Biochemical Persistence Research Articles

Identifying Patients in Whom the Follow-Up Scheme after Robot-Assisted Radical Prostatectomy Could Be Optimized in the First Year after Surgery: Reducing Healthcare Burden.

The currently advised follow-up scheme of PSA testing after robot-assisted radical prostatectomy (RARP) is strict and might pose a burden to our healthcare system. We aimed to optimize the 1-year follow-up scheme for patients who undergo RARP. All patients with histologically-proven prostate cancer (PCa) who underwent RARP between 2018 and August 2022 in the Prostate Cancer Network in the Netherlands were retrospectively evaluated. We excluded patients who underwent salvage RARP and patients who had <1 year of PSA follow-up. Postoperative PSA values were collected. Biochemical persistence (BCP) was defined as PSA level >0.10 ng/mL at 0-4 months after RARP, whereas biochemical recurrence (BCR) was defined as PSA level >0.2 ng/mL at any time point after RARP. We aimed to identify a group of patients who had a very low risk of BCR at different time points after surgery. Of all 1155 patients, BCP was observed in 151 (13%), of whom 79 (6.8%) had PSA ≥ 0.2 ng/mL. BCR further developed in 51 (4.7%) and 37 (3.4%) patients at 5-8 and 9-12 months after RARP, respectively. In 12 patients, BCR was found at 5-8 months after RARP in the absence of BCP. These patients represented 1.2% (12/1004) of the entire group. In other words, 98.8% (992/1004) of patients who had an unmeasurable PSA level at 0-4 months after RARP also had an unmeasurable PSA level 5-8 months after surgery. Limitations are the retrospective design and incomplete follow-up. Patients with an unmeasurable PSA level at 3-4 months after RARP may not need to be retested until 12 months of follow-up, as almost 100% of patients will not have the biochemically recurrent disease at 5-8 months of follow-up. This will reduce PSA testing substantially at the cost of hardly any missed patients with recurrent disease.

PSMA PET Validates Higher Rates of Metastatic Disease for European Association of Urology Biochemical Recurrence Risk Groups: An International Multicenter Study.

The European Association of Urology (EAU) prostate cancer guidelines panel recommends risk groups for biochemical recurrence (BCR) of prostate cancer to identify men at high risk of progression or metastatic disease. The rapidly growing availability of PSMA-directed PET imaging will impact prostate cancer staging. We determined the rates of local and metastatic disease in BCR and biochemical persistence (BCP) of prostate cancer stratified by EAU BCR risk groups and BCP. Methods: Patients with BCR or BCP were enrolled under the same prospective clinical trial protocol conducted at 3 sites (n = 1,777 [91%]: UCLA, n = 662 [NCT02940262]; University of California San Francisco, n = 508 [NCT03353740]; University of Michigan, n = 607 [NCT03396874]); 183 patients with BCP from the Universities of Essen, Bologna, and Munich were included retrospectively. Patients with BCR had to have sufficient data to determine the EAU risk score. Multivariate, binomial logistic regression models were applied to assess independent predictors of M1 disease. Results: In total, 1,960 patients were included. Post-radical prostatectomy EAU BCR low-risk, EAU BCR high-risk, and BCP groups yielded distant metastatic (M1) detection in 43 of 176 (24%), 342 of 931 (37%), and 154 of 386 (40%) patients. For postradiotherapy EAU BCR low-risk and EAU BCR high-risk groups, the M1 detection rate was 113 of 309 (37%) and 110 of 158 (70%), respectively. BCP, high-risk BCR, and higher levels of serum prostate-specific antigen were significantly associated with PSMA PET M1 disease in multivariate regression analysis. PSMA PET revealed no disease in 25% and locoregional-only disease in 33% of patients with post-radical prostatectomy or postradiotherapy EAU BCR high risk. Conclusion: Our findings support the new EAU classification; EAU BCR high-risk groups have higher rates of metastatic disease on PSMA PET than do the low-risk groups. Discordant subgroups, including metastatic disease in low-risk patients and no disease in high-risk patients, warrant inclusion of PSMA PET stage to refine risk assessment.

Preoperative PSMA-PET/CT as a predictor of biochemical persistence and early recurrence following radical prostatectomy with lymph node dissection.

This study aims to evaluate the predictive value of lymph nodes (LN) suspicious for metastases on preoperative prostate-specific membrane antigen (PSMA) PET/CT for biochemical persistence (BCP) and early biochemical recurrence (BCR) following robotic-assisted radical prostatectomy (RARP) with extended pelvic LN dissection (ePLND). We evaluated 213 patients with intermediate and high-risk prostate cancer (PCa) who underwent clinical staging with preoperative 68Ga- or 18F-PSMA-PET/CT scan and subsequent RARP with ePLND. Patients were grouped as PSMA- or PSMA+ depending on their LN status on PSMA-PET/CT and subdivided according to histological LN status in pN0 or pN1. Diagnostic accuracy of PSMA-PET/CT for the detection of pN1 was evaluated. BCP was defined as a first postoperative serum PSA level ≥0.1 ng/mL 6-12 weeks following RP. Early BCR was defined as detectable PSA > 0.2 ng/mL within 12 months of follow-up. Univariable logistic regression analyses were used to evaluate the effect of PSMA+ on BCP and BCR. Forty patients (19%) were PSMA+. The overall incidence of pN1 was 23%. Sensitivity, specificity, PPV and NPV on a per patient level for the detection of pN1 was 29%, 84%, 35%, and 80% respectively. BCP was observed in 26 of 211 patients (12%) and early BCR in 23 of 110 patients (21%). The presence of PSMA+ was a significant predictor for BCP (OR 7.1, 2.9-17.1 95% CI) and BCR (OR 8.1, 2.9-22.6 95% CI). Preoperative PSMA-PET/CT may be a valuable tool for patient counseling for RARP and ePLND as it is a significant predictor for the risk of postoperative BCP and early BCR. We conclude that an ePLND should not be avoided in men with intermediate or high-risk PCa and preoperative negative PSMA-PET/CT, as 20% have microscopic LN metastasis.

PD61-02 PREOPERATIVE PSMA PET/CT AS A PREDICTOR OF BIOCHEMICAL PERSISTENCE AND EARLY BIOCHEMICAL RECURRENCE

You have accessJournal of UrologyProstate Cancer: Localized: Surgical Therapy V (PD61)1 Sep 2021PD61-02 PREOPERATIVE PSMA PET/CT AS A PREDICTOR OF BIOCHEMICAL PERSISTENCE AND EARLY BIOCHEMICAL RECURRENCE Diederik Baas, Melline Schilham, Joost de Baaij, Eric Vrijhof, Robert Hoekstra, Rick Hermsen, Diederik Somford, and Jean-Paul van Basten Diederik BaasDiederik Baas More articles by this author , Melline SchilhamMelline Schilham More articles by this author , Joost de BaaijJoost de Baaij More articles by this author , Eric VrijhofEric Vrijhof More articles by this author , Robert HoekstraRobert Hoekstra More articles by this author , Rick HermsenRick Hermsen More articles by this author , Diederik SomfordDiederik Somford More articles by this author , and Jean-Paul van BastenJean-Paul van Basten More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002098.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: This study aims to evaluate the predictive value of suspected lymph nodes (LN) metastases on prostate-specific-membrane-antigen (PSMA) PET/CT for biochemical persistence (BCP) and early biochemical recurrence (BCR) following radical prostatectomy (RP) with extended pelvic lymph node dissection (ePLND). METHODS: RP patients between September 1st, 2016 and October 1st, 2020 were evaluated. Men with intermediate or high-risk PCa with preoperative 68Ga/18F-PSMA PET/CT and subsequent ePLND were included. Performance of PSMA PET/CT was determined on a per patient level. BCP was defined as a serum PSA level ≥0.1 ng/mL between 6-20 weeks following RP. Early BCR was defined as detectable PSA >0.2 ng/mL ≤12 months of follow-up. Patients were grouped as PSMA- or PSMA+ depending on their LN status on PSMA PET/CT and subdivided according to histological LN status (pN) as determined by ePLND. RESULTS: From 1058 consecutive RP patients, 213 met the inclusion criteria. Median number of resected LN was 20 (IQR 15-26). PSMA PET/CT versus histological results of ePLND are presented in Table 1. Sensitivity, specificity, PPV, NPV and accuracy for preoperative detection of metastatic LNs were 29%, 83%, 33%, 80% and 71% respectively. BCP was observed in 26 of 211 patients (12%) and early BCR in 23 of 110 patients (21%). The incidence of BCP and BCR for patients subdivided according to their PSMA and pN status is illustrated in Figure 1. No correction was made for other risk factors. Patients with PSMA+/pN1 had a significantly increased risk of BCP and BCR compared with PSMA-/pN1 (p=0.004; p <0.001). CONCLUSIONS: ePLND should not be avoided in men with a pre-operative negative PSMA PET/CT, as 20% of patients do have histological N1 disease. Men with positive pre-operative PSMA PET/CT and confirmed pN1 disease have a significantly increased risk of BCP and early BCR compared to those with negative PSMA PET/CT. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e1066-e1066 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Diederik Baas More articles by this author Melline Schilham More articles by this author Joost de Baaij More articles by this author Eric Vrijhof More articles by this author Robert Hoekstra More articles by this author Rick Hermsen More articles by this author Diederik Somford More articles by this author Jean-Paul van Basten More articles by this author Expand All Advertisement Loading ...

Survival analysis of patients with prostate cancer and unfavorable risk factors treated with radical prostatectomy and salvage radiotherapy after biochemical recurrence and persistence

ObjectiveSurvival analysis of patients with prostate cancer (PCa) with adverse prognostic factors (APF) treated with radical prostatectomy (RP) and salvage radiotherapy (SRT) after biochemical recurrence (BR) or biochemical persistence (BP). Materials and methodsRetrospective analysis of 446 patients with at least one of the following APF: Gleason score ≥8, pathologic stage ≥pT3 and/or positive surgical margins. BR criteria used was PSA level over 0.4ng/ml.A survival analysis using Kaplan–Meier was performed to compare the different variable categories with log-rank test. In order to identify risk factors for SRT response and cancer specific survival (CSS) we performed univariate and multivariate analyses using Cox regression. ResultsMean follow up: 72 (IQR 27–122) months, mean time to BR: 42 (IQR 20–112) months, mean PSA level at BR: 0.56 (IQR 0.42–0.96). BR was present in 36.3% of the patients. Biochemical response to SRT was observed in 121 (75.7%) patients.Recurrence-free survival (RFS) rates after SRT at 3, 5, 8 and 10 years were 95.7%, 92.3%, 87.9%, and 85%; overall survival (OS) rates after 5, 10 and 15 years was 95.6%, 86.5% and 73.5%, respectively. CSS rates at 5, 10 and 15 years were 99.1%, 98.1% and 96.6%.Only time to BR <24 months (HR=2.55, p=.01) was identified as an independent risk factor for RFS after SRT. ConclusionsIn these patients, RP only controls the disease in approximately half of the cases. Multimodal sequential treatment (RP+SRT when needed) increases this control, achieving high CSS rates and biochemical control in over 87% of the patients. Patients with time to recurrence >24 months responded better to rescue treatment.

Análisis de supervivencia de los pacientes con cáncer de próstata con factores patológicos desfavorables tratados con prostatectomía radical y radioterapia de rescate tras la recidiva y persistencia bioquímica

ObjectiveSurvival analysis of patients with prostate cancer (PCa) with adverse prognostic factors (APF) treated with radical prostatectomy (RP) and salvage radiotherapy (SRT) after biochemical recurrence (BR) or biochemical persistence (BP). Materials and methodsRetrospective analysis of 446 patients with at least one of the following APF: Gleason score ≥8, pathologic stage ≥pT3 and/or positive surgical margins. BR criteria used was PSA level over 0.4ng/ml.A survival analysis using Kaplan-Meier was performed to compare the different variable categories with log-rank test. In order to identify risk factors for SRT response and cancer specific survival (CSS) we performed univariate and multivariate analyses using Cox regression. ResultsMean follow up: 72 (IQR 27-122) months, mean time to BR: 42 (IQR 20-112) months, mean PSA level at BR: 0.56 (IQR 0.42-0.96). BR was present in 36.3% of the patients. Biochemical response to SRT was observed in 121 (75.7%) patients.Recurrence-free survival (RFS) rates after SRT at 3, 5, 8 and 10years were 95.7%, 92.3%, 87.9%, and 85%; overall survival (OS) rates after 5, 10 and 15years was 95.6%, 86.5% and 73.5%, respectively. CSS rates at 5, 10 and 15years were 99.1%, 98.1% and 96.6%.Only time to BR <24months (HR=2.55, P=.01) was identified as an independent risk factor for RFS after SRT. ConclusionsIn these patients, RP only controls the disease in approximately half of the cases. Multimodal sequential treatment (RP+SRT when needed) increases this control, achieving high CSS rates and biochemical control in over 87% of the patients. Patients with time to recurrence >24months responded better to rescue treatment.

68Ga-PSMA-11 PET/CT in recurrent hormone-sensitive prostate cancer (HSPC): a prospective single-centre study in patients eligible for salvage therapy.

The primary objective is to assess the efficacy of 68Ga-PSMA-11-PET/CT to detect recurrent location(s) in hormone-sensitive prostate cancer (PCa). Secondary objectives are (1) to evaluate changes in clinical management; (2) to determine which covariates independently predict positive scan; (3) to assess 68Ga-PSMA-11-PET/CT performance in different settings of PSA relapse. Inclusion criteria include (1) histologically diagnosed PCa; (2) previous radical therapy; (3) proven biochemical recurrence (BCR) or biochemical persistence (BCP); (4) hormone-sensitive PCa (HSPC); (5) androgen deprivation therapy (ADT)-free for at least 6months; (6) PSA < 1.5ng/mL or any PSA in case of negative choline-PET/CT (n= 38). Changes in clinical management were defined by multidisciplinary tumour-board. Clinical settings were BCP (group-1, n= 25); first-time BCR (group-2, n= 121); BCR after salvage therapy (group-3, n= 77). Two hundred twenty-three (223) consecutive patients were enrolled: median PSA = 0.65ng/mL (0.2-8.9) and median PSAdt = 9.3months (0.4-144.6). 96.9% received RP as primary therapy. 68Ga-PSMA-11-PET/CT positivity rate was 39.9% (CI95% 33.5-46.7%). Disease confined to pelvis was detected in 23.3% of cases. At least one distant lesion was observed in 16.6% of cases. Secondary objectives are as follows: (1) changes in clinical management were observed in 34.5% of patients; (2) PSA, PSAdt and T stage > 3a were independent predictors (all p< 0.03); (3) 68Ga-PSMA-11-PET/CT positivity rate was 56% (in group 1, 36.3% in group 2, 40.3% in group 3. This study attested the overall good performance of 68Ga-PSMA-11-PET/CT to detect PCa locations in HSPC patients eligible for salvage therapy, influencing the therapy management in 35.4% of cases. Furthermore, patient characteristics are influencing factors of 68Ga-PSMA-11-PET/CT positivity rate and should be considered to reduce false negative scan.

Gallium-68-prostate-specific membrane antigen (68 Ga-PSMA) positron emission tomography (PET)/computed tomography (CT) predicts complete biochemical response from radical prostatectomy and lymph node dissection in intermediate- and high-risk prostate cancer.

To determine the value of gallium-68-prostate-specific membrane antigen (68 Ga-PSMA)-11 positron emission tomography (PET) /computed tomography (CT) in men with newly diagnosed prostate cancer. We analysed results of 140 men with intermediate- and high-risk prostate cancer. All men underwent 68 Ga-PSMA-11 PET/CT and multiparametric magnetic resonance imaging (mpMRI) before radical prostatectomy (RP) with extended pelvic lymph node (LN) dissection. For each patient, the clinical and pathological features were recorded. Prostate-specific antigen (PSA) was documented at staging scan, and after RP, at a median (interquartile range) of 110(49-132)days. A PSA level of ≥0.03ng/mL was classified as biochemical persistence (BCP). Logistic regression was performed for association of clinical variables and BCP. In these 140 patients with intermediate- and high-risk prostate cancer, 27.1% had PSMA PET/CT-positive findings in the pelvic LNs. Sensitivity and specificity for detection of LN metastases were 53% and 88% (PSMA PET/CT) and 14% and 99% (mpMRI), respectively. The overall BCP rate was 25.7%. The BCP rate was 16.7% in men who were PSMA PET/CT LN-negative compared to 50% in men who were PSMA PET/CT LN-positive (P<0.05). The presence of PSMA-positive pelvic LNs was more predictive of BCP after RP than cT-stage, PSA level, and the Gleason score, adjusted for surgical margins status. 68 Ga-PSMA-11 PET/CT is highly predictive of BCP after RP, and should play an important role informing men with intermediate- or high-risk prostate cancer.

Predictors and outcomes of biochemical persistence versus recurrence after radical prostatectomy for prostate cancer diagnosed in the era of PSA screening.

e15041 Background: Biochemical persistence (BCP) and biochemical recurrence (BCR) after radical prostatectomy (RP) may portend poor outcomes. There is a paucity of data on patients with BCP after RP and no studies that compare patients with BCP and BCR. We evaluate clinical and pathologic characteristics, predictors, and outcomes of patients with BCP vs. BCR in a large contemporary cohort treated with RP. Methods:From 2001-2008, 4047 patients underwent robot-assisted RP (RARP) for localized prostate cancer at a single institution. After excluding 336 patients who were lost to follow up, there were 3711 patients for the study. BCR was defined as a PSA ≥ 0.2 ng/ml with a confirmatory value. BCP was defined as a detectable PSA at the first postoperative draw within 3 months of surgery. Patients with BCP and BCR were compared and multivariable regression analysis was used to identify factors predicting BCP and metastasis. Results: A total of 345 (9.2%) patients had a detectable PSA at a mean follow up of 33.4 months, of whom 114 (33%) had BCP and 231 (67%) had BCR. Patients with a BCP had a significantly higher preoperative PSA (11.7 vs. 8.3), biopsy high-grade disease (36 vs. 21%), biopsy perineural invasion (35 vs. 21%), final pathologic high-grade disease (58 vs. 29%), tumor volume (32 vs. 26%), pathologic angiolymphatic invasion (26 vs. 14%), seminal vesicle invasion (32 vs. 16%), and N1 disease (15 vs. 2.6%). Predictors of BCP on multivariable analysis of all recurrences were biopsy perineural invasion (OR-1.8, 95% CI- 1.02 to 3.1, p=0.043), seminal vesicle invasion (OR-2.7, 95% CI- 1.2 to 6.2, p=0.021), and N1 disease (OR-6.6, 95% CI- 2 to 21.5, p=0.002). 21 patients developed metastatic disease (BCP=14, BCR=7, p=0.01). Of all patients with post-RARP PSA elevation (BCP and BCR), only BCP (OR-3.2, p=0.022) and high-grade disease (OR-2.9, p=0.043) predicted metastasis. Conclusions: Patients with BCP have more aggressive disease on biopsy and pathology than patients with BCR and are more likely to develop distant metastasis. Only higher pathologic stage predicts BCP over BCR. Of all patients with a post-RARP PSA elevation, only BCP and ≥ Gleason 8 disease predicted metastasis.

472 PREDICTORS AND OUTCOMES OF BIOCHEMICAL PERSISTENCE VS. RECURRENCE AFTER RADICAL PROSTATECTOMY FOR PROSTATE CANCER DIAGNOSED IN THE ERA OF PSA SCREENING

INTRODUCTION AND OBJECTIVES: Biochemical persistence (BCP) and biochemical recurrence (BCR) after radical prostatectomy (RP) may portend poor outcomes. There is a paucity of data on patients with BCP after RP and no studies that compare patients with BCP and BCR. We evaluate clinical and pathologic characteristics, predictors, and outcomes of patients with BCP vs. BCR in a large contemporary cohort of patients treated with RP. METHODS: From 2001–2008, 4047 patients underwent robotassisted RP (RARP) for localized prostate cancer at a single institution. After excluding 336 patients who were lost to follow up, there were 3711 patients evaluable for the study. BCR was defined as a PSA 0.2 ng/ml with a confirmatory value. BCP was defined as a detectable PSA at the first postoperative draw within 3 months of surgery. Patients with BCP and BCR were compared and multivariable regression analysis was used to identify factors predicting BCP and metastasis. RESULTS: A total of 345 (9.2%) patients had a detectable PSA at a mean follow up of 33.4 months, of whom 114 (33%) had BCP and 231 (67%) had BCR. Patients with a BCP had a significantly higher preoperative PSA (11.7 vs. 8.3), biopsy high-grade disease (36 vs. 21%), biopsy perineural invasion (35 vs. 21%), final pathologic highgrade disease (58 vs. 29%), tumor volume (32 vs. 26%), pathologic angiolymphatic invasion (26 vs. 14%), seminal vesicle invasion (32 vs. 16%), and N1 disease (15 vs. 2.6%). Predictors of BCP on multivariable analysis of all recurrences were biopsy perineural invasion (OR1.8, 95% CI1.02 to 3.1, p 0.043), seminal vesicle invasion (OR-2.7, 95% CI1.2 to 6.2, p 0.021), and N1 disease (OR-6.6, 95% CI2 to 21.5, p 0.002). 21 patients developed metastatic disease (BCP 14, BCR 7, p 0.01). Of all patients with post-RARP PSA elevation (BCP and BCR), only BCP (OR-3.2, p 0.022) and high-grade disease (OR2.9, p 0.043) predicted metastasis. CONCLUSIONS: Patients with BCP have more aggressive disease on biopsy and pathology than patients with BCR and are more likely to develop distant metastasis. Only higher pathologic stage predicts BCP over BCR. Of all patients with a post-RARP PSA elevation, only BCP and Gleason 8 disease predicts metastasis.