CRPC-free Survival Research Articles

Serum CCL2 Is a Prognostic Biomarker for Non-Metastatic Castration-Sensitive Prostate Cancer.

Purpose: Prostate-specific antigen (PSA) is a useful prostate cancer (PC) biomarker, but some cases reported that PSA does not correlate with the Gleason score. Serum chemokine (CC motif) ligand 2 (CCL2) has been reported to be a potential complementary PSA biomarker, but it remains unclear whether it can be applied to non-metastatic castration-sensitive prostate cancer (nmCSPC) or each section of the stages. Serum CCL2′s usefulness was investigated as a prognostic nmCSPC biomarker in this study. Methods: Serum samples were collected from 379 patients who underwent prostate biopsy at Kanazawa University Hospital from 2007 to 2013. A total of 230 patients with nmCSPC were included in this study of the 255 patients with histologically diagnosed prostate cancer. The serum CCL2 efficacy as a prognostic nmCSPC biomarker was investigated retrospectively. Results: An independent significant predictor of worse OS was CCL2 ≥ 280 pg/dL and CRP ≥ 0.5 mg/dL in multivariate analysis. Gleason score ≥ 8 and CCL2 ≥ 280 pg/dL were independent significant predictors of CRPC-free survival (CFS) worsening in multivariate analysis. Serum CCL2 was a predictive biomarker for OS and CFS in nmCSPC. Furthermore, CCL2 ≥ 280 pg/mL patients had significantly worse visceral metastasis-free survival than those with CCL2 < 280 pg/mL. Conclusion: This study is the first to demonstrate serum CCL2 utility as a biomarker to predict OS and CFS in nmCSPC.

Is time to castration resistant prostate cancer a potential intermediate end-point for time to metastasis among men initiating androgen deprivation therapy for non-metastatic prostate cancer with rapid PSA doubling time (

Metastasis-free survival (MFS) is a surrogate for overall survival (OS) in men with non-metastatic castration-resistant prostate cancer (CRPC), but this endpoint may take years to develop in men with non-metastatic castrate-sensitive disease. The study objective was to examine whether progression to CRPC is a potential intermediate endpoint for developing metastatic disease in patients with biochemical recurrence (BCR) after radical prostatectomy (RP). Men with BCR following RP who had PSA doubling times (PSADT) < 9 months and no metastasis at the time of initiating androgen deprivation therapy (ADT) (n = 210) were included. The primary objective was to assess the correlation between CRPC-free survival (CRPC-FS) and MFS, and the secondary objective was to assess the correlation between time to metastasis and time to CRPC. Kendall's Tau was used to test the correlation for the primary and secondary outcomes. The median MFS was 104 months (95% CI: 83-114) and median CRPC-FS was 100 months (95% CI: 80-114). Based on the Kaplan-Meier curve, the greatest difference in time to MFS and CRPC-FS was around 70% free survival, which was reached at 61.2 months for MFS and 49.6 months for CRPC-FS. Kendall's Tau for the correlation between CRPC-FS and MFS and between time to CRPC and time to metastasis was 0.867 (95% CI: 0.765-0.968) and 0.764 (95% CI: 0.644-0.884), respectively. Given the high correlation between CRPC-FS and MFS, after validation, CRPC-FS may serve as a potential intermediate endpoint in trials for men with BCR initiating ADT following local therapy.

Veterans affairs seamless phase II/III randomized trial of standard systemic therapy with or without PET-directed local therapy for oligorecurrent prostate cancer (VA STARPORT).

TPS5112 Background: Two diverging paradigms have been studied in recent years to improve the survival of men with recurrent metastatic prostate cancer (PCa). First, multiple recent phase II randomized trials have demonstrated improved long-term progression-free survival (PFS) with metastasis-directed therapy (MDT) in men with oligorecurrent PCa in the absence of systemic therapy. Yet, most patients receiving MDT for oligorecurrent PCa develop progression in new areas, arguing that systemic therapy is needed to treat occult metastases. The second approach that has recently been studied is whether escalating systemic therapy by adding novel androgen receptor axis targeted agents or chemotherapy improves outcomes in men with metastatic PCa. Multiple phase III randomized trials demonstrate that enhancing hormonal therapy with these therapeutic agents improves progression-free survival (PFS) and overall survival. Therefore, these agents have been integrated into today’s standard systemic therapy (SST) for metastatic recurrence, and SST is the current NCCN guidelines standard of care for recurrent metastatic PCa. The primary goal of our study is to determine if adding PET-directed local therapy (PDLT) to SST improves disease control compared to SST alone in Veterans with oligorecurrent PCa. Methods: VA STARPORT is a phase II/III randomized trial open at 16 VA medical centers comparing SST with or without PDLT in Veterans with oligorecurrent PCa. Key eligibility criteria include prior localized PCa with biochemical recurrence after initial curative-intent local therapy and workup including any FDA-approved PCa PET/CT that reveals oligorecurrence in 1-5 metastatic lesions. The primary endpoint is castration-resistant prostate cancer-free survival (CRPC-free survival). Secondary endpoints include radiographic PFS, clinical PFS, freedom from index lesion progression, toxicity, quality of life, and prostate cancer-specific and overall survival. SST is delivered with an intent for indefinite SST using any NCCN guideline-concordant regimen in both arms. PDLT (Arm 2) consists of surgery or radiation to metastases and any present prostate/prostate bed local recurrence. Metastasis-directed radiation can consist of stereotactic body radiotherapy or elective nodal radiotherapy per clinician discretion from dose/fractionation options defined in the protocol. All participants undergo somatic tumor sequencing using the VA National Precision Oncology Program. Germline sequencing and tumor banking in a separate biorepository study is recommended. Assuming a hazard ratio of 0.60 for SST + PDLT vs SST, two-sided alpha = 0.05 and 90% power, a total of 464 participants will be randomized to generate 166 primary events (CRPC-free survival) by the end of the 48-month active study phase. The study began enrollment in August 2021. Clinical trial information: NCT04787744.

MP48-17 ONCOLOGICAL OUTCOMES IN PATIENTS WITH RECURRENT PROSTATE CANCER STAGED WITH PSMA PET/CT: RESULTS FROM 3 EUROPEAN TERTIARY CENTERS

MP48-17 ONCOLOGICAL OUTCOMES IN PATIENTS WITH RECURRENT PROSTATE CANCER STAGED WITH PSMA PET/CT: RESULTS FROM 3 EUROPEAN TERTIARY CENTERS

MP48-13 THE KEY ROLE OF CONCOMITANT ANDROGEN-DEPRIVATION THERAPY ON THE EFFICACY OF IMAGING GUIDED TREATMENTS IN MEN WITH BIOCHEMICAL RECURRENT PROSTATE CANCER AFTER RADICAL PROSTATECTOMY AND POSITIVE 68GA-PSMA PET/CT SCAN

MP48-13 THE KEY ROLE OF CONCOMITANT ANDROGEN-DEPRIVATION THERAPY ON THE EFFICACY OF IMAGING GUIDED TREATMENTS IN MEN WITH BIOCHEMICAL RECURRENT PROSTATE CANCER AFTER RADICAL PROSTATECTOMY AND POSITIVE 68GA-PSMA PET/CT SCAN

Veterans affairs seamless phase II/III randomized trial of standard systemic therapy with or without PET-directed local therapy for oligorecurrent prostate cancer (VA STARPORT).

TPS203 Background: Two diverging paradigms have been studied in recent years to improve the survival of men with recurrent metastatic prostate cancer (PCa). First, multiple recent phase II randomized trials have demonstrated improved long-term progression-free survival (PFS) with metastasis-directed therapy (MDT) in men with oligorecurrent PCa in the absence of systemic therapy. Yet, most patients receiving MDT for oligorecurrent PCa develop progression in new areas, arguing that systemic therapy is needed to treat occult metastases. The second approach that has recently been studied is whether escalating systemic therapy by adding novel androgen receptor axis targeted agents or chemotherapy improves outcomes in men with metastatic PCa. Multiple phase III randomized trials demonstrate that enhancing hormonal therapy with these therapeutic agents improves progression-free survival (PFS) and overall survival. Therefore, these agents have been integrated into today’s standard systemic therapy (SST) for metastatic recurrence, and SST is the current NCCN guidelines standard of care for recurrent metastatic PCa. The primary goal of our study is to determine if adding PET-directed local therapy (PDLT) to SST improves disease control compared to SST alone in Veterans with oligorecurrent PCa. Methods: VA STARPORT is a phase II/III randomized trial open at 16 VA medical centers comparing SST with or without PDLT in Veterans with oligorecurrent PCa. Key eligibility criteria include prior localized PCa with biochemical recurrence after initial curative-intent local therapy and workup including any FDA-approved PCa PET/CT that reveals oligorecurrence in 1-5 metastatic lesions. The primary endpoint is castration-resistant prostate cancer-free survival (CRPC-free survival). Secondary endpoints include radiographic PFS, clinical PFS, freedom from index lesion progression, toxicity, quality of life, and prostate cancer-specific and overall survival. SST is delivered with an intent for indefinite SST using any NCCN guideline-concordant regimen in both arms. PDLT (Arm 2) consists of surgery or radiation to metastases and any present prostate/prostate bed local recurrence. Metastasis-directed radiation can consist of stereotactic body radiotherapy or elective nodal radiotherapy per clinician discretion from dose/fractionation options defined in the protocol. All participants undergo somatic tumor sequencing using the VA National Precision Oncology Program. Germline sequencing and tumor banking in a separate biorepository study is recommended. Assuming a hazard ratio of 0.60 for SST + PDLT vs SST, two-sided alpha = 0.05 and 90% power, a total of 464 participants will be randomized to generate 166 primary events (CRPC-free survival) by the end of the 48-month active study phase. The study began enrollment in August 2021. Clinical trial information: NCT04787744.

Outcome of docetaxel in treatment of metastatic hormone-sensitive prostate cancer and correlation with hemoglobin, albumin, lymphocyte and platelets score.

We aimed to evaluate the outcome of treatment with docetaxel plus androgen deprivation therapy (ADT) in newly diagnosed patients with metastatic high tumor burden hormone-sensitive prostate cancer (mHSPC) and correlated the outcome with hemoglobin, albumin, lymphocyte and platelets (HALP) score. Six cycles of docetaxel plus ADT were given to 50 patients with high burden mHSPC. Baseline HALP score was calculated and disease outcome was tabulated; moreover, the prognostic impact of the HALP score in response to treatment and survival was calculated. We found a significant association between high HALP score and response to treatment where a higher rate of complete response occurred in patients with a high HALP score than in patients with a low HALP score (53.8% vs. 5.4% respectively, p-value = 0.001). Patients with ≥ 12-month-duration castration-resistant prostate cancer (CRPC) had a significantly higher HALP score compared to patients with a lower HALP score (84.6% vs. 35.1% respectively, p-value = 0.002); 18-month-duration CRPC-free survival was significantly greater in patients with higher HALP score than patients with a lower HALP score (23.1% and 5.4% respectively, p-value < 0.001). Patients with a high HALP score had insignificantly higher mean overall survival than patients with a low HALP score (mean: 22.91 and 20.66 months respectively, p-value = 0.230). Our results confirmed the benefits of treatment with docetaxel plus ADT in high-burden mHSPC with accepted tolerance. HALP score was found to be an independent predictive factor for benefit from therapy; we can apply it as an easy way to stratify patients for appropriate selection of treatment for better tolerance and outcome.

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.

Prognostic model with alkaline phosphatase, lactate dehydrogenase and presence of Gleason pattern 5 for worse overall survival in low-risk metastatic hormone-sensitive prostate cancer.

Randomized trials showed the survival benefits of the combined use of androgen receptor axis-targeted agents with androgen deprivation therapy in metastatic hormone-sensitive prostate cancer (mHSPC), regardless of the risk. However, treating patients with low-risk mHSPC with such intensive treatment is still debatable. This retrospective study included 155 low-risk patients among 467 mHSPC patients treated in our affiliated institutions. The association between predictive factors and treatment outcomes was estimated using the Kaplan-Meier method and log-rank test. Predictive factors for castration resistant prostate cancer (CRPC)-free survival were investigated using Cox regression analyses. During the median follow-up of 39months, 38.7% of patients developed CRPC and 14.2% died. In the multivariate analyses, a presence of Gleason pattern 5 (hazard ratio [HR] 2.04), high alkaline phosphatase (HR 1.007) and high lactate dehydrogenase (HR 1.009) were significant predictive factors for shorter CRPC-free survival. Finally, 155 patients were stratified into favorable- and unfavorable-risk groups based on the numbers of the predictive factors. The overall survival (OS) in the unfavorable-risk group (total scores: 2-3) was significantly worse than that of the favorable-risk group (total score: 0-1) (P=0.02). This prognostic model was assessed with 50 low-risk mHSPC patients from the external validation dataset and found both the time to CRPC, and the OS in the unfavorable-risk group was significantly worse than that of the favorable-risk group (P<0.01). The combination of Gleason pattern 5, high alkaline phosphatase and lactate dehydrogenase can predict those with worse OS in low-risk mHSPC patients.

Does surgery benefit patients with oligometastatic or metastatic prostate cancer? -Aretrospective cohort study and meta-analysis.

To evaluate long-term oncological outcomes of radical prostatectomy (RP) plus androgen deprivation therapy (ADT) in oligometastatic prostate cancer (PCa) patients. Our study included oligometastatic PCa patients hospitalized between January 1, 2010 and December 31, 2015, who received ADT with or without RP. We evaluated survival by employing Kaplan-Meier methods, with log-rank tests and univariate and multivariate Cox regression analyses. A meta-analysis of previously published studies was additionally performed. The median follow-up times of both groups were 68.4 months (interquartile range = 56.5-85.0). In this cohort study, significant statistical difference in preoperative total prostate-specific antigen(tPSA;p = .121), clinical T stage (p = .115), and N stage (p = .394) were not found between the two groups. Meanwhile, the difference in overall survival (OS) between the two groups did not reach statistical significance (p = .649). A significant difference was not observed in castration-resistant prostate cancer (CRPC)-free survival between two groups as well (p = .183). Numbers of metastases might be an independent prognosis factor (p = .05) for OS, and postoperative tPSA is a risk predictor for CRPC-free survival (p = .032). A meta-analysis of four relevant studies demonstrated significant statistical difference in clinical improvement with RP plus ADT over ADT alone in OS survival (p < .001;hazard ratio [HR] = 0.51; 95% confidence interval [CI] = 0.38-0.69) instead of CRPC-free survival (p = .42; HR = 0.86; 95% CI = 0.59-1.24). The addition of RP to ADT for the treatment of oligometastatic PCawas associated with an improved OS instead of CRPC-free survival.

Biopsy-detected Gleason grade 5 tumor is an additional prognostic factor in metastatic hormone-sensitive prostate cancer.

A Gleason score ≥ 8, metastatic tumor burden, and visceral metastasis are known prognostic factors for patients with metastatic hormone-sensitive prostate cancer (mHSPC). Notably, however, these indicators have not been fully validated internationally. We aimed in this present study to further analyze the factors that influence the prognosis of mHSPC. In this retrospective study, we identified 201 patients with newly diagnosed mHSPC between 2008 and 2014 and collected their clinical information. Cox proportional hazard regression models were used to identify prognostic factors in mHSPC. The mean age of the patients at presentation was 70years (interquartile range (IQR), 64-76years). The prostate-specific antigen level was 141ng/mL (IQR, 58.8-464.5ng/mL). Of the 201 study patients, 191 (94.5%) and 131 (65.2%) cases had a biopsy Gleason score ≥ 8 and grade 5, respectively. More than 4 metastases were detected in 134 patients. Castration-resistant prostate cancer (CRPC) was evident in 160 cases after a mean follow-up period of 46.6months. By multivariable analysis, a Gleason grade of 5 and bone metastasis lesion count ≥ 4 were found to be significantly associated with CRPC-free survival (hazard ratio (HR), 1.45; 95% confidence interval (CI), 1.01-2.07) and (HR 2.02; 95% CI 1.39-2.92) and overall survival (HR 1.67 95%; CI 1.16-2.42) and (HR 1.67 95%; CI 1.16-2.41). Bone metastases ≥ 4 and a Gleason grade 5 are independent prognostic factors for CRPC-free and overall survival in mHSPC. A Gleason grade 5 is therefore a new prognostic indicator in mHSPC.

Long-term follow-up comparing salvage radiation therapy and androgen-deprivation therapy for biochemical recurrence after radical prostatectomy

The salvage treatments for biochemical recurrence (BCR) include local external beam radiation therapy (RT) and systemic androgen-deprivation therapy (ADT). We reviewed patients who underwent radical prostatectomy (RP) and developed BCR at three institutions. After excluding patients whose nadir prostate-specific antigen (PSA) was higher than 0.2ng/mL, those who received neoadjuvant/adjuvant therapy, and those whose BCR was not treated until their PSA exceeded 4.0ng/mL, the remaining 335 patients comprised the cohort of this study. Salvage RT and ADT were performed for 154 and 181 patients, respectively. After the failure of salvage RT, all patients received subsequent ADT. The starting point of this study was the timing of BCR and the endpoint was the development of castration-resistant prostate cancer (CRPC). During the mean follow-up period of 8.5years after BCR, CRPC was observed in 13 patients administered RT and 24 patients administered ADT. Kaplan-Meier curves demonstrated no significant difference in CRPC-free survival between the RT and ADT groups (10-year CRPC-free survival 89.9 vs. 86.3%, p = 0.199). On the other hand, we found a significant difference in CRPC-free survival between the RT and ADT groups in 50 high-risk patients with two risk factors of Grade Group ≥ 4 and PSA-doubling time < 6months (10-year CRPC-free survival 73.4 vs. 40.3%, p = 0.040). This study revealed that salvage RT increases the CRPC-free survival rate compared with salvage ADT in high-risk patients with Grade Group ≥ 4 and PSA-doubling time < 6months.

External Validation of the Long Short-Term Memory Artificial Neural Network-Based SCaP Survival Calculator for Prediction of Prostate Cancer Survival.

PurposeDecision-making for treatment of newly diagnosed prostate cancer (PCa) is complex due to the multiple initial treatment modalities available. We aimed to externally validate the SCaP (Severance Study Group of Prostate Cancer) Survival Calculator that incorporates a long short-term memory artificial neural network (ANN) model to estimate survival outcomes of PCa according to initial treatment modality.Materials and MethodsThe validation cohort consisted of clinicopathological data of 4,415 patients diagnosed with biopsy-proven PCa between April 2005 and November 2018 at three institutions. Area under the curves (AUCs) and time-to-event calibration plots were utilized to determine the predictive accuracies of the SCaP Survival Calculator in terms of progression to castration-resistant PCa (CRPC)–free survival, cancer-specific survival (CSS), and overall survival (OS).ResultsExcellent discrimination was observed for CRPC-free survival, CSS, and OS outcomes, with AUCs of 0.962, 0.944, and 0.884 for 5-year outcomes and 0.959, 0.928, and 0.854 for 10-year outcomes, respectively. The AUC values were higher for all survival endpoints compared to those of the development cohort. Calibration plots showed that predicted probabilities of 5-year survival endpoints had concordance comparable to those of the observed frequencies. However, calibration performances declined for 10-year predictions with an overall underestimation.ConclusionThe SCaP Survival Calculator is a reliable and useful tool for determining the optimal initial treatment modality and for guiding survival predictions for patients with newly diagnosed PCa. Further modifications in the ANN model incorporating cases with more extended follow-up periods are warranted to improve the ANN model for long-term predictions.

Can post-treatment free PSA ratio be used to predict adverse outcomes in recurrent prostate cancer?

To assess whether free PSA ratio (FPSAR) at biochemical recurrence (BCR) can predict metastasis, castrate-resistant prostate cancer (CRPC), and cancer-specific survival (CSS), following therapy for localised disease. A single-centre retrospective cohort study (NCT03927287) including a discovery cohort composed of patients with an FPSAR after radical prostatectomy (RP) or radiotherapy (RT) between 2000 and 2017. For validation, an independent Biobank cohort of patients with BCR after RP was tested. Using a defined FPSAR cut-off, the metastasis-free-survival (MFS), CRPC-free survival, and CSS were compared. Multivariable Cox models determined the association between post-treatment FPSAR, metastases, and CRPC. Overall, 822 patients (305 RP- and 363 RT-treated patients and 154 Biobank patients) were analysed. In the RP cohort, a total of 272/305 (89.1%) and 33/305 (10.9%) had a FPSAR test incidentally and reflexively, respectively. In the RT cohort, 155/363 (42.7%) and 208/263 (57.3%) had a FPSAR test incidentally and reflexively, respectively. However, in the prospective Biobank RP cohort, FPSAR testing was done on all samples of patients diagnosed with BCR. A FPSAR cut-off of 0.10 was determined using receiver operating characteristic analyses in both the RP and RT cohorts. A FPSAR of <0.10 resulted in longer median MFS (14.8 vs 9.3years and 14.8 vs 13years, respectively), and longer median CRPC-free survival (median not reached vs 9.9years and 20.7 vs 13.8years, respectively). Multivariable analyses showed that a FPSAR of ≥0.10 was associated with increased metastasis in the RP cohort (hazard ratio [HR] 1.915, 95% confidence interval [CI] 1.241-2.955) and RT cohort (HR 1.754, 95% CI 1.112-2.769), and increased CRPC in the RP cohort (HR 2.470, 95% CI 1.493-4.088). Findings were validated in the Biobank cohort. A post-treatment FPSAR of ≥0.10 is associated with more aggressive disease, suggesting a potentially novel role for this biomarker.

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.

Evaluation of Gleason Grade Group 5 in a Contemporary Prostate Cancer Grading System and Literature Review.

The aim of this study was to validate contemporary grading systems, in particular, the Gleason grade group (GGG)5. We retrospectively reviewed the clinicopathologic data of 176 patients who underwent radical prostatectomy and whose pathologic results were GGG 4 or 5. The endpoints were biochemical recurrence (BCR) and castration-resistant prostate cancer (CRPC). The GGG 4 group was composed of 69 patients. The GGG 5 group consisted of 78 patients with GS 4+5 and 29 patients with GS 5+4 or higher. The 5-year BCR-free survival rates for men with GGG 4, GS 4+5, and GS 5+4 or higher were 59%, 54%, and 20%, respectively, and the 5-year CRPC-free survival rates were 98%, 100%, and 88%, respectively. Both the BCR- and CRPC-free survival rates were significantly higher in GS 4+5 than in GS 5+4 or higher (P< .001 and P= .002, respectively), but there were no significant differences between GGG 4 and GS 4+5 (P= .702 and P= .803, respectively). The multivariate analysis demonstrated that GS 5+4 or higher (hazard ratio, 3.4; P= .002) and lymphovascular invasion (hazard ratio, 3.4; P< .001) greatly affected BCR. Our follow-up study revealed that men with GS 4+5 and those with GGG 4 had a similar prognosis. However, there was a significant discrepancy in prognosis between GS 4+5 and GS 5+4 or higher. This suggested that GGG 4 and 5 in the contemporary prostate cancer grading system should be reviewed. Furthermore, lymphovascular invasion may be useful to subgroup these pathologically high-risk patients.

Prognostic Value of the LATITUDE and CHAARTED Risk Criteria for Predicting the Survival of Men with Bone Metastatic Hormone-Naïve Prostate Cancer Treated with Combined Androgen Blockade Therapy: Real-World Data from a Japanese Multi-Institutional Study.

Background The CHAARTED and LATITUDE trials demonstrated a prolonged overall survival (OS) for metastatic hormone-naïve prostate cancer (mHNPC) patients who receive up-front docetaxel or abiraterone acetate. These studies used their own risk criteria: CHAARTED trial defines high- and low-volume diseases and LATITUDE trial targeting a high-risk disease. The present study explored whether or not the CHAARTED and LATITUDE criteria were useful for predicting the outcome in Japanese bone mHNPC patients, including elderly patients (≥70 years). Methods A total of 532 mHNPC patients diagnosed from 2004 to 2014 in multithird referral cancer centers were enrolled in this study. All patients had bone metastasis and received combined androgen blockade treatment as an initial hormonal therapy. Results The number of patients with CHAARTED low-volume and high-volume diseases was 178 (33.5%) and 354 (66.5%), respectively. On the contrary, the number of patients with LATITUDE low-risk and high-risk diseases was 157 (29.5%) and 375 (70.5%), respectively. A total of 307 (57.7%) patients were defined as having both CHAARTED high-volume and LATITUDE high-risk disease. The median castration-resistant prostate cancer- (CRPC-) free survival was 12.5 months for the CHAARTED high volume, 56.9 months for the CHAARTED low volume, 13.6 months for the LATITUDE high risk, and 37.3 months for the LATITUDE low risk, respectively. The OS was 50.1 months in patients with CHAARTED high-volume disease, 95.1 months in patients with CHAARTED low-volume disease, 54.0 months in patients with LATITUDE high-risk disease, and 92.7 months in patients with LATITUDE low-risk disease, respectively. This trend was also observed in elderly (≥70 years old) patients. Conclusions The patients with CHAARTED high-volume disease or LATITUDE high-risk disease showed a shorter CRPC-free survival and a shorter OS than those in the CHAARTED low-volume disease group or in the LATITUDE low-risk group among Asian Japanese bone metastatic HNPC patients.

Early PSA decline as a predictor of progression in patients with metastatic castration-naïve prostate cancer (mCNPC) treated with abiraterone acetate and prednisone (AA/P).

e17542 Background: Treatment intensification with androgen deprivation therapy (ADT) plus AA/P is a standard of care in patients with metastatic castration naïve prostate cancer (mCNPC). Despite initial responses, nearly all men will eventually progress to castration resistant disease (CRPC). Early changes in PSA while on ADT plus AA/P has significant clinical and therapeutic implications for mCNPC patients, yet limited data is available. We aimed to assess PSA patterns while on therapy with ADT plus AA/P and time to CRPC. Methods: mCNPC patients treated with ADT plus AA/P between June 2017 and February 2019 at the Cleveland Clinic, were included. The primary objective was to describe patterns of PSA change evaluated using a longitudinal mixed model at time 0, 3, 6, 9, and 12 months from AA/P initiation. Other endpoints of interest included PSA progression by PCWG3 and CRPC-free survival at 12 and 18 months. Results: A total of 130 patients, 82% Caucasian, median age 69 years, with 50% with de-novo mCNPC, 47% high-volume (60.8% Gleason score ≥8, 16.2% visceral disease, and 53.8%had ≥3 bony lesions) were included. Half of the patients achieved undetectable PSA ( &lt; 0.03) while on therapy. The median time to PSA &lt; 0.03 was 13.1 months (95%CI, 7.6-NE). The greatest PSA reduction occurred at the first 3 months (80%, p &lt; 0.0001), changes after 3 months were small, (4% from 3 to 6 months, p &lt; 0.0001; 3% from 6 to 9 months, p &lt; 0.0001) and not significant from 9 to 12 months. The 12 and 18-months mCRPC-free survival after initiation of ADT plus AA/P was 88.1% and 81.3%, respectively. A PSA &gt; 0.2 at 3 months was associated with a shorter time to mCRPC (p = 0.002). Similarly, a PSA reduction &lt; 98% at 3 months was associated with worse outcomes (12 mo CRPC survival 68.0% vs. 94.9%, respectively; p &lt; 0.001). Conclusions: In this data set, timing and depth of serologic response predicted the early development of CRPC in patients receiving ADT plus AA/P. Further validation is ongoing using data from large randomized clinical trials.

Association of tumor burden with the eligibility of upfront therapy in patients with castration-naive prostate cancer: A multicenter retrospective study.

107 Background: Although several large-scale studies reported a robust benefit of upfront therapy for mHNPC, not all patients with mHNPC experienced mCRPC progression. As there is a concern for overtreatment in patients with low-risk/volume disease, we aimed to identify potential candidates for upfront therapy in patients with metastatic hormone-naïve prostate cancer (mHNPC). Methods: We retrospectively evaluated 679 patients with mHNPC who were initially treated with conventional androgen deprivation therapy. We defined the patients with progression to metastatic castration-resistant prostate cancer (mCRPC) as potential candidates for upfront therapy. To estimate the suitable candidate for upfront therapy, we retrospectively compared mCRPC progression rate, mCRPC-free survival, and overall survival (OS) after castration-resistance (OS-CR) between the low- and high-volume disease groups. Furthermore, we tried to develop a novel prediction model using deep learning algorithm. Results: The number of patients with mCRPC progression (potential candidates for upfront therapy) was 119 (52%) and 319 (71%) in the low- and high-volume disease groups. The mCRPC progression rate and CRPC-free survival were significantly worse in high-volume disease group ( P &lt; 0.01), but no difference was found for OS-CR. Multivariate Cox regression analysis showed no significant association between tumor volume and OS-CR (HR 1.14, P=0.52). The deep learning model showed not high accuracy of mCRPC prediction (AUC 0.66). Conclusions: Approximately a half of patients with low-volume disease had progression to mCRPC. As the OS-CR in the patients with low-volume disease showed poor prognosis as well as those with high-volume disease, upfront therapy may be needed for a half of patients with low-volume disease.

The association between PSA pattern changes and progression in patients with metastatic hormone-sensitive prostate cancer (mHSPC) treated with abiraterone and prednisone (AA/P).

18 Background: Despite treatment with AA/P, many patients with mHSPC will develop castrate resistant disease (CRPC). Early recognition of progression is difficult. Changes in PSA patterns in patients with mHSPC treated with AA/P may help identify evolution to mCRPC. Methods: All patients with mHSPC who initiated ADT and AA/P from June 2017 to February 2019 at the Cleveland Clinic were eligible. Patterns of PSA change were evaluated using a longitudinal mixed model at time 0, 3, 6, 9, and 12 months (mo) from AA/P initiation. Time to PSA&lt;0.03 and CRPC were estimated using Kaplan-Meier method. Progression was defined as a PSA rise at two consecutive time points. Results: Of the 143 patients who initiated AA/P, 134 men (median Gleason score 8, baseline PSA 15.0 ng/mL) with follow up were included. 52% had de novo mHSPC, 47.8% had prior therapy (21% surgery, 20% radiation, 7% both), and 16% had visceral disease. PSA levels dropped 98.2% in the first 3 mo (p&lt;0.001), slowed from 3-9 mo (p&lt;0.05) and plateaued after 9 mo. The % PSA reduction from time 0 to the other time points was small. The median time to PSA&lt;0.03 was 11 mo. Of those who progressed to CRPC, the reduction within the first 3 mo was more significant than in those who did not (Table). Measurable PSA was higher in patients who progressed to CRPC at all-time points and plateaued by 6 mo. 12-mo CRPC-free after AA/P was 86.7% (95% CI: 79.2, 94.1). Patients with ≥ 98% 3-mo PSA reduction had better CRPC-free survival than patients with &lt;98% reduction (12-mo CRPC-free: 94.4% vs 78.4%), p&lt;0.001. Conclusions: The degree of PSA decline within 3 mo of AA/P may be used as treatment efficacy measurement. Tracking PSA pattern changes may alert clinicians for potential progression, consider frequent PSA and imaging, as well as initiate sequential therapy.[Table: see text]