Treatment Of High-risk Prostate Cancer Research Articles

Cardiorespiratory fitness and cardiovascular mortality after prolonged androgen deprivation therapy for prostate cancer.

11576 Background: Androgen deprivation therapy (ADT) plays a pivotal role in management of prostate cancer (PC), with prolonged ADT favored over short-term use in the definitive treatment of high risk PC with radiation. Objectives: To compare cardiorespiratory fitness (CRF) and cardiovascular (CV) mortality among patients with PC with and without ADT exposure, and to explore how duration of ADT exposure influences CRF and CV mortality risk. Methods: This is a retrospective study of patients referred for exercise treadmill testing (ETT) after a diagnosis of PC. PC risk classification was based on Gleason score (GS) at diagnosis: high risk GS ≥ 8, intermediate risk GS= 7, and low risk GS ≤ 6. CRF was categorized according to metabolic equivalents (METs): METs ≥ 8 defined as good CRF and METs < 8 as reduced CRF. ADT exposure was grouped as short-term (≤ 6 months) versus prolonged (> 6 months). Results: 616 patients underwent an ETT a median of 4.8 years (interquartile range: 2.0-7.9) after diagnosis of PC. 150 patients (24.3%) received ADT prior to ETT; 51 with short-term versus 99 with prolonged exposure. 524 (85.1%) patients had ≥ 2 CV risk factors, and 28 CV deaths occurred over 4.2 (interquartile range: 2.3-7.1) years following the ETT. Reduced CRF was more frequent among ADT-exposed versus ADT-naive patients (48.7 versus 32.6%, p< 0.001). Prolonged ADT was associated with reduced CRF (odds ratio (OR): 2.71; 95% confidence interval (CI): 1.31-5.61; p=0.007) and increased CV mortality (hazard ratio (HR): 3.87; 95% CI: 1.16-12.96; p=0.03) in adjusted analyses. In contrast, short-term ADT exposure was not independently associated with either reduced CRF (OR 1.71; 95% CI: 1.00-2.94); p=0.05) or CV mortality (HR: 1.60; 95% CI: 0.51-5.01; p=0.42). Conclusions: Among patients with PC and high baseline CV risk, > 6 months ADT exposure but not less was associated with reduced CRF and increased CV mortality. Reduced CRF may in part mediate increased CV mortality risk. Exercise interventions concurrent with prolonged ADT warrants investigation to potentially offset risk.

27-year patterns in high-risk prostate cancer treatment in a racially diverse, equal-access health care setting.

e16583 Background: Despite the significant stage migration of prostate cancer (CaP), a large proportion of patients harbor high-risk disease. Few CaP series provide long term outcomes with the ability to assess disparities in diverse populations. We examined 27-year outcomes among men treated for high risk CaP in a large, racially diverse, equal access system. Methods: A retrospective cohort study was conducted of patients enrolled into the Center for Prostate Disease Research (CPDR) Multi-Center National Database from 1990-2017. There were 2,241 CaP patients who were NCCN-defined high risk, had a self-reported race of Caucasian (CA) or African American (AA), and had a primary treatment of hormonal therapy (HT), radical prostatectomy (RP), radiation therapy (RT) or no treatment (NoTX). Demographic and clinico-pathological variables were evaluated and stratified by race and treatment. Primary study outcomes included temporal patterns in race-specific treatment intensity and type(s). Secondary outcomes included biochemical recurrence (BCR)-free survival (BRFS) and distant metastasis-free survival (DMFS). Unadjusted Kaplan-Meier estimation curves and multivariable Cox proportional hazards analysis were used. Results: Mean patient age at CaP diagnosis and follow-up time were 68.1 years and 7.8 years, respectively. AAs made up 26.9% of the study cohort. Median prostate specific antigen level was 20.9 ng/mL (IQR: 7.8 - 35.0). 52% of patients had a biopsy Gleason score of 8 or greater. 714 (31.9%) underwent RP, 966 (43.1%) underwent RT, 288 (12.9%) received primary HT, and 273 (12.2%) had NoTX. A decreasing trend of HT, with stable rates of RP and RT, was observed. Median time to BCR after RP and RT was 1.3 and 3.1 years, respectively. After RP and RT, 51.2% and 39.3% experienced BCR while 10.9% and 12.7% experienced distant metastasis, respectively. There were no significant racial differences in treatment intensity, treatment type, BRFS or DMFS. Conclusions: In this longitudinal series, there was racial comparability for all study outcomes. Moreover, in this high-risk patient series with long-term follow up (median = 6.9 years), nearly 50% did not experience BCR, and only 1 in 10 men developed metastasis.

Triple treatment of high-risk prostate cancer. A matched cohort study with up to 19 years follow-up comparing survival outcomes after triple treatment and treatment with hormones and radiotherapy

Purpose: To evaluate the efficacy of a triple treatment strategy, including surgery, on high risk prostate cancer comparing long-term survival outcome with a cohort receiving standard radiotherapy with endocrine therapy.Materials and methods: This study compared two cohorts in survival outcomes, matched on the year of diagnosis and age. In both groups there was a curative intention to treat localized high-risk prostate cancer (one or more of Gleason score 8–10, PSA 20–50 or stage T3), diagnosed between 1995–2010, follow-up at the end of 2014. Triple treatment group: 153 patients treated primarily with radical prostatectomy with neoadjuvant endocrine treatment, and a majority with adjuvant radiotherapy. Standard radiotherapy group: 702 patients with a treatment of either external radiotherapy or high dose brachytherapy combined with external beam therapy, both modalities in combination with neoadjuvant endocrine therapy.Results: The prostate-cancer-specific mortality was 10% for the triple treatment group and 15% for the standard radiotherapy group during the period, HR = 2.01 (1.17–3.43), p = 0.011. The corresponding overall mortality was 26% vs 29%, HR = 1.54 (1.09–2.17), p = 0.015. High Gleason score was the dominating risk factor for early death due to the disease. Clinical T-stage was not an independent risk factor for death in this population.Conclusion: Adding surgery in a multimodal treatment model in high-risk prostate cancer showed significantly better survival outcome compared with the current standard of radiotherapy. Surgery in this group is, therefore, compelling and that also includes a clinical T3-stage of the disease. The study is limited by possible selection bias for the two treatment models.

Preoperative radiotherapy for high-risk prostate cancer (PORT-PC) trial.

TPS137 Background: Prostatectomy has become the most common treatment for high-risk prostate cancer. After prostatectomy, risk features for local recurrence include extra-capsular extension and/or seminal vesicle invasion (pT3 disease) and positive surgical margins. Post-operative radiotherapy is recommended for patients with pT3 disease, positive margins and/or Group Grade 4-5 and has been shown to reduce the risk of recurrence. In planning adjuvant radiotherapy, the clinical target volume is the prostate bed which is difficult to delineate once the prostate has been surgically removed and can be overestimated by following the location of surgical clips. As such, controversy exists as to the optimal target volume. Guidelines suggest including a significant portion of the posterior and inferior aspects of the bladder, and anterior aspect of the rectum exposing a significant amount of normal tissue to high dose radiation. Pre-operative radiotherapy potentially offers the following advantages: 1) reduced radiation dose to normal tissues; 2) ability to utilize stereotactic body radiotherapy (SBRT) with real-time MRI guidance 3) patient convenience with less fractions and 4) radiobiologic advantage of high dose per fraction treatment delivery. Methods: This is a modified dose escalation trial for patients with high-risk prostate cancer defined as cT3 on MRI or Group Grade 4-5 disease. Patients will sequentially undergo 1) placement of a rectal SpaceOAR, 2) SBRT on the ViewRay MRIdian linear accelerator and 3) prostatectomy. As a modified dose escalation study, patients will be accrued starting at 5 Gy x 5 (up to 8 Gy x 5) with 3 patients per cohort with Grade 4 or 5 gastrointestinal (GI) and/or genitourinary (GU) adverse event related to preoperative radiotherapy as an unacceptable dose limiting toxicity.The primary endpoint is that a patient can undergo a radical prostatectomy after SBRT without a post-operative GI or GU grade 4 or 5 toxicity within 30 days related to preoperative radiotherapy. Secondary objectives include assessment of acute toxicity and quality of life scores. Exploratory analyses include analysis of tumor and normal biopsied and resected tissue and serum markers and interpretation of pre- and post-SBRT MRIs. Clinical trial information: NCT03663218.

Radical Prostatectomy and Pelvic Lymph Node Dissection in Kaiser Permanente Southern California: 15-Year Experience.

Radical prostatectomy (RP) with pelvic lymph node dissection (PLND) is the standard treatment of high-risk prostate cancer. High-risk patients and those with lymph node metastasis (LNM) require further treatment. We review outcomes of RP+PLND in Kaiser Permanente Southern California (KPSC). Patients who underwent RP+PLND in KPSC from January 1, 2001, to July 1, 2015 were included. Patient charts were retrospectively reviewed for demographic information and clinicopathologic data which were used to calculate positive surgical margin rate, LNM, adjuvant treatment, 5-year biochemical recurrence, and overall survival. Univariate and multivariate logistic regression analyses were used to identify factors associated with margin positivity. Patients (N = 1829) underwent RP+PLND (241 high-risk, 943 intermediate-risk, 645 low-risk). Positive margin rates were 17.8%, 14.8%, and 11.9% in the high, intermediate- and low-risk groups. Biochemical recurrence rates were 22% in high-risk and 12.1% in the low-risk category. Androgen deprivation use was 4.1% in the high-risk group and 0.9% in the low-risk group. Five-year overall survival was 92.5% in lymph node-positive patients and 94.9% in lymph node-negative patients (p = 0.8). On multivariate analysis, age (odds ratio [OR] = 1.02, p = 0.02), prebiopsy prostate-specific antigen (OR = 1.02, p < 0.001), and clinical T stage (OR = 1.49, p = 0.01) were associated with margin positivity. In KPSC, RP+PLND was performed in patients with low-, intermediate-, and high-risk prostate cancer. Age, prebiopsy prostate-specific antigen, and clinical stage were associated with positive surgical margins in patients with LNM. Recipients of RP+PLND with LNM and positive surgical margins required adjuvant treatment.

Multi-institutional analysis of high-risk prostate cancer patients treated with stereotactic body radiotherapy.

51 Background: Stereotactic Body Radiotherapy (SBRT) delivers ablative doses of radiation (RT) over a course of five treatments and has been increasingly used as a definitive RT option for low- and intermediate-risk prostate cancer (PCa). Ongoing prospective trials are evaluating the efficacy of SBRT for high-risk PCa, but clinical outcomes reports are limited. Methods: Patients treated for high-risk PCa between 2006-2017 at any of five institutions were included. SBRT doses ranged from 35-40 Gy in 5 fractions per institutional standards, with one institution using an integrated boost approach. The Phoenix definition was used to define biochemical failure (BCR). Physician-reported genitourinary (GU) and gastrointestinal (GI) toxicity outcomes were scored using the Radiation Therapy Oncology Group or Common Terminology Criteria for Adverse Events systems. Results: In total, 182 patients were included in this study with a median follow-up time of 38.4 months (mos). The median age was 72. Most patients (72%) had Gleason 8-10 disease. Sixty-eight percent of patients received androgen deprivation therapy (ADT) for a median of 9 mos (interquartile range 6-9 mos). The rate of distant metastases was 3.8%. There were no acute Grade 3 (G3) or higher GU or GI toxicities. Three patients (1.6%) experienced a late G3 GU toxicity and one patient (0.5%) experienced a late G3 GI toxicity. The incidence of BCR was significantly higher in patients who did not receive ADT (30% vs. 15%, p = 0.02 by Chi-square). Conclusions: In this multi-institutional study, SBRT demonstrated an acceptable safety profile for the treatment of high-risk PCa. Longer term follow-up is necessary to evaluate the oncologic efficacy of this approach, but given the potentially higher incidence of BCR without ADT, ADT likely has an important oncologic role even with SBRT regimens.

The research progress on the treatment of high-risk prostate cancer

前列腺癌(PCa)是男性泌尿生殖系统最常见的恶性肿瘤之一，近年来在我国发病率和死亡率都呈明显上升趋势。在治疗上，中、低危前列腺癌单靠根治性手术就能获得较好的疗效，而高危前列腺癌因其侵袭性强、易复发和易转移等特点，最佳治疗选择一直存在争议。手术、放疗、化疗、去势治疗等多种治疗方案都对高危前列腺癌的治疗有积极的作用，同时也暴露出各种弊端。随着微创外科和新兴放疗技术的应用，为高危前列腺癌的治疗提供了更多的选择。本文就高危前列腺癌的治疗进展作一综述。

Definitive external-beam radiotherapy versus radical prostatectomy in clinically localized high-risk prostate cancer: a retrospective study

BackgroundOptimal treatment of high-risk prostate cancer remains controversial. We aimed to compare treatment outcomes of prostate cancer patients treated with definitive external-beam radiotherapy (ExRT) or radical prostatectomy (RP).MethodsThe records of 120 high-risk clinical stage T2b-T4 N0 M0 prostate cancer patients treated with definitive ExRT or RP were reviewed. Patients with pretreatment prostate-specific antigen (PSA) levels ≥20 ng/mL or clinical ≥T3 stage or Gleason score (GS) ≥8 were included in the study. Biochemical failure free survival (BFFS), distant metastasis free survival (DMFS), cancer-specific survival (CSS) and overall survival (OS) were analyzed. Cox regression analysis was performed to determine predictors of BF.ResultsSeventy-two patients received definitive ExRT with androgen-deprivation therapy in 95.8% and 48 patients underwent RP with pelvic lymph node dissection. Mean age (67.7 ± 6.6 vs 64.5 ± 7.6 year, p = 0.017) and the rate of patients with PSA levels ≥20 ng/mL (69.4% vs 47.9%, p = 0.022) were higher in the definitive ExRT group than the RP group. Distributions of GS and clinical T stage were similar. Mean follow-up was 60.2 ± 30.3 months in the definitive ExRT group and 41.3 ± 21.5 months in the RP group (p < 0.001). Twenty-five % of the RP group received adjuvant ExRT and 41.7% received salvage ExRT. Biochemical failure was significantly higher (52.1% vs 21.4%, p < 0.001) and the mean BFFS was significantly lesser (34.4 ± 3.9 vs 97.8 ± 5.9 months, p < 0.001) in the RP group than the definitive ExRT group. However, DMFS, CSS and OS were similar in both groups. In multivariate analysis, being in the RP group significantly increased the risk of BF (p < 0.001). Furthermore, not receiving pelvic lymphatic irradiation in the definitive ExRT group (p = 0.048) and having positive surgical margin in the RP group (p = 0.050) increased the risk of BF.ConclusionsBF was significantly higher and the mean BFFS was significantly lesser in high-risk prostate cancer patients undergoing RP than definitive ExRT while DMFS, CSS and OS were similar in both treatment groups.

Screening Prostate-Specific Antigen and Early Detection

Prostate cancer early detection based on screening with prostate-specific antigen (PSA) has been a highly controversial topic over the years. Early detection and treatment of high-risk prostate cancer explains a large proportion of greater than 50% reduction in age-standardized prostate cancer mortality observed since the early 1990s. However, this public health success has come at the cost of high levels of overdiagnosis of low-risk tumors, and many men have suffered from overtreatment of these entirely indolent lesions. Data from randomized trials increasingly clearly indicate a prostate cancer mortality advantage with screening. Other cohort studies, moreover, suggest that an early, baseline PSA test around age 45 or 50 years can predict cancer risk over years and decades, potentially allowing subsequent screening intervals to be personalized, further reducing both over- and underdiagnosis. Other aspects of a smarter screening paradigm include focused attention on men at higher risk based on ancestry, family history, and other factors; consideration of other variables together with PSA; selective use of secondary testing with emerging blood and urine tests; and reservation of treatment only for men at risk of prostate cancer mortality. Such an approach should be able to reduce further prostate cancer morbidity and mortality, while minimizing the harms of over-diagnosis and overtreatment. This review contains 4 figures, 1 table, and 88 references. Key Words: Prostate cancer, prostate-specific antigen, early detection, cancer screening, guidelines, risk stratification, epidemiology, PLCO, ERSPC, USPSTF, CISNET

The effect of additional chemotherapy on high-risk prostate cancer: a systematic review and meta-analysis.

ObjectiveThe role of additional chemotherapy in the treatment of high-risk prostate cancer (PCa) remains a controversy. This meta-analysis aimed to investigate the effect of additional chemotherapy on high-risk PCa.MethodsRandomized controlled trials (RCTs) about additional chemotherapy for high-risk PCa were searched in PubMed, MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials. We extracted HRs of overall survival (OS) and progression-free survival (PFS) for each trial and performed the meta-analysis using Review Manager 5.3.ResultsEight RCTs involving 4,007 patients were included. Data from four trials, which could collect OS, showed that additional chemotherapy could not significantly improve the OS in patients with high-risk PCa (HR: 0.93; 95% CI: 0.79–1.09; P=0.37). However, the pooled analysis suggested significantly longer PFS in high-risk PCa patients treated with additional chemotherapy (HR: 0.81; 95% CI: 0.74–0.90; P<0.0001). The meta-analysis showed additional chemotherapy to androgen-deprivation therapy improved PFS (HR: 0.82; 95% CI: 0.74–0.91; P=0.0002). Greater improvement in PFS was found in high-risk PCa patients treated with additional docetaxel-based chemotherapy (HR: 0.73; 95% CI: 0.64–0.83; P<0.00001). No prolonged PFS was observed in high-risk PCa patients with non-docetaxel-based chemotherapy (HR: 0.97; 95% CI: 0.83–1.14; P=0.74).ConclusionAdditional chemotherapy, especially docetaxel-based chemotherapy, could significantly improve the PFS in high-risk PCa patients. More evidence about the effect of additional chemotherapy on OS is needed. Further investigations in PCa should also focus on the suitable population for chemotherapy as well as optimal use of chemotherapy.

Ten-year survival after High-Dose-Rate Brachytherapy combined with External Beam Radiation Therapy in high-risk prostate cancer: A comparison with the Norwegian SPCG-7 cohort

BackgroundThe survival benefit of dose-escalation with High-Dose-Rate brachytherapy (HDR-BT) boost combined with External Beam Radiotherapy (EBRT) for the treatment of high-risk prostate cancer (PCa) remains debatable. We investigated 10-year PCa-specific mortality (PCSM) and overall mortality (OM) in high-risk patients treated with HDR-BT/EBRT (calculated EQD2 = 102 Gy) compared to EBRT alone (70 Gy). MethodsHDR-BT boosts (10 Gy × 2) were given 2 weeks apart followed by 50 Gy conformal EBRT (2 Gy × 25) to the prostate and seminal vesicles. The HDR-BT/EBRT group (N:325) received Androgen Deprivation Therapy for a median duration of 2 years. The historical control group (N:296), received a median dose of 70 Gy (2 Gy × 35) to the prostate and seminal vesicles with lifelong Anti-Androgen Treatment. For each treatment group PCSM and OM were established by competing-risk analyses and Kaplan–Meier analyses respectively. Differences were evaluated by the logrank test. Independent associations were established by Cox regression analyses. Significance level set to p < 0.05. ResultsMedian follow-up was 104 and 120 months for the HDR-BT/EBRT and the EBRT group respectively. A 3.6-fold decreased risk of PCSM (p < 0.01) and a 1.6-fold decreased risk of OM (p = 0.02) in the HDR-BT/EBRT cohort compared to the EBRT-only group were revealed. Ten-year OM and PCSM rates were 16% and 2.5% in the HDR-BT/EBRT group versus 23% and 8.2% in the EBRT-only group respectively.Both treatment modality (HR = 3.59, 95%CI 1.50–8.59) and Gleason score (HR = 2.48, 95%CI 1.18–5.21) were associated with PCSM. Only treatment modality (HR = 1.63, 95%CI = 1.08–2.44) was significantly associated with OM. ConclusionsMen with high-risk PCa have a significantly reduced PCSM and OM rates when treated with dose-escalated radiotherapy achieved by HDR-BT/EBRT compared to EBRT alone (70 Gy). A Gleason score of 8–10 was independently associated with increased risk of PCSM. Randomized studies are warranted. SummaryObservational study of 10-year survival in high-risk Prostate Cancer (PCa) after High-Dose-Rate brachytherapy combined with External Beam Radiation Therapy (HDR-BT/EBRT) compared to EBRT alone. The combined HDR-BT/EBRT treatment was found to give a 3.6-fold decrease in Prostate Cancer Specific Mortality (PCSM) and a 1.6-fold decrease in Overall Mortality (OM). Gleason score and type of treatment strongly influenced PCSM whereas only treatment modality was associated with OM.The observed benefits of dose-escalation warrant future randomized trials.

68Ga-PSMA PET/CT and PET/MRI in high-risk prostate cancer patients.

Treatment of high-risk prostate cancer (HRPCa) is challenging. Local staging and metastatic evaluation are important for the patient management. Recently, prostate-specific membrane antigen (PSMA)-based imaging modalities such as PSMA PET/CT and PET/MRI have received significant attention for detection of recurrent prostate cancer sites with elevated prostate-specific antigen levels, after therapy. Current evidence suggests that these imaging modalities may also have a role for the management of patients with HRPCa. In this review, we discuss PSMA-based imaging modalities in the management of patients with HRPCa.

Long-term oncological results of treatment for high-risk prostate cancer using radical prostatectomy in a cancer hospital

ObjectivesTo analyze the most relevant oncologic results of treatment using radical prostatectomy (RP) for high-risk prostate cancer (HRPC) in a specialist cancer hospital. Material and methodsA descriptive retrospective study of RP was conducted at our center from 1986 to 2017 on HRPC whose primary objective was to determine overall survival (OS) and cancer-specific survival (CSS). The study's secondary objectives were to determine biochemical progression-free survival (BPFS), metastasis-free survival (MFS), rescue therapy-free survival (RTFS), hormone therapy-free survival (HTFS) and the development of castration-resistant prostate cancer. We performed a Cox regression analysis to establish predictive models and to better understand the weight of each variable that defines high risk. ResultsA total of 2093 RPs were performed, 480 (22.9%) of which were for HRPC. The median follow-up for the overall series was 79.57 months (P25–75 37.92–135.16). Lymphadenectomy was not performed in 6.5% of the cases. The lymphadenectomy was of the obturator type in 51.2% of the cases and extended in 42.3%. Overall survival at 5, 10 and 15 years was 89.8% (95% CI 86.7–92.9%), 73.3% (95% CI 68–78.6%) and 51.4% (95% CI 43.8–59%), respectively. CSS at 5, 10 and 15 years was 94.8% (95% CI 92.4–97.2%), 84.0% (95% CI 79.3–88.7%) and 75.5% (95% CI 68.8–82.2%), respectively. MFS at 5, 10 and 15 years was 87.4% (95% CI 84.1–90.7%), 72.2% (95% CI 66.7–77.7%) and 61.7% (95% CI 54.3–69.1%), respectively. A total of 120 patients of 477 analyzed (25.1%) required rescue radiation therapy, and 293/477 never required hormone therapy (61.4%). Of the 93 pN1 patients, 33 (35.5%) did not require hormone therapy. The time from RP to biochemical progression was the variable with the greatest prognostic weight for MFS, CSS and overall survival. ConclusionsRP plus extended lymphadenectomy should be the first therapeutic maneuver when feasible within a multimodal strategy. A longer follow-up of the series is needed to validate the hypothesis of better oncologic results based on the earlier implementation of rescue radiation therapy, extended lymphadenectomy and drugs that prolong survival in the CRPC phase.

Work-up and treatment of prostate cancer before and after publication of the first national guidelines on prostate cancer care in Sweden

Background and Objectives: In 2007, the Swedish National Board of Health and Welfare published the first Swedish guidelines on prostate cancer (PCa) to improve care and decrease geographical and social inequalities. The aim of this analysis was to assess how these guidelines affected PCa care.Materials and Methods: Work-up and treatment for men diagnosed with PCa between 1998 and 2014 were assessed by use of data in the Prostate Cancer data Base Sweden (PCBaSe) with information from the National Prostate Cancer Register (NPCR) and other healthcare registries and demographic databases.Results: Overall, there were modest improvements in the performance for 14 selected quality indicators, with some notable exceptions. There was a strong increase in the use of active surveillance for very low-risk PCa, up from 56% in 2009 to 92% in 2014, and use of bone imaging for high-risk PCa up from 50% in 2008 to 77% in 2014. There were large differences in work-up and treatment of PCa between healthcare providers with modest decreases over time. The differences between counties were larger than differences according to socioeconomic status with one exception: use of curative treatment for high-risk PCa was more common in men with high income, highest versus lowest tertile, OR 2.74 (95% CI, 1.85-4.06).Conclusion: The modest improvements in PCa care after the publications of national guidelines indicate that if these are to make an impact on care, feedback to each point of care on their performance as well as local quality improvement programs implementing the guidelines are needed.

PV-0629: External beam RT with brachytherapy vs prostatectomy in treatment of high-risk prostate cancer

PV-0629: External beam RT with brachytherapy vs prostatectomy in treatment of high-risk prostate cancer

Radical Prostatectomy in High-Risk Prostate Cancer Patients: Results of a Single- Institution Study

Objective: To evaluate long-term outcomes of radical prostatectomy and bilateral pelvic lymph node dissection (RP) for high-risk prostate cancer (PC).Material and Method: A retrospective review of high-risk PC patients who received RP, identified from medical records. We collected data from Songklanagarind Hospital, Prince of Songkla University from 2007 to 2015. The Kaplan-Meier method and Cox proportional regression models were used to analyze clinical recurrence (CR) and biochemical recurrence (BCR).Results: In 79 patients, the median follow-up was 27.2 months. The 3-year and 5-year biochemical free survival in men with high-risk PC were 67.7% and 62.9% respectively. Multivariate analysis shows that pathologic stage 3a (hazard ratio=4.87; 95% confidence interval=1.01-23.38) was independently associated with cancer control.Conclusion: Data support the belief that RP has a place in the treatment of high-risk PC. RP was a long-term cancer control in patients with high-risk PC. Only pathologic staging was independently associated with cancer control outcome.

Is There an Optimal Treatment for High-Risk Prostate Cancer?

The management of patients with high-risk localized prostate cancer typically requires multimodality therapy. However, the optimal approach remains

The importance of the need for better systemic therapy in the definitive treatment of high-risk prostate cancer regardless of whether the initial treatment modality was external beam radiation, I-125 brachytherapy, or radical prostatectomy.

65 Background: While androgen deprivation therapy (ADT) is a common form of systemic therapy for treating high-risk prostate cancer (HRCaP), distant metastases development remains the predominate form of failure. We present a description of the sites of failure after treatment of HRCaP with External Beam Radiation (EBRT), I-125 Brachytherapy (PB), or Radical Prostatectomy (RP). This is accompanied by an analysis of prostate cancer-specific mortality (PCSM) after clinical failure. Methods: The study includes 2186 patients with HRCaP according to NCCN guidelines (684 EBRT, 409 PB, and 1093 RP). The association of PCSM with clinical and pathologic variables was assessed with Fine and Gray regression with non-PCSM mortality treated as a competing event. Results: The median f/u is 52 months. Overall, there were 323 clinical failures (sites of first failures: 287 distant (DM), 34 local (LF), 2 DM + LF). The median time to the diagnosis of DM was 44 months. ADT was used in 93% of EBRT, 53% of PB and 19% of RP patients. Further details regarding the development of DM is shown in Table 1. The type of initial treatment was not associated with PCSM after DM (Table 1). The only factor significantly associated with PCSM was Gleason Score (p = 0.0372). Conclusions: DM is the primary mode of failure after definitive treatment of HRCaP. The type of initial definitive treatment did not affect PCSM after DM. The cure rates of all forms of definitive treatment of HRCaP would benefit from better systemic therapy. [Table: see text]

Monitoring of Circulating Tumor Cells in Patients With High-Risk Nonmetastatic Prostate Cancer Treated With Radiation Therapy and Hormones: Preliminary Data of an Observational Prospective Phase 2 Study

Circulating tumor cells (CTCs) are a cellular source repeatedly obtainable by blood sampling that could serve as a surrogate marker for treatment efficacy. The presence of CTCs is an established marker for prognosis in men with castration-resistant prostate cancer. In contrast, the value of CTCs detection in men with localized high-risk prostate cancer is unknown. The purpose of this study is to evaluate the proportion of patients with high-risk prostate cancer (HRPCa) that presents CTCs in peripheral blood (PB) before and after androgen deprivation therapy (ADT) and radiation therapy (RT) in order to establish its prognostic value. We present preliminary data of CTCs monitoring detection. Hypothesis: The detection of CTCs is a potential surrogate marker for treatment efficacy in HRPCa. Prospective analysis of biological material obtained from PB samples in 65 patients with HRPCa treatment naïve between 2014 and 2016. Blood samples were analyzed to detect CTCs using an immunomagnetic method based on the CellSearch system in 4 periods of time: 1) Before starting any treatment; 2) following neoadjuvant ADT and prior to RT; 3) at the end of RT; 4) 6-12 months following the end of RT in those patients with 0 CTCs in the first determination and positive CTCs in the following determinations. A cut off of 0 vs ≥ 1CTCs/7.5ml blood was defined as a threshold for negative versus positive CTCs status. We also analyzed whether CTCs presence was associated with clinic-pathological features using the chi-square or Fisher exact test. The median age was 71 years and median PSA was 12.6 ng/ml. Twenty-eight patients had Gleason score ≥ 8 and 48 patients had clinical stage T3. CTCs were detected in 5/66 patients (7.5%) at diagnosis (baseline), in 8/62 (12.9%) following neoadjuvant ADT and in 11/59 (18.6%) at the end of RT with a median CTC count/7.5ml of 1 (range:1-136). Only 1 patient presented positive CTCs detection 6-13 months after RT. Positive CTCs status (at any period) did not correlate with patient age, pre-treatment PSA, T stage, N stage or Gleason score. The preliminary data obtained from this observational feasibility study showed an infrequent detection of CTCs in patients with HRPCa with no correlation to known clinical prognostic factors. The positive cases for CTCs after ADT and RT (mostly with very low levels and not maintained over time) are probably due to a passive mechanism associated with the destruction of the tumor. A more acute assessment method to detect CTCs together with larger cohorts with extended follow-up are needed to validate this finding.

The survival impact of neoadjuvant hormonal therapy before radical prostatectomy for treatment of high-risk prostate cancer.

Several randomized controlled trials assessed the outcomes of patients treated with neoadjuvant hormonal therapy (NHT) before radical prostatectomy (RP). The majority of them included mainly low and intermediate risk prostate cancer (PCa) without specifically assessing PCa-related death (PCRD). Thus, there is a lack of knowledge regarding a possible effect of NHT on PCRD in the high-risk PCa population. We aimed to analyze the effect of NHT on PCRD in a multicenter high-risk PCa population treated with RP, using a propensity-score adjustment. This is a retrospective multi-institutional study including patients with high-risk PCa defined as: clinical stage T3-4, PSA >20 ng ml-1 or biopsy Gleason score 8-10. We compared PCRD between RP and NHT+RP using competing risks analysis. Correction for group differences was performed by propensity-score adjustment. After application of the inclusion/exclusion criteria, 1573 patients remained for analysis; 1170 patients received RP and 403 NHT+RP. Median follow-up was 56 months (interquartile range 29-88). Eighty-six patients died of PCa and 106 of other causes. NHT decreased the risk of PCRD (hazard ratio (HR) 0.5; 95% confidence interval (CI) 0.32-0.80; P=0.0014). An interaction effect between NHT and radiotherapy (RT) was observed (HR 0.3; 95% CI 0.21-0.43; P<0.0008). More specifically, of patients who received adjuvant RT, those who underwent NHT+RP had decreased PCRD rates (2.3% at 5 year) compared to RP (7.5% at 5 year). The retrospective design and lack of specific information about NHT are possible limitations. In this propensity-score adjusted analysis from a large high-risk PCa population, NHT before surgery significantly decreased PCRD. This effect appeared to be mainly driven by the early addition of RT post-surgery. The specific sequence of NHT+RP and adjuvant RT merits further study in the high-risk PCa population.