Nadir Prostate-specific Antigen Level Research Articles

Remission Depth in Metastatic Hormone-Sensitive Prostate Cancer Is Associated With Prognosis in Patients With Initial Prostate-Specific Antigen Values Above 100 Ng/ML.

Recently, new drugs have caused a paradigm shift in the treatment of metastatic hormone-sensitive prostate cancer (HSPC). Meanwhile, research has identified several prognostic factors of metastatic HSPC. The present study focused on remission depth in metastatic HSPC and evaluated its association with remission depth. We analyzed 427 patients diagnosed with metastatic HSPC with serum initial prostate-specific antigen (PSA) > 100 ng/ml. The nadir serum PSA value was used as a marker of remission depth for each duration to castration resistanceby using receiver operating characteristic (ROC) curves.Cox proportional hazards regression was used to assess for any correlation of progression-free survival (PFS) and overall survival (OS) with the nadir PSA level. The cut-off value for the nadir PSA level per time to castration resistance (TTCR) at three, five, seven, and nine years was calculated. The nadir PSA value alone was able to predict prognosis because of its high sensitivity, high specificity, and high AUC in ROC analysis. The nadir PSA level can be an independent prognostic marker not only for TTCR but also for OS on multivariate analysis. We identified the cut-off value for nadir PSA per TTCR period in patients with metastatic HSPC. The nadir PSA value alone can predict prognosis; this demonstrates utility in routine clinical practice due to its simplicity and accuracy.

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.

The Association Between [68Ga]PSMA PET/CT Response and Biochemical Progression in Patients with High-Risk Prostate Cancer Receiving Neoadjuvant Therapy.

Our previous study found that the prostate-specific membrane antigen (PSMA) PET/CT response of primary prostate cancer (PCa) to neoadjuvant therapy can predict the pathologic response. This study was designed to investigate the association between [68Ga]PSMA PET/CT changes and biochemical progression-free survival (bPFS) in high-risk patients who underwent neoadjuvant therapy before radical prostatectomy (RP). Methods: Seventy-five patients with high-risk PCa in 2 phase II clinical trials who received neoadjuvant therapy before RP were included. The patients received androgen deprivation therapy plus docetaxel (n = 33) or androgen deprivation therapy plus abiraterone (n = 42) as neoadjuvant treatment. All patients had serial [68Ga]PSMA PET/CT scans before and after neoadjuvant therapy. Age, initial prostate-specific antigen level, nadir prostate-specific antigen level before RP, tumor grade at biopsy, treatment regimen, clinical T stage, PET imaging features, pathologic N stage, and pathologic response on final pathology were included for univariate and multivariate Cox regression analyses to identify independent predictors of bPFS. Results: With a median follow-up of 30 mo, 18 patients (24%) experienced biochemical progression. Multivariate Cox regression analyses revealed that only SUVmax derived from posttreatment [68Ga]PSMA PET/CT and pathologic response on final pathology were independent factors for the prediction of bPFS, with hazard ratios of 1.02 (95% CI, 1.00-1.04; P = 0.02) and 0.12 (95% CI, 0.02-0.98; P = 0.048), respectively. Kaplan-Meier analysis revealed that patients with a favorable [68Ga]PSMA PET/CT response (posttreatment SUVmax < 8.5) or a favorable pathologic response (pathologic complete response or minimal residual disease) had a significantly lower rate of 3-y biochemical progression. Conclusion: Our results indicated that [68Ga]PSMA PET/CT response was an independent risk factor for the prediction of bPFS in patients with high-risk PCa receiving neoadjuvant therapy and RP, suggesting [68Ga]PSMA PET/CT to be an ideal tool to monitor response to neoadjuvant therapy.

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

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

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

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

Proton Therapy for Localized Prostate Cancer: Long-Term Clinical Outcomes at a Comprehensive Cancer Center

<h3>Purpose/Objective(s)</h3> To assess the effectiveness and toxicity of proton therapy for patients with localized prostate cancer at a comprehensive cancer center. <h3>Materials/Methods</h3> Patients (n=2773) participating in two prospective clinical trials were treated from May 2006 through January 2020 at a comprehensive care center and stratified according to the National Comprehensive Cancer Network guidelines (n=640 low-risk [LR], n=850 favorable-intermediate risk [F-IR], n=851 unfavorable-intermediate risk [U-IR], n=315 high risk [HR], and n=117 very high risk [VHR]). Median patient age was 66 years; median follow-up time was 7.0 years. Median prostate-specific antigen (PSA) level at 7 years was 0.3 ng/mL (interquartile range [IQR] 0.2–0.4). Pelvic lymph node irradiation was given to 29 of 2773 patients (1%) (2/851 [0.2%] U-IR, 11/315 [3.5%] HR, and 16/117 [13.7%] VHR). The median PT dose was 78 Gy in 1.8–2.0 Gy(RBE) per fraction; 63% of patients received 78 Gy(RBE) in 39 fractions, and 29% received 76 Gy(RBE) in 38 fractions. Androgen deprivation therapy (ADT) was used in 1471 patients (53%) (68/640 [10.6%] LR, 329/850 [38.7%] F-IR, 642/851 [75.4%] U-IR, 315/315 [100%] HR, and 117/117 [100%] VHR), with a median duration of 6 months for U-IR and 24 months for HR and VHR groups. Biochemical failure was defined as post-treatment nadir PSA level + 2 ng/mL. Toxicity was graded according to the modified RTOG/EORTC morbidity scale. Descriptive statistics and Kaplan-Meier estimates were used to assess toxicity and survival. <h3>Results</h3> Freedom from biochemical relapse (FFBR) rates at 5 and 10 years were 98.3% (95% confidence interval [CI] 96.9-99.1%) and 97% (95% CI 94.8-98.3%) for the LR group; 98.3% (95% CI 97.0-99.0%) and 93.6% (95% CI 90.6-95.7%) for the F-IR; 94.2% (95% CI 92.1-95.7%) and 90.2% (95% CI 87.3-92.5%) for the U-IR; 94.3% (95% CI 90.1-96.8%) and 85.2% (95% CI 77.1-90.8%) for the HR; and 86.1% (95% CI, 74.7-92.9%) and 68.5% (95% CI, 50.9-82.1%) for the VHR group. Two patients died of prostate cancer, one VHR (at 19.5 months) and the other U-IR (at 28.5 months). The overall rate of acute grade ≥3 genitourinary (GU) toxicity was 6/2773 (0.22%). The overall rates of late grade ≥3 GU and gastrointestinal (GI) toxicities were 23/2773 (0.83%) and 26/2773 (0.94%). Maximum toxicities experienced were grade 4 acute GU in 1 patient, grade 4 late GU in 2 patients, and grade 4 late GI in 6 patients. <h3>Conclusion</h3> Long-term clinical outcomes for men treated with proton therapy for localized prostate cancer were excellent in all risk groups. The benefits of pelvic lymph node radiation therapy may be greatest in the VHR group, whereas the benefits of ADT may be highest in the U-IR, HR, and VHR groups.

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.

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.

Nadir prostate-specific antigen as a prognostic factor of 10-year cancer-specific survival of prostate cancer patients with bone metastases

Background: In Taiwan, the proportion of men with newly diagnosed bony metastatic prostate cancer (PC) is approximately 30%. The present study aims to determine the 10-year cancer-specific survival rate and clinical prognostic factors of men with newly diagnosed bone metastatic PC that were treated with hormone therapy.Materials and Methods: Between January 1983 and December 2008, 257 patients with bone metastatic PC were identified at initial diagnosis. Clinical and pathological data were collected from their medical chart records. Performance status, body mass index, clinical symptoms, initial serum prostate-specific antigen (PSA), nadir PSA level (nPSA), and treatment modality were reviewed retrospectively. Statistical methods included descriptive statistics, bivariate analyses, Kaplan–Meier survival analyses, and Cox regression analysis for investigating the relationship between the clinical factors and disease survival.Results: The average follow-up time was 36.4 months (±29.1 months) and the median survival time was 58.1 months. Using Kaplan–Meier survival analyses, the overall 10-year survival rate was 33%. The multivariate Cox regression hazard model revealed that patients with a posttreatment nPSA level >10 ng/mL have a higher probability of death than those with an nPSA <0.5 ng/mL (Hazard ration: 2.63, 95% confidence interval: 1.16–5.97, P = 0.020).Conclusion: Posttreatment nadir serum PSA level significantly influences the survival of patients with bone metastatic PC. A lower limit of 0.5 ng/mL for the nPSA level is a valuable prognostic factor for survival in patients initially diagnosed with bone metastatic PC and treated with hormone therapy.

A prospective phase-II trial of biweekly docetaxel plus androgen deprivation therapy in patients with previously-untreated metastatic castration-na\xefve prostate cancer

IntroductionThe aim of this prospective phase II study was to evaluate the efficacy and safety of biweekly docetaxel plus androgen-deprivation therapy (ADT) in patients with metastatic castration-naïve prostate cancer (mCNPC).Patients and methodsPatients with histologically-proven, previously-untreated mCNPC received ADT plus docetaxel, 40 mg/m2. Docetaxel was repeated every 2 weeks, up to 12 cycles. Endpoints included castration-resistant prostate cancer (CRPC)-free survival, prostate-specific antigen (PSA) response, and safety.ResultsA total of 42 patients were registered and analyzed for final outcomes. Of the 42 patients, 36 (86%) completed the 12 planned cycles of docetaxel plus ADT. During a median follow up of 25 months, all but two patients (95%) achieved a PSA response with a nadir PSA level of 0.42 ng/ml (range 0.01–1280.87). The median CRPC-free survival was 26.4 months (95% confidence interval [CI] 20.9–32.0) with a one-year CRPC-free rate of 79% (33 patients, 95% CI 66–91). Multivariable analysis revealed that the performance status of the Eastern Cooperative Oncology Group 0 was independently associated with longer CRPC-free survival (hazard ratio [HR] 0.27, 95% CI 0.07–0.99). The most common adverse events of any grade were anemia (95%), followed by nail changes (33%), fatigue (29%), and oral mucositis (26%). Severe (grade 3 or higher) adverse events were infrequent: pneumonitis (n = 2), diarrhea (n = 1), and neutropenia (n = 1).ConclusionOur results suggest that biweekly docetaxel plus ADT is feasible, and clinical efficacy does not seem to be compromised compared to a standard triweekly docetaxel 75 mg/m2 plus ADT regimen.

Prostate-specific antigen nadir and testosterone level at prostate-specific antigen failure following radiation and androgen suppression therapy for unfavorable-risk prostate cancer and the risk of all-cause and prostate cancer-specific mortality.

Although both PSA nadir (PSAn) and testosterone levels at PSA failure are known prognostic factors in men undergoing radiation therapy (RT) and androgen deprivation therapy (ADT) for unfavorable-risk prostate cancer (PC), it is unclear whether their prognostic significance is independent or overlapping. Seventy-five men treated with RT with or without 6months of ADT for unfavorable-risk nonmetastatic PC enrolled in 2 prospective clinical trials between 1986 and 2001 formed the study cohort. Competing risks and Cox multivariable regression were used to assess whether low versus normal serum testosterone at the time of PSA failure and higher PSAn after initial therapy were independently associated with the risk of PC-specific (PCSM) and all-cause mortality (ACM) adjusting for PC prognostic factors. After a median follow-up of 15.34years (interquartile range, 6.66-16.88years), there were 53 deaths (73.3%): 30 (56.6%) were from PC. Low testosterone at PSA failure was significantly associated with an increased risk of PCSM (adjusted HR [AHR], 7.77; 95% CI, 1.14-52.99; P=.04) and ACM (AHR, 3.01; 95% CI, 1.01-8.96; P=.05), as was higher PSAn (PCSM AHR, 1.03; 95% CI, 1.01-1.05; P<.01; ACM AHR, 1.04; 95% CI, 1.02-1.07; P<.01), although the prognostic significance of PSAn was only noted in men with a normal testosterone at PSA failure. Low testosterone level at PSA failure in high-risk patients with PC treated with RT is associated with increased PCSM and ACM risk. In men with normal testosterone levels at the time of PSA failure, an elevated PSAn was associated with worse PCSM and ACM risk. This study investigates whether the prostate-specific antigen (PSA) nadir and normal versus low testosterone at the time of PSA failure provide mutually exclusive or overlapping prognostic information following treatment with radiation and androgen deprivation therapy for unfavorable-risk patients with prostate cancer using data from 2 prospective clinical trials. It was found that both provided prognostic information; however, higher PSA nadir was only found to be of prognostic significance in men with normal testosterone levels at PSA failure.

Impact of perioperative factors on nadir serum prostate-specific antigen levels after holmium laser enucleation of prostate.

ObjectiveTo investigate the relationship of preoperative prostate size, urinary retention, positive urine culture, and histopathological evidence of prostatitis or incidental prostate cancer on baseline and 3‐month nadir prostate‐specific antigen (PSA) value after Holmium laser enucleation of prostate (HoLEP).Patients and methodsData from 90 patients who underwent a HoLEP by En‐bloc technique were analyzed. PSA values at baseline and at 3‐month follow‐up, preoperative urinary retention and urine culture status, weight of resected tissue, and histopathological evidence of prostatitis or prostate cancer were recorded. We performed univariable and multivariable gamma‐regression analyses to determine the impact of the aforementioned perioperative variables on preoperative PSA, 3‐month postoperative PSA, and change in PSA.ResultsSerum PSA reduced significantly at 3 months from 6.3 ± 5.9 ng/mL to 0.6 ± 0.6 ng/mL. On both univariable and multivariable analysis, 3‐month nadir level was independent of all preoperative factors examined, except preoperative urinary retention status. Although patients with smaller prostate (resected tissue weight <40 g) had less percentile reduction in PSA when compared with those with larger prostate (resected tissue weight >80 g) (77.67% vs 89.06%; P < .001), patients from both these groups noted a similar PSA nadir level after 3 months (0.54 vs 0.56 ng/dL). The drop in PSA level after HoLEP remained stable up to 1‐year follow‐up.ConclusionsPSA nadir 3 months after HoLEP remains relatively consistent across patients, regardless of preoperative prostate size, PSA value, urine culture status, and histopathological evidence of prostatitis or incidental prostate cancer.

Oncological Outcome of Combining Cytoreductive Prostatectomy and Metastasis-Directed Radiotherapy in Patients with Prostate Cancer and Bone Oligometastases: A Retrospective Cohort Study.

BackgroundThe current standard of care for metastatic prostate cancer (mPCa) is androgen deprivation therapy (ADT) with or without anti-androgen and chemotherapy. The aim of this study was to evaluate the efficacy and safety of a multimodal approach including local primary tumor therapy, metastasis-directed therapy (MDT), and hormonal therapy in patients with oligometastatic prostate cancer (PCa).MethodsWe reviewed data of patients with PCa and bone oligometastases at diagnosis treated in three institutions with ADT followed by cytoreductive surgery with or without metastases-directed radiotherapy. Oligometastases were defined as the presence of five or fewer metastatic lesions with the absence of visceral metastases. In this retrospective cohort study, 58 patients underwent cytoreductive radical prostatectomy and ADT. Of these, 26 patients (45%) received stereotactic body radiation therapy (SBRT) to all metastatic sites as a MDT. Oncological outcomes were analyzed using the Kaplan–Meier method.ResultsThe median follow-up period was 46.2 months. Of the 58 patients, the 3-year castration-resistant prostate cancer (CRPC)-free survival and cancer-specific survival was 75.9% and 91.4%, respectively. Pre- or post-treatment predictive factors for progression to CRPC, including prostate-specific antigen (PSA) level at diagnosis ≥20 ng/mL, Gleason grade groups 5, clinical T stage cT3b-4, PSA nadir level of ≥0.05 ng/mL, and no MDT with SBRT, were significantly associated with progression to CRPC. Subgroup analysis showed that the MDT group had significantly better CRPC-free survival than the non-MDT group with Gleason grade groups 1–4 (HR=0.228; 95% CI= 0.056–0.926). A total of 3.4% of the patients had grade 2 acute genitourinary toxicities and 5.2% had grade 2 acute gastrointestinal toxicities. No late grade >2 adverse events were observed.ConclusionThis multi-center, retrospective cohort study revealed the feasibility of combining cytoreductive prostatectomy and metastasis-directed radiotherapy for newly-diagnosed oligometastatic PCa. This treatment strategy has the potential to delay the progression to CRPC.

Efficacy of repeated PSMA PET-directed radiotherapy for oligorecurrent prostate cancer after initial curative therapy

PurposeTo assess the outcome of prostate cancer (PCa) patients diagnosed with oligorecurrent disease and treated with a first and a second PSMA (prostate-specific membrane antigen ligand) PET(positron-emission tomography)-directed radiotherapy (RT).Patients and methodsThirty-two patients with oligorecurrent relapse after curative therapy received a first PSMA PET-directed RT of all metastases. After biochemical progression, all patients received a second PSMA PET-directed RT of all metastases. The main outcome parameters were biochemical progression-free survival (bPFS) and androgen deprivation therapy-free survival (ADT-FS). The intervals of BPFS were analyzed separately as follows: the interval from the last day of PSMA PET-directed RT to the first biochemical progression was defined as bPFS_1 and the interval from second PSMA PET-directed RT to further biochemical progression was defined as bPFS_2.ResultsThe median follow-up duration was 39.5 months (18–60). One out of 32 (3.1%) patients died after 47 months of progressive metastatic prostate cancer (mPCa). All patients showed biochemical responses after the first PSMA PET-directed RT and the median prostate-specific antigen (PSA) level before RT was 1.70 ng/mL (0.2–3.8), which decreased significantly to a median PSA nadir level of 0.39 ng/mL (range <0.07–3.8; p = 0.004). The median PSA level at biochemical progression after the first PSMA PET-directed RT was 2.9 ng/mL (range 0.12–12.80; p = 0.24). Furthermore, the PSA level after the second PSMA PET-directed RT at the last follow-up (0.52 ng/mL, range <0.07–154.0) was not significantly different (p = 0.36) from the median PSA level (1.70 ng/mL, range 0.2–3.8) before the first PSMA PET-directed RT. The median bPFS_1 was 16.0 months after the first PSMA PET-directed RT (95% CI 11.9–19.2) and the median bPFS_2 was significantly shorter at 8.0 months (95% CI 6.3–17.7) after the second PSMA PET-directed RT (p = 0.03; 95% CI 1.9–8.3). Multivariate analysis revealed no significant parameter for bPFS_1, whereas extrapelvic disease was the only significant parameter (p = 0.02, OR 2.3; 95% CI 0.81-4.19) in multivariate analysis for bPFS_2. The median ADT-FS was 31.0 months (95% CI 20.1–41.8) and multivariate analysis showed that patients with bone metastases, compared to patients with only lymph node metastases at first PSMA PET-directed RT, had a significantly higher chance (p = 0.007, OR 4.51; 95% CI 1.8–13.47) of needing ADT at the last follow-up visit.ConclusionIf patients are followed up closely, including PSMA PET scans, a second PSMA PET-directed RT represents a viable treatment option for well-informed and well-selected patients.

MP09-19 PSA KINETICS IN INITIAL ANDROGEN DEPRIVATION THERAPY IS A PROGNOSTIC FACTOR IN PATIENTS WITH METASTATIC CASTRATION RESISTANT PROSTATE CANCER

INTRODUCTION AND OBJECTIVE:We determine whether the nadir prostate-specific antigen level (PSA nadir) and time to nadir (TTN) during initial androgen deprivation therapy (ADT) are prognostic factor...

Impact of nadir PSA level and time to nadir during initial androgen deprivation therapy on prognosis in patients with metastatic castration-resistant prostate cancer.

241 Background: It is unknown whether the nadir prostate-specific antigen level (PSA nadir) and time to nadir (TTN) during initial androgen deprivation therapy (ADT) are prognostic factors in metastatic castration resistant prostate cancer (mCRPC) patients. Methods: We reviewed the Michinoku Urological Cancer Study Group database, including 321 mCRPC patients. Optimal cutoff values for PSA nadir and TTN on survival were calculated with the receiver operating characteristic (ROC) curve. Patients were stratified into unfavorable (higher PSA nadir and/or shorter TTN) and favorable (lower PSA nadir and longer TTN) groups. The inversed probability of treatment weighing (IPTW) adjusted Cox proportional hazard model was performed to evaluate the impact of the unfavorable group on overall survival (OS) after CRPC diagnosis. Results: Median age and follow-up period were 71 years and 35 months, respectively. ROC curve analysis demonstrated cutoffs of PSA nadir &gt;0.64 ng/mL and TTN &lt;7 months. The unfavorable group included 248 patients who had significantly shorter OS after mCRPC and CRPC-free survival. The Cox proportional and IPTW-adjusted multivariate analyses revealed that the unfavorable group had a negative impact on OS in mCRPC patients (hazards ratio [HR] 2.98, P &lt; 0.001). Conclusions: Higher PSA nadir and shorter TTN during the initial ADT are poor prognostic factors in patients with mCRPC.[Table: see text]

The Relationships between Survivals and Early Salvage Androgen Deprivation Therapy for Non-Organ Confined Prostate Cancer after Radical Prostatectomy.

Androgen deprivation therapy (ADT) is one salvage treatment used when prostate-specific antigen (PSA) recurs after radical prostatectomy (RP), especially in high-risk prostate cancer (PC) patients. However, the optimal timing for salvage ADT (SADT) is still unclear. In this study, we analyzed the efficacy of early SADT for non-organ confined PC. We investigated pathologically confirmed, non-organ confined PC patients who received SADT for PSA recurrence after RP. Patients with distant metastasis, those with lymph node involvement confirmed by lymph node dissection, and those who received neo-adjuvant or adjuvant therapy were excluded. Early SADT was defined as ADT initiated before PSA levels reached 0.5 ng/ml from the nadir PSA level after RP. Univariable and multivariable Cox regression analyses were performed for distant metastasis-free, PC-specific, and overall survival. Data from 345 patients were analyzed. The median follow-up duration was 82 months. The median PSA level was 10.9 ng/ml. Patients with T3b or T4 stage cancers represented 24.9% of the cohort; those with a Gleason score ≥9 represented 15.1%. The 10-year distant metastasis-free survival, PC-specific survival and overall survival were 87.1%, 92.0%, 80.9%, respectively. In univariable and multivariable Cox regression analyses, SADT that was initiated when PSA levels were less than 0.5 ng/mL was significantly associated with improved distant metastasis-free survival, PC-specific survival, and overall survival in non-organ confined PC. Early SADT initiated in patients with PSA levels <0.5 ng/mL was associated with increased distant metastasis-free survival, PC-specific survival, and overall survival in non-organ confined PC after RP.

Whole-gland ablation therapy versus active surveillance for low-risk prostate cancer: a prospective study.

IntroductionThe objective of this study is assess the outcomes of whole-gland ablation (high-intensity focused ultrasound (HIFU), cryotherapy and brachytherapy) and active surveillance (AS) in patients with low-risk prostate cancer (PCa).Material and methodsThis prospective non-randomised study included 155 patients with low-risk PCa managed with either ablative therapy or AS. Follow-up included mpMRI, biopsies, prostate-specific antigen (PSA), quality of life and complications for up to 24 months. The primary endpoint was cancer progression. The secondary endpoint was the impact of each treatment on the quality of life.ResultsMean total preoperative PSA was 8.8 ±1.5 ng/ml. Of 155 patients, 125 received treatment: 45 – HIFU; 45 – cryoablation; 35 – brachytherapy. Thirty were under AS. Mean nadir PSA levels were 0.64 ±0.55 ng/ml for HIFU, 0.53 ±0.38 ng/ml for cryoablation and 0.48 ±0.34 ng/ml for brachytherapy. In the AS group, mean PSA was 9.9 ±3.8 ng/ml. Biochemical relapse-free survival rates at 24 months were 81.8% for HIFU, 85% for cryoablation, 93.9% for brachytherapy and 93.3% for AS. In only one HIFU patient relapse was not confirmed on biopsy. Increased anxiety was found in up to 6.7% after treatment and in 36.7% of patients undergoing AS. The Kaplan-Meier analysis revealed no statistical differences between the techniques.ConclusionsWhole-gland ablative therapy can be considered a viable treatment modality for carefully selected patients with low-risk PCa who are reluctant to select AS due to anxiety.

Effect of Prior Local Treatment and Prostate-Specific Antigen Kinetics during Androgen-Deprivation Therapy on the Survival of Castration-Resistant Prostate Cancer

Prostate-specific antigen (PSA) kinetics predicts survival in castration-resistant prostate cancer (CRPC); however, the influence of prior treatment on this relationship is unclear. Patients with CRPC were stratified according to time to PSA nadir and time to CRPC progression to investigate their prognostic significance on prostate cancer-specific survival (PCSS) and whether PSA kinetics may serve as prognosticators regardless of prior local treatment. This multicenter retrospective study included 295 patients diagnosed with CRPC between September 2009 and November 2017. PSA kinetics during androgen-deprivation therapy (ADT) including %PSA decline, PSA nadir level, time to PSA nadir, and time to CRPC progression was investigated. Subgroup analysis was performed according to the prior history of local curative treatment. Patients who did not receive prior local treatment with ≥6 months to PSA nadir and <12 months to CRPC, showed lower PCSS rates than those with <6 months to PSA nadir (23.3% vs. 45.3%; p = 0.031) and ≥12 months to CRPC (20.0% vs. 47.8%; p = 0.001). In patients who had received local treatment, PSA kinetic parameters did not influence PCSS. Our results indicate that time to PSA nadir and time to CRPC progression are prognosticators of PCSS in patients with CRPC who did not previously receive curative local treatment.

CLINICAL STUDY OF THE PROSTATE CANCERS WITH A SERUM PROSTATE SPECIFIC ANTIGEN LEVEL OF MORE THAN 100 ng/ml AT THE FIRST DIAGNOSIS

In patients with prostate cancer high serum prostate specific antigen (PSA) at diagnosis was generally regarded as a strong impression of advanced disease with distant metastasis and poor prognosis. (Objective) We reported a retrospective study of prognostic factor and Overall survival (OS) in patients with prostate specific antigen (PSA) level of greater than 100 ng/ml (PSA≥100 ng/ml). (Subjects and methods) Between January 2002 and December 2015, 60 patients were diagnosed prostate cancer with PSA≥100 ng/ml and performed hormonal monotherapy at Kanazawa Medical University hospital. We evaluated initial PSA level, Gleason score, Gleason Grading Group, clinical stage, site of metastasis, PSA nadir level, Time to PSA nadir (TTN), serum Hemoglobin (Hb) level, serum C-Reactive Protein (CRP) level, serum Lactate Dehydrogenase (LDH) level, serum Alkaline Phosphatase (ALP) level, clinical passage and survival time. (Results) The median age of the patients was 73 years old (54-90) and the initial PSA levels ranged from 100 ng/ml to 15,823 ng/ml (median 390).Prognostic factors of overall survival were site of metastasis, Gleason score, Gleason Grading Group, PSA nadir level, TTN, serum CRP level, serum LDH level and serum ALP level at the diagnosis. In multivariate analysis serum LDH level remained an independent predictor of OS.