox regression models were used to analyze the relationships between clinicopathological characteristics and survival. Survival analyses were conducted using the Kaplan‐Meier method and log‐rank test with or without propensity score matching. Prognoses, including MFS and overall survival, were prominently inferior among patients with persistent PSA compared with those without persistent PSA. In multivariate analysis, androgen deprivation therapy (ADT) plus radiotherapy (RT) was associated with better MFS than ADT alone among patients with persistent PSA (hazard ratio = 0.37; 95% confidence interval = 0.15‐0.93; p = 0.034). Similarly, MFS and overall survival were significantly better for ADT plus RT than for ADT alone among patients with persistent PSA after propensity score matching. This study indicated that PSA persistence in LNI prostate cancer increased the risk of poor prognoses, and intensive treatment featuring the addition of RT to ADT might improve survival.

MP48-09 TOXICITY PROFILE OF IMMEDIATE POST-PROSTATECTOMY RADIATION THERAPY: RESULTS FROM A LARGE MULTI-INSTITUTIONAL SERIES

MP48-09 TOXICITY PROFILE OF IMMEDIATE POST-PROSTATECTOMY RADIATION THERAPY: RESULTS FROM A LARGE MULTI-INSTITUTIONAL SERIES

68Ga-prostate-specific membrane antigen positron emission tomography/computed tomography for patients with favorable intermediate-risk prostate cancer.

Current guidelines do not support the use of pretreatment imaging in patients with favorable intermediate-risk prostate cancer. 68Ga-prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT) is more accurate than conventional imaging for preoperative staging. We aimed to evaluate whether pretreatment 68Ga-PSMA PET/CT is beneficial for identifying pathological lymph node involvement (LNI) and adverse pathology among patients with favorable intermediate-risk prostate cancer. We reviewed 88 patients with favorable intermediate-risk prostate cancer who underwent 68Ga-PSMA PET/CT prior to radical prostatectomy and lymph node dissection from 2016-2020. The primary endpoint was the presence of pathological LNI. Association between pretreatment characteristics and outcomes were evaluated. Preoperative 68Ga-PSMA PET/CT showed suspicious uptake in lymph nodes in 4/88 patients (5%), hence, 20 patients would need to be scanned to identify a patient with a positive lymph node on imaging. Two patients had pathological LNI, only one of whom showed 68Ga-PSMA PET/CT uptake prior to surgery. The sensitivity, specificity, positive predictive value, and negative predictive values of 68Ga-PSMA PET/CT for identifying LNI were 50%, 97%, 25%, and 99%, respectively. After surgery, four patients had evidence of prostate-specific antigen (PSA) persistence. The rate of PSA persistence was higher among patients with LNI on preoperative 68Ga-PSMA PET/CT (2/4, 50% vs. 2/84, 2%, p=0.009). Preoperative imaging of favorable intermediate-risk prostate cancer patients using 68Ga-PSMA PET/CT showed a low yield for identifying patients at higher risk. Consistent with current guidelines, our findings do not support the routine use of PET/CT in this group of patients. Future prospective studies are needed to validate our findings.

Salvage radiotherapy (SRT) in combination with pembrolizumab in patients with PSA persistence or biochemical recurrence after radical prostatectomy due to prostate cancer.

TPS212 Background: Goal of our study is to evaluate the efficacy and safety of immunotherapy in combination with standard salvage radiation therapy (SRT) in patients with biochemical recurrence (BCR) or prostate-specific antigen (PSA) persistence after radical prostatectomy (RP). The combination of immunotherapy (IO) with radiation therapy might provide a clinical benefit to patients with recurrent prostate cancer due to an induction of increased activity of the immune system against cancerous tissue (abscopal effect). Primary endpoint is complete biochemical response (PSA level below detection level) 60 weeks after start of trial treatment, which further defines prognosis of patients. Further explorative endpoints like radiographic progression-free survival, PSA-nadir level and time to PSA-nadir, time to initiation of subsequent therapy (secondary ADT or NHA) and quality of life as well as adverse events will be evaluated. Methods: The trial is as a phase II, open-label, single arm monocenter trial which evaluates the combination of pembrolizumab as study medication in combination with SRT. Pembrolizumab will be administered in a three-weekly scheme up to one year of treatment. A concomitant ADT is administered in high-risk patients only (PSA &gt; 0.7ng/ml or cN+ in imaging studies). All patients will be staged with PSMA PET-CT, if applicable. Additionally, blood and urine samples will be collected for correlative biomarker studies. A total of 49 patients are planned to be enrolled in this explorative study within 2 years. INCLUSION CRITERIA (excerpt) Histologically confirmed diagnosis of an adenocarcinoma of the prostate and a BCR or PSA persistence after RP. Histology of the RP specimen needs to fulfill the following criteria: adenocarcinoma of the prostate, Gleason score 7-10; pNX or pN0 or pN1 (max. 2 lymph nodes involved). Imaging within 30 days prior to study inclusion is mandatory (([68Ga] or [18F] PSMA PET-CT as standard imaging modality, alternatively CT abdomen and full-body bone scan). PSA value between ≥0.2 and ≤1.0 ng/ml, measured at least six weeks postoperatively. EXCLUSION CRITERIA (excerpt) Prior-therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137). Prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to registration (like neo-adjuvant androgen deprivation therapy (ADT), secondary hormone ablation or taxan-based chemotherapy). Distant metastases or suspicious lymph nodes outside the lower pelvis in imaging with PSMA PET-CT (patients with PET positive bone lesions that are morphologically not clearly suspicious of metastases and would not change clinical practice can be included). Clinical trial information: NCT04931979.

Narrative Review of the Post-Operative Management of Prostate Cancer Patients: Is It Really the End of Adjuvant Radiotherapy?

Simple SummaryAmong patients with prostate cancer who have been operated on, a subset harboring high-risk features will present with a biochemical recurrence (BCR). Adjuvant radiotherapy (aRT) was proven to significantly reduce the risk of BCR when compared to salvage radiotherapy (SRT) but suffered from several limitations: a lack of patient selection criteria, a higher treatment-related morbidity and an uncertain benefit for long-term clinical endpoints. In the same clinical setting, early SRT (eSRT) appears as non-inferior to aRT with a lower morbidity, replacing aRT as the preferred option. In this review, we insist on the need for multidisciplinary discussions to fully comprehend the individual characteristics of each patient and propose the best treatment strategy for every patient.Despite three randomized trials indicating a significant reduction in biochemical recurrence (BCR) in high-risk patients, adjuvant radiotherapy (aRT) was rarely performed, even in patients harboring high-risk features. aRT is associated with a higher risk of urinary incontinence and is often criticized for the lack of patient selection criteria. With a BCR rate reaching 30–70% in high-risk patients, a consensus between urologists and radiation oncologists was needed, leading to three different randomized trials challenging aRT with early salvage radiotherapy (eSRT). In these three different randomized trials with event-free survival as the primary outcome and a planned meta-analysis, eSRT appeared as non-inferior to aRT, answering, for some, this never-ending question. For many, however, the debate persists; these results raised several questions among urologists and radiation oncologists. BCR is thought to be a surrogate for clinically meaningful endpoints such as overall survival and cancer-specific survival but may be poorly efficient in comparison with metastasis-free survival. Imaging of rising prostate-specific antigen (PSA), post-operative persistent PSA and BCR was revolutionized by the broader use of MRI and nuclear imaging such as PET-PSMA; these imaging modalities were not analyzed in the previous randomized trials. A sub-group of very high-risk patients could possibly benefit from an adjuvant radiotherapy; but their usual risk factors such as high Gleason score or invaded surgical margins mean they are unable to be selected. More precise biomarkers of early BCR or even metastatic-relapse were developed in this setting and could be useful for the patients’ stratification. In this review, we insist on the need for multidisciplinary discussions to fully comprehend the individual characteristics of each patient and propose the best treatment strategy for every patient.

The value of magnetic resonance imaging-ultrasound fusion targeted biopsies for clinical decision-making among patients with previously negative transrectal ultrasound biopsy and persistent prostate-specific antigen elevation.

Targeted biopsy approaches have been shown to increase the detection of clinically significant prostate cancer (csPCa) within index prostate lesions. We report our initial experience with magnetic resonance imaging-ultrasound fusion biopsies (MRI-TB) in a population of men who had a previously negative transrectal ultrasound (TRUS) biopsy, persistent prostate-specific antigen (PSA) elevation, and ongoing suspicion of PCa. Patients were followed prospectively to assess for changes in clinical management following targeted biopsy. We prospectively followed the first 122 patients undergoing MRI-TB at our institution. All men had clinical suspicion of PCa, prior negative TRUS biopsies, and persistent PSA elevation. A total of 177 index lesions were identified on multiparametric MRI and reviewed using the Prostate Imaging Reporting and Data System (PI-RADS) v2 scoring system. Lesions classified as PI-RADS ≥3 received targeted biopsy. Biopsy-naive patients and those on active surveillance were excluded. The primary outcome was detection rate of csPCa, defined as International Society of Urological Pathology (ISUP) Grade Group (GG) ≥2. Multivariate analysis was used to determine predictors of csPCa on fusion biopsy. Prior to fusion biopsy, patients had a mean of 17.9±8.6 negative core biopsies per patient and a median PSA of 9.5 (standard deviation [SD] 6.2) ng/nl. MRI-TB resulted in diagnosis of csPCa in 42/122 (34.4%) patients. Clinically significant PCa was found in eight (13.1%), 14 (21.9%), and 25 (48.1%) of PI-RADS 3, 4, and 5 lesions, respectively. The location of csPCa was within the peripheral zone (55.3%), transitional zone (40.4%), and central zone (8.5%). Clinical outcomes of patients with newly diagnosed csPCa show 4.8%, 57.1%, and 38.1% receiving active surveillance, radiation treatment, and radical prostatectomy, respectively. Predictors for csPCa were presence of PI-RADS 5 lesions, age, length of time from MRI to biopsy, and smaller prostate volumes. MRI-TB yields high detection rates for csPCa in men with elusive PSA elevation and frequently guides a change in clinical management. Clinical decision-making based on MRI findings and PI-RADS lesion scores are best informed by an understanding of institutional reporting patterns.