Start Of Androgen Deprivation Therapy Research Articles

1596O Decipher mRNA score for prediction of survival benefit from docetaxel at start of androgen deprivation therapy (ADT) for advanced prostate cancer (PC): An ancillary study of the STAMPEDE docetaxel trials

1596O Decipher mRNA score for prediction of survival benefit from docetaxel at start of androgen deprivation therapy (ADT) for advanced prostate cancer (PC): An ancillary study of the STAMPEDE docetaxel trials

Population-based study of disease trajectory after radical treatment for high-risk prostate cancer.

To investigate long-term disease trajectories among men with high-risk localized or locally advanced prostate cancer (HRLPC) treated with radical radiotherapy (RT) or radical prostatectomy (RP). Men diagnosed with HRLPC in 2006-2020, who received primary RT or RP, were identified from the Prostate Cancer data Base Sweden (PCBaSe) 5.0. Follow-up ended on 30 June 2021. Treatment trajectories and risk of death from prostate cancer (PCa) or other causes were assessed by competing risk analyses using cumulative incidence for each event. In total, 8317 men received RT and 4923 men underwent RP. The median (interquartile range) follow-up was 6.2 (3.6-9.5) years. After RT, the 10-year risk of PCa-related death was 0.13 (95% confidence interval [CI] 0.12-0.14) and the risk of death from all causes was 0.32 (95% CI 0.31-0.34). After RP, the 10-year risk of PCa-related death was 0.09 (95% CI 0.08-0.10) and the risk of death from all causes was 0.19 (95% CI 0.18-0.21). The 10-year risks of androgen deprivation therapy (ADT) as secondary treatment were 0.42 (95% CI 0.41-0.44) and 0.21 (95% CI 0.20-0.23) after RT and RP, respectively. Among men who received ADT as secondary treatment, the risk of PCa-related death at 10 years after initiation of ADT was 0.33 (95% CI 030-0.36) after RT and 0.27 (95% CI 0.24-0.30) after RP. Approximately one in 10 men with HRLPC who received primary RT or RP had died from PCa 10 years after diagnosis. Approximately one in three men who received secondary ADT, an indication of PCa progression, died from PCa 10 years after the start of ADT. Early identification and aggressive treatment of men with high risk of progression after radical treatment are warranted.

Systemic interrogation of immune-oncology-related proteins in patients with locally advanced prostate cancer undergoing androgen deprivation and intensity-modulated radiotherapy

PurposeThe primary objective was to establish whether blood-based leucine-rich alpha-2-glycoprotein (LRG1) can predict outcomes in patients with locally advanced prostate cancer undergoing androgen-deprivation therapy (ADT) and radiotherapy (RT) and to determine how it may relate to 92 immune-oncology (I-O)-related proteins in this setting.MethodsBaseline blood level of LRG1 from patients treated with ADT and RT enrolled in the CuPCa (n = 128) and IMRT (n = 81) studies was measured using ELISA. A longitudinal cohort with matched blood samples from start of ADT, start of RT, and end of RT protocol from 47 patients from the IMRT cohort was used to establish levels of I-O proteins by high-multiplexing Proximal Extension Assay by Olink Proteomics.Statistical analyses using Kaplan–Meier, Cox regression, and LIMMA analyses were applied to predict the prognostic value of LRG1 and its correlation to I-O proteins.ResultsHigh baseline levels of LRG1 predicted a low frequency of treatment failure in patients undergoing ADT + RT in both the CuPCa and the IMRT cohorts. LRG1 was moderately correlated with CD4, IL6, and CSF1. We identified I-O proteins predicting metastatic failure (MF) at different timepoints.ConclusionLRG1 biomarker is associated with I-O proteins and can be used to improve stratification and monitoring of prostate cancer patients undergoing ADT + RT. This work will require further in-depth analyses in independent cohorts with treatment outcome data.Graphical abstractStudy outline. A) Study cohorts. B) Sampling time points in a longitudinal cohort.

Biochemical progression free and overall survival among Black men with stage IV prostate cancer in South Africa: Results from a prospective cohort study.

Men of African descent are disproportionately affected by prostate cancer (PCa), and many have metastatic disease at presentation. In South Africa (SA), androgen deprivation therapy (ADT) is the first-line treatment for stage IV PCa. To identify predictors of overall survival (OS) in Black South African men with stage IV PCa treated with ADT. Men diagnosed with prostate cancer (3/22/2016-10/30/2020) at Chris Hani Baragwanath Academic Hospital in Soweto, Johannesburg, were recruited for the Men of African Descent with Cancer of the Prostate study. We included men with newly diagnosed stage IV PCa treated with ADT who had a prostate-specific antigen (PSA) level drawn prior to initiation of ADT and had ≥1 PSA drawn ≥12 weeks after ADT start. We used Kaplan-Meier statistics to estimate OS and Cox regression models to identify predictors of OS. Of the 1097 men diagnosed with prostate cancer, we included 153 men with stage IV PCa who received ADT and met PSA requirements. The median age was 68.0 years (interquartile range 64-73 years). Median OS from time of ADT initiation was 3.39 years (95% confidence interval (CI): 3.14%-noncalculable), while biochemical progression-free survival was 2.36 years (95% CI: 2.03%-3.73%). Biochemical progression (HR 3.52, 95% CI: 1.85%-6.70%), PSA nadir level >4 ng/mL (HR 3.77, 95% CI: 1.86%-7.62%), alkaline phosphatase level at diagnosis >150 IU/dL (HR 3.09, 95% CI: 1.64%-5.83%), and hemoglobin at diagnosis <13.5 g/dL (HR 2.90, 95% CI: 1.28%-6.56%) were associated with worse OS. In this study, we identified factors associated with poor OS among Black South African men with stage IV PCa treated with ADT. These factors may be useful in identifying patients for upfront treatment escalation, including the use of docetaxel chemotherapy or escalation of therapy at the time of biochemical progression. In this study, we found that high alkaline phosphatase level, anemia at diagnosis, and high PSA nadir after initiation of androgen deprivation therapy are associated with worse overall survival among Black South African men treated with androgen deprivation therapy for metastatic prostate cancer.

Assessing racial differences in time to treatment escalation following androgen-deprivation therapy among veterans with prostate cancer.

5078 Background: Androgen deprivation therapy (ADT) is standard care first-line (1L) systemic treatment for advanced and metastatic prostate cancer (PC). Currently, there are no population-level studies assessing the duration of 1L ADT and time to treatment escalation (chemotherapy [CT], novel hormonal therapy [NHT], or non-steroidal antiandrogen [NSAA]). Methods: We performed a retrospective population-level analysis to assess the association between race and time to treatment escalation after ADT in the Veterans Affairs Health Care System. From 2001-2021, 164,477 patients (pt) diagnosed with PC and treated with ADT alone were identified. Baseline demographic and clinical characteristics were sorted by race: Non-Hispanic White (NHW), Non-Hispanic Black (NHB), Hispanic, Other and compared among groups using chi square tests for categorical variables and Kruskal-Wallis tests for continuous variables. The primary outcome was time from ADT to treatment escalation, defined as receipt of NHT, NSAA, or CT. Men with no evidence of treatment escalation were censored at time of death or most recent visit. We estimated 5-year event rates by race using Kaplan-Meier (KM) analyses. Univariable and multivariable Cox proportional hazards models were used to test the association between race and time to treatment escalation with time of ADT as time zero. Multivariable models were adjusted for age, year, time from PC diagnosis to ADT, Charlson Comorbidity Index and BMI at ADT start along with PSA, testosterone level, and receipt of radiation therapy (RT) prior to ADT. Results: NHB were youngest (p&lt;0.001), started ADT in more recent years (p&lt;0.001), had the highest pre-ADT PSA (p&lt;0.001) and testosterone levels (p&lt;0.001), the most comorbidities (p&lt;0.001), and the highest rate of RT prior to ADT (p&lt;0.001) relative to other groups. During a median (Q1, Q3) follow-up of 55.2 (25.0, 102.4) months, 31,288 pt (19%) had treatment escalation, of which 12,093 (39%) were NHTs, 14,842 (47%) were NSAAs, 3,895 (12%) were CT and 458 (2%) were other 2nd line therapies. Compared to NHW, NHB had significantly lower rate of treatment escalation in univariable (HR=0.89, 95% CI=0.87-0.92) and multivariable analysis (HR=0.82, 95% CI=0.80-0.84). KM estimates at 5-year for the percent free from escalation was 80.5 (80.2-80.8%) in NHW vs. 83.0 (82.6-83.4%) in NHB. Rate of treatment escalation was similar for Hispanics and other races compared to NHW, with 5-year KM estimates of 81.0 (80.3-81.7%) and 81.0 (80.0-82.0%) for Hispanics and other races, respectively. Conclusions: This study assessing racial differences in time to treatment escalation of men receiving 1L ADT found that NHB had a significantly lower rate of treatment escalation. Whether this decreased rate of treatment escalation among NHB men represents improved outcomes (i.e. lower risk of progression) or undertreatment requires further study.

Variations in the Uptake of Active Surveillance for Prostate Cancer and Its Impact on Outcomes

BackgroundRegional differences in active surveillance (AS) uptake for prostate cancer (PC) illustrate an inequality in treatment strategies. ObjectiveTo examine the association between regional differences in AS uptake and transition to radical treatment, start of androgen deprivation therapy (ADT), watchful waiting, or death. Design, setting, and participantsA Swedish population-based cohort study was conducted including men in the National Prostate Cancer Register in Sweden with low-risk or favorable intermediate-risk PC, starting AS from January 1, 2007 and continuing till December 31, 2019. InterventionRegional tradition of low, intermediate, or high proportions of immediate radical treatment. Outcomes measurements and statistical analysisProbabilities of transition from AS to radical treatment, start of ADT, watchful waiting, or death from other causes were assessed. Results and limitationsWe included 13 679 men. The median age was 66 yr, median PSA 5.1 ng/ml, and median follow-up 5.7 yr. Men from regions with a high AS uptake had a lower probability of transition to radical treatment (36%) than men from regions with a low AS uptake (40%; absolute difference 4.1%; 95% confidence interval [CI] 1.0–7.2), but not a higher probability of AS failure defined as the start of ADT (absolute difference 0.4%; 95% CI –0.7 to 1.4). There were no statistically significant differences in the probability of transition to watchful waiting or death from other causes. Limitations include uncertainty in the estimation of remaining lifetime and transition to watchful waiting. ConclusionsA regional tradition of a high AS uptake is associated with a lower probability of transition to radical treatment, but not with AS failure. A low AS uptake suggests overtreatment. Patient summaryThere are considerable regional differences in active surveillance (AS) uptake for prostate cancer. This study compared the outcomes of AS in different regions and found no association between AS uptake and failure of AS; it suggests that a low AS uptake indicates overtreatment.

Major adverse cardiovascular events after androgen deprivation therapy in patients with prostate cancer with hypercholesterolemia.

348 Background: Prostate cancer (PCa) patients treated with androgen deprivation therapy (ADT) may experience major adverse cardiovascular events (MACE). It is unclear how much of MACE is caused by ADT itself. High cholesterol has been associated with lower MACE risk in older men, not on statin therapy. This study evaluates MACE risk after ADT initiation for patients with and without hypercholesterolemia using real-world data. Methods: US electronic medical records (2010-2020) of PCa patients (n=45,059) receiving LHRH agonist/antagonist injections were analyzed to calculate the risk of MACE since ADT initiation in patients with and without hypercholesterolemia. Hypercholesterolemia was defined as having taken hypercholesterolemia medication or diagnosis with hypercholesterolemia prior to the first MACE event after ADT start. Exclusion criteria included lack of ADT initiation date or MACE within six months prior to ADT initiation. MACE was defined as myocardial infarction, stroke, and death from any cause. Kaplan-Meier event-free survival curves and cox regression were used to compare MACE risk between patients with and without hypercholesterolemia. Results: The dataset contained 178,388 LHRH injection entries and 7,681 MACE. MACE risk was only 1.8% lower (19.0% vs 20.8%) after 4 years for patients with hypercholesterolemia compared to those without (across 10 years, unadjusted: HR=0.88, 95% CI [0.83, 0.92] and adjusted: HR=0.85, 95% CI [0.77, 0.94]). Conclusions: Patients with hypercholesterolemia appear to have slightly lower MACE rates. This may be due to the use of statins, which can reduce the incidence of CV events in a general population. Our analysis of data over the most recent decade from ~45,000 PCa patients is likely an accurate reflection of the real world. Clinicians should monitor PCa patients with underlying CV risk factors and help educate them on lifestyle changes that could impact treatment outcomes.

Linac-based stereotactic salvage reirradiation for intraprostatic prostate cancer recurrence: toxicity and outcomes

BackgroundThe rates of local failure after curative radiotherapy for prostate cancer (PC) remain high despite more accurate locoregional treatments available, with one third of patients experiencing biochemical failure and clinical relapse occurring in 30–47% of cases. Today, androgen deprivation therapy (ADT) is the treatment of choice in this setting, but with not negligible toxicity and low effects on local disease. Therefore, the treatment of intraprostatic PC recurrence represents a challenge for radiation oncologists. Prostate reirradiation (Re-I) might be a therapeutic possibility. We present our series of patients treated with salvage stereotactic Re‑I for intraprostatic recurrence of PC after radical radiotherapy, with the aim of evaluating feasibility and safety of linac-based prostate Re‑I.Materials and methodsWe retrospectively evaluated toxicities and outcomes of patients who underwent salvage reirradiation using volumetric modulated arc therapy (VMAT) for intraprostatic PC recurrence. Inclusion criteria were age ≥ 18 years, histologically proven diagnosis of PC, salvage Re‑I for intraprostatic recurrence after primary radiotherapy for PC with curative intent, concurrent/adjuvant ADT with stereotactic body radiation therapy (SBRT) allowed, performance status ECOG 0–2, restaging choline/PSMA-PET/TC and prostate MRI after biochemical recurrence, and signed informed consent.ResultsFrom January 2019 to April 2022, 20 patients were recruited. Median follow-up was 26.7 months (range 7–50). After SBRT, no patients were lost at follow-up and all are still alive. One- and 2‑year progression free survival (PFS) was 100% and 81.5%, respectively, while 2‑year biochemical progression-free survival (bFFS) was 88.9%. Four patients (20%) experienced locoregional lymph node progression and were treated with a further course of SBRT. Prostate reirradiation allowed the ADT start to be postponed for 12–39 months. Re‑I was well tolerated by all patients and none discontinued the treatment. No cases of ≥ G3 genitourinary (GU) or gastrointestinal (GI) toxicity were reported. Seven (35%) and 2 (10%) patients experienced acute G1 and G2 GU toxicity, respectively. Late GU toxicity was recorded in 10 (50%) patients, including 8 (40%) G1 and 2 (10%) G2. ADT-related side effects were found in 7 patients (hot flashes and asthenia).ConclusionLinac-based SBRT is a safe technique for performing Re‑I for intraprostatic recurrence after primary curative radiotherapy for PC. Future prospective, randomized studies are desirable to better understand the effectiveness of reirradiation and the still open questions in this field.

Time to castration resistance is a novel prognostic factor of cancer-specific survival in patients with nonmetastatic castration-resistant prostate cancer

We aimed to identify prognostic factors of cancer-specific survival (CSS) in non-metastatic castration-resistant prostate cancer (M0CRPC) patients. The final analysis of this retrospective cohort included 82 patients who were diagnosed as M0CRPC between 1998 and 2018 at the University of Tokyo Hospital. CRPC was defined as prostate-specific antigen (PSA) progression (increased PSA ≥ 25% and ≥ 2 ng/mL above the nadir or detection of a metastatic lesion). The median value of age and PSA at the time of CRPC were 76 (range 55–94) years and 2.84 (range 2.04–22.5) ng/mL, respectively. The median follow-up time from CRPC diagnosis was 38 (range 3–188) months. The prognostic factors of CSS were ‘PSA doubling time (PSADT) ≤ 3 months’, ‘time to CRPC diagnosis from the start of androgen deprivation therapy (TTCRPC) ≤ 12 months’, of which TTCRPC was a novel risk factor of CSS. In the multivariate analysis, ‘PSADT ≤ 3 months’ and TTCRPC ≤ 12 months’ remained as statistically significant predictors of CSS. Novel risk stratification was developed based on the number of these risk factors. The high-risk group showed a hazard ratio of 4.416 (95% confidence interval 1.701–11.47, C-index = 0.727).

Predictors of overall survival among Black South African men treated with androgen-deprivation therapy for metastatic prostate cancer.

5046 Background: Men in sub-Saharan Africa (SSA) are disproportionately affected by prostate cancer (PCa), and many have metastatic disease (mPCA) at presentation. In SSA, androgen deprivation therapy (ADT) is the first-line treatment for mPCa, and often the only available therapy. Treatment failure and death is common. We identified predictors of overall survival (OS) in Black South African (SA) men with mPCa on ADT. Methods: We performed a retrospective analysis of prospectively gathered data from men diagnosed with mPCA (3/22/2016 - 10/30/2020) at Chris Hani Baragwanath Hospital in Johannesburg, which was also a study site for the concurrent Men of African Descent and Carcinoma of the Prostate study. We included men with mPCA treated with ADT (received at least 1 dose of luteinizing hormone-releasing hormone agonist and/or had surgical castration), who had ≥1 PSA level drawn ≥12 weeks after ADT start. OS was defined from ADT start to death. PSA progression (PSA-P) definition was adapted from PCWG 3. Cox regression models were used to identify predictors of OS. PSA-P was treated as a time-dependent covariate. Results: Of 200 men with mPCa, we excluded 6 who did not receive ADT and 41 without sufficient data for PSA-P analysis. Of 153 men, 26.8% were &lt;65 years old and 12% had a family history of PCa. Median PSA at diagnosis was 71.5 ng/mL (interquartile range (IQR) 20.7-432.6), median alkaline phosphatase level (ALP) 108 IU/L (79-224) and median hemoglobin (Hb) 13 g/dL (IQR 10-15). Median PSA nadir was 2.8 ng/mL (IQR 0.55-17.93). The rate of PSA-P at 1- and 2-years was 12.1% [95%CI 5.9-17.8] and 37.5% [95%CI 26.1-47.2]. The median follow-up was 2.75 years, and the 3-year OS was 61.9% [95%CI 52.7-72.6]. Cox proportional hazard ratio (HR) models of risk factors for OS are shown in Table 1. PSA-P was a strong predictor of OS. Men with PSA nadir &gt;4ng/mL after ADT start had a HR for death of 3.77 [1.86-7.62]. Men with ALP &gt;150 IU/L and those with Hb &lt;13.5g/dL at diagnosis were also at higher risk for death (HR 3.09 [1.64-5.83] and HR 2.00 [1.28-6.56] respectively). Conclusions: Among Black men in SA treated with ADT for mPCA, PSA-P strongly predicts OS. In this cohort, high ALP and anemia at diagnosis, and PSA nadir &gt;4ng/mL after ADT start are associated with higher risk for death. These factors can be used identify high risk men with mPCA, for whom early treatment escalation to chemotherapy should be considered. [Table: see text]

PSMA PET findings in patients with undetectable PSA more than 3 years after docetaxel for metastatic castration-sensitive prostate cancer (mCSPC).

e17046 Background: Multiple treatment options combined with androgen deprivation therapy (ADT) provide a survival advantage in mCSPC. In this prospective study, mCSPC patients were treated with docetaxel and Prostvac, a therapeutic cancer vaccine. Since initiation of the study, a phase 3 trial of Prostvac did not show independent clinical activity in metastatic castration-resistant prostate cancer. Still, this study offers a chance to evaluate responses to docetaxel-based therapy in mCSPC. More specifically, with FDA approval of prostate-specific membrane antigen (PSMA) PET imaging in just the last year, there is a paucity of data regarding the use of this scan in long-term responders to therapies for mCSPC. Methods: Eligible patients included those with mCSPC and ECOG PS of ≤ 2. As per the CHAARTED regimen, patients started docetaxel within 4 months of initiating ADT with a plan to receive 75mg/m2 for 6 cycles. Patients were randomized to receive Prostvac prior to, concurrent with, or after docetaxel. Restaging was done annually with CT and Tc99 bone scan. The study was powered to evaluate immune responses, which is being reported separately. For this analysis, patients were evaluated as one group. Ten patients are in follow up with continued PSA values of ≤ 0.2 ng/mL and 7/10 were evaluated with 18F-DCFPyL PSMA PET. Results: Seventy-three patients enrolled. Median age was 63 years with a range of 41-86 years. Race distribution was 71.6% White, 20.3% Black, 4.1% other, and 4.1% unknown. Gleason 6, 7, and 8 to 10 was 4.1%, 21.6%, and 68.9% of patients, respectively, with 5.4% being unknown. Median pre-ADT PSA was 34.75 ng/mL. Low-volume disease represented 41.1% of patients and high-volume was 58.9%. After 2 years from the start of ADT, 22% of patients had PSA values of ≤ 0.2 ng/mL. This included 37% of the low-volume group and 12% of the high-volume group. Three years from starting ADT, 14% of patients had PSA values ≤ 0.2 ng/mL (20% of the low-volume group, 9% of the high-volume group). Of the 7 patients who remain in follow-up with PSA values ≤ 0.2 ng/mL and who were evaluated with PSMA PET, median time from start of ADT was 4 years with a range of 3.5-6 years. These patients either had no evidence of disease or minimal residual findings on CT/Tc99 bone scan. Four of the 7 patients still had residual areas of uptake on PSMA PET. Conclusions: Patients treated with docetaxel for mCSPC have the potential for long-term clinical responses. In these long-term responders, despite prolonged PSA response and minimal findings on conventional CT and Tc99 scans, more than half of patients still had findings on PSMA PET imaging. Further studies are required to better understand the clinical implications of these findings and the role of PSMA PET in mCSPC. Clinical trial information: NCT02649855.

Impact of Three-Month Androgen Deprivation Therapy on [68Ga]Ga-PSMA-11 PET/CT Indices in Men with Advanced Prostate Cancer-Results from a Pilot Prospective Study.

Simple SummaryPositron emission tomography/computed tomography (PET/CT) with prostate-specific membrane antigen (PSMA)-specific tracers is gaining traction for prostate cancer imaging. The aim of this pilot study was to evaluate PSMA PET/CT imaging response in 30 patients who had undergone three months of androgen deprivation therapy (ADT). Different imaging indices and the modified PET response criteria in solid tumors 1.0 served as outcome measures. Most patients showed a consistent reduction of PSMA PET/CT indices over three months. A total of 24 (80%) participants were partial responders. Patients in the International Society of Urological Pathology grade group 5 (n = 16) showed a less prominent reduction of the imaging indices, and none of them reached a complete response. Collectively, our data support the clinical usefulness of PSMA PET/CT imaging for monitoring treatment response after the first three months of ADT.Purpose: The purpose of this pilot prospective study is to examine the gallium-68-prostate-specific membrane antigen-11 ([68Ga]Ga-PSMA-11) positron emission tomography/computed tomography (PET/CT) imaging response in patients with advanced or metastatic hormone-naïve prostate cancer (PC) after 3 months of androgen deprivation therapy (ADT). Methods: We prospectively included men with untreated, clinical stage III or IV PC scheduled to receive ADT for at least 6 months. [68Ga]Ga-PSMA-11 PET/CT images were obtained before the start of ADT and 10–14 weeks thereafter. The following indices were examined: maximum standardized uptake value (SUVmax), mean SUV, PSMA total volume, and PSMA total lesion values of the prostate, nodes, bones, and whole-body. The therapeutic response was assessed using the modified PET response criteria in solid tumors 1.0. A subgroup analysis of patients with the International Society of Urological Pathology (ISUP) grade group 5 versus <5 was also performed. Results: A total of 30 patients were eligible. All PSMA PET/CT indices were significantly reduced (p < 0.001) after 3 months of ADT. Twenty-four (80%) patients showed partial response. Complete response, stable disease, and disease progression were observed in two patients each. Sixteen patients with ISUP grade group 5 showed a less prominent SUVmax reduction (p = 0.006), and none of them reached complete response. Conclusions: Three months of ADT in patients with untreated, advanced PC significantly reduced PSMA PET/CT indices. While most participants partially responded to ADT, patients with ISUP grade group 5 showed a less prominent SUVmax reduction. Collectively, our pilot results indicate that [68Ga]Ga-PSMA-11 PET/CT imaging holds promise to monitor treatment response after the first three months of ADT.

Survival outcomes and characterization of patients (pts) with metastatic castration-sensitive prostate cancer (mCSPC) undergoing intensified androgen deprivation therapy (ADT) who do not achieve an optimal PSA response (PSA ≤0.2 ng/mL).

123 Background: In pts with mCSPC undergoing intensified ADT, achieving a PSA nadir ≤0.2 ng/mL “anytime” after the start of treatment was associated with a significantly improved overall survival (OS) versus those with a PSA &gt;0.2 ng/mL: HR 0.17 (95% CI, 0.13-0.23) (Chi AUA 2021, abstract 1281). Our objective was to validate these findings in a real-world population and characterize the clinical and tumor genomic landscape according to PSA response. Methods: In this IRB-approved study, patient-level data were collected retrospectively. Eligibility: presence of mCSPC undergoing intensified ADT with either docetaxel or novel hormonal therapy (NHT) started within 3 months of diagnosis, availability of PSA nadir, and availability of tumor comprehensive genomic profiling (CGP) prior to start of ADT. Variants of unknown significance and genomic aberrations present in &lt;5% pts were excluded. Optimal PSA response (OR): PSA≤0.2 ng/mL. Study endpoints: PFS was calculated per PCWG-2 defined PSA progression or radiographic progression or clinical progression whichever occurred first; OS was defined as start of therapy to date of death or censored after last follow-up. The relationship between PSA nadir and both PFS and OS was assessed in the context of Cox proportional hazards. Gene prevalence was compared using a chi square test. Results: 134 pts were eligible and included. Optimal responders (OR) (n=104) and non-OR (n=30): median age at diagnosis 63 vs 65 years; median PSA at ADT start 18.1 vs 74.5 ng/mL; high volume of disease 48% vs 77%. For OR and non-OR: median PFS, 60.6 vs 13.2 (P&lt;0.001); median OS, 94.9 vs 35.2 months (P&lt;0.001) respectively. Multivariate analysis is described in the table. Conclusions: Only a minority of pts with mCSPC do not achieve an optimal PSA response with intensified ADT. Those non-OR have worse outcomes on treatment with intensified ADT. Herein we externally validate that achieving a PSA nadir ≤0.2 ng/mL is correlated with superior OS. Detailed genomic landscape of these pts will be presented in the meeting.[Table: see text]

O22 ANDROGEN DEPRIVATION THERAPY AND THE RISK FOR INGUINAL HERNIA

Abstract Aim To investigate whether androgen deprivation therapy (ADT) for prostate cancer increases the risk for inguinal hernia. Material and Methods A population-based nested case-control study based on data from the Prostate Cancer Database Sweden. The cohort included men with prostate cancer who had not received curative treatment. Men who had been diagnosed with inguinal hernia or had undergone inguinal hernia repair (n = 1324) were cases and controls were men, not diagnosed, nor operated on for inguinal hernia, matched on birth year (n = 13 240). Conditional multivariate logistic regression models were used to assess any temporal association between ADT and inguinal hernia, adjusting for confounders. Results Odds Ratio [OR] for repair of inguinal hernia 0-1 years from start of ADT was 0.5 (95% confidence Interval (CI)) 0.38-0.68), between 1 and 3 years after, the OR was 0.35 (95% CI 0.26-0.47), 3-5 years after, the OR was 0.39 (95% CI 0.26-0.56), 5-7 years after, the OR was 0.6, (95% CI: 0.41-0.97), and &amp;gt; 9 years after, the OR was 3.68 (95% CI 2.45-5.53). Conclusions The marked increase in OR for inguinal hernia after 9 years of ADT supports the hypothesis that low testosterone levels increase the risk for inguinal hernia. The low risk for inguinal hernia during the first eight years on ADT is likely caused by selection of men with advanced cancer unlikely to be diagnosed or treated for inguinal hernia. This finding may support the hypothesis that sex hormones plays a crucial role in inguinal hernia development.

Androgen Deprivation Therapy and the Risk for Inguinal Hernia: An Observational Nested Case Control Study

It has been suggested that hypogonadism increases the risk for inguinal hernia (IH). The aim of this study was to investigate any association between androgen deprivation therapy (ADT) for prostate cancer and increased risk for IH. The study population in this population-based nested case-control study was based on data from the Prostate Cancer Database Sweden. The cohort included all men with prostate cancer who had not received curative treatment. Men who had been diagnosed or had undergone IH repair (n = 1,324) were cases and controls, where not diagnosed, nor operated on for IH, matched only on birth year (n = 13,240). Conditional multivariate logistic regression models were used to assess any temporal association between ADT and IH, adjusting for marital status, education level, prostate cancer risk category, Charlson Comorbidity Index, ADT, time since prostate cancer diagnosis, and primary prostate cancer treatment. Odds ratio (OR) for diagnosis/repair of IH 0 to 1 year from start of ADT was 0.5 (95% confidence interval [CI] = [0.38, 0.68]); between 1 and 3 years after, the OR was 0.35 (95% CI = [0.26, 0.47]); between 3 and 5 years after, the OR was 0.39 (95% CI = [0.26, 0.56]); between 5 and 7 years after, the OR was 0.6 (95% CI = [0.41, 0.97]); and >9 years after, the OR was 3.68 (95% CI = [2.45, 5.53]). The marked increase in OR for IH after 9 years of ADT supports the hypothesis that low testosterone levels increase the risk for IH. The low risk for IH during the first 8 years on ADT is likely caused by selection of men with advanced cancer unlikely to be diagnosed or treated for IH.

Intermittent Androgen Deprivation Therapy Plus Comprehensive Stereotactic Radiotherapy for Oligometastatic Prostate Cancer (CROP)

<h3>Purpose/Objective(s)</h3> The standard treatment for metastatic prostate cancer is systemic therapy. This prospective phase I/II study assessed the utility of SBRT to all tumor sites plus intermittent androgen deprivation therapy (ADT) in patients with hormone sensitive oligometastatic prostate cancer. Endpoints included incidence of SBRT induced late toxicities and clinical outcomes including cumulative incidences of developing biochemical progression, new metastases, restarting ADT, castration resistant prostate cancer (CRPC), and overall survival (OS). <h3>Materials/Methods</h3> Synchronous and metachronous metastatic disease presentations were eligible if there were ≤ 5 metastases, with ≤ 3 metastases in any one organ system. Conventional scans (CT/bonescan +/- MRI) were used to stage patients at baseline, although novel PET imaging was optional. SBRT was delivered to all sites of disease, including the prostate if not previously treated. SBRT dose was site dependent but was generally 30-35 Gy in 5 fractions for lymph nodes and non-spine bone lesions, 24-28 Gy in 2 fractions for spine, and 35 Gy in 5 fractions to the prostate. ADT was started prior to or immediately after SBRT and was continued for 1 year before moving to an intermittent approach. ADT was to be restarted when the PSA reached ≥ 10 ng/mL or earlier if clinically indicated (development of new metastases or rapidly rising PSA). Toxicity (CTCAE v4.0) and PSA measurements were collected every 4 months during follow-up. Conventional scans were performed at a minimum of once per year, but more frequent imaging was allowed at the discretion of the physician. Time zero was start of ADT or SBRT, whichever was earlier. <h3>Results</h3> 92 patients with 158 metastases were accrued with a median age of 74 years. Median follow-up time was 37 months. Median baseline PSA was 8.5 ng/mL (range 0.78 – 179.8). 39 (42%) patients had Gleason score of 8-10. 32 (35%) patients had synchronous disease presentation. 14 (15%) patients were staged with PET imaging. 5 (5%) patients developed late grade 3 GU toxicity and 6 (7%) patients developed a late SBRT induced bone fracture. There were no grade 4/5 toxicities. Median PSA nadir was 0.02 ng/mL. 50% of patients reached a PSA nadir of ≤ 0.02 ng/mL, while 92% of patients reached a PSA nadir of < 1 ng/mL. The cumulative incidence (CI) of biochemical progression (PSA nadir + 2 ng/mL) was 54% at 4 years. The 4-year CI of developing new metastases and local failure of irradiated sites was 42.8% and 7%, respectively. The 4-year CI of restarting ADT and developing CRPC was 62% and 25%, respectively. OS was 79% at 4 years. <h3>Conclusion</h3> The incidence of grade ≥ 3 toxicity was low when combining SBRT with intermittent ADT for hormone sensitive oligometastatic prostate cancer. With > 3 years of median follow-up, outcomes are promising compared to historical results of using ADT alone, particularly with regards to the development of CRPC. Further work will be done to identify potential predictors of clinical outcomes.

Oligometastatic Disease Detection with 68Ga-PSMA-11 PET/CT in Hormone-Sensitive Prostate Cancer Patients (HSPC) with Biochemical Recurrence after Radical Prostatectomy: Predictive Factors and Clinical Impact.

Simple SummaryThe early treatment of oligometastatic disease (OMD) is a promising therapeutic option for prostate cancer as it has the potential of delaying androgen-deprivation therapy (ADT) and disease progression. Next-generation imaging targeting the prostate-specific membrane antigen (PSMA-PET/CT) is considered the most accurate technique for recurrent prostate cancer. Finding clinico-pathological factors predicting positivity with OMD detection on PSMA-PET/CT, as well as assessing its impact on treatment management, were the main objectives of our study. We selected a homogenous population of ADT-free prostate cancer patients with a PSMA-PET/CT performed at biochemical recurrence (BCR) after radical prostatectomy (RP). OMD was detected in 44% of patients for a total positivity rate of 60%. PSA at the moment of PET, PSAdt, and the absence of previous salvage treatment were factors predicting PSMA-PET/CT positivity with OMD. A change in clinical management occurred in more than half of the patients, mostly to perform metastasis-directed therapy after OMD detection.Metastasis-directed therapy (MDT) in oligometastatic prostate cancer has the potential of delaying the start of androgen deprivation therapy (ADT) and disease progression. We aimed to analyze the efficacy of PSMA-PET/CT in detecting oligometastatic disease (OMD), to look for predictive factors of OMD, and to evaluate the impact of PSMA-PET/CT findings on clinical management. We retrospectively analyzed a homogeneous population of 196 hormone-sensitive prostate cancer patients (HSPC), considered potential candidates for MDT, with a PSMA-PET/CT performed at biochemical recurrence (BCR) after radical prostatectomy (RP). Multivariable logistic regression analysis was performed based on several clinico-pathological factors. Changes in clinical management before and after PSMA-PET/CT were analyzed. The OMD detection rate was 44% for a total positivity rate of 60%. PSMA-PET/CT positivity was independently related to PSA (OR (95% CI), p) (1.7 (1.3–2.3), p < 0.0001) and PSAdt (0.4 (0.2–0.8), p = 0.013), and OMD detection was independently related to PSA (1.6 (1.2–2.2), p = 0.001) and no previous salvage therapy (0.3 (0.1–0.9), p = 0.038). A treatment change was observed in 58% of patients, mostly to perform MDT after OMD detection (60% of changes). This study showed that PSMA-PET/CT is an excellent imaging technique to detect OMD early in HSPC patients with BCR after RP, changing therapeutic management mostly into MDT.

650TiP PARADIGM: Plasma analysis for response assessment and to direct the management of metastatic prostate cancer (mPCa)

Adding docetaxel or androgen receptor signalling inhibitor (ARSI) at start of androgen deprivation therapy (ADT) for mPCa improves progression-free survival (PFS) and overall survival (OS). Duration of benefit is variable; although serum PSA at 7 months (mth) associates with differential outcome, physicians still lack the tools to identify who will develop early resistance and require alternative or intensified treatments.

PSMA-11-PET/CT versus choline-PET/CT to guide stereotactic ablative radiotherapy for androgen deprivation therapy deferral in patients with oligometastatic prostate cancer

BackgroundIn patients with oligometastatic recurrent prostate cancer, standard treatment is androgen deprivation therapy (ADT). However, ADT has many potential side effects that may result in impaired quality of life. Early identification to select patients suitable for stereotactic ablative radiotherapy (SABR) is of utmost importance to prevent or delay start of ADT and its side effects. Because Prostate-Specific Membrane Antigen-11-Positron Emission Tomography (PSMA-11-PET) has a higher sensitivity than choline-PET, we hypothesise that PSMA-11-PET based SABR results in longer response duration and subsequent longer delay in starting ADT than choline-PET. MethodsPatients with oligometastatic (≤4 metastases) recurrent prostate cancer (with no local recurrence) based on PSMA-11-PET or choline-PET treated with SABR from January 2012 until December 2017 were included. Primary endpoint was ADT-free survival. Secondary endpoints were Prostate Specific Antigen (PSA) response after SABR and time to PSA rise after SABR. ResultsFifty patients (n = 40 PSMA-11-PET and n = 10 choline-PET) with in total 72 lesions were included. Median follow-up was 24.3 months. PSMA-11-PET enabled eligibility of patients with lower PSA levels than choline-PET (median 1.8 versus 4.2 ng/mL, p = 0.03). The PSMA-11-PET group had a significant longer PSA response duration (median 34.0 months (95% confidence interval (CI), 16.0–52.0) versus 14.7 months (95% CI 4.7–24.7), p = 0.004) with a subsequent longer ADT-free survival (median 32.7 months (95% CI, 20.8–44.5) versus 14.9 months (95% CI, 5.7–24.1), p = 0.01). ConclusionsWith PSMA-11-PET we are able to select patients with oligometastatic recurrent prostate cancer suitable for SABR in an earlier disease stage at lower PSA levels. PSMA-11-PET guided SABR resulted in a significant longer response duration and ADT-free survival compared with choline-PET and can therefore prevent or delay ADT related side effects.

Patients with undetectable PSA 2 years after docetaxel for metastatic castration sensitive prostate cancer (mCSPC).

e17044 Background: Patients with mCPSC have multiple treatment options to combine with androgen deprivation therapy (ADT) including docetaxel, abiraterone, enzalutamide and apalutamide, all of which have demonstrated a survival advantage. While oral anti-androgens are administered daily until progression but are less toxic, docetaxel has more upfront side effects. One of the advantages of using docetaxel is that the 6-cycle regimen (over approximately 4 months) potentially affords patients a respite from daily therapies thereafter. Furthermore, docetaxel may be more cost-effective. In this prospective study, mCSPC patients were treated with docetaxel and Prostvac, a therapeutic cancer vaccine. Since this study was initiated, Prostvac did not demonstrate independent clinical activity in a phase 3 trial in metastatic castration resistant prostate cancer. Nonetheless, this study provides an opportunity to evaluate responses to docetaxel-based therapy in mCSPC. Methods: Eligible patients included those with mCSPC and ECOG of ≤ 2. All patients were treated with docetaxel and were planned to receive 75mg/m2 for 6 cycles within 4 months of starting ADT, as per the CHAARTED regimen. Patients were randomized to receive Prostvac prior to, concurrent with or after docetaxel. Patients were restaged annually with CT and Tc99 bone scan. The study was powered to evaluate immunologic responses, which is ongoing. For the purposes of this analysis, all patients were analyzed as one group and long-term PSA responses were evaluated. Results: The study enrolled 73 patients. Age range was 41-86 with a median of 63 years. Race distribution was 71.6% White, 20.3% Black, 4.1% other, and 4.1% unknown. Gleason scores were 6 (4.1%), 7 (21.6%), and 8-10 (68.9%), with 5.4% being unknown. Median pre-ADT PSA was 34.75 ng/mL. Low-volume disease represented 41.1% of patients and high-volume was 58.9%. After 2 years from the start of ADT, 22% of all patients had PSA values of ≤ 0.2 ng/mL. This included 37% of the low-volume group and 12% of the high-volume group. Three years from the start of ADT, 14% of all patients had PSA values ≤ 0.2 ng/mL (20% of the low-volume group, 9% of the high-volume group). Conclusions: These data highlight long-term outcomes of 6 cycles of docetaxel for men with mCSPC. Although there are concerns about the short-term toxicity of docetaxel, there is potential for prolonged stable disease after ̃4 months of chemotherapy that allows these patients to defer additional oral anti-androgen therapy for years in some patients. The proportions of patients presented here are an underestimate of those who could continue to be monitored for slowly rising, but low PSAs, before starting the next line of therapy. Additional research is required to determine the optimal therapeutic sequence for men diagnosed with mCSPC and long-term implications for quality of life and cost-effectiveness. Clinical trial information: NCT02649855.