Early PSA Change after [177Lu]PSMA-617 Radioligand Therapy as a Predicator of Biochemical Response and Overall Survival

Purpose: Radioligand therapy with [177Lu]PSMA-617 (PSMA-RLT) is a promising therapeutic option for metastatic castration-resistant prostate cancer (mCPRP). This study assessed the prognostic value of early PSA measurements during PSMA-RLT. Methods: 27 patients with mCRPC scheduled for PSMA-RLT were prospectively enrolled for a serial short-interval PSA-assessment. Change in PSA (∆%PSA) during two treatment cycles was correlated with biochemical response (BR) and change in tumor volume on PET (TV) after 16 weeks (w16), as well as overall survival (OS). PCWG3 criteria and the recently recommended threshold of ∆%PSA ≤ −30% were assessed for their predictive value. Results: ∆%PSA first correlated with BR, TV and OS after 4 weeks (c1w4). At c1w4, ∆%PSA ≤ −30% was associated with the biochemical response at w16 (p = 0.003) and a longer median OS (p = 0.025), whereas the PCWG3-derived threshold of ∆%PSA ≤ −50% showed no such correlation. In contrast, ∆%PSA ≥ 25% at c1w4 was associated with biochemical progression at w16 (p = 0.003) and a shorter median OS (p < 0.001). Conclusion: PSA changes as early as four weeks after PSMA-RLT allow a significant prediction of later biochemical and PET-based imaging response, as well as OS. At this early time point, a more lenient threshold for a PSA decrease of at least 30% appears better-suited for the prediction of a positive biochemical response and longer OS. In contrast, the PCWG3-derived threshold for PSA increase (+25%) reliably anticipates biochemical progression and shorter OS.

Novel hormonal agents for metastatic Castration-Resistant Prostate Cancer: comparing outcomes. A single-center retrospective study

Introduction: Prostate cancer is the most common cancer in men, accounting for 15% of all diagnosed cancers and is the sixth leading cause of cancerrelated deaths amongst men worldwide. Abiraterone and enzalutamide were the first two novel hormonal agents approved for the treatment of metastatic prostate cancer but there is a lack of quality evidence regarding which is associated with better outcomes and who would benefit the most with one or another of these drugs. Objective: To evaluate the clinical outcomes of real-world patients submitted to treatment with novel hormonal agents, enzalutamide and abiraterone, for castration resistant metastatic prostate cancer in an academic center.Patients and methods: We retrospectively reviewed patients treated for castration-resistant prostate cancer with either abiraterone or enzulatamide between January 1, 2016 and December 31, 2019. The primary endpoints were biochemical response, biochemical progression, radiological progression, clinical deterioration (attributed to disease progression) and death. Results: Enzalutamide had a higher biochemical response rate than abiraterone in patients with mCRPC (77.1% vs 58.1%, p = 0.016). Achieving a biochemical response was associated with a lower risk of biochemical progression (OR: 0.248, p = 0.017) and death (OR: 0.302, p = 0.038). Conclusions: Enzalutamide conferred higher biochemical response rate than abiraterone in patients with mCRPC. Despite the trend to better performance of other endpoints in the enzalutamide group, it did not achieve statistical significance. Well-designed prospective studies are needed to elucidate the comparative efficacies of these agents.

Dynamic Changes in Prostate-Specific Antigen After Androgen Deprivation Therapy for Prostate Cancer are Strongly Associated with Biochemical Progression-Free Survival: A Multicenter Retrospective Analysis

Objectives: The risk factors for prostate cancer to progress to castration-resistant prostate cancer after androgen deprivation treatment (ADT) are still not to be well defined. We conducted this investigation in an attempt to determine factors that predicted the prognosis in a series of patients with prostate cancer after ADT. Methods: We retrospectively analyzed the database of patients treated with androgen deprivation prostate cancer who were hospitalized in the Second Affiliated Hospital of Bengbu Medical College and Maoming People's Hospital from 2015.1.1 to 2020.12.30. PSA dynamic changes, including nadir PSA (nPSA), time to nadir PSA (TTN), were examined regularly. Cox risk proportional regression model was used for univariate and multivariate analysis; Kaplan-Meier survival curve and Log-rank test were used to compare and analyze differences in biochemical progression-free survival (bPFS) between groups. Results: During the follow-up with a median time of 43.5 months, a total of 163 men were included in the study. The median bPFS of the two groups with nPSA lower than 0.2ng/ml and ≥0.2ng/ml were 27.6 months and 13.5, respectively, with significant differences between the groups (Log-rank p<0.001); The median bPFS of the two groups with TTN ≥9 months and less than 9 were 27.8 months and 13.5 months, respectively, with significant differences between the groups (Log rank p<0.001). Conclusions: PSA dynamic changes after androgen deprivation treatment of prostate cancer can be used as prognostic indicators for bPFS. The lower the nadir PSA value and the longer the time to nadir, the longer the bPFS of patients with prostatic cancer after androgen deprivation treatment.

Corticosteroid switch from prednisone to dexamethasone in metastatic castration-resistant prostate cancer patients with biochemical progression on abiraterone acetate plus prednisone

Background To assess the efficacies and potential predictors of a corticosteroid switch in metastatic castration-resistant prostate cancer (mCRPC) patients with biochemical progression on abiraterone acetate plus prednisone (A + P). Methods Patients with mCRPC treated between April 2016 and August 2020, who experienced biochemical progression on A + P and then switched to A plus dexamethasone (D), were retrospectively identified. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were PSA response, overall survival (OS), and safety. Results One hundred and thirty consecutive cases were enrolled. The median PFS and OS on A + D were 5.0 and 18.7 months, respectively. The best PSA decline of ≥50% (PSA50) and ≥ 30% (PSA30) were observed in 29.2 and 46.2% patients, respectively. Lower PSA at corticosteroid switch (≤ 20 ng/mL; median PFS, HR 0.63, p = 0.019; median OS, HR 0.38, p = 0.001) and longer mCRPC-free survival (≥ 18 months; median PFS, HR 0.61, p = 0.013; median OS, HR 0.51, p = 0.015) were identified as independent prognostic predictors associated with longer PFS and OS. A risk stratification tool was developed to select candidates for corticosteroid switch based on the independent prognostic predictors of PFS and OS. Conclusions A corticosteroid switch from prednisone to dexamethasone is effective for mCRPC which progressed on A + P treatment. Patients with lower PSA at corticosteroid switch and/or longer mCRPC-free survival may gain more benefits by the corticosteroid switch.

Five-Year Outcomes of Stereotactic Body Radiation Therapy (SBRT) for Prostate Cancer-The Largest Experience in China

Objective To evaluate the efficacy and toxicity of SBRT for localized prostate cancer (PCa). Moreover, it is the largest-to-date pilot study to report 5-year outcomes of SBRT for localized PCa from China. Methods In this retrospective study, 133 PCa patients in our center were treated by SBRT with CyberKnife (Accuray) from October 2012 to July 2019. Follow-up was performed every 3 months for evaluations of efficacy and toxicity. Biochemical progression-free survival (bPFS) and toxicities were assessed using the Phoenix definition and the Common Terminology Criteria for Adverse Events (CTCAE) v.5.0 respectively. Factors predictive of bPFS were identified with COX regression analysis. Results 133 patients (10 low-, 21 favorable intermediate-, 31 unfavorable intermediate-, 45 high-, and 26 very high risk cases on the basis of the NCCN risk classification) with a median age of 76 years (range: 54–87 years) received SBRT. The median dose was 36.25Gy (range: 34-37.5Gy) in 5 fractions. Median follow-up time was 57.7 months (3.5–97.2 months). The overall 5-year bPFS rate was 83.6% for all patients. The 5-year bPFS rate of patients with low-, favorable intermediate-, unfavorable intermediate-, high-, and very high risk PCa was 87.5%, 95.2%, 90.5%, 86.3%, and 61.6% respectively. Urinary symptoms were all alleviated after SBRT. All the patients tolerated SBRT with only 1 (0.8%) and 1 (0.8%) patient reporting grade-3 acute and late genitourinary (GU) toxicity, respectively. There were no grade 4 toxicities. Gleason score (P < 0.001, HR = 7.483, 95%CI: 2.686–20.846) was the independent predictor of bPFS rate after multivariate analysis Conclusion SBRT is an efficient and safe treatment modality for localized PCa with high 5-year bPFS rates and acceptable toxicities.

A phase II randomized controlled trial of exercise on biochemical progression in men with prostate cancer on active surveillance.

5080 Background: Men with prostate cancer (PCa) undergoing active surveillance (AS) are at increased risks of cardiovascular death and disease progression. Any intervention that can address these issues during AS would be highly beneficial. Clinical and preclinical studies have demonstrated the benefits of exercise to improve cardiovascular health in cancer patients and suggested the potential role of exercise in suppressing PCa progression in men with PCa undergoing AS. Therefore, the purpose of this study was to investigate the effects of exercise on cardiorespiratory fitness and biochemical progress of PCa in men with PCa on AS. Methods: The Exercise During Active Surveillance for Prostate Cancer (ERASE) Trial was a single-centre, two-armed, randomized controlled trial in Edmonton, Canada. 52 men with localized PCa who were undergoing AS were randomized to high-intensity interval training (HIIT; n = 26) or usual care (UC; n = 26). The HIIT group performed thrice-weekly, supervised, aerobic HIIT on a treadmill at 85-95% of peak cardiorespiratory fitness (VO2peak) for 12 weeks. The primary outcome was VO2peak, and the secondary and exploratory outcomes included biochemical progression of PCa (prostate-specific antigen [PSA]), PSA kinetics, and growth of prostate cancer cell line LNCaP. Results: 46/52 participants (88%) completed the postintervention VO2peak assessment and adherence to HIIT was 96%. Compared to UC, HIIT significantly improved VO2peak (adjusted between-group mean difference, 1.6 ml·kg-1·min-1; 95% confidence interval [CI], 0.3 to 2.9; p= 0.014). HIIT also significantly reduced PSA level (adjusted between-group mean difference, -1.1 ug/L; 95% CI, -2.1 to 0.0; p= 0.043) and PSA velocity ( p= 0.040), and suppressed LNCaP cell growth ( p =0.024). No significant differences were found in PSA doubling time ( p= 0.10) and testosterone ( p= 0.24). Conclusions: The ERASE Trial is the first randomized controlled trial to demonstrate the impact of HIIT exercise for improving physical fitness and inhibiting biochemical progression of PCa in men with localized PCa on AS. Our findings suggest that supervised aerobic HIIT may be a promising intervention in this clinical setting. Larger-scale randomized controlled trials are warranted to determine if improvements in physical fitness and PCa-related markers translate into improved long-term clinical outcomes in these men such as disease progression, receipt of radical treatments, posttreatment complications, and survival. Clinical trial information: NCT03203460.

Efficacy of PSMA PET-Guided Radiotherapy for Oligometastatic Castrate-Resistant Prostate Cancer

PurposeTo assess the outcome of radiotherapy (RT) to all PSMA ligand positive metastases for patients with castrate-resistant prostate cancer (mCRPC).Patients and methodsA total of 42 patients developed oligometastatic mCRPC and received PSMA PET-guided RT of all metastases. The main outcome parameters were biochemical progression-free survival (bPFS), and second-line systemic treatment free survival (SST-FS).ResultsA total of 141 PSMA ligand-positive metastases were irradiated. The median follow-up time was 39.0 months (12-58 months). During the follow-up five out of 42 (11.9%) patients died of progressive mPCa. Five out of 42 (11.9%) patients showed no biochemical responses and presented with a PSA level ≥10% of the baseline PSA at first PSA level measurement after RT and were classified as non-responders. The median PSA level before RT was 4.79 ng/mL (range, 0.4-46.1), which decreased significantly to a median PSA nadir level of 0.39 ng/mL (range, &lt;0.07-32.8; p=0.002). The median PSA level at biochemical progression after PSMA ligand-based RT was 2.75 ng/mL (range, 0.27-53.0; p=0.24) and was not significantly different (p=0.29) from the median PSA level (4.79 ng/mL, range, 0.4-46.1) before the PSMA ligand-based RT. The median bPFS was 12.0 months after PSMA ligand PET-based RT (95% CI, 11.2-15.8) and the median SST-FS was 15.0 months (95% CI, 14.0-21.5).ConclusionIn well-informed and closely followed-up patients, PSMA PET-guided RT represents a viable treatment option for patients with oligometastatic mCRPC to delay further systemic therapies.