Prostate-specific Antigen Nadir Research Articles

Randomized, Open-Label Phase 2 Study of Apalutamide plus Androgen Deprivation Therapy versus Apalutamide Monotherapy versus Androgen Deprivation Monotherapy in Patients with Biochemically Recurrent Prostate Cancer.

Purpose This randomized phase 2 study sought to assess the treatment effect of a finite duration of apalutamide with and without androgen deprivation therapy (ADT) in biochemically recurrent prostate cancer (BCR PC). Materials and Methods. Patients with BCR PC after primary definitive therapy and prostate-specific antigen (PSA) doubling time ≤12 months were randomized to open-label apalutamide (240 mg/d) alone, apalutamide plus ADT, or ADT alone (1 : 1:1 ratio) for 12 months followed by a 12-month observation period (NCT01790126). Mean changes from baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P) at 12 months (primary endpoint) and other prespecified assessments of health-related quality of life (HRQoL), PSA nadir, time to PSA progression, time to testosterone recovery, recovered testosterone >150 ng/dL without PSA progression at 24 months, and molecular markers were evaluated. Results In 90 enrolled patients (apalutamide plus ADT (n = 31), apalutamide (n = 29), ADT (n = 30)), FACT-P at 12 months was not significantly different between apalutamide, ADT and apalutamide, and ADT groups. Addition of apalutamide to ADT prolonged time to PSA progression but this change did not reach statistical significance (hazard ratio (HR): 0.56, 95% confidence interval (CI): 0.23–1.36, P=0.196); time to testosterone recovery was similar in the ADT-containing groups. In apalutamide plus ADT, apalutamide, and ADT groups, 37.9%, 37.0%, and 19.2% of patients, respectively, had testosterone >150 ng/dL at 24 months without confirmed PSA progression. Of the few biomarkers expressed in blood, EPHA3 was significantly associated with shorter time to PSA progression (P=0.02) in the overall population. Conclusions HRQoL was similar in patients treated with apalutamide alone, ADT alone, or their combination, although apalutamide plus ADT did not demonstrate statistically significant noninferiority in change from baseline in overall HRQoL. The aggregated efficacy and safety outcomes support further evaluation of apalutamide plus ADT in BCR PC.

Neoadjuvant androgen deprivation therapy combined with abiraterone acetate in patients with locally advanced or metastatic prostate cancer: When to perform radical prostatectomy?

The surgical timing after neoadjuvant androgen-deprivation therapy (ADT) plus abiraterone acetate (AA) for patients with locally advanced or metastatic prostate cancer (PCa) is unknown. We divided patients with locally advanced or metastatic PCa into three groups according to prostate-specific antigen (PSA) nadir after neoadjuvant ADT plus AA: group 1 (PSA ≤ 0.2ng/ml), group 2 (0.2< PSA ≤ 4.0ng/ml), and group 3 (PSA > 4.0ng/ml).The median PSA baseline levels in groups 1, 2, 3 were 118.42 (32.03-457.78), 143.48 (17.7-8100.16), and153.35 (46.44-423.31) ng/ml, respectively. The median times of progression to CRPC in groups 1, 2,and 3 were 30, 26, and 26 months, respectively. Compared to patients with PSA nadir >0.2ng/ml, patients with PSA nadir <0.2ng/ml presented with longer PFS (p= 0.048).Our results suggested that, in patients with locally advanced or metastatic PCa, the time to progression to CRPC was longer after radical prostatectomy when PSA decreased below 0.2ng/ml using neoadjuvant ADT plus AA.

Holmium laser enucleation of the prostate in men on active surveillance for prostate cancer with refractory lower urinary tract symptoms secondary to enlarged prostates.

The surgical treatment of men with lower urinary tract symptoms (LUTS) and significantly enlarged symptomatic prostates on active surveillance (AS) for low-risk prostate cancer (PCa) is not well defined. We report our single-institution initial experience with holmium laser enucleation of the prostate (HoLEP) for LUTS in men with low-risk PCa being managed with AS. Men on AS who underwent HoLEP between 2013 and 2019 were identified. Data regarding preoperative cancer workup, prostate-specific antigen (PSA), perioperative outcomes, and voiding parameters were analyzed. Postoperative surveillance for PCa including PSA nadir, prostate magnetic resonance imaging, prostate biopsy (PBx), and PSA at last follow-up were evaluated. Twenty men met the inclusion criteria. Preoperative mean max flow 7.9 ml/s, median postvoid residual 101 cc, and mean transrectal ultrasound prostate size 99 cc. Patients had a median adjusted preoperative PSA of 8.5 (interquartile range[IQR]: 4.8-13.2) ng/ml. Mean resected tissue weight was 65.5 gwith improved postoperative flow rate and significantly decreased residual. A total of 5/20 men had PCa in the specimen (all GleasonGrade Group 1).The median postoperative PSA nadir was 1.2 (IQR: 0.5-1.8) ng/ml at median of 5 months. At the last follow-up (median 18.5 months, IQR: 10.5-37.8), the median postoperative PSA was 1.4 (IQR: 0.63-2.48) ng/ml. Nine men underwent postoperative multiparametric magnetic resonance imaging(mpMRI) with the identification of a new prostate imaging reporting and data system 5 lesion in onepatient who underwent negative fusion biopsy. Five men underwent post-HoLEP PBx with progression in two patients, who both successfully underwent radical prostatectomy. Men on AS for low-risk PCa can safely undergo HoLEP with significantly improved voiding parameters. Postoperative monitoring with PSA, mpMRI, and PBx can detect disease progression requiring definitive treatment. Further research is needed to optimize surveillance strategies and long-term cancer-specific outcomes.

Epidemiology and natural history of non-metastatic castration-resistant prostate cancer in Russia

Aim. To study the clinical and demographic profile of patients with non-metatstatic castration-resistant prostate cancer (nmCRPC) and clinical approaches to the treatment of nmCRPC in the context of daily medical practice before and after progression M1 stage.Materials and methods. The multicenter non-interventional epidemiological study were included 200 patients with a documented diagnosis of nmCRPC from 2019 to 2020. Each patient visited twice: start and after 6 months. Of the 200 patients included, 9 were excluded from the analysis presented in this article: 1 patient had no information on inclusi- on criteria, 1 patient did not meet the inclusion criteria, 7 patients did not attend visit 2. Thus, data are presented for 191 patients.Results and conclusion. The median age was 74.3 years (range 55 to 91). 72 % (137/191) had a disability group. The most common comorbidities were hypertension (n = 115) and hypercholesterolemia (n = 56). The median time from the diagnosis of prostate cancer to the development of castration resistance (diagnosis of nmCRPC) was 75 months. Prostate specific antigen (PSA) nadir (0.37 ng/ml on average) was achieved after 15 months of prostate cancer therapy (median time to reach PSA nadir). At the same time, PSA doubling time in most cases (47.6 %; 91/191) was less than 6 months, 18.8 % of persons (36/191) had PSA doubling time for more than 10 months.

Salvage Radiotherapy Plus Androgen Deprivation Therapy for High-Risk Prostate Cancer with Biochemical Failure after High-Intensity Focused Ultrasound as Primary Treatment.

We conduct a retrospective analysis of salvage radiotherapy plus androgen deprivation therapy (SRT+ADT) for high-risk prostate cancer patients with biochemical failure after high-intensity focused ultrasound (HIFU) as the primary treatment. A total of 38 patients, who met the criteria of biochemical failure and were consecutively treated with SRT+ADT, were enrolled. All patients received intensity modulated radiotherapy with a median dose of 70 Gy to the clinical target volume. ADT was given before, during or after the course of SRT with the duration of ≦6 months (n = 14), 6–12 months (n = 12) or >12 months (n = 12). The median follow-up was 45.9 months. A total of 10 (26.3%) patients had biochemical failure after SRT+ADT. The cumulative 5-year biochemical progression free survival (b-PFS) and overall survival (OS) rate was 73.0% and 80.3%, respectively. A nadir prostate-specific antigen (nPSA) value 0.02 ng/mL was observed to predict the b-PFS in multivariate analysis. The 5-year b-PFS was 81.6% for those with nPSA < 0.02 compared with 25.0% with nPSA ≧ 0.02. The adverse effects related to SRT+ADT were mild in most cases and only three (8%) patients experienced grade 3 urinary toxicities. For high-risk prostate cancer after HIFU as primary treatment with biochemical failure, our study confirms the feasibility of SRT+ADT with high b-PFS, OS and low toxicity.

Assessing radiation dose for postoperative radiotherapy in prostate cancer: Real world data.

BACKGROUNDApproximately 30% of patients with localized prostate cancer (PCa) who undergo radical prostatectomy will develop biochemical recurrence. In these patients, the only potentially curative treatment is postoperative radiotherapy (PORT) with or without hormone therapy. However, the optimal radiotherapy dose is unknown due to the limited data available. AIMTo determine whether the postoperative radiotherapy dose influences biochemical failure-free survival (BFFS) in patients with PCa. METHODSRetrospective analysis of patients who underwent radical prostatectomy for PCa followed by PORT-either adjuvant radiotherapy (ART) or salvage radiotherapy (SRT)-between April 2002 and July 2015. From 2002 to 2010, the prescribed radiation dose to the surgical bed was 66-70 Gy in fractions of 2 Gy; from 2010 until July 2015, the prescribed dose was 70-72 Gy. Patients were grouped into three categories according to the total dose administered: 66-68 Gy, 70 Gy, and 72 Gy. The primary endpoint was BFFS, defined as the post-radiotherapy prostate-specific antigen (PSA) nadir + 0.2 ng/mL. Secondary endpoints were overall survival (OS), cancer-specific survival (CSS), and metastasis-free survival (MFS; based on conventional imaging tests). Treatment-related genitourinary (GU) and gastrointestinal (GI) toxicity was evaluated according to Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria. Finally, we aimed to identify potential prognostic factors. BFFS, OS, CSS, and MFS were calculated with the Kaplan-Meier method and the log-rank test. Univariate and multivariate Cox regression models were performed to explore between-group differences in survival outcome measures.RESULTSA total of 301 consecutive patients were included. Of these, 93 (33.6%) received ART and 186 (66.4%) SRT; 22 patients were excluded due to residual macroscopic disease or local recurrence in the surgical bed. In this subgroup (n = 93), 43 patients (46.2%) were Gleason score (GS) ≤ 6, 44 (47.3%) GS 7, and 6 (6.5%) GS ≥ 8; clinical stage was cT1 in 51 (54.8%), cT2 in 35 (39.3%), and cT3 in one patient (1.1%); PSA was < 10 ng/mL in 58 (63%) patients, 10-20 ng/mL in 28 (30.6%), and ≥ 20 ng/mL in 6 (6.4%) patients. No differences were found in BFFS in this patient subset versus the entire cohort of patients (P = 0.66). At a median follow-up of 113 months (range, 4-233), 5- and 10-year BFFS rates were 78.8% and 73.7%, respectively, with OS rates of 93.3% and 81.4%. The 5-year BFFS rates in three groups were as follows: 69.6% (66-68 Gy), 80.5% (70 Gy) and 82.6% (72 Gy) (P = 0.12):the corresponding 10-year rates were 63.9%, 72.9%, and 82.6% (P = 0.12), respectively. No significant between-group differences were observed in MFS, CSS, or OS. On the univariate analysis, the following variables were significantly associated with BFFS: PSA at diagnosis; clinical stage (cT1 vs cT2); GS at diagnosis; treatment indication (ART vs SRT); pre-RT PSA levels; and RT dose 66 -68 Gy vs. 72 Gy (HR: 2.05; 95%CI: 1.02-4.02, P = 0.04). On the multivariate analysis, the following variables remained significant: biopsy GS (HR: 2.85; 95%CI: 1.83-4.43, P < 0.001); clinical stage (HR: 2.31; 95%CI: 1.47-4.43, P = 0.01); and treatment indication (HR: 4.11; 95%CI: 2.06-8.17, P < 0.001). Acute grade (G) 1 GU toxicity was observed in 11 (20.4%), 17 (19.8%), and 3 (8.3%) patients in each group (66-68 Gy, 70 Gy and 72 Gy), respectively (P = 0.295). Acute G2 toxicity was observed in 2 (3.7%), 4 (4.7%) and 2 (5.6%) patients, respectively (P = 0.949). Acute G1 GI toxicity was observed in 16 (29.6%), 23 (26.7%) and 2 (5.6%) patients in each group, respectively (P = 0.011). Acute G2 GI toxicity was observed in 2 (3.7%), 6 (6.9%) and 1 (2.8%) patients, respectively (P = 0.278). No cases of acute G3 GI toxicity were observed.CONCLUSIONThe findings of this retrospective study suggest that postoperative radiotherapy dose intensification in PCa is not superior to conventional radiotherapy treatment.

The clinical relative biological effectiveness and prostate-specific antigen kinetics of carbon-ion radiotherapy in low-risk prostate cancer.

To evaluate the clinical relative biological effectiveness (RBE) of carbon-ion radiotherapy (C-ion RT) for prostate cancer. The records of 262 patients with low-risk prostate cancer (median age, 65 [47-80] years) treated with C-ion RT at QST Hospital, National Institutes for Quantum Science and Technology in Japan during 2000-2018 were reviewed retrospectively. Four different protocol outcomes and prostate-specific antigen (PSA) responses were evaluated. The median follow-up was 8.4 years. The Kaplan-Meier method was used to estimate the biochemical or clinical failure-free rate (BCFFR). Clinical RBE was calculated using the tumor control probability model. The 5-, 7-, and 10-year BCFFRs were 91.7%, 83.8%, and 73.2%, respectively. The 10-year BCFFRs of patients who received C-ion RT at 66 Gy (RBE) in 20 fractions, 63 Gy (RBE) in 20 fractions, and 57.6Gy (RBE) in 16 fractions were 81.4%, 70.9%, and 68.9%, respectively. The PSA level and density during follow-up were better in the patients treated with the lower fraction size. A higher PSA nadir and shorter time to PSA nadir were risk factors for biochemical or clinical failure by multivariate Cox regression. The tumor control probability analysis showed that the estimated clinical RBE values to achieve an 80% BCFFR at 10 years for 20, 16, and 12 fractions were 2.19 (2.18-2.24), 2.16 (2.14-2.23), and 2.12 (2.09-2.21), respectively. Using clinical data from low-risk prostate cancer patients, we showed the clinical RBE of C-ion RT decreased with increasing dose per fraction.

A Prospective Study of Stereotactic Body Radiotherapy (SBRT) with Concomitant Whole-Pelvic Radiotherapy (WPRT) for High-Risk Localized Prostate Cancer Patients Using 1.5 Tesla Magnetic Resonance Guidance: The Preliminary Clinical Outcome.

Simple SummaryMagnetic resonance (MR)-guided stereotactic body radiotherapy (MRgSBRT) with concomitant whole-pelvic nodal radiotherapy (WPRT) represents a novel radiotherapy paradigm for high-risk prostate cancer (HR-PC), potentially improving online image guidance and clinical outcomes. This is the first prospective study aims to report the preliminary clinical experiences and treatment outcome of 1.5 Tesla adaptive MRgSBRT with concomitant WPRT in HR-PC patients (72.5 ± 6.8 years). Forty-two consecutive localized HR-PC patients were treated by online adaptive MRgSBRT (8 Gy(prostate)/5 Gy(WPRT) × 5 fractions) combined with androgen deprivation therapy (ADT) and followed up (median: 251 days, range: 20–609 days). The maximum cumulative acute gastrointestinal (GI)/ genitourinary (GU) grade 1 and 2 toxicity rates were 19.0%/81.0% and 2.4%/7.1%, respectively. The subacute (>30 days) GI/GU grade 1 and 2 toxicity rates were 21.4%/64.3% and 2.4%/2.4%, respectively. No grade 3 toxicities were reported. Patient-reported quality of life (QoL) showed insignificant changes in urinary, bowel, sexual, and hormonal domain scores during the follow-up period. All patients had early post-MRgSBRT biochemical responses, while biochemical recurrence (prostate-specific antigen nadir + 2 ng/mL) occurred in one patient at month 18. The early results suggested favorable treatment-related toxicities and encouraging patient-reported QoLs, but long-term follow-up is still needed. Background: Conventionally fractionated whole-pelvic nodal radiotherapy (WPRT) improves clinical outcome compared to prostate-only RT in high-risk prostate cancer (HR-PC). MR-guided stereotactic body radiotherapy (MRgSBRT) with concomitant WPRT represents a novel radiotherapy (RT) paradigm for HR-PC, potentially improving online image guidance and clinical outcomes. This study aims to report the preliminary clinical experiences and treatment outcome of 1.5 Tesla adaptive MRgSBRT with concomitant WPRT in HR-PC patients. Materials and methods: Forty-two consecutive HR-PC patients (72.5 ± 6.8 years) were prospectively enrolled, treated by online adaptive MRgSBRT (8 Gy(prostate)/5 Gy(WPRT) × 5 fractions) combined with androgen deprivation therapy (ADT) and followed up (median: 251 days, range: 20–609 days). Clinical outcomes were measured by gastrointestinal (GI) and genitourinary (GU) toxicities according to the Common Terminology Criteria for Adverse Events (CTCAE) Scale v. 5.0, patient-reported quality of life (QoL) with EPIC (Expanded Prostate Cancer Index Composite) questionnaire, and prostate-specific antigen (PSA) responses. Results: All MRgSBRT fractions achieved planning objectives and dose specifications of the targets and organs at risk, and they were successfully delivered. The maximum cumulative acute GI/GU grade 1 and 2 toxicity rates were 19.0%/81.0% and 2.4%/7.1%, respectively. The subacute (>30 days) GI/GU grade 1 and 2 toxicity rates were 21.4%/64.3% and 2.4%/2.4%, respectively. No grade 3 toxicities were reported. QoL showed insignificant changes in urinary, bowel, sexual, and hormonal domain scores during the follow-up period. All patients had early post-MRgSBRT biochemical responses, while biochemical recurrence (PSA nadir + 2 ng/mL) occurred in one patient at month 18. Conclusions: To our knowledge, this is the first prospective study that showed the clinical outcomes of MRgSBRT with concomitant WPRT in HR-PC patients. The early results suggested favorable treatment-related toxicities and encouraging patient-reported QoLs, but long-term follow-up is needed to confirm our early results.

Clinical Implications of Nadir Serum Prostate-Specific Antigen Levels After Transurethral Enucleation of the Prostate.

ObjectiveProstate-specific antigen levels after transurethral enucleation of the prostate may serve as indicators of residual cancer foci. The objective of this study was to investigate the association between the post-transurethral enucleation of the prostate nadir prostate-specific antigen level and prostate cancer.Materials and MethodsWe retrospectively reviewed the data of 428 men who underwent transurethral enucleation of the prostate between March 2015 and April 2021. Based on the following exclusion criteria, we excluded 106 men from our analysis: men with metastatic prostate cancer, incomplete transurethral enucleation of the prostate, and missing prostate-specific antigen or prostate size data. Three hundred and twenty-two patients were finally enrolled in our study. These patients were classified into four groups according to the surgical pathology: benign, transition zone (cancer only in the adenoma or transition zone), peripheral zone, and transition and peripheral zones. The optimal cutoff post-transurethral enucleation of the prostate nadir prostate-specific antigen level that predicted residual prostate cancer was determined using receiver operating characteristic curve analysis.ResultsIn total, 71 (22.0%) men exhibited prostate cancer (median follow-up, 38.0 months). The benign and combined cancer groups showed similar adenoma removal rates (103.0% and 106.7%, respectively). The median nadir prostate-specific antigen levels after transurethral enucleation of the prostate were 0.76, 0.63, 1.79, and 1.70 ng/ml in the benign, transition zone, peripheral zone, and transition and peripheral zone groups, respectively (p < 0.001), with no difference between the benign and transition zone groups (p = 0.458); this suggested that complete transurethral enucleation of the prostate removed all cancer nests in the adenoma in the transition zone group. Receiver operating characteristic curve analysis showed that nadir prostate-specific antigen ≧1.7 ng/ml predicted residual cancer (area under the curve: 0.787) or cancer with a Gleason score of ≧7 (area under the curve: 0.816) in the remaining prostate. Limitations include the retrospective design and the perioperative peripheral zone biopsy rate.ConclusionsThe post-transurethral enucleation of the prostate nadir prostate-specific antigen ≧1.7 ng/ml after complete transurethral enucleation of the prostate can predict significant residual cancer. Prostate cancer patients with low post-transurethral enucleation of the prostate prostate-specific antigen levels can be conservatively managed.

Biochemical Failure Is Not a Surrogate End Point for Overall Survival in Recurrent Prostate Cancer: Analysis of NRG Oncology/RTOG 9601.

Metastasis-free survival (MFS), but not event-free survival, is a validated surrogate end point for overall survival (OS) in men treated for localized prostate cancer. It remains unknown if this holds true in biochemically recurrent disease after radical prostatectomy. Leveraging NRG/RTOG 9601, we aimed to determine the performance of intermediate clinical end points (ICEs) as surrogate end points for OS in recurrent prostate cancer. NRG/RTOG 9601 randomly assigned 760 men with recurrence after prostatectomy to salvage radiation therapy with 2 years of placebo versus bicalutamide 150 mg daily. ICEs assessed were biochemical failure (BF) per NRG/RTOG 9601 (prostate-specific antigen nadir + 0.3-0.5 ng/mL or initiation of salvage hormone therapy; [BF1]) and NRG/RTOG 0534 (prostate-specific antigen nadir+2 ng/mL; [BF2]), distant metastasis (DM), and MFS (DM or death). Surrogacy was assessed by the Prentice criteria and a two-stage meta-analytic approach (condition one assessed at the patient level with Kendall's τ and condition two assessed by randomly dividing the entire trial cohort into 10 pseudo trial centers and calculating the average R2 between treatment hazard ratios for ICE and OS). BF1, BF2, DM, and MFS satisfied the four Prentice criteria. However, with the two-condition meta-analytic approach, there was strong correlation between MFS and OS (τ = 0.86), moderate correlation between DM and OS (τ = 0.66), and weaker correlation between BF1 (τ = 0.25) or BF2 (τ = 0.40) and OS. Similarly, for condition two, the treatment effect of antiandrogen therapy on MFS and OS were correlated (R2 = 0.67), but this was not true for BF1 (R2 = 0.09), BF2 (R2 = 0.12), or DM (R2 = 0.18) and OS. MFS is also a strong surrogate for OS in men receiving salvage radiation therapy for recurrence after prostatectomy. Caution should be used when inferring survival benefit from effects on BF in biochemically recurrent prostate cancer. Lack of comorbidity data did not allow us to assess whether BF in men with no/minimal comorbidity could serve as a surrogate for OS.

Progression time of de novo metastases in relation to castration resistant prostate cancer at a tertiary care hospital in Southern Thailand

Objective: Androgen deprivation therapy (ADT) is often the treatment of choice in metastatic prostate cancer patients. However, there is currently an insufficiency of biomarker-related data that can be used in order to predict how the disease would respond to ADT. In this study we evaluated the clinical response to ADT, including factors which are affecting the progression of the disease into castration-resistant prostate cancer (CRPC) in patients with de novo metastatic prostate cancer. Materials and Methods: This retrospective study incorporated patients with metastatic prostate cancer who received ADT at our center from January 2008 to December 2019. Baseline characteristics, mode of ADT, prostate-specific antigen (PSA), blood chemistry, Gleason score (GS) grade group, location, and the number of metastases were analyzed. The risk factors affecting the progression of the disease were identified. Results: Data from 125 patients were included in the study. One hundred patients (80%) were classified as suffering from high volume metastatic prostate cancer and six patients (6%) with visceral metastasis. Baseline PSA in high volume and low volume metastatic prostate cancer were defined as 500 ng/ml and 215.1 ng/ ml respectively. Eighty-one patients (64.8%) received a gonadotrophin-releasing hormone (GnRH) agonist while 42 patients (33.6%) underwent bilateral orchi- ectomy. Time to CRPC in high and low volume metastasis was 12 months and 23 months respectively. Patients with Alkaline Phosphatase (ALP) ≥350 U/L had 8.5 months to CRPC while patients with ALP &lt;350 U/L had 15 months. High GS grade group (3-5), short time to PSA nadir (&lt;6 months), PSA nadir level (≥ 2 ng/ ml), and serum ALP ≥350 U/L were independent factors associated with shorter time to CRPC. Conclusion: The clinical management of metastatic prostate cancer is challenging; the main aims of treatment are to prolong overall survival whilst maintaining quality of life. Patients with aggressive tumors, high volume metastasis, short time to nadir (TTN), high PSA nadir level, and high ALP level were independent factors associated with shorter time to CRPC.

Cancer de la prostate de risque intermédiaire traité par irradiation externe exclusive : focus sur les sites anatomiques de récidive dans deux essais français

PurposeRetrospective description of anatomical sites of relapse based on (18F)-choline PET-CT, (68Ga)-prostatic specific-membrane antigen PET-CT, bone scan, and prostate magnetic resonance imaging (MRI) data. Materials and methodsFrom two French prospective cohorts, patients treated with exclusive radiotherapy for an intermediate-risk cancer were identified during their follow-ups. They were included if they presented a rising of the prostate-specific antigen (PSA) associated with the realization of an imaging showing the sites of recurrences. ResultsTwo hundred and sixty-three patients were included. After a median follow-up of 76 months (interquartile range [IQR] 67–95), 65 patients had biochemical recurrence and positive imaging. The median nadir PSA was 0.6ng/mL and the median PSA at recurrence was 3.4ng/mL. A single lesion was found in 48% of cases, 2 to 4 lesions in 43% of cases and more than 4 lesions in 9% of cases. The sites of relapse identified were prostate (37/65), prostate only (19/65), seminal vesicles (9/65) Pelvic nodes (35/65), extrapelvic nodes (15/65) and bone (13/65). ConclusionsThe majority of relapses presented as a single lesion localized in the pelvis.

Association of prostate-specific antigen (PSA) response and overall survival (OS) in patients with metastatic hormone-sensitive prostate cancer (mHSPC) from the phase 3 ARASENS trial.

5078 Background: Reductions in PSA level have been associated with improved OS in patients (pts) with mHSPC. In ARASENS (NCT02799602), darolutamide (DARO) + androgen-deprivation therapy (ADT) in combination with docetaxel significantly reduced the risk of death by 32.5% (hazard ratio [HR] 0.675; 95% confidence interval [CI] 0.568–0.801; P&lt; 0.0001) vs ADT + docetaxel in pts with mHSPC. We report the association between PSA response and OS from ARASENS. Methods: Pts with mHSPC were randomized 1:1 to DARO 600 mg twice daily or matching PBO + ADT and docetaxel. Serum PSA was measured at screening and every 12 weeks. Exploratory analyses included time to PSA progression (≥25% increase from PSA nadir [lowest or at study entry] and PSA increase ≥2 ng/mL ≥12 weeks from nadir [both confirmed by a second value ≥3 weeks later]) and undetectable PSA (&lt; 0.2 ng/mL for 2 samples ≥3 weeks apart) at 24, 36, and 52 weeks and any time during treatment. Comparisons between treatment groups were performed using the Cochran-Mantel Haenszel test stratified by randomization stratification factors (metastatic spread according to TNM classification and alkaline phosphatase levels at study entry). Post hoc landmark analyses evaluated the association between undetectable PSA at weeks 24 and 36 and OS for the overall population. Results: Of 1306 randomized pts, 1305 were included in the full analysis set (DARO 651; PBO 654), both with ADT and docetaxel. Median (range) PSA levels at study entry were 30.3 (0.0–9219.0) and 24.2 (0.0–11,947.0) ng/mL, respectively. DARO significantly prolonged time to PSA progression (HR 0.255; 95% CI 0.208–0.313; P&lt; 0.0001). Undetectable PSA was achieved in more pts receiving DARO (48.7%) vs PBO (23.9%) at 24 weeks, and the rate continued to increase at 36 and 52 weeks in the DARO group to 57.1% and 60.2%, respectively, vs minimal change in the PBO group (25.1% and 26.1%). Undetectable PSA levels at any time were achieved in 67.3% in the DARO group and 28.6% in the PBO group. A treatment difference in undetectable PSA based on non-overlapping 95% CIs was observed at all time points. For the overall population, OS was improved for pts who achieved undetectable PSA levels vs those who did not at 24 weeks (HR 0.398; 95% CI 0.321–0.493) and 36 weeks (HR 0.351; 95% CI 0.284–0.434). Additional baseline and safety data by PSA level will be reported. Conclusions: The combination of DARO + ADT and docetaxel significantly prolonged the time to PSA progression and more pts receiving DARO vs PBO achieved undetectable PSA levels, reflecting strong PSA response over time. In pts with mHSPC, achievement of undetectable PSA at 24 and 36 weeks was associated with improved OS, with risk of death reduced by 60% and 65%, respectively, vs those who did not achieve undetectable PSA at 24 and 36 weeks. Clinical trial information: NCT02799602.

PD22-09 DISTINGUISHING BETWEEN PROSTATE SPECIFIC ANTIGEN BOUNCE AND BIOCHEMICAL RECURRENCE FOLLOWING STEREOTACTIC BODY RADIOTHERAPY FOR PROSTATE CANCER

You have accessJournal of UrologyCME1 May 2022PD22-09 DISTINGUISHING BETWEEN PROSTATE SPECIFIC ANTIGEN BOUNCE AND BIOCHEMICAL RECURRENCE FOLLOWING STEREOTACTIC BODY RADIOTHERAPY FOR PROSTATE CANCER Ashley Monaco, Jessica Sommer, Jordan Mendelson, Jonathan Haas, Anthony Corcoran, and Aaron Katz Ashley MonacoAshley Monaco More articles by this author , Jessica SommerJessica Sommer More articles by this author , Jordan MendelsonJordan Mendelson More articles by this author , Jonathan HaasJonathan Haas More articles by this author , Anthony CorcoranAnthony Corcoran More articles by this author , and Aaron KatzAaron Katz More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002564.09AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: While prostate specific antigen (PSA) bounce following radiation therapy for prostate cancer (PCa) treatment is well established, the parameters to predict this occurrence and differentiate it from biochemical recurrence (BCR) following stereotactic body radiotherapy (SBRT) are unknown. The purpose of this study is to investigate associations between pre-treatment and post-treatment variables among patients experiencing PSA bounce, BCR, or neither following SBRT. METHODS: An IRB-approved PCa database was reviewed for patients who underwent primary SBRT. Patients with less than 18 months of follow-up or were missing >3 PSA measurements following SBRT were excluded. Patients were divided into outcome groups experiencing PSA bounce, BCR, or neither. PSA bounce was defined as a rise of >0.2 ng/mL over the pre-rise nadir followed by a decline without intervention. BCR was defined by Phoenix criteria. Pre-treatment and post-treatment characteristics were analyzed between groups. Results that were significant when comparing PSA bounce to BCR were then analyzed in a multivariate logistic regression model to determine predictors for PSA bounce. RESULTS: We analyzed 170 men with a median age of 72 (52-87) years with an average follow-up time of 75 + 21 months, of which 28 (16%) experienced PSA bounce and 42 (25%) had BCR (Table 1). Pre-treatment D’Amico and Capra risk, Gleason group, PSA, prostate volume, prostate density and post-treatment PSA velocity were not associated with PSA bounce when compared to BCR or non-BCR/bounce cohorts. Compared to those who did not experience PSA bounce/BCR, those with PSA bounce were younger (p <.05), had lower PSA doubling time (p <.001), and took longer to reach PSA nadir (p <.001). Compared to BCR group, men with PSA bounce had lower PSA nadir and took longer to reach nadir, both of which were significant predictors for PSA bounce (OR: 4.3, p <.05; OR: 0.90, p <.001). PSA bounce occurred significantly earlier than BCR (16 vs. 33 months; p <.001). CONCLUSIONS: While there is overlap among patients who experience PSA bounce or BCR following SBRT, the timing of which the PSA rise occurs, the PSA nadir value, and the time to PSA nadir are useful variables in the management of a rising PSA in patients following SBRT. Source of Funding: Department of Urology, NYU Langone Hospital – Long Island © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e407 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Ashley Monaco More articles by this author Jessica Sommer More articles by this author Jordan Mendelson More articles by this author Jonathan Haas More articles by this author Anthony Corcoran More articles by this author Aaron Katz More articles by this author Expand All Advertisement PDF DownloadLoading ...

The addition of androgen deprivation therapy and pelvic lymph node treatment to prostate bed salvage radiotherapy (NRG Oncology/RTOG 0534 SPPORT): an international, multicentre, randomised phase 3 trial

In men with a detectable prostate-specific antigen (PSA) level after prostatectomy for prostate cancer, salvage prostate bed radiotherapy (PBRT) results in about 70% of patients being free of progression at 5 years. A three-group randomised trial was designed to determine whether incremental gains in patient outcomes can be achieved by adding either 4-6 months of short-term androgen deprivation therapy (ADT) to PBRT, or both short-term ADT and pelvic lymph node radiotherapy (PLNRT) to PBRT. The international, multicentre, randomised, controlled SPPORT trial was done at 283 radiation oncology cancer treatment centres in the USA, Canada, and Israel. Eligible patients (aged ≥18 years) were those who after prostatectomy for adenocarcinoma of the prostate had a persistently detectable or an initially undetectable and rising PSA of between 0·1 and 2·0 ng/mL. Patients with and without lymphadenectomy (N0/Nx) were eligible if there was no clinical or pathological evidence of lymph node involvement. Other eligibility criteria included pT2 or pT3 disease, prostatectomy Gleason score of 9 or less, and a Zubrod performance status of 0-1. Eligible patients were randomly assigned to receive PBRT alone at a dose of 64·8-70·2 Gy at 1·8 Gy per fraction daily (group 1), PBRT plus short-term ADT (group 2), or PLNRT (45 Gy at 1·8 Gy per fraction, and then a volume reduction made to the planning target volume for the remaining 19·8-25 ·2 Gy) plus PBRT plus short-term ADT (group 3). The primary endpoint was freedom from progression, in which progression was defined as biochemical failure according to the Phoenix definition (PSA ≥2 ng/mL over the nadir PSA), clinical failure (local, regional, or distant), or death from any cause. A planned interim analysis of 1191 patents with minimum potential follow-up time of 5 years applied a Haybittle-Peto boundary of p<0·001 (one sided) for comparison of 5-year freedom from progression rates between the treatment groups. This trial is registered with ClinicalTrials.gov, NCT00567580. The primary objectives of the trial have been completed, although long-term follow-up is continuing. Between March 31, 2008, and March 30, 2015, 1792 eligible patients were enrolled and randomly assigned to the three treatment groups (592 to group 1 [PBRT alone], 602 to group 2 [PBRT plus short-term ADT], and 598 to group 3 [PLNRT plus PBRT plus short-term ADT]). 76 patients subsequently found to be ineligible were excluded from the analyses; thus, the evaluable patient population comprised 1716 patients. At the interim analysis (n=1191 patients; data cutoff May 23, 2018), the Haybittle-Peto boundary for 5-year freedom from progression was exceeded when group 1 was compared with group 3 (difference 17·9%, SE 2·9%; p<0·0001). The difference between groups 2 and 3 did not exceed the boundary (p=0·0063). With additional follow-up beyond the interim analysis (the final planned analysis; data cutoff May 26, 2021), at a median follow-up among survivors of 8·2 years (IQR 6·6-9·4), the 5-year freedom from progression rates in all 1716 eligible patients were 70·9% (95% CI 67·0-74·9) in group 1, 81·3% (78·0-84·6) in group 2, and 87·4% (84·7-90·2) in group 3. Per protocol criteria, freedom from progression in group 3 was superior to groups 1 and 2. Acute (≤3 months after radiotherapy) grade 2 or worse adverse events were significantly more common in group 3 (246 [44%] of 563 patients) than in group 2 (201 [36%] of 563; p=0·0034), which, in turn, were more common than in group 1 (98 [18%] of 547; p<0·0001). Similar findings were observed for grade 3 or worse adverse events. However, late toxicity (>3 months after radiotherapy) did not differ significantly between the groups, apart from more late grade 2 or worse blood or bone marrow events in group 3 versus group 2 (one-sided p=0·0060) attributable to the addition of PLNRT in this group. The results of this randomised trial establish the benefit of adding short-term ADT to PBRT to prevent progression in prostate cancer. To our knowledge, these are the first such findings to show that extending salvage radiotherapy to treat the pelvic lymph nodes when combined with short-term ADT results in meaningful reductions in progression after prostatectomy in patients with prostate cancer. National Cancer Institute.

MP55-20 OUTCOMES OF PRIMARY CRYOTHERAPY FOR LOCALIZED PROSTATE CANCER: 14-YEARS SINGLE INSTITUTION EXPERIENCE

You have accessJournal of UrologyCME1 May 2022MP55-20 OUTCOMES OF PRIMARY CRYOTHERAPY FOR LOCALIZED PROSTATE CANCER: 14-YEARS SINGLE INSTITUTION EXPERIENCE Andrew Wang, Greg Mansour, and Robert Given Andrew WangAndrew Wang More articles by this author , Greg MansourGreg Mansour More articles by this author , and Robert GivenRobert Given More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002634.20AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Cryoablation, a minimally invasive ablative therapy, is recommended as an alternative treatment for localized prostate cancer (PCa) given its favorable side effect profiles on bladder and bowel function, especially in those with low- and intermediate-risk disease who are not suitable for surgery or radiation therapy. Long-term outcomes are not well characterized in the literature. We aim to report our experience with the procedure at our institution. METHODS: We retrospectively reviewed all men who underwent primary whole-gland cryoablation for localized prostate cancer at our institution from 2005 through 2019. Functional and oncologic outcomes were assessed. Recurrence-free survival was studied using Kaplan-Meier survival analysis. RESULTS: Of the 276 patients, 80% had D’Amico high- (22.8%) or intermediate- (57.6%) risk disease. Average age was 71.2 years while median follow-up was 4.7 years. Majority of the patients (83%) achieved prostate-specific antigen (PSA) nadir <0.4 ng/ml. This was associated with improved disease-free survival (p <0.00001). De novo incontinence (2%) and De novo ED rates (12%) were relatively low, and complications such as urethral stricture (n=1) and rectal urethral fistula (n=0) were extremely rare. 5 year clinical recurrence-free survival was 70% overall and 94% for low-, 86% for intermediate-, and 63% for high-risk patients in our cohort. CONCLUSIONS: Primary whole-gland cryoablation is a safe and durable medium-term treatment alternative to radiation therapy and radical prostatectomy for patients with low- and intermediate risk disease. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e946 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Andrew Wang More articles by this author Greg Mansour More articles by this author Robert Given More articles by this author Expand All Advertisement PDF DownloadLoading ...

Cytoreductive prostate cryoablation and metronomic cyclophosphamide for metastatic hormone-sensitive prostate cancer.

Aim: This study reports the outcomes of cytoreductive prostate cryoablation and metronomic cyclophosphamide for the treatment of metastatic hormone-sensitive prostate cancer (mHSPC). Methods: Patients with mHSPC from the authors' prostate cancer database who had received cytoreductive prostate cryoablation and metronomic cyclophosphamide were identified retrospectively. Results: Eight consecutive patients were enrolled in the study. All the patients tolerated combination therapy. The median metastatic castration-resistant prostate cancer-free survival was 62.5months. Seven patients (87.5%) had a prostate-specific antigen nadir <0.1ng/ml. Dysuria and hematuria before prostate cryoablation disappeared within 1 month after cryosurgery, and no incontinence was seen after prostate cryoablation. No local therapy was needed during follow-up. Conclusion: Cytoreductive prostate cryoablation and metronomic cyclophosphamide prove an effective and safe combination therapy for mHSPC.

Comparison of Testosterone and Prostate-Specific Antigen Nadir Value between Castration Resistant Prostate Cancer and Non-Castration Resistant Prostate Cancer Patients after Androgen Deprivation Therapy - A Single Center Study in Indonesia

BACKGROUND: Prostate cancer is the second most commonly occurring cancer in adult males worldwide. Androgen deprivation therapy (ADT) is the mainstay treatment for patients with advanced prostate cancer. However, despite the low testosterone level (indicative of ADT success), most advanced prostate cancers progress into an androgen unresponsive or castrate resistant state; such cases are defined as castrate-resistant prostate cancer (CRPC) and were associated with worse outcomes and more rapid prostate cancer progression. This study aimed to compare the value of nadir testosterone level and nadir PSA in CRPC and non-CRPC patients who received ADT. AIM: This study was aimed to compare value of nadir testosterone level and nadir PSA in CRPC and non-CRPC patients who received ADT. METHODS: Prostate cancer patients receiving ADT in dr. Hasan Sadikin Bandung General Hospital in September 2018–September 2020 without previous history of CRPC and surgical castration, and prostate cancer with histopathological confirmation were included to the study. The patients prior had received complete blockade ADT with luteinizing hormone agonist (LHRH) goserelin acetate 10.8 mg injected subcutaneously per 3 months and oral anti-androgen bicalutamide 50 mg orally daily. Testosterone and PSA levels were assessed on 1st, 3rd, 6th, and 12th month. Patients then were grouped into CRPC group and non-CRPC group and further subdivided according testosterone levels (&lt;20 and 20–500 ng/dL). Paired t-test and Chi-square test were used to analyze statistical difference (p &lt; 0.05 deemed significant). RESULTS: Significantly higher baseline PSA (p = 0.002) and nadir PSA (p = 0.013) were found on the CRPC group. Nadir testosterone in CRPC group was higher than non-CRPC group but statistically insignificant (p = 0.849). Time to CRPC is faster in nadir testosterone 20–50 ng/dl group than in &lt;20 ng/dl group but statistically insignificant (p = 0.837). CONCLUSION: Prostate cancer patients who had high baseline PSA and nadir PSA after ADT need a longer follow-up time and more frequent testing of the testosterone and PSA values. It can predict the incidence of CRPC and to ensure that prostate cancer patients receive adequate therapy.

Urethra Sparing With Target Motion Mitigation in Dose-Escalated Extreme Hypofractionated Prostate Cancer Radiotherapy: 7-Year Results From a Phase II Study.

PurposeTo explore whether the rectal distension-mediated technique, harnessing human physiology to achieve intrafractional prostate motion mitigation, enables urethra sparing by inverse dose painting, thus promoting dose escalation with extreme hypofractionated stereotactic ablative radiotherapy (SABR) in prostate cancer.Materials and MethodsBetween June 2013 and December 2018, 444 patients received 5 × 9 Gy SABR over 5 consecutive days. Rectal distension-mediated SABR was employed via insertion of a 150-cm3 air-inflated endorectal balloon. A Foley catheter loaded with 3 beacon transponders was used for urethra visualization and online tracking. MRI-based planning using Volumetric Modulated Arc Therapy - Image Guided Radiotherapy (VMAT-IGRT) with inverse dose painting was employed in delivering the planning target volume (PTV) dose and in sculpting exposure of organs at risk (OARs). A 2-mm margin was used for PTV expansion, reduced to 0 mm at the interface with critical OARs. All plans fulfilled Dmean ≥45 Gy. Target motion ≥2 mm/5 s motions mandated treatment interruption and target realignment prior to completion of the planned dose delivery.ResultsPatient compliance to the rectal distension-mediated immobilization protocol was excellent, achieving reproducible daily prostate localization at a patient-specific retropubic niche. Online tracking recorded ≤1-mm intrafractional target deviations in 95% of treatment sessions, while target realignment in ≥2-mm deviations enabled treatment completion as scheduled in all cases. The cumulative incidence rates of late grade ≥2 genitourinary (GU) and gastrointestinal (GI) toxicities were 5.3% and 1.1%, respectively. The favorable toxicity profile was corroborated by patient-reported quality of life (QOL) outcomes. Median prostate-specific antigen (PSA) nadir by 5 years was 0.19 ng/ml. The cumulative incidence rate of biochemical failure using the Phoenix definition was 2%, 16.6%, and 27.2% for the combined low/favorable–intermediate, unfavorable intermediate, and high-risk categories, respectively. Patients with a PSA failure underwent a 68Ga-labeled prostate-specific membrane antigen (68Ga-PSMA) scan showing a 20.2% cumulative incidence of intraprostatic relapses in biopsy International Society of Urological Pathology (ISUP) grade ≥3.ConclusionThe rectal distension-mediated technique is feasible and well tolerated. Dose escalation to 45 Gy with urethra-sparing results in excellent toxicity profiles and PSA relapse rates similar to those reported by other dose-escalated regimens. The existence of intraprostatic recurrences in patients with high-risk features confirms the notion of a high α/β ratio in these phenotypes resulting in diminished effectiveness with hypofractionated dose escalation.

The slope associated with nadir prostate‐specific antigen is prognostically significant in men with hormone‐sensitive prostate cancer after primary androgen deprivation therapy

BackgroundPrognostic indicators based on the initial prostate‐specific antigen (PSA) levels, nadir PSA, and time to PSA nadir were calculated to evaluate prognosis after primary androgen deprivation therapy (PADT), as these have been reported in very few studies. We attempted to evaluate the prognostic role of the slope associated with nadir PSA in patients treated with PADT.MethodsA total of 107 patients who were treated with PADT from 2015 to 2019 were reviewed. The Kaplan–Meier method and Cox regression model were used to analyze the prognostic significance of the slope associated with nadir PSA in predicting progression‐free survival (PFS) and overall survival (OS).ResultsAfter PADT, the median follow‐up duration was 40.1 months; 66 patients (61.7%) had disease progression, and 33 patients (30.8%) died. In the univariate analysis, T stage, N stage, nadir PSA, time to PSA nadir, nadir PSA declining slope (nPSA‐DS), nadir PSA percentage declining slope (nPSA‐PDS), and nadir PSA line slope (nPSA‐LS) were significant predictors for PFS and OS. The multivariate analysis showed that a higher nPSA‐DS (> − 0.74) and lower PSA nadir (≤0.16 ng/ml) were independent predictors for prolonged survival. The significance of nPSA‐DS and nPSA was supported by the analysis of nPSA‐DS and nPSA as time‐dependent covariates. The combined analyses demonstrated that patients with a higher nPSA‐DS and lower PSA nadir had the best PFS and OS.ConclusionsThe slope associated with the nadir PSA of nPSA‐DS was a significant independent predictor for patients treated with PADT. Nadir PSA and nPSA‐DS have a synergistic effect on prognosis.