Prostate-specific Antigen Nadir Research Articles

Early Endpoints in High-risk Localized Prostate Cancer: Exploratory Analysis of Three Radiation Therapy Oncology Group Phase 3 Studies

BackgroundEarly endpoints in clinical trials of high-risk localized prostate cancer (HRLPC) that resemble those monitored in real-world practice could expedite clinical development. ObjectiveTo assess the association of prostate-specific antigen (PSA) recurrence (PSA-R)-based early endpoints with metastasis-free survival (MFS), overall survival (OS), and prostate cancer (PC)-specific survival (PCSS), and to identify clinically undetectable disease. Design, setting, and participantsA post hoc analysis of patients with HRLPC from Radiation Therapy Oncology Group studies 9202, 9902, and 0521 was performed. InterventionLong-term adjuvant androgen-deprivation therapy (ADT) and post-primary definitive radiotherapy. Outcome measurements and statistical analysisEvent-free survival (EFS; PSA-R, locoregional recurrence [LRR], distant metastasis [DM], or death), biochemical failure (PSA-R), general clinical failure (PSA-R, LRR, DM, ADT initiation, or death), and no evidence of disease (NED; alive patients without PSA-R, LRR, DM, and subsequent PC therapy, and with testosterone recovery) were assessed for association with MFS, OS, and PCSS using correlation and landmark analyses, Kaplan-Meier method, and Cox proportional-hazard model. PSA-R was defined as PSA nadir + 2 ng/ml; PSA nadir + 2 ng/ml and rising; PSA >5, 10, and 25 ng/ml; or PSA doubling time (PSADT) <6 mo. Results and limitationsAmong assessed early endpoints, EFS with PSA nadir + 2 ng/ml and rising, or with PSA >5 ng/ml was associated with MFS, OS, and PCSS. No development of EFS with PSADT <6 mo or ADT initiation event or achievement of NED at 3 yr was associated with prolonged OS, MFS, and PCSS (hazard ratio [95% confidence interval], 0.53 [0.45–0.64], 0.63 [0.52–0.76], and 0.26 [0.18–0.36], or 0.56 [0.48–0.66], 0.62 [0.52–0.74], and 0.26 [0.19–0.37]) after the landmark time. Older studies performed before the current guidance should be interpreted with caution. ConclusionsWe identified EFS with PSA nadir + 2 ng/ml and rising, PSA >5 ng/ml, or PSADT <6 mo ± ADT initiation and NED as potentially promising early endpoints in HRLPC that should be validated further. Patient summaryWe identified novel clinical measures that may expedite the development of new medicines for patients with localized prostate cancer at a high risk of progression. These measures, which took into account prostate-specific antigen assessments and other clinical characteristics, should be confirmed in future studies. We also defined a novel measure of no evidence of disease that can help treating physicians identify patients with clinically undetectable disease.

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.

Biochemical recurrence (BCR) among patients (pts) with prostate cancer (PC) after radiation therapy (RT).

e17111 Background: RT is a frequent primary treatment for pts with clinically localized PC. Despite its frequent success, 30-50% of pts eventually present with BCR, defined as rising prostate-specific antigen (PSA). BCR is associated with a higher risk of developing distant metastasis and ultimately death from PC. Understanding BCR occurrence and its impact on clinical outcomes is important for optimizing diagnostic and therapeutic strategies for recurrent disease. Methods: This is a retrospective cohort study using nationally representative Electronic Medical Records (EMR) data from Optum© from 1/2010-9/2021. Eligible pts were adults who underwent RT after PC diagnosis, had ≥ 3 available PSA values after initiating RT, and had EMR activity for at least 6 mo before and 12 mo after RT. Pts with a history of prior malignancy except nonmelanoma skin cancers and pts with metastatic PC (mPC) at baseline (BL) or within 3 months after RT were excluded. The BL period was 6 mo before RT initiation. Primary outcome was frequency of BCR, defined as rising PSA (PSA ≥ nadir + 2 ng/mL); secondary analyses included % of pts who progressed to mPC, castration-resistant PC (CRPC), and death after BCR and factors impacting time to BCR. Results: 9,292 RT pts were included in this analysis. Key pt characteristics/outcomes are shown in the Table. Median (range) age was 69.0 (40-88) y, 83.2% of pts were White, and 13.4% were Black. Median PSA nadir was 0.11 ng/mL, 32.5% of pts had received androgen deprivation therapy (ADT) during BL period, and median (Q1-Q3) follow-up from RT initiation was 3.8 (2.4-5.7) y. Overall, 10.2% of pts developed BCR. Among BCR pts (n = 949), 51.2% had a PSA doubling time (PSADT) &lt; 6 mo and 16.9% had a PSADT between 6-10 mo; 35.0% developed mPC, 30.2% developed CRPC, and 23.4% died. In multivariate Cox regression models, the BL factor associated with the highest risk of developing BCR was PSA ≥ 20 ng/mL. Conversely, the risk of developing BCR was lower for pts who received ADT during BL. Conclusions: This real-world (RW) study evaluates BCR occurrence in pts who underwent RT with a curative intent from a large US database. The study confirms BL PSA as an important prognostic marker for BCR, while use of ADT before RT is associated with a lower risk of BCR. A considerable % of pts with BCR developed mPC (35%) or died (23%) during the study period. Novel treatment strategies are needed to delay BCR and further progression to advanced PC in pts with high-risk localized disease. [Table: see text]

PD16-03 PROGNOSTIC VALUE OF PROSTATE-SPECIFIC ANTIGEN KINETICS DURING TREATMENT OF ADVANCED PROSTATE CANCER WITH ABIRATERONE AND ENZALUTAMIDE: MULTICENTER ANALYSIS

You have accessJournal of UrologyCME1 Apr 2023PD16-03 PROGNOSTIC VALUE OF PROSTATE-SPECIFIC ANTIGEN KINETICS DURING TREATMENT OF ADVANCED PROSTATE CANCER WITH ABIRATERONE AND ENZALUTAMIDE: MULTICENTER ANALYSIS Byeong Jin Kang, Kyung Hwan Kim, Hong Koo Ha, Ja Yoon Ku, Hyeok Jun Goh, Soodong Kim, and Chan Ho Lee Byeong Jin KangByeong Jin Kang More articles by this author , Kyung Hwan KimKyung Hwan Kim More articles by this author , Hong Koo HaHong Koo Ha More articles by this author , Ja Yoon KuJa Yoon Ku More articles by this author , Hyeok Jun GohHyeok Jun Goh More articles by this author , Soodong KimSoodong Kim More articles by this author , and Chan Ho LeeChan Ho Lee More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003271.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: This multicenter study aimed to investigate the prognostic value of prostate-specific antigen (PSA) kinetics during the treatment of advanced Prostate Cancer (PCa) with Abiraterone and Enzalutamide. METHODS: This multicenter retrospective study evaluated 255 patients with advanced PCa treated with Abiraterone and Enzalutamide between September 2013 and May 2022. All the patients used only one of the two drugs. This study analyzed the following clinical variables: age, clinical TNM stage, Gleason grade, HSPC or CRPC, non-metastatic or metastatic, PSA at the initiation of treatment, Time to PSA nadir, Velocity of PSA decline, and PSA nadir after treatment. We analyzed PSA progression, Radiographic progression-free survival (rPFS), and overall survival (OS) with Kaplan-Meier curves and Cox proportional hazard models. We defined PSA progression, rPFS, and OS based on Prostate Cancer Working Group 2 criteria. RESULTS: The number of patients treated with Abiraterone and Enzalutamide were 94 (36.9%) and 161 (63.1%), respectively. Abiraterone showed a better prognosis than Enzalutamide for PSA progression (log-rank, p<0.05) but not for rPFS and OS (log-rank, p=0.11, and p=0.07). The group with a Time to PSA nadir of 3.4 months or longer had a significantly better prognosis in all of PSA progression, rPFS, and OS (log-rank, p<0.05 for each). The group with the Velocity of PSA decline of 3.9 ng/mL/month or less showed a better prognosis in PSA progression (log-rank, p=0.017) and rPFS (log-rank, p=0.027) but not in OS (log-rank, p=0.984). The group with a PSA nadir of 3.2 ng/mL or less had a better prognosis in all PSA progression, rPFS, and OS (log-rank, p<0.05 for each). In Cox regression analysis, PSA nadir and Time to PSA nadir (p<0.05, for each) were significant factors for PSA progression, rPFS, and OS, respectively. However, the Velocity of PSA decline was only significantly associated with OS (p<0.05). CONCLUSIONS: In advanced PCa patients treated with Abiraterone and Enzalutamide, PSA kinetics can be a prognostic indicator of progression and OS. Patients with a longer time to nadir, lower PSA nadir, and slower velocity of PSA decline are more likely to have a better prognosis. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e489 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Byeong Jin Kang More articles by this author Kyung Hwan Kim More articles by this author Hong Koo Ha More articles by this author Ja Yoon Ku More articles by this author Hyeok Jun Goh More articles by this author Soodong Kim More articles by this author Chan Ho Lee More articles by this author Expand All Advertisement PDF downloadLoading ...

Salvage Stereotactic Reirradiation for Local Recurrence in the Prostatic Bed After Prostatectomy: A Retrospective Multicenter Study

BackgroundManagement of local recurrence of prostate cancer (PCa) in the prostatic bed after radical prostatectomy (RP) and radiotherapy remains challenging. ObjectiveTo assess the efficacy and safety of salvage stereotactic body radiotherapy (SBRT) reirradiation in this setting and evaluate prognostic factors. Design, setting, and participantsWe conducted a large multicenter retrospective series that included 117 patients who were treated with salvage SBRT for local recurrence in the prostatic bed after RP and radiotherapy in 11 centers across three countries. Outcome measurements and statistical analysisProgression-free survival (PFS; biochemical, clinical, or both) was estimated using the Kaplan-Meier method. Biochemical recurrence was defined as prostate-specific antigen nadir +0.2 ng/ml, confirmed by a second increasing measure. The cumulative incidence of late toxicities was estimated using the Kalbfleisch-Prentice method by considering recurrence or death as a competing event. Results and limitationsThe median follow-up was 19.5 mo. The median SBRT dose was 35 Gy. The median PFS was 23.5 mo (95% confidence interval [95% CI], 17.6–33.2). In the multivariable models, the volume of the recurrence and its contact with the urethrovesical anastomosis were significantly associated with PFS (hazard ratio [HR]/10 cm3 = 1.46; 95% CI, 1.08–1.96; p = 0.01 and HR = 3.35; 95% CI, 1.38–8.16; p = 0.008, respectively). The 3-yr cumulative incidence of grade ≥2 late GU or GI toxicity was 18% (95% CI, 10–26). In the multivariable analysis, a recurrence in contact with the urethrovesical anastomosis and D2% of the bladder were significantly associated with late toxicities of any grade (HR = 3.65; 95% CI, 1.61–8.24; p = 0.002 and HR/10 Gy = 1.88; 95% CI, 1.12–3.16; p = 0.02, respectively). ConclusionsSalvage SBRT for local recurrence in the prostate bed may offer encouraging control and acceptable toxicity. Therefore, further prospective studies are warranted. Patient summaryWe found that salvage stereotactic body radiotherapy after surgery and radiotherapy allows for encouraging control and acceptable toxicity in locally relapsed prostate cancer.

Oncological and Functional Outcomes for Men Undergoing Salvage Whole-gland Cryoablation for Radiation-resistant Prostate Cancer

BackgroundThere is no consensus on the optimal approach for salvage local therapy in radiation-resistant/recurrent prostate cancer (RRPC). ObjectiveTo investigate oncological and functional outcomes for men treated with salvage whole-gland cryoablation (SWGC) of the prostate for RRPC. Design, setting, and participantsWe retrospectively reviewed our prospectively collected cryosurgery database between January 2002 and September 2019 for men who were treated with SWGC of the prostate at a tertiary referral center. InterventionSWGC of the prostate. Outcome measurements and statistical analysisThe primary outcome was biochemical recurrence–free survival (BRFS) according to the Phoenix criterion. Secondary outcomes included metastasis-free survival, cancer-specific survival, and adverse events. Results and limitationsA total of 110 men with biopsy-proven RRPC were included in the study. Median follow-up for patients without biochemical recurrence (BCR) after SWGC was 71 mo (interquartile range [IQR] 42.3–116). BRFS was 81% at 2 yr and 71% at 5 yr. A higher prostate-specific antigen (PSA) nadir after SWGC was associated with worse BRFS. The median International Index of Erectile Function-5 score was 5 (IQR 1–15.5) before SWGC and 1 (IQR 1–4) after SWGC. Stress urinary incontinence, strictly defined as the use of any pads after treatment, was 5% at 3 mo and 9% at 12 mo. Clavien-Dindo grade ≥3 adverse events occurred in three patients (2.7%). ConclusionsIn patients with localized RPPC, SWGC achieved excellent oncological outcomes with a low rate of urinary incontinence, and represents an alternative to salvage radical prostatectomy. Patients with fewer positive cores and lower PSA tended to have better oncological outcomes following SWGC. Patient summaryFor men with prostate cancer that persists after radiotherapy, a freezing treatment applied to the whole prostate gland can achieve excellent cancer control. Patients who did not have elevated prostate-specific antigen (PSA) at 6 years after this treatment appeared to be cured.

Nadir Prostate-specific Antigen as an Independent Predictor of Survival Outcomes: A Post Hoc Analysis of the PROSPER Randomized Clinical Trial.

This post hoc analysis of PROSPER evaluated the relationship between depth of PSA decline and clinical outcomes in enzalutamide-treated men with nonmetastatic castration-resistant prostate cancer. PROSPER was an international, randomized, double-blind, placebo-controlled, phase 3 trial that demonstrated significantly improved metastasis-free survival and overall survival with androgen deprivation therapy plus enzalutamide vs placebo. A total of 905 enzalutamide-treated men were included in this post hoc analysis. Metastasis-free survival (primary endpoint) and overall survival (secondary endpoint) were evaluated for 4 mutually exclusive subgroups defined by PSA decline: <50% (reference); ≥50% to <90%; ≥90%, nadir ≥0.2 ng/mL; and ≥90%, nadir <0.2 ng/mL. Medians and 95% confidence intervals were determined using a 12-month landmark analysis; hazard ratios and P values were based on an unstratified Cox proportional analysis model. In enzalutamide-treated men, PSA declines of <50%, ≥50% to <90%, ≥90% with nadir ≥0.2 ng/mL, and ≥90% with nadir <0.2 ng/mL were associated with median metastasis-free survival in months (95% confidence intervals) of 22.1 (14.8-not reached), 34.2 (29.4-not reached), 36.6 (33.4-not reached), and not reached, respectively, and overall survival in months (95% confidence intervals) of 40.8 (31.7-44.9), 54.4 (49.0-67.0), 64.3 (63.4-not reached), and not reached, respectively. There was a statistically significant correlation between greater depth of PSA decline and improved clinical outcomes, suggesting a previously underappreciated relationship between changes in PSA levels and clinical outcomes in nonmetastatic castration-resistant prostate cancer.

Irreversible electroporation for prostate cancer using PSMA PET-CT.

To demonstrate the clinical usefulness of prostate-specific membrane antigen (PSMA) positron emission tomography (PET) computerized tomography (CT) for irreversible electroporation (IRE) in prostate cancer patients. From January to May 2021, 17 men were diagnosed with localized prostate cancer through preoperative mpMRI and [18F] florastamin PSMA PET-CT imaging, followed by transperineal MRI-ultrasound fusion-guided biopsy. The patients underwent IRE focal therapy at the target lesions under general anesthesia. To evaluate the treatment outcome, serum prostate-specific antigen (PSA) levels were followed up in the 1st, 3rd, 6th, 9th, 12th months, and mpMRI was taken in the 1st and 12th months, followed by MR fusion biopsy in the 12th month post-IRE. The mean age of the patients was 66.1±9.3 with a median PSA of 7.5ng/ml. After the treatment, PSA nadir was 4.06±3.4, and 11 (64.7%) achieved decline of PSA more than 50% from the baseline. Rate of negative biopsy for prostate cancer is 88% (15/17) at 12monthsMR fusion biopsy after the IRE treatment. Among the relapsed cases, 1 (6.9%) patient recurred at margin of treated area, and 1 (6.9%) patient was from outfield recurrence. When excluding initial four patients, none of the patients had cancer recur. When treating with IRE focal therapy, PSMA-PET CT is a potentially valuable diagnostic approach for localizing prostate cancer; it supports the detection of lesions with conventional mpMRI, enabling to perform the procedure more completely.

Low hemoglobin and PSA kinetics are prognostic factors of overall survival in metastatic castration-resistant prostate cancer patients

The objective of this study was to identify the prognostic factors and to propose a new risk model in metastatic castration-resistant prostate cancer (mCRPC) patients. The clinical data were retrospectively obtained for 102 mCRPC patients who received cancer treatment between 2005 and 2018 at the University of Tokyo Hospital. We investigated clinical and pathological parameters, including prostate-specific antigen (PSA) kinetic profiles under androgen deprivation treatment, and identified predictors of overall survival (OS). The median age and PSA were 73 (Interquartile range [IQR], 68–79) years and 5.00 (IQR, 2.77–13.6) ng/ml. The median follow-up was 34 (IQR, 17–56) months. In univariate analysis, ‘lymph node metastasis’, ‘Hemoglobin (Hb)’, ‘Time to nadir PSA (TNPSA)’, ‘PSA doubling time (PSADT)’, ‘Time to CRPC’, and ‘presence of pain’ were prognostic factors. Multivariate analysis identified ‘Hb < 11 g/dL’, ‘TNPSA < 7 months’ and ‘PSADT < 5 months’ as independent prognostic factors of OS. The high-risk group (patients with two or three factors) demonstrated shorter OS (23 vs. 50 months) with an increased risk of death (HR = 2.997; 95% CI 1.632–5.506; P = 0.0004). The proposed risk stratification model may contribute to the prediction of survival and provide supportive information in treatment decision-making.

Nadir prostate-specific antigen after salvage cryotherapy as a potential prognostic factor for oncologic outcomes

Nadir prostate-specific antigen after salvage cryotherapy as a potential prognostic factor for oncologic outcomes

Prognostic significance of nadir PSA value and time to nadir PSA in patients with metastatic castration-naive prostate cancer receiving first-line hormonotherapy.

The current study aimed to evaluate the effect of the time duration to reach the lowest prostate-specific antigen (PSA) from the onset of first-line hormonal treatment (time to nadir PSA, TTNpsa) on survival in castration-naive metastatic prostate cancer (CN-MPC) patients. Eighty patients who had PSA response >80% with first-line hormonal therapy (luteinizing hormone-releasing hormone, LH-RH analog +/- bicalutamide) were included in this study. Under androgen deprivation therapy (ADT), a significant positive correlation was found between TTNpsa, nadir PSA (Npsa) duration, and progression-free survival (PFS) ( p < 0.001) and overall survival (OS) ( p < 0.001). There was no correlation between TTNpsa and Npsa duration. TTNpsa and Npsa durations were independently correlated with PFS and OS. In patients with TTNpsa value ≥19 weeks, the median PFS was 126 (95% CI, 68-184) weeks compared with TTNpsa <19-week group in which the median PFS was 44 (95% CI, 26-62) weeks ( p = 0.033). In patients with TTNpsa value ≥19 weeks, the median OS was 242 (95% CI, 169-315) weeks compared with TTNpsa <19-week group in which the OS was 156 (95% CI, 89-223) weeks ( p = 0.018). The median nadir PSA value was 1 ng/mL. The median PFS was significantly longer in the patient group with ≤1 ng/mL (137 weeks, 95% CI, 50-224) compared with the group with >1 ng/mL (41 weeks, 95% CI, 34-48) ( p < 0.001). The median OS was significantly longer in the patient group with nadir PSA ≤1 ng/mL (296 weeks, 95% CI, 220-272) compared to the group with >1 ng/mL (131 weeks, 95% CI, 84-178) ( p = 0.002). In patients with nadir PSA ≤1 ng/mL ( n = 40), there was no relationship between TTNpsa and Npsa duration with both PFS and OS. However, in patients with nadir PSA >1 ng/mL ( n = 40) subgroup, there was a significant positive correlation between TTNpsa and PFS, and OS ( p < 0.001, P = 0.016, respectively). In CN-MPC who received first-line ADT, especially in the group with the nadir PSA value >1 ng/mL, the duration of TTNpsa was positively correlated with PFS and OS.

Clinical value of normal saline injection for expansion of the anterior perirectal space during prostate cryoablation.

The objective of this study is to describe the technique and evaluate the clinical value of normal saline (NS) injection for expanding the anterior perirectal space during prostate cryoablation for prostate cancer (PCa) patients. PCa patients who received cryoablation between August 2014 and December 2019 were enrolled, and the technique of NS injection was adopted. The complications were evaluated. The prostate-specific antigen (PSA) nadir and biochemical progression-free survival (bPFS) were measured in localized PCa patients who received cryoablation as the primary treatment. A total of 159 PCa patients were included. Among 147 patients with the data of anterior perirectal space, the median (interquartile range [IQR]) distance of estimated iceball edge beyond the prostatic capsule was 8.3 (7.0-10.0) mm. No cases of urethrorectal fistula were reported; 29 patients developed urinary retention and 25 patients presented scrotal edema. All complications below Clavien-Dindo grade IIIb disappeared within 7 weeks after surgery. Urinary incontinence was reported in 6 patients. Among localized PCa patients, the median (IQR) follow-up time was 56.5 (36.0-73.5) months. The estimated 5-year bPFS was 82.3% overall, 82.8% for low-to intermediate-risk PCa patients, and 82.1% for high-risk PCa patients. For 52 patients received cryoablation alone, the median (IQR) PSA nadir was 0.147 (0.027-0.381) ng/mL. The technique of NS injection for expanding the anterior perirectal space during cryoablation surgery could avoid urethrorectal fistula and might benefit localized PCa patients with lower PSA nadir and longer bPFS.

Prostate-specific Antigen Kinetics During Androgen-deprivation Therapy Predict Response to Enzalutamide in Metastatic Castration-resistant Prostate Cancer.

No practical predictive biomarkers exist to date for the response to androgen receptor-axis targeted (ARAT) therapies in metastatic castration-resistant prostate cancer (mCRPC). This study investigated whether prostate-specific antigen (PSA) kinetics in primary androgen-deprivation therapy for advanced hormone-sensitive prostate cancer may be associated with the response to ARAT agents in mCRPC. This study assessed 102 patients with mCRPC treated with enzalutamide or abiraterone to evaluate the associations between clinical outcomes and PSA kinetics, including the ratio of initial to nadir PSA (I/N PSA) level in primary combined androgen blockade. The PSA response was defined as a ≥50% decrease at 3 months from baseline in patients with mCRPC. In patients treated with enzalutamide, the optimal cut-off I/N PSA value for PSA response was 531 ng/ml (sensitivity=66.7%, specificity=88.2%, area under the curve=0.73, using a receiver operating characteristic curve). The PSA response was 83.3% and 25.0% in the high and low I/N PSA groups, respectively. The median overall survival and radiographic progression-free survival from enzalutamide initiation were longer for the high compared to the low I/N PSA group. Multivariate analysis revealed I/N PSA (hazard ratio=0.275, p=0.026) as an independent risk factor for overall survival in the patients treated with enzalutamide. In contrast, I/N PSA showed no predictive ability for PSA response in patients treated with abiraterone. In patients with mCRPC, I/N PSA can be a practical predictive biomarker for response to the ARAT agent enzalutamide.

Ten-year outcomes of whole-pelvic intensity-modulated radiation therapy for prostate cancer with regional lymph node metastasis.

Management of pelvic node-positive prostate cancer has been challenging and controversial. We conducted a study to evaluate the outcomes of whole-pelvic (WP) simultaneous integrated boost (SIB) intensity-modulated radiation therapy (IMRT) combined with androgen deprivation therapy (ADT). A total of 67 consecutive patients with cT1c-4N1M0 prostate cancer were definitively treated by WP SIB-IMRT. Neoadjuvant ADT (median: 8.3months) was administered in all cases. WP SIB-IMRT was designed to simultaneously deliver 78, 66.3, and 58.5Gy in 39 fractions to the prostate plus seminal vesicles, metastatic lymph nodes (LNs), and the pelvic LN region, respectively. Adjuvant ADT (median: 24.7months) was administered in 66 patients. The median follow-up period was 81.6months (range: 30.5-160.7). Biochemical relapse-free, overall, and prostate cancer-specific survival rates at 10 years were 59.8%, 79.6%, and 86.3%, respectively. Loco-regional recurrence was not observed. Being in International Society of Urological Pathology grade group 5 and having a posttreatment detectable nadir prostate-specific antigen (PSA) level (≥0.010 ng/ml) were significantly associated with worse prostate cancer-specific survival and progression of castration resistance. The 10-year cumulative incidence rates of grade 2 and 3 late toxicities were, respectively, 1.5% and 0% for genitourinary, 0% and 1.5% for gastrointestinal events. No grade 4 acute or late toxicities were observed. WP SIB-IMRT can be safely administered to patients with pelvic node-positive prostate cancer. Since grade group 5 and detectable nadir PSA levels are risks for castration resistance, we may need to increase the intensity of treatment for such cases.

Adjusting the duration of androgen deprivation therapy (ADT) based on nadir PSA for high risk localized prostate cancer patients treated with definitive external beam radiation therapy and ADT

BackgroundA nadir Prostate-Specific Antigen (nPSA) of 0.06 ng/mL has been shown to be a strong independent predictor of biochemical recurrence-free survival (bRFS) in patients with intermediate or high-risk (HR) prostate cancer treated with definitive external beam radiation therapy (RT) and androgen deprivation therapy (ADT). We aimed to examine the association between the duration of ADT and bRFS in HR localized prostate cancer, based on nPSA.MethodsBetween 1998 and 2015, 204 patients with HR localized prostate cancer were identified. Of them, 157 patients (77.0%) reached the desired nPSA of < 0.06 ng/mL (favorable group), while 47 (23.0%) did not (unfavorable group). Duration of ADT varied among patients depending on physician preference, patient tolerance, and/or compliance. Survival outcomes were calculated using Kaplan–Meier methods and predictors of outcomes using multi-variable cox regression model.ResultsIn the favorable group, ADT for at least 12 months lead to superior bRFS compared to ≤ 9 months of ADT (P = 0.036). However, no significant difference was seen when examining the value of receiving ADT beyond 12, 18, or 24 months, respectively. On univariate analysis for bRFS, the use of ADT for at least 12 months was significant (P = 0.012) as well as time to nadir PSA (tnPSA), (≤ 6 vs > 6 months); (P = 0.043). The presenting T stage was borderline significant (HR 3.074; 95% CI 0.972–9.719; P = 0.056), while PSA at presentation, Gleason Score and age were not. On multivariate analysis, the use of ADT for 12 months (P = 0.012) and tnPSA (P = 0.037) remained significant. In the unfavorable group, receiving ADT beyond 9 and 12 months was associated with improved bRFS (P = 0.044 and 0.019, respectively). However, beyond 18 months, there was no significant difference.ConclusionIn HR localized prostate cancer patients treated with definitive RT and ADT, the total duration of ADT may be adjusted according to treatment response using nPSA. In patients reaching a nPSA below 0.06 ng/mL, a total of 12 months of ADT may be sufficient, while in those not reaching a nPSA below 0.06 ng/mL, a total duration of 18 months is required.

Head-to-head comparisons of [68Ga]Ga-PSMA-11 PET/CT, multiparametric MRI, and prostate-specific antigen for the evaluation of therapeutic responses to neoadjuvant chemohormonal therapy in high-risk non-metastatic prostate cancer patients: a prospective study.

The optimal tool to evaluate the tumour therapeutic responses to neoadjuvant chemohormonal therapy (NCHT) in patients with high-risk non-metastatic prostate cancer (PCa) remains uncertain. We compared the role of [68Ga]-labeled prostate-specific membrane antigen (PSMA)-11 positron emission tomography/computerized tomography ([68Ga]Ga-PSMA-11 PET/CT), multiparametric MRI (mpMRI), and prostate-specific antigen (PSA) and assessed the practical value of the recent European Association of Urology and European Association of Nuclear Medicine (EAU/EANM) recommended criteria of PSMA PET/CT to evaluate the therapeutic responses to NCHT in patients with high-risk non-metastatic PCa. This prospective study included 72 high-risk non-metastatic PCa patients receiving NCHT followed by radical prostatectomy from June 2021 to March 2022. PSA testing, [68Ga]Ga-PSMA-11 PET/CT, and mpMRI scanning were conducted in all patients before and after NCHT. Therapeutic responses to NCHT were evaluated with PSA, RECIST 1.1, PERCIST 1.0, and EAU/EANM recommended criteria. Postoperative pathological results were considered the reference standard. A favourable pathological response was defined as pathologic complete remission (pCR) or minimal residual disease (MRD). Diagnostic accuracy was assessed by sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), positive predictive value (PPV), negative predictive value (NPV), and Cohen's kappa index. Logistic regression analysis was used to determine the independent predictive value of [68Ga]Ga-PSMA-11 PET/CT-derived parameters. All cases experienced a marked decrease in PSA levels after NCHT. Twenty-four (33.33%) cases experienced a favourable pathological response, including five (6.94%) cases of pCR and 19 (26.39%) cases of MRD. According to the results of [68Ga]Ga-PSMA-11 PET/CT, EAU/EANM recommended criteria indicated that 20 (27.78%) cases had a CR, whereas PERCIST 1.0 criteria indicated that 23 (31.94%) cases had a CR. There was a strong association between EAU/EANM recommended criteria and PERCIST 1.0 criteria (Pearson's R=0.857). The sensitivity (75.00%, 79.17% vs. 58.33%, 58.33%), specificity (95.83%, 91.67% vs. 83.33%, 68.75%), PLR (18.00, 9.50 vs. 3.50, 1.87), NLR (0.26, 0.23 vs. 0.50, 0.61), PPV (90.0%, 82.6% vs. 63.6%, 48.3%), and NPV (88.5%, 89.8% vs. 80.0%, 76.7%) of [68Ga]Ga-PSMA-11 PET/CT (including EAU/EANM recommended criteria and PERCIST 1.0 criteria) to predict favourable pathological responses were all superior to those of mpMRI and nadir PSA. The kappa index to predict a favourable pathological response was 0.257 for PSA, 0.426 for RECIST 1.1, 0.716 for PERCIST 1.0, and 0.739 for EAU/EANM recommended criteria. Multivariate logistic analysis revealed that the post-NCHT maximum standardized uptake value (SUVmax) before radical prostatectomy was an independent predictor of a favourable pathological response to NCHT. [68Ga]Ga-PSMA-11 PET/CT had a better concordance with a favourable pathological response to NCHT compared with nadir PSA and mpMRI. EAU/EANM recommended criteria and PERCIST 1.0 criteria performed equally to identify pathological responders when [68Ga]Ga-PSMA-11 PET/CT was used as a therapeutic response assessment tool.

Evaluation of factors predicting response to abiraterone acetate in metastatic castration-resistant prostate cancer: A prospective study

Background/Objectives: In the current era, abiraterone acetate is mainstay of the treatment strategies of castration-resistant prostate cancer and proven to prolong overall survival. We aimed to prospectively identify factors associated with duration of response to abiraterone. Patients and methods: All metastatic castration-resistant prostate cancer patients eligible for abiraterone were included in the study from February 2019 till March 2020. All baseline data and potential factors associated recorded and follow-up with prostate-specific antigen (PSA), and required investigations were done at 1 month interval. Duration of PSA response was recorded, and patients were divided in five groups on the basis of duration of response. Univariate and multivariate analyses of potential factors were done, and data analysis was done with SPSS (Statistical Package for the Social Sciences) version 21.0. Results: In this study, after univariate analysis, seven factors were associated with longer duration of response to abiraterone. These were PSA at diagnosis (hazard ratio (HR) = −1.011 (95% confidence interval (CI) = 1.003–1.020), p-value = 0.008), PSA at start of abiraterone (HR = −1.018 (95% CI = 1.011–1.025), p-value = 0.0001), nadir PSA (HR = −1.063 (95% CI = 1.024–1.104), p-value = 0.001), prostate-specific antigen doubling (PSAD) time (HR = −0.745 (95% CI = 0.672–0.827), p-value = 0.001), raised alkaline phosphatase (ALP) (HR = −1.002 (95% CI = 1.001–1.003), p-value = 0.001), neutrophil/lymphocyte ratio (NLR) (HR = −2.16 (95% CI = 1.672–2.81), p-value = 0.001) and &lt;5 bone metastasis (HR = −0.235 (95% CI = 0.130–0.422), p-value = 0.01). But after multivariate analysis, nadir PSA achieved, PSAD, NLR and ⩽5 bone metastasis were predictors of better response to abiraterone. Conclusion: This study had identified that less nadir PSA achieved, long PSAD time, low NLR and limited number of skeletal metastases were potential factors for better PSA response to abiraterone. Level of evidence: 1

Prostate-specific antigen nadir within 1 year of radiotherapy combined with hormone therapy predicts cancer-specific mortality and biochemical recurrence-free survival in prostate cancer patients

BackgroundIn this study, we investigated the ability of prostate-specific antigen (PSA) 12 months after (nPSA12) external beam radiotherapy (EBRT) combined with androgen deprivation therapy (ADT) to predict biochemical recurrence-free survival (BRFS), overall survival (OS), and prostate cancer-specific mortality (PCSM) in intermediate- and high-risk prostate cancer patients.MethodsWe retrospectively reviewed the clinical data of 338 intermediate- and high-risk prostate cancer patients treated with EBRT with ADT at our institution between 2000 and 2018. The median radiation dose was 76 Gy, the median initial PSA level was 17 ng/mL (range, 1–228 ng/mL), and the median duration of ADT was 24 months (range, 6–167 months). The median PSA level 1 months after EBRT was 0.06 ng/mL (range, 0–25.6 ng/mL). Univariate and multivariate analyses were performed. Patient survival was assessed using the Kaplan-Meier method and Cox proportional hazards regression analyses.ResultsThe median follow-up time was 5 years (range, 1–20 years). Multivariate analysis revealed that nPSA was an independent and significant factor associated with OS, PCSM, and BRFS (P = 0.008, P = 0.001, P = 0.04). Furthermore, the time to nPSA12 was an independent predictor of PCSM and BRFS (P = 0.042, P = 0.021). Pelvic irradiation was also significantly associated with worse OS and PCSM (P = 0.004, P = 0.01). Additionally, age (≤ 70 or > 70 years) and hormone therapy duration (6 months, 1–3 years, or > 3 years) were significantly associated with OS and PCSM, respectively (P = 0.004, P = 0.02). For high risk, nPSA and nPSA12 were an independent predictor for BRFS. (P = 0.021, P = 0.029)ConclusionThe nPSA12 level of > 0.06 ng/mL may independently predict worse PCSM and BRFS in intermediate- and high-risk prostate cancer patients undergoing EBRT and ADT. Additionally, for high risk, nPSA > 0.06 ng/mL and nPSA12 > 0.06 ng/mL may independently predict worse BRFS.

Racial Analysis of Clinical and Biochemical Outcomes in Patients With Prostate Cancer Treated With Low-Dose-Rate Brachytherapy

Black men in the United States experience significantly higher incidence of and mortality from prostate cancer (PCa) than non-Black men. The cause of this disparity is multifactorial, though inequitable access to curative radiation modalities, including low-dose-rate (LDR) brachytherapy, may contribute. Despite this, there are few analyses evaluating the potential of different radiation therapies to mitigate outcome disparities. Therefore, we examined the clinical outcomes of Black and non-Black patients treated with definitive LDR brachytherapy for PCa. Data were collected for all patients treated with definitive LDR brachytherapy between 2005 and 2018 on a retrospective institutional review board approved protocol. Pearson χ2 analysis was used to assess demographic and cancer differences between Black and non-Black cohorts. Freedom from biochemical failure (FFBF) was calculated using Kaplan-Meier analysis. Univariate and multivariate analyses were used to identify factors predictive of biochemical failure. One hundred and sixty-seven patients were included in the analysis (Black: n=81; 48.5%) with a median follow-up of 88.4 months. Black patients were from lower income communities (P < .01), had greater social vulnerability (P < .01), and had a longer interval between diagnosis and treatment (P=.011). Overall cumulative FFBF was 92.3% (95% confidence interval [CI], 87.8%-96.8%) at 5 years and 87.7% (95% CI, 82.0%-93.4%) at 7 years. There was no significant difference in FFBF in Black and non-Black patients (P=.114) and Black race was not independently predictive of failure (hazard ratio, 1.51; 95% CI, 0.56-4.01; P=.42). Overall survival was comparable between racial groups (P=.972). Only nadir prostate-specific antigen was significantly associated with biochemical failure on multivariate (hazard ratio, 3.57; 95% CI, 02.44-5.22; P < .001). Black men treated with LDR brachytherapy achieved similar FFBF to their non-Black counterparts despite poorer socioeconomic status. This suggests that PCa treatment with brachytherapy may eliminate some disparities in clinical outcomes.

Salvage external beam radiotherapy after HIFU failure in localized prostate cancer: A single institution experience

High-intensity focused ultrasound (HIFU) remains investigational as primary treatment for localized prostate cancer but is sometimes offered to select patients. At HIFU failure, data guiding salvage treatment is limited to small retrospective series with short follow-up. We evaluated our institutional experience using salvage radiation therapy (SRT) after HIFU failure. We conducted a retrospective analysis of patients with local failure post-HIFU who received salvage image-guided external beam radiation therapy (EBRT) delivered via intensity-modulated radiotherapy (IMRT). Our primary endpoint was biochemical failure-free survival (bFFS) defined as prostate-specific antigen (PSA) nadir + 2 ng/mL. Secondary endpoints included metastasis-free survival (MFS) and overall survival (OS). Endpoints were evaluated using Kaplan-Meier analysis. From 2013 to 2018, 12 out of 96 patients treated with primary HIFU received SRT via conventional or moderate hypofractionation. Median time from HIFU to SRT was 13.5 months. Seven patients had stage migration to high-risk disease at the time of SRT. Mean PSA prior to SRT was 8.2ug/L and mean nadir post-SRT was 1.2ug/L. Acute International Prostate Symptom Score (IPSS) as well as International Index of Erectile Dysfunction (IIEF) scores were similar to baseline (p = 0.5 and 0.1, respectively). Late toxicities were comparable to those reported after primary EBRT for localized prostate cancer. At a median follow-up of 46 months, the OS was 100%. The 5-year bFFS and MFS were both 83.3%. To our knowledge, we report one of the largest series on contemporary SRT post HIFU failure. We show that SRT is feasible, effective and carries no additional acute or delayed toxicity.