Castration-resistant Prostate Cancer-free Survival Research Articles

Predictors of Progression to Castration-resistant Prostate Cancer After Radical Prostatectomy in High-risk Prostate Cancer Patients.

To examine the specific time frame and identify associated risk factors from commencement of hormonal therapy to the onset of castration-resistant prostate cancer among patients who have developed biochemical recurrence following radical prostatectomy. We retrospectively reviewed the records of 92 patients who developed biochemical recurrence and received hormonal therapy as initial salvage treatment after radical prostatectomy for high-risk localized prostate cancer from 2005 to 2021. The castration-resistant prostate cancer-free survival rates from the commencement of salvage hormonal therapy were analyzed using log-rank methods. Cox proportional hazard regression was performed to analyze the risk factors associated with acquiring castration resistance. The patients were stratified based on those risk factors. During a median follow-up duration of 57 months, 24 (26.1%) patients developed castration-resistant prostate cancer. The 5- and 10-year castration-resistant prostate cancer-free survival rates were 73.6% and 54.5%, respectively. A multivariate analysis showed that Grade Group of 5 and prostate-specific antigen doubling time at biochemical recurrence of ≤3 months were independent predictors of castration-resistant prostate cancer. The 5-year castration-resistant prostate cancer-free survival rates in the low- and high-risk groups, stratified according to the aforementioned factors, were 85.4% and 47.6%, respectively. Patients in high Grade Group and short prostate-specific antigen doubling time after radical prostatectomy are more likely to develop resistance to salvage hormonal therapy.

Evaluating the effectiveness of cytoreductive surgery in oligometastatic prostate cancer: insights from quantitative analysis and retrospective cohort studies.

Oligometastatic prostate cancer (OmPCa) is characterized by a restricted number of metastatic lesions confined to a limited organ range, presenting a distinct clinical challenge. The role of cytoreductive prostatectomy (CRP) in managing this specific metastatic stage has gained attention but remains controversial. This study aims to assess the effectiveness of CRP in OmPCa by synthesizing outcomes from previous studies and analyzing data from a multicenter, retrospective cohort. We focused on evaluating overall survival (OS), progression-free survival (PFS), cancer-specific survival (CSS), and castration-resistant prostate cancer-free survival (CRPCFS) as primary outcomes. A multicenter comparative retrospective analysis was also conducted on OmPCa patients treated with CRP versus those receiving androgen deprivation therapy (ADT) alone from January 2008 to June 2018. We gathered and analyzed data on patient demographics, tumor characteristics, surgical outcomes, and survival metrics. The quantitative analysis included 18 studies(2 randomized controlled trial (RCT) and 16 non-RCT studies),comprising a total of 1733 patients with oligometastatic prostate cancer,this is the largest number of samples included in the same subject research at present.The pooled analysis demonstrated that cytoreductive surgery was associated with significantly improved OS (hazard ratio [HR]: 0.50, 95% confidence interval[CI]: 0.40-0.60) ,PFS (HR: 0.39, 95%[CI]: 0.27-0.51) ,CSS (HR: 0.44, 95%[CI]: 0.23-0.65) and CRPCFS (HR: 0.48, 95%[CI]: 0.36-0.59) compared to non-surgical management.In addition,OS ,PFS and CRPCFS showed better results in the CRP group in all analyses(RCT and non-RCT).Additionally,in our multicenter retrospective research analysis, 64 patients with oligometastatic prostate cancer were included ,32 underwent CRP (50%), and 32 underwent ADT alone (50%).The median follow-up time was 40.1 (18.9-51.3) months.The OS (P=0.0182), PFS (P=0.0297), and CRPCFS (P=0.0125) had statistical difference between the two matched cohorts.Moreover,we observed 8(25%) cases of perioperative complications, with the most common being urinary incontinence(9.4%). Incorporating CRP alongside ADT in the treatment protocol for OmPCa significantly enhances patient outcomes in terms of OS, PFS, and CRPC-free survival, underscoring the potential benefit of this surgical approach in the specified patient population.

Analysis of the immune-inflammatory indices for patients with metastatic hormone-sensitive and castration-resistant prostate cancer

BackgroundInflammation plays a pivotal role in the progression of prostate cancer (PCa). Several immune-inflammatory indices, including neutrophil to lymphocyte ratio (NLR), derived neutrophil to lymphocyte ratio (dNLR), lymphocyte to monocyte ratio (LMR) and platelet to lymphocyte ratio (PLR), lung immune prognostic index (LIPI), systemic inflammation response index (SIRI) and systemic immune inflammation index (SII), have demonstrated their prognostic values in several solid malignancies. However, Comparisons of superiority with these seven indices’ predictive efficacy within metastatic hormone-sensitive PCa (mHSPC) and metastatic castration-resistant PCa (mCRPC) remain uncertain.MethodsWe retrospectively included 407 patients diagnosed with mHSPC and 158 patients with mCRPC at West China Hospital from 2005 to 2022. The seven immune-inflammatory indices were computed based on hematological data of mHSPC at initial diagnosis and mCRPC at progression to CRPC. Prognostic value for castration-resistant prostate cancer-free survival (CFS), overall survival (OS), prostate-specific antigen progression-free survival (PSA-PFS) and prostate-specific antigen (PSA) response was assessed using Kaplan–Meier curves, Cox regression models, and chi-square tests. The predictive performance of each immune-inflammatory index was assessed using the area under the curve (AUC) in time-dependent receiver operating characteristic curve (ROC) analysis and C-index calculation.ResultsAll seven immune-inflammatory indices were significantly associated with CFS and OS in the mHSPC cohort, as well as with PSA response, PSA-PFS, and OS in the mCRPC cohort. In the mHSPC cohort, LIPI consistently exhibited higher AUC values compared to NLR, dNLR, LMR, PLR, SII, and SIRI for predicting CFS and OS. This indicates that LIPI had a superior discriminative ability compared to the other indices (C-index of LIPI: 0.643 and 0.686 for CFS and OS, respectively). Notably, the predictive advantage of LIPI over other indices in the mHSPC stage diminished in the mCRPC stage.ConclusionsThis study firstly confirmed the prognostic value of SII, SIRI and LIPI in mHSPC and mCRPC, and revealed that LIPI had a higher predictive power than NLR, dNLR, LMR, PLR, SII and SIRI in mHSPC. These non-invasive indices can enable clinicians to quickly assess the prognosis of patients.

Comparison of oncological outcomes of upfront androgen receptor signaling inhibitors and combined androgen blockade in Japanese patients with metastatic castration-sensitive prostate cancer.

In recent years, randomized controlled trials have demonstrated that upfront androgen receptor signaling inhibitors (ARSIs) prolong overall survival (OS) compared with androgen deprivation therapy (ADT) alone or combined androgen blockade (CAB) in patients with metastatic castration-sensitive prostate cancer (mCSPC). However, it remains unclear whether upfront ARSI is superior to CAB in Asian populations, among which the efficacy of ADT/CAB is considered relatively high. In this study, we compared the oncological outcomes of upfront ARSI and CAB in Japanese patients with mCSPC. Patients with mCSPC who underwent systemic therapy between May 2009 and October 2023 were enrolled retrospectively. Propensity score matching (PSM) was performed to compare the castration-resistant prostate cancer-free survival (CRPC-FS), cancer-specific survival (CSS), and OS between patients treated with upfront ARSI (ARSI group) and those treated with CAB (CAB group). In total, 30 and 142 patients were enrolled in the ARSI and CAB groups, respectively. After PSM (25 patients in each group), CRPC-FS was significantly longer in the ARSI group than in the CAB group (median: 36.7 vs. 12.3 months, hazard ratio: 0.44, 95% confidence interval: 0.20-0.97, p = 0.035). No significant differences were observed in CSS or OS between the two groups. In conclusion, when compared to CAB, upfront ARSI might have the potential to extend CRPC-FS among individuals in the Japanese population.

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

TPS5120 Background: The concept of metastasis-directed therapy (MDT) using radiation or surgery for oligometastatic (OM) prostate cancer (pCa) has evolved from an anecdotal hypothesis to a promising approach that may optimally balance toxicity and oncologic efficacy. Recently, there have been multiple smaller phase II randomized trials that have shown a signal of efficacy for MDT in OM pCa. Most studies have compared MDT to observation alone as the control arm, included only recurrent OM patients, and included up to 3-5 sites of metastasis. It is in this context, that the VA STARPORT trial was initiated in 2021 to definitively determine the role of MDT in Veterans with oligorecurrent pCa in 1-5 sites. Yet, the diagnosis and management of metastatic pCa have since evolved. The SABR-COMET-10 trial recently completed enrollment and compares systemic therapy alone or with MDT in patients with 1-10 metastases from various histologies. While pCa PET/CT imaging was only available for Veterans with biochemical recurrence in 2021, PSMA PET/CT now allows for the improved diagnosis of OM in Veterans with de novo pCa—a growing cohort of patients without a clear standard of care. Therefore, to maximize the impact and generalizability of the trial, VA STARPORT has been amended to allow for de novoOM and 1-10 metastases. The primary goal of VA STARPORT is to determine if adding PET-directed local therapy (PDLT) to standard systemic therapy (SST) improves disease control compared to SST alone in Veterans with recurrent and de novooligometastatic pCa. Methods: VA STARPORT is a phase II/III randomized trial open at 18 VA medical centers comparing SST alone (Arm 1) or with PDLT (Arm 2) in Veterans with OM pCa. Key eligibility criteria include recurrent or de novohormone-sensitive metastatic pCa and 1-10 metastatic lesions on any FDA-approved pCa PET/CT. 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 using any NCCN guideline-concordant regimen in both arms. PDLT can be either radiation or surgery to all sites of cancer. Regarding local therapy, de novo patients in Arm 1 receive prostate-directed RT, and in Arm 2 receive PDLT to all metastases and the prostate. For recurrent patients in Arm 1 there is no local therapy, while in Arm 2 patients receive PDLT. All participants undergo somatic tumor sequencing using the VA National Precision Oncology Program. 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 CRPC-free survival events by the end of the active study phase. Recruitment is ongoing and 150 patients have been enrolled. Clinical trial information: NCT04787744 .

Psoas mass index at the level of the third lumbar vertebra on computed tomography is a prognostic predictor for metastatic castration-sensitive prostate cancer.

Computed tomography-defined low skeletal muscle mass is associated with oncological outcomes in patients with prostate cancer. However, its association with the outcomes of hormone-treated metastatic castration-sensitive prostate cancer remains unclear. We aimed to determine the association between metastatic castration-sensitive prostate cancer and psoas muscle parameters. We retrospectively reviewed 121 patients with N1 and/or M1 metastatic castration-sensitive prostate cancer who underwent primary androgen deprivation therapy between 2005 and 2021, either by administration of luteinizing hormone-releasing hormone agonist/antagonist or by surgical castration accompanied by bicalutamide, a first-generation antiandrogen. Before treatment administration, the psoas muscle index at the level of the third lumbar vertebra (psoas muscle area [cm2]/height2 [m2]) and the mean Hounsfield units of the psoas muscle were evaluated using non-contrast computed tomography and in relation to oncological outcomes. The median follow-up was 56.9months. Furthermore, during follow-up, 82 (67.7%) and 53 (43.8%) patients progressed to castration-resistant prostate cancer and died, respectively. Multivariate analysis of castration-resistant prostate cancer-free survival and overall survival showed significant differences in the Gleason score, clinical N-stage, and psoas muscle index (median cutoff: 3.044 cm2/m2). Pretreatment psoas muscle index is an independent predictor of poor castration-resistant prostate cancer-free survival and overall survival in patients with N1 and/or M1 metastatic castration-sensitive prostate cancer.

Assessment of treatment outcomes: cytoreductive surgery compared to radiotherapy in oligometastatic prostate cancer - an in-depth quantitative evaluation and retrospective cohort analysis.

The management of oligometastatic prostate cancer, defined by its few metastatic sites, poses distinct clinical dilemmas. Debates persist regarding the most effective treatment approach, with both cytoreductive surgery and radiotherapy being key contenders. The purpose of this research is to thoroughly evaluate and compare the effectiveness of these two treatments in managing patients with oligometastatic prostate cancer. A comprehensive search of the literature was carried out to find pertinent publications that compared the results of radiation and cytoreductive surgery for oligometastatic prostate cancer.A meta-analysis was conducted in order to evaluate both the short- and long-term survival.Furthermore, utilizing institutional patient data, a retrospective cohort research was conducted to offer practical insights into the relative performances of the two treatment regimens. Five relevant studies' worth of data were included for this meta-analysis, which included 1425 patients with oligometastatic prostate cancer.The outcomes showed that, in comparison to radiation, cytoreductive surgery was linked to a substantially better Cancer Specific Survival (CSS) (hazard ratio [HR]: 0.70, 95% [CI]: 0.59-0.81, P<0.001) and Overall Survival (OS)(HR, 0.80; 95% [CI], 0.77-0.82; P < 0.01).The two therapy groups' Progression Free Survival (PFS) and Castration Resistant Prostate Cancer Free Survival(CRPCFS), however, did not differ significantly (HR: 0.56, 95% CI: 0.17-1.06; HR: 0.67, 95% CI: 0.26-1.02, respectively). Out of the 102 patients who were recruited in the retrospective cohort research, 36 had Cytoreductive Surgery(CRP), 36 had radiation therapy (primary lesion), and 30 had radiation therapy (metastatic lesion). The follow-up time was 46.3 months (18.6-60.0) on average. The enhanced OS in the CRP group (OS Interquartile Range (IQR): 45-60 months) in comparison to the radiation group (OS IQR: 39.0-59.0 months and 25.8-55.0 months respectively) was further supported by the cohort research. Furthermore, CRP had a better OS than both radiation (primary region) and radiotherapy (metastatic region), with the latter two therapeutic methods having similar OS. This meta-analysis and retrospective research provide valuable insights into the comparative efficacy of cytoreductive surgery and radiotherapy for oligometastatic prostate cancer. While short term survival(PFS,CRPCFS) were similar between the two groups, cytoreductive surgery exhibited superior CSS and OS.Adverse event rates were manageable in both modalities.These findings contribute to informed treatment decision-making for clinicians managing oligometastatic prostate cancer patients. Further prospective studies and randomized controlled trials are essential to corroborate these results and guide personalized therapeutic approaches for this distinct subset of patients.

Role of Bone Scan Index (BSI) in the Prognosis and Treatment Efficacy in Castration-Sensitive Prostate Cancer Patients with Bone Metastasis

Bone is the most common metastatic site in prostate cancer (PCa). Although the extent of disease (EOD) grade is used for evaluating burden of bone metastasis, the accuracy of bone metastasis classification needs improvement. Bone scan index (BSI) was developed as a quantitative tool to enhance the interpretability and clinical relevance of the bone scan. This study aimed to explore the role of BSI using BONENAVI® software in determining the prognosis and treatment efficacy in castration-sensitive PCa (mCSPC) patients with bone metastasis. We retrospectively reviewed 61 mCSPC patients with bone metastasis who had received primary androgen deprivation therapy (PADT) at our institution. All patients received PADT with luteinizing hormone-releasing hormone agonist or surgical castration accompanied by first-generation antiandrogen, bicalutamide. Bone scans were performed with ⁹⁹[m]Tc-MDP. BSI (%) was divided into two groups (＜1.0 and ≧1.0), and BSI response rates(change at 0 months to after 6 months) were determined using thresholds of 45% decline. Castration-resistant prostate cancer (CRPC) -free survival (CRPC-FS) and Overall survival (OS) rates were analyzed using the Kaplan-Meier method. The median follow-up was 41. 9 months. Overall, 16 patients (26. 2%) died. Multivariate analysis on pretreatment factors revealed that hemoglobin (P＝0.03) and BSI (P＝0.04) were independent prognostic factors for OS. The 5-year OS rates in patients with low BSI and high BSI were 84.6% and 39.2%, respectively (P＝0.02). In 40 patients who had a bone scan before and after PADT, OS rates in patients with a good response (≧45%) were significantly higher than those with a poor response (＜45%) (P＝0.001). Nadir PSA titers within 6 months after the start of treatment (P＝0.005), Hb (P＝0.003), and BSI change (P＝0.014) were independent prognostic factors for OS. In mCSPC patients with bone metastases, BSI at diagnosis was an important predictor of CRPC progression and OS as a pre-treatment factor, and BSI change rate and PSA nadir as post-treatment factors.

Role of Positive Biopsy Core Ratio in Prostate Cancer Patients.

The percentage of positive cores (PPC) is increasingly recognized as a prognostic factor in prostate cancer. However, the usefulness of PPC for patients undergoing androgen deprivation therapy (ADT) and high-risk group has not been adequately studied. A retrospective analysis was conducted of 255 patients who underwent prostate biopsy (all-case group). We examined the efficacy of PPC as a prognostic biomarker. Eighty-nine patients were treated with ADT alone (ADT group), and 107 patients were classified as high-risk (high-risk group). The median duration of follow-up was 112.4 months, 85.3 months, and 110.0 months for the all-case, ADT, and high-risk groups, respectively. Patients with PPC >60% had significantly shorter prostate cancer-specific survival (CSS) and castration-resistant prostate cancer-free survival (CFS) in the all-case and ADT groups. In the high-risk group, patients with PPC >60% had shorter CFS but no difference in CSS. Multivariate analysis showed that significant independent predictors of prostate CSS were the presence of metastasis at diagnosis and PPC >60% in the all-case and ADT groups. PPC may be a prognostic factor in ADT treated and high-risk prostate patients.

A Novel Nomogram for Identifying the Patients at Risk for Rapid Progression of Advanced Hormone-Sensitive Prostate Cancer.

The goal of this study was to assess the prognostic impact of the lower urinary tract symptoms (LUTS) in advanced prostate cancer (PCa) patients before progression to castration-resistant prostate cancer (CRPC). A retrospective analysis of the follow-up data for 152 CRPC patients was performed. Severe LUTS symptom was defined as an International Prostate Symptoms Score (IPSS) ≥20 at baseline. Cox regression analysis was conducted to assess CRPC prognostic factors. Nomogram model was created and assessed using the concordance index (C-index), calibration curves, receiver operating characteristic (ROC) curves, and decision curve analyses (DCA). The median CRPC free survival of patients with severe LUTS was 20.5 months, significantly longer than that (7.5 months) of less symptomatic patients. Furthermore, severe LUTS, the hemoglobin, albumin, lymphocyte, and platelet (HALP) score, and Gleason sum were determined to be independent prognostic markers and combined to establish a nomogram, which performed well in the customized prediction of CRPC progression at 6th, 12th, 18th and 24th month. The C-index (0.794 and 0.816 for the training and validation cohorts, respectively), calibration curve, and ROC curve all validated the prediction accuracy. DCA curve showed that it could be effective in helping doctors make judgments. The Nomogram-related risk score separated the patients into two groups with notable progression differences. Severe LUTS was significantly associated with decreased risk for rapid progression to CRPC. The developed nomogram could help identify patients who are at a high risk of rapid CRPC progression and provide tailored follow-up and therapeutic advice.

Treatment Results of High-dose-rate Brachytherapy and External Beam Radiation With Long-term Androgen Deprivation Therapy for Patients With Metastatic Prostate Cancer.

A recent clinical trial indicated the usefulness of local radiation therapy of the prostate in patients with low-volume metastatic prostate cancer. High-dose-rate brachytherapy (HDR-BT) is used mainly for high-risk, localized, and locally advanced cases. However, few studies exist on the efficacy of HDR-BT and external beam radiation therapy (EBRT) for metastatic prostate cancer. We conducted a retrospective analysis of 39 patients diagnosed with regional lymph node metastasis and/or a limited number of metastases who underwent HDR-BT and EBRT with long-term androgen deprivation therapy. We utilized Cox's proportional hazards models to identify predictors of oncological outcomes. Treatment outcomes, including biochemical recurrence-free survival (BCRFS), clinical progression-free survival (CPFS), and castration-resistant prostate cancer-free survival (CRPCFS), were compared according to the clinical stage. The median follow-up duration was 49 months (range=23-136 months). The 5-year BCRFS, CPFS, CRPCFS, and cancer-specific survival rates were 62.2%, 67.2%, 83.2%, and 93.4%, respectively. Based on Kaplan-Meier analysis, N1M0 and N0-1M1b showed favorable outcomes compared with N1M1a. Multivariate analysis revealed that N1M1a prostate cancer was an independent risk factor for poor BCRFS, CPFS, and CRPCFS. HDR-BT and EBRT with androgen deprivation therapy is a feasible approach for patients with newly diagnosed regional and low-metastatic-burden prostate cancer. However, in our cohort M1a prostate cancer had significantly inferior outcomes. A well-controlled prospective study is imperative to confirm our results.

The prognostic significance of the clinical T stage and Grade Group in patients with locally advanced prostate cancer treated via high-dose-rate brachytherapy and external beam radiation.

Although the optimal management of locally advanced prostate cancer (PCa) remains unclear, local definitive therapy, thus combined radiotherapy and androgen deprivation, is one option. We evaluated the long-term outcomes of patients with locally advanced PCa who underwent high-dose-rate brachytherapy (HDR-BT) and external beam radiation therapy (EBRT). We retrospectively analyzed 173 patients with locally advanced PCa (cT3a-4N0-1M0) who underwent HDR-BT and EBRT. We employed Cox's proportional hazards models to identify pre-treatment predictors of oncological outcomes. Treatment outcomes (biochemical recurrence-free survival [BCRFS], clinical progression-free survival [CPFS], and castration-resistant prostate cancer-free survival [CRPCFS] were compared according to the combination of the pre-treatment predictors. The 5-year BCRFS, CPFS, and CRPCFS rates were 78.5, 91.7, and 94.4% respectively; there were two PCa deaths. Multivariate analysis revealed that the clinical T stage (cT3b and cT4) and Grade Group (GG) 5 status were independent risk factors for poor BCRFS, CPFS, and CRPCFS. In the GG ≤ 4 group, the Kaplan-Meier curves for BCRFS, CPFS, and CRPCFS revealed excellent outcomes. However, in the GG5 group, patients with cT3b and cT4 PCa evidenced significantly poorer oncological outcomes than those with cT3a PCa. The clinical T stage and GG status were significantly prognostic of oncological outcomes in patients with locally advanced PCa. In patients of GG ≤ 4 PCa, HDR-BT was effective even in patients with cT3b or cT4 PCa. However, in patients with GG5 PCa, careful monitoring is essential, particularly of patients with cT3b or cT4 PCa.

MP61-17 PROGNOSTIC BENEFIT OF NEOADJUVANT CHEMOHORMONAL THERAPY COMPARED WITH EXTENDED PELVIC LYMPH NODE DISSECTION IN PATIENTS WITH HIGH-RISK PROSTATE CANCER TREATED WITH ROBOT ASSISTED RADICAL PROSTATECTOMY

You have accessJournal of UrologyCME1 Apr 2023MP61-17 PROGNOSTIC BENEFIT OF NEOADJUVANT CHEMOHORMONAL THERAPY COMPARED WITH EXTENDED PELVIC LYMPH NODE DISSECTION IN PATIENTS WITH HIGH-RISK PROSTATE CANCER TREATED WITH ROBOT ASSISTED RADICAL PROSTATECTOMY Takuya Oishi, Shingo Hatakeyama, Ryuji Tabata, Daiji Fujimori, Mamoru Fukuda, Tesuo Shinozaki, Noritaka Ishii, Hiromichi Iwamura, Teppei Okamoto, Hayato Yamamoto, Takahiro Yoneyama, Yasuhiro Hashimoto, Satoru Sato, and Chikara Ohyama Takuya OishiTakuya Oishi More articles by this author , Shingo HatakeyamaShingo Hatakeyama More articles by this author , Ryuji TabataRyuji Tabata More articles by this author , Daiji FujimoriDaiji Fujimori More articles by this author , Mamoru FukudaMamoru Fukuda More articles by this author , Tesuo ShinozakiTesuo Shinozaki More articles by this author , Noritaka IshiiNoritaka Ishii More articles by this author , Hiromichi IwamuraHiromichi Iwamura More articles by this author , Teppei OkamotoTeppei Okamoto More articles by this author , Hayato YamamotoHayato Yamamoto More articles by this author , Takahiro YoneyamaTakahiro Yoneyama More articles by this author , Yasuhiro HashimotoYasuhiro Hashimoto More articles by this author , Satoru SatoSatoru Sato More articles by this author , and Chikara OhyamaChikara Ohyama More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003319.17AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: We aimed to evaluate the impact of the robot-assisted radical prostatectomy (RARP) plus extended pelvic lymph node dissection (ePLND) on prognosis in comparison with neoadjuvant chemohormonal therapy (NCHT) without ePLND. METHODS: We retrospectively evaluated 452 patients with high-risk prostate cancer (PC) defined as: any of PSA 20 ng/mL, Gleason score 8-10, or cT2c-3 who were treated with RARP between Jan. 2012 and Feb. 2021. Patients were divided into two groups: RARP with ePLND (ePLND group) and NCHT plus RARP without ePLND (NCHT group). We compared the complication rate (Clavien-Dindo classification), biochemical recurrence-free survival (BCR-FS), castration-resistant prostate cancer-free survival (CRPC-FS), and overall survival (OS) between the groups. Multivariable Cox regression analysis was performed to assess the impact of treatment on prognosis. RESULTS: We identified 150 and 302 patients in the ePLND and NCHT groups, respectively. The postoperative complication rate was significantly higher in the ePLND group than that in the NCHT group (p<0.001). BCR-FS, CRPC-FS, and OS were significantly longer in the NCHT group than those in the ePLND group. Multivariable Cox regression analyses showed that NCHT was significantly associated with the reduced risk of BCR (hazard ratio 0.24, p<0.001) and CRPC progression (hazard ratio 0.23, p=0.003), but not for OS (HR 0.26, p=0.098). CONCLUSIONS: NCHT plus RARP without ePLND may reduce the risk of postoperative complications, BCR, and CRPC progression in comparison with ePLND during RARP. Source of Funding: none © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e859 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Takuya Oishi More articles by this author Shingo Hatakeyama More articles by this author Ryuji Tabata More articles by this author Daiji Fujimori More articles by this author Mamoru Fukuda More articles by this author Tesuo Shinozaki More articles by this author Noritaka Ishii More articles by this author Hiromichi Iwamura More articles by this author Teppei Okamoto More articles by this author Hayato Yamamoto More articles by this author Takahiro Yoneyama More articles by this author Yasuhiro Hashimoto More articles by this author Satoru Sato More articles by this author Chikara Ohyama More articles by this author Expand All Advertisement PDF downloadLoading ...

PSMA-PET Guided Treatment in Prostate Cancer Patients with Oligorecurrent Progression after Previous Salvage Treatment

Prostate Specific Membrane Antigen-Positron Emission Tomography (PSMA-PET) is used to select recurrent prostate cancer (PCa) patients for metastases-directed therapy (MDT). We aimed to evaluate the oncologic outcomes of second-line PSMA-guided MDT in oligo-recurrent PCa patients. we performed a retrospective analysis of 113 recurrent PCa after previous radical prostatectomy and salvage therapies with oligorecurrent disease at PSMA-PET (≤3 lesions in N1/M1a-b) in three high-volume European centres. Patients underwent second-line salvage treatments: MDT targeted to PSMA (including surgery and/or radiotherapy), and the conventional approach (observation or Androgen Deprivation Therapy [ADT]). Patients were stratified according to treatments (MDT vs. conventional approach). Patients who underwent MDT were stratified according to stage in PSMA-PET (N1 vs. M1a-b). The primary outcome of the study was Progression-free survival (PFS). Secondary outcomes were Metastases-free survival (MFS) and Castration Resistant PCa free survival (CRPC-FS). Kaplan-Meier analyses assessed PFS, MFS and CRPC-FS. Multivariable Cox regression models identified predictors of progression and metastatic disease. Overall, 91 (80%) and 22 (20%) patients were treated with MDT and the conventional approach, respectively. The median follow-up after PSMA-PET was 31 months. Patients who underwent MDT had a similar PFS compared to the conventional approach (p = 0.3). Individuals referred to MDT had significantly higher MFS and CRPC-FS compared to those who were treated with the conventional approach (73.5% and 94.7% vs. 30.5% and 79.5%; all p ≤ 0.001). In patients undergoing MDT, no significant differences were found for PFS and MFS according to N1 vs. M1a-b disease, while CRPC-FS estimates were significantly higher in patients with N1 vs. M1a-b (100% vs. 86.1%; p = 0.02). At multivariable analyses, age (HR = 0.96) and ADT during second line salvage treatment (HR = 0.5) were independent predictors of PFS; MDT (HR 0.27) was the only independent predictor of MFS (all p ≤ 0.04) Conclusion: Patients who underwent second-line PSMA-guided MDT experienced higher MFS and CRPC-FS compared to men who received conventional management.

Predictors of Recurrence After Metastasis-directed Therapy in Oligorecurrent Prostate Cancer Following Radical Prostatectomy

BackgroundMetastasis-directed therapy (MDT) is performed to delay systemic treatments for oligorecurrent disease after primary prostate cancer (PCa) treatment. ObjectiveThe aim of this study was to identify the predictors of therapeutic response of MDT for oligorecurrent PCa. Design, setting, and participantsbicentric, retrospective study, including consecutive patients who underwent MDT for oligorecurrent PCa after radical prostatectomy (RP; 2006–2020) was conducted. MDT encompassed stereotactic body radiation therapy (SBRT), salvage lymph node dissection (sLND), whole-pelvis/retroperitoneal radiation therapy (WP[R]RT), or metastasectomy. Outcome measurements and statistical analysisndpoints were 5-yr radiographic progression-free survival (rPFS), metastasis-free survival (MFS), palliative androgen deprivation treatment (pADT)-free survival, and overall survival (OS) together with prognostic factors for MFS following primary MDT. Survival outcomes were studied by Kaplan-Meier survival and univariable Cox regression (UVA). Results and limitationsA total of 211 MDT patients were included; 122 (58%) developed a secondary recurrence. Salvage lymph node dissection was performed in 119 (56%), SBRT in 48 (23%), and WP(R)RT in 31 (15%) of the cases. Two patients received sLND + SBRT and one received sLND + WPRT. Eleven (5%) patients received metastasectomies. The median follow-up since RP was 100 mo, while follow-up after MDT was 42 mo. The 5-yr rPFS, MFS, androgen deprivation treatment(–free survival, castration-resistant prostate cancer–free survival, CSS, and OS after MDT were 23%, 68%, 58%, 82%, 93%, and 87% respectively. There was a statistically significant difference between cN1 (n = 114) and cM+ (n = 97) for 5-yr MFS (83% vs 51%, p < 0.001), pADT-free survival (70% vs 49%, p = 0.014), and CSS (100% vs 86%, p = 0.019). UVA was performed to assess the risk factors (RFs) for MFS in cN1 and cM+. Alpha was set at 10%. RFs for MFS in cN1 were lower initial prostate-specific antigen (PSA) at the time of RP (hazard ratio [95% confidence interval] 0.15 [0.02–1.02], p = 0.053], pN stage at RP (2.91 [0.83–10.24], p = 0.096), nonpersisting PSA after RP (0.47 [0.19–1.12], p = 0.089), higher PSA at primary MDT (2.38 [1.07–5.24], p = 0.032), and number of positive nodes on imaging (1.65 [1.14–2.40], p < 0.01). RFs for MFS in cM+ were higher pathological Gleason score (1.86 [0.93–3.73], p = 0.078), number of lesions on imaging (0.77 [0.57–1.04], p = 0.083), and cM1b/cM1c (non-nodal metastatic recurrence; 2.62 [1.58–4.34], p < 0.001). ConclusionsFollowing MDT, 23% of patients were free of a second recurrence at 5-yr follow-up. Moreover, cM+ patients had significantly worse outcomes in terms of MFS, pADT-free survival, and CSS. The RFs for a metastatic recurrence can be used for counseling patients, to inform prognosis, and potentially select candidates for MDT. Patient summaryIn this paper, we looked at the outcomes of using localized, patient-tailored treatment for imaging-detected recurrent prostate cancer in lymph nodes, bone, or viscera (maximum five recurrences on imaging). Our results showed that targeted treatment of the metastatic lesions could delay the premature use of hormone therapy.

CYCLONE 3: A phase 3, randomized, double-blind, placebo-controlled study of abemaciclib in combination with abiraterone plus prednisone in men with high-risk, metastatic, hormone-sensitive prostate cancer (mHSPC).

TPS289 Background: Landmark trials have established a survival benefit for novel hormonal agents (NHA) added to androgen deprivation therapy (ADT) for mHSPC. Yet, there is a significant medical need to expand therapeutic options, especially for pts with high-risk mHSPC who experience poorer outcomes. Abemaciclib is an oral selective inhibitor of cyclin-dependent kinase 4 and 6 (CDK4 &amp; 6) dosed on a continuous schedule, approved for the treatment of node-positive high-risk early-stage and advanced or metastatic HR+, HER2- breast cancer. Analogous to the estrogen receptor signaling pathway in breast cancer, there is evidence that the androgen receptor axis activates CDK4 &amp; 6 to sustain prostate cancer cell proliferation, and upregulation of cyclin D1 is a potential mechanism of resistance to NHA therapy. In preclinical models, abemaciclib induces cell cycle arrest and inhibition of prostate tumor growth. Methods: CYCLONE 3 (NCT05288166) is a global, randomized, double-blind, placebo-controlled study evaluating the addition of abemaciclib to abiraterone+prednisone (AP) in pts with high-risk mHSPC. Approximately 900 pts with high-risk mHSPC defined by ≥4 bone metastasis and/or visceral disease will be randomised in a 1:1 ratio to the AP + abemaciclib or AP + placebo arm. Up to 3 months of ADT prior to randomization is permitted; prior D for mHSPC will be excluded per planned protocol amendment. Pts who have not undergone orchiectomy will continue ADT. Stratification factors are de novo mHSPC and visceral metastases. Primary endpoint is investigator-assessed radiographic progression-free survival (rPFS). Key secondary endpoints include rPFS assessed by blinded independent central review, castration-resistant prostate cancer-free survival, overall survival, time to pain progression, safety and pharmacokinetics. Enrollment is open at approximately 270 sites across 25 countries. Clinical trial information: NCT05288166 .

Regional location of lymph node metastases predicts survival in patients with de novo metastatic prostate cancer.

To report the regional locations of metastases and to estimate the prognostic value of the pattern of regional metastases in men with metastatic hormone-sensitive prostate cancer (mHSPC), we retrospectively analyzed 870 mHSPC patients between November 28, 2009, and February 4, 2021, from West China Hospital in Chengdu, China. The patients were initially classified into 5 subgroups according to metastatic patterns as follows: simple bone metastases (G1), concomitant bone and regional lymph node (LN) metastases (G2), concomitant bone and nonregional LN (NRLN) metastases (G3), lung metastases (G4), and liver metastases (G5). In addition, patients in the G3 group were subclassified as G3a and G3b based on the LN metastatic plane (below or above the diaphragm, respectively). The associations of different metastatic patterns with castration-resistant prostate cancer-free survival (CFS) and overall survival (OS) were analyzed by univariate and multivariate analyses. The results showed that patients in G1 and G2 had relatively favorable clinical outcomes, patients in G3a and G4 had intermediate prognoses, and patients in G3b and G5 had the worst survival outcomes. We observed that patients in G3b had outcomes comparable to those in G5 but had a significantly worse prognosis than patients in G3a (median CFS: 8.2 months vs 14.3 months, P = 0.015; median OS: 38.1 months vs 45.8 months, P = 0.038). In conclusion, metastatic site can predict the prognosis of patients with mHSPC, and the presence of concomitant bone and NRLN metastases is a valuable prognostic factor. Furthermore, our findings indicate that the farther the NRLNs are located, the more aggressive the disease is.

Transcriptional Profile Associated with Clinical Outcomes in Metastatic Hormone-Sensitive Prostate Cancer Treated with Androgen Deprivation and Docetaxel.

Simple SummaryThe combination of androgen deprivation therapy (ADT) with docetaxel (DX) or/and with novel anti-androgen receptor therapies have become standards for the treatment of patients with metastatic hormone-sensitive prostate cancer (mHSPC). However, metastatic PC remains incurable, and biomarkers for individual treatment selection are needed. We propose here that molecular alterations associated with castration resistance may predict the clinical evolution of mHSPC patients. To test this hypothesis, we designed a custom expression panel of 184 genes and tested it in tumor biopsies from patients with mHSPC treated with ADT+DX. We found that AR and ESR signatures and ESR2 gene expression correlate with a good prognosis. The lower expression of TSG (PTEN, TP53 and RB1) signature, as well as high ARV7 and low RB1 gene expression, were associated with adverse clinical outcomes. The usefulness of transcriptomic analysis of such signatures as a strategy for personalized treatment selection should be further explored.(1) Background: Androgen deprivation therapy (ADT) and docetaxel (DX) combination is a standard therapy for metastatic hormone-sensitive prostate cancer (mHSPC) patients. (2) Methods: We investigate if tumor transcriptomic analysis predicts mHSPC evolution in a multicenter retrospective biomarker study. A customized panel of 184 genes was tested in mRNA from tumor samples by the nCounter platform in 125 mHSPC patients treated with ADT+DX. Gene expression was correlated with castration-resistant prostate cancer-free survival (CRPC-FS) and overall survival (OS). (3) Results: High expression of androgen receptor (AR) signature was independently associated with longer CRPC-FS (hazard ratio (HR) 0.6, 95% confidence interval (CI) 0.3–0.9; p = 0.015), high expression of estrogen receptor (ESR) signature with longer CRPC-FS (HR 0.6, 95% CI 0.4–0.9; p = 0.019) and OS (HR 0.5, 95% CI 0.2–0.9, p = 0.024), and lower expression of tumor suppressor genes (TSG) (RB1, PTEN and TP53) with shorter OS (HR 2, 95% CI 1–3.8; p = 0.044). ARV7 expression was independently associated with shorter CRPC-FS (HR 1.5, 95% CI 1.1–2.1, p = 0.008) and OS (HR 1.8, 95% CI 1.2–2.6, p = 0.004), high ESR2 was associated with longer OS (HR 0.5, 95% CI 0.2–1, p = 0.048) and low expression of RB1 was independently associated with shorter OS (HR 1.9, 95% CI 1.1–3.2, p = 0.014). (4) Conclusions: AR, ESR, and TSG expression signatures, as well as ARV7, RB1, and ESR2 expression, have a prognostic value in mHSPC patients treated with ADT+DX.

Usefulness of serum CCL2 as prognostic biomarker in prostate cancer: a long-term follow-up study

Prostate-specific antigen is considered the most useful biomarker for prostate cancer, but not in all cases. In a previous study, we have shown that a risk classification combining prostate-specific antigen ≥100ng/mL and chemokine (CC motif) ligand 2≥320pg/mL can predict survivals. We investigated the long-term usefulness of serum chemokine (CC motif) ligand 2 as a complementary biomarker to prostate-specific antigen and developed a novel risk classification system. Serum samples were collected from 379 patients who underwent prostate biopsy at Kanazawa University Hospital between 2007 and 2013, and 255 patients with histologically diagnosed prostate cancer were included in this study. We retrospectively examined the efficacy of serum chemokine (CC motif) ligand 2 as a prognostic biomarker. Patients with chemokine (CC motif) ligand 2≥320pg/mL exhibited a significantly shorter overall survival, prostate cancer-specific survival and castration-resistant prostate cancer-free survival than those with chemokine (CC motif) ligand 2<320pg/mL. Multivariate analysis was performed to determine whether chemokine (CC motif) ligand 2 was a useful prognostic factor. Independent significant predictors of worse overall survival were prostate-specific antigen≥100ng/mL, Gleason score≥8 and chemokine (CC motif) ligand 2≥320pg/dL. Prognostic predictors of prostate cancer-specific survival or cancer-free survival in multivariate analysis were prostate-specific antigen≥100ng/mL and Gleason score≥8. A novel risk classification system was created to predict overall survival in patients based on the number of risk factors present (chemokine (CC motif) ligand 2≥320pg/mL, prostate-specific antigen≥100ng/mL, Gleason score≥8). Scores 2 or 3, 1 and 0 indicated Poor, Intermediate and Good risk groups, respectively. This study demonstrated the utility of serum chemokine (CC motif) ligand 2 level as a predictive biomarker of long-term overall survival in prostate cancer. A novel risk classification system that predicts long-term overall survival based on the combined indications of chemokine (CC motif) ligand 2 level, prostate-specific antigen level and Gleason score may be a useful prognostic tool for prostate cancer.

Estrogen receptor β and TMPRSS2-ERG expression association with clinical outcomes in metastatic hormone-sensitive prostate cancer.

5077 Background: TMPRSS2-ERG fusion has been associated with estrogen receptor (ER) signalling in prostate cancer (PC). The isoform beta of ER (ERβ), encoded by ESR2, is considered anti-proliferative and tumor-suppressive. In preclinical studies, ESR2 has shown an inhibitory role towards TMPRSS2-ERG, resulting in decreased proliferation and tumor regression. In this clinical series, we sought to investigate the correlation between TMPRSS2-ERG and ESR2 expression and its impact on clinical outcomes in a cohort of patients (pts) with metastatic hormone-sensitive PC (mHSPC). Methods: This is a multicenter retrospective biomarker study. TMPRSS2-ERG and ESR2 were tested in total mRNA from FFPE tumor samples by nCounter platform (Nanostring Technologies). TMPRSS2-ERG and ESR2 expression were correlated with castration-resistant PC free survival (CRPC-FS) and overall survival (OS) by Kaplan Meier and multivariate Cox modeling. R (v.3.6.3) software was used for statistical analysis. Results: 218 mHSPC pts were included: 125 received androgen deprivation therapy (ADT) with Docetaxel and 93 ADT alone. Median age was 66.4 years (range 46.3-84.6), 75.7% ( N= 165) presented with de novo mHSPC, 15.1% ( N= 33) had visceral metastasis and 68.3% ( N= 149) had high volume disease. Median follow-up was 38.8 months (m) (range 6.7-223.5) and 189 pts (86.7%) developed CRPC. Five pts were excluded due to lack of follow-up. Median time to CRPC was 18.8 m (95% CI 15.8-20.5) and median OS was 48.8 m (95% CI 43.2-59.1). Pts were grouped according to TMPRSS2-ERG fusion detection in TE positive (TE+) ( N= 108, 49.5%) and TE negative (TE-) ( N= 110, 50.5%) and according to ESR2 expression levels segregated into tertiles in ESR2 high (ESR2+) ( N= 74, 33.9%) or ESR2 low-mid (ESR2-) ( N= 144, 66.1%). TE+ status was associated to higher ESR2 levels ( P= 0.03). The TE+/ESR2+ group showed longer CRPC-FS and OS, compared with the other groups, as shown in the table. TE+/ESR2 expression was independently associated with longer CRPC-FS (HR 0.3, 95% CI 0.2-0.5, P&lt; 0.001) and OS (HR 0.3, 95% CI 0.2-0.5, P&lt; 0.001). Moreover, a significant interaction between treatment (ADT vs ADT+Docetaxel) and TE+/ESR2+ status related to CRPC-FS was found (HR: 0.38, P= 0.014), suggesting that TE+/ESR2+ pts may benefit more from ADT than from the combination of ADT+Docetaxel. Conclusions: Our study suggests a protective role of ESR2 within a subgroup of mHSPC pts characterized by TMPRSS2-ERG fusion, which warrants further investigation of ESR2 as a prognostic factor, for treatment selection and as a potential pathway for targeted treatment in PC. [Table: see text]