Adjuvant Adjuvant Androgen Deprivation Therapy Research Articles

PD16-07 POST-PROSTATECTOMY ADJUVANT ANDROGEN DEPRIVATION THERAPY-- PATIENT OPINIONS AND GOALS OF CARE

You have accessJournal of UrologyCME1 Apr 2023PD16-07 POST-PROSTATECTOMY ADJUVANT ANDROGEN DEPRIVATION THERAPY-- PATIENT OPINIONS AND GOALS OF CARE Max Levitt, Ameeta Nayak, Dean Fergusson, Luke Lavallee, Christopher Morash, Ilias Cagiannos, and Rodney Breau Max LevittMax Levitt More articles by this author , Ameeta NayakAmeeta Nayak More articles by this author , Dean FergussonDean Fergusson More articles by this author , Luke LavalleeLuke Lavallee More articles by this author , Christopher MorashChristopher Morash More articles by this author , Ilias CagiannosIlias Cagiannos More articles by this author , and Rodney BreauRodney Breau More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003271.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Despite the proven benefit of adjuvant androgen deprivation therapy (ADT) for patients receiving primary radiation, few studies evaluate adjuvant ADT after prostatectomy. We surveyed Canadian prostate cancer patients about adjuvant ADT with the goal of informing an adjuvant ADT clinical trial. METHODS: An electronic survey was devised and distributed using a modified Dillman approach. The survey was sent to members of Prostate Cancer Canada, a patient advocacy group. In addition to demographic information, we asked patients about their experience with prostate cancer, if they received post-operative therapy, and about their opinions to inform the design of an adjuvant ADT clinical trial. The survey was sent on May 2021, and all responses were received by July 2021. RESULTS: Forty patients completed the survey. The average participant age was 71±7.3 years old. The average age at prostate cancer diagnosis was 64±6.7 years. Thirty-eight (95%) patients were previously treated with radical prostatectomy and 24 (60%) subsequently developed biochemical recurrence. If it had been available, 30 (75%) participants indicated that they would have been interested in an adjuvant ADT trial to prevent biochemical recurrence. Most (15; 37.5%) stated that 12 months would be the longest duration of ADT that they would consider. The remainder of participants would have considered up to 6 months (9; 22.5%), up to 18 months (3; 7.5%), up to 24 months (5; 12.5%), or greater than 24 months (8; 20%) of adjuvant ADT. A daily oral tablet (31; 52.5%) or injection every 6 months (9; 22.5%) were favoured in a clinical trial over an injection at shorter time intervals. The most important outcomes for a trial of adjuvant ADT were prevention of cancer related death (38; 95%) and cancer recurrence (37; 92%). If 1 year of adjuvant ADT reduced PSA recurrence by 50%, many (29; 47.5%) stated they would have chosen this intervention. CONCLUSIONS: Few trials have assessed adjuvant ADT after radical prostatectomy and many patients claim they would have been interested in participating in a trial if it had been available. Based on these results, a randomized trial is warranted and patient preferences should be incorporated in trial design. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e491 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Max Levitt More articles by this author Ameeta Nayak More articles by this author Dean Fergusson More articles by this author Luke Lavallee More articles by this author Christopher Morash More articles by this author Ilias Cagiannos More articles by this author Rodney Breau More articles by this author Expand All Advertisement PDF downloadLoading ...

Pituitary-testis axis dysfunction following adjuvant androgen deprivation therapy.

Men with high-risk, non-metastatic prostate cancer receive adjuvant androgen deprivation therapy (ADT) for at least 2 years according to Danish guidelines. It remains unclarified if patients regain the function of the pituitary-testis axis after cessation of ADT. Thus, we aimed to investigate the function of the pituitary-testis axis following adjuvant ADT. In this study, we included men who underwent external beam radiation therapy and ADT for high-risk prostate cancer. All patients underwent assessment of testosterone deficiency (TD) symptoms, full biochemical assessment of the pituitary-testis axis, and dynamic stimulatory tests of gonadotropin (gonadotropin-releasing hormone (GnRH) test) and testosterone production (human chorionic gonadotrophin (hCG) test). Patients were diagnosed with TD based on a combination of TD symptoms and testosterone below age-specific reference ranges. TD was characterized as primary, secondary, or mixed based on serum gonadotropins and stimulatory tests. We found that among the 51 patients included in the study, the median time on ADT was 3.2 years and median time since ADT cessation was 3.8 years. Twenty-eight patients were diagnosed with TD; 10 had primary TD (testicular dysfunction), 11 secondary TD (pituitary dysfunction), and 7 mixed TD (combined pituitary and testicular dysfunction). An inadequate testosterone response to hCG stimulation was shown in 42 patients, whereas only 11 patients had a subnormal gonadotropin response to GnRH. We conclude that persistent TD is a common long-term consequence of adjuvant ADT in prostate cancer survivors, equally distributed between pituitary and testicular dysfunction. The study emphasizes the necessity for systematic follow-up of full pituitary-testis axis function in patients receiving adjuvant ADT.

Complete androgen blockade vs. medical castration alone as adjuvant androgen deprivation therapy for prostate cancer patients following radical prostatectomy: a retrospective cohort study.

Background:Till date, the optimal treatment strategy for delivering adjuvant androgen deprivation therapy (ADT) in localized and locally advanced prostate cancer (PCa), as a lower stage in PCa progression compared with metastatic PCa, is still unclear. This study compares the efficacy of castration alone with complete androgen blockade (CAB) as adjuvant ADT in patients with localized and locally advanced PCa undergoing radical prostatectomy (RP).Methods:Patients diagnosed with PCa, without lymph node or distant metastasis, who received RP in West China Hospital between January 2009 and April 2019, were enrolled in this study. We performed survival, multivariable Cox proportional hazard regression, and subgroup analyses.Results:A total of 262 patients were enrolled, including 107 patients who received castration alone and 155 patients who received CAB. The survival analysis revealed that there was no significant difference between the two groups (hazard ratios [HR] = 1.07, 95% confidence intervals [95% CI] = 0.60–1.90, P = 0.8195). Moreover, the multivariable Cox model provided similarly negative results before and after adjustment for potential covariant. Similarly, there was no significant difference in the clinical recurrence between the two groups in both non-adjusted and adjusted models. Furthermore, our subgroup analysis showed that CAB achieved better biochemical recurrence (BCR) outcomes than medical castration alone as adjuvant ADT for locally advanced PCa (P for interaction = 0.0247, HR = 0.37, 95% CI = 0.14–1.00, P = 0.0497).Conclusion:Combined androgen blockade achieved better BCR outcomes compared with medical castration alone as adjuvant ADT for locally advanced PCa without lymph node metastasis.

Post-prostatectomy adjuvant androgen deprivation therapy- Current opinions and practices of Canadian urologists.

Despite the proven benefit of adjuvant androgen deprivation therapy (ADT) for patients receiving primary radiation, there are few studies evaluating adjuvant ADT after prostatectomy. In the absence of evidence, opinions and practice patterns vary. We surveyed Canadian prostate cancer surgeons about their use of adjuvant ADT and their opinions on the design of a potential adjuvant ADT trial. An electronic survey was devised and distributed using a modified Dillman approach. The survey was sent to 38 Canadian urologists that perform radical prostatectomy and representing all 17 major academic institutions in Canada and all 10 Canadian provinces. Reminders were sent three and four weeks following the original request. In addition to demographic information, we asked surgeons about their current use of postoperative adjuvant ADT and their opinion about the need for a clinical trial. To inform trial design, we asked respondents their opinions about which patients should be eligible, what duration of ADT was most appropriate, and which outcomes are clinically meaningful. The survey was sent in February 2020 and all responses were received by March 2020. All 38 (100%) invited urologists completed the survey. Only 3 (7%) respondents currently offer postoperative adjuvant ADT as an option for patients without metastases. 35 (92%) urologists believed that a trial is needed before short-term adjuvant treatment should be offered to prevent recurrence. 15 (45%) urologists believed an adjuvant ADT trial was most appropriate for patients with an estimated PSA recurrence risk of >25% and 16 (42%) believed a recurrence risk of >50% was most appropriate. 25 (66%) respondents believed 12-month was the optimal duration of treatment with adjuvant ADT for a randomized trial. 37 (97%) respondents felt that prolonging the time to PSA recurrence and/or pelvic radiation was a clinically important outcome. The majority (20; 53%) of respondents would recommend 12 months of adjuvant ADT in their practice if a randomized trial showed a 50% relative risk reduction in PSA recurrence at 5-year postoperative. The vast majority of Canadian prostate cancer surgeons do not offer adjuvant ADT following prostatectomy in patients without metastases. Based on the results from this survey, a randomized trial was considered warranted and feasible, and would influence patient care.

Testosterone Therapy in Men with Biochemical Recurrence and Metastatic Prostate Cancer: Initial Observations

Introduction: Although prostate cancer (PCa) has long been considered an absolute contraindication for testosterone therapy (TTh), growing literature suggests TTh may be safely offered to men with localized PCa. We here present a single-center series of men treated with TTh for relief of symptoms, despite having more advanced disease, namely biochemical recurrence (BCR) or metastatic PCa (MET). Methods: We identified men treated with TTh with BCR, MET, or adjuvant androgen deprivation therapy (ADT). Consent included risks of rapid PCa progression and death. Laboratory and clinical results were analyzed. Results: Twenty-two men received TTh: 7 with BCR, 13 with MET, and 2 with adjuvant ADT. Median age was 70.5 years (range 58–94). Median TTh duration was 12 months (range 2–84) overall, including 20 months for BCR and 9.5 months for MET. Mean serum testosterone (T) increased from 210 to 1111 ng/dL. Median PSA (interquartile range) increased from 3.1 ng/mL (0.2–4.5) to 13.3 ng/mL (3.4–22) in the BCR group, 6.3 ng/mL (1.2–31) to 17.8 ng/mL (6.2–80.1) in the MET group, and <0.1 to 0.3 ng/mL in the ADT group. All patients reported symptom relief, especially improved vigor and well-being. Overall mortality was 13.6% and PCa-specific mortality was 4.5% during the period of TTh and 6 months after discontinuation. Seven of 10 with follow-up imaging within 12 months showed no progression. Five men have died: three during TTh and two succumbed at 2 years or longer after discontinuing TTh. One of the three deaths during TTh was PCa-specific. Three men developed significant bone pain at 7–41 months; two discontinued TTh and one continued, after focal radiation. There were no cases of rapid-onset complications, vertebral collapse, or pathological fracture. Conclusions: These initial observations indicate TTh was not associated with precipitous progression of PCa in men with BCR and MET, suggesting a possible role for TTh in selected men with advanced PCa whose desire for improved quality of life is paramount.

Clinical characteristics and treatment strategies of prostate mucinous adenocarcinoma: the multi-center summary of 36 cases

Objective To review the clinical characteristics of prostate mucinous adenocarcinoma cases and update literatures , and recommend the corresponding clinical treatment strategy. Methods From October 2010 to March 2018, 36 cases of prostate mucinous adenocarcinoma were involved from 5 urinary centers in China, including 9 cases from Shanghai Changhai Hospital, 4 cases from Wuhan Tongji Hospital, 13 cases from Shanghai Renji Hospitals, 8 cases from the First Affiliated Hospital of Nanjing Medical University, and 2 cases from Sichuan West China Hospitals. The patients′ age were (66.8±7.2) years (53-83 years) and the median PSA was 22.89 ng / ml (2.67-1786 ng / ml). Prostate biopsy confirmed Gleason score 3+ 3 points in 6 cases, 3+ 4 points in 9 cases, 4+ 3 points in 5 cases, 8 points in 11 cases, and 9 to 10 points in 5 cases. According to D′Amico risk stratification, 2 patients were in the low-risk group, 9 in the intermediate-risk group, and 25 in the high-risk group. Eight cases underwent radical retroperitoneal prostatectomy, 13 cases underwent laparoscopic radical prostatectomy, and 12 cases underwent robotic laparoscopic radical prostatectomy. Twenty-three cases underwent pelvic lymphadenectomy, including 12 cases of bilateral obturator lymph node dissection, and 11 cases of bilateral obturator+ intraorbital+ para-vascular para-aortic lymphadenectomy. Results All 36 operations were completed successfully.Twenty-three cases underwent pelvic lymphadenectomy, including 12 of bilateral obturator lymph node dissection, and 11 of bilateral obturator, intraorbital, and para-aortic lymphadenectomy. Pathological examination showed 9 cases of prostate mucinous adenocarcinoma, 26 cases of mucinous adenocarcinoma with acinar adenocarcinoma, and 1 case of mucinous adenocarcinoma with neuroendocrine and immunohistochemical positive of MUC2(+ ). Among 33 cases undergoing radical surgery, the pathological stage of ≤T2b in 12 cases (36.3%), T2c in 7 cases (21.2%), T3a in 7 cases (21.2%), T3b in 6 cases (18.2%), and T4 in 1 case (3.0%). Four cases had positive pelvic lymph nodes and 9 cases had positive margin. The median follow-up period was 26 months (6-48 months). The biochemical recurrence occurred in 6 patients one year after surgery, including 3 cases in the intermediate-risk group and 3 cases in the high-risk group. Six cases with postoperative biochemical recurrence and 19 cases with PSA>0.2 ng/ml after radical or palliative resection underwent adjuvant androgen deprivation therapy(ADT), no postoperative adjuvant radiotherapy or chemotherapy was administered, and 4 cases progressed to castration-resistant prostate cancer. Four cases with CRPC were in the high-risk group and had underwent radical surgery, and the median period progressed to CRPC was 26 months(3-37months)with 2 cases of death. However, there was no significant difference in the rate of biochemical recurrence and the incidence of CRPC in the low-risk group, the intermediate-risk group and the high-risk group. In addition, 2 cases had metastases, with pelvic MRI presenting pelvic multiple nodular mass in one case which was consistent with recurrence and metastasis at the 5th month after radical surgery, and pathological examination presenting the mucinous adenocarcinoma being neurosecretory in another case and mestastasis being detected on glans at the 3rd months after radical surgery. The recovery rate of urinary continience at 6 and 12 months after radical surgery was 86.2%(31/36) and 89.7%(32/36) respectively. Conclusions Prostate mucinous adenocarcinoma is a variant of acinar adenocarcinoma. This study clarifies prostate mucinous adenocarcinoma of Chinese patients with high Gleason scores, advanced pathological stage, variant in prognosis, and prone to recurrence and metastasis. For treatment strategy, the low-risk and intermediate-risk mucinous adenocarcinoma is recommended undergoing radical surgery, and the prognosis maybe good. High-risk mucinous adenocarcinoma could treated with radical surgery or palliative surgery with adjuvant ADT, and most high-risk patients can benefite, with a small number of poor prognosis. Key words: Prostatic neoplasms; Mucinous adenocarcinoma; Biochemical recurrence; Castration-resistant

Adjuvant androgen-deprivation therapy following prostate total cryoablation in high-risk localized prostate cancer patients — Open-labeled randomized clinical trial

PurposeTo investigate the efficacy and safety profile of 12-month adjuvant androgen-deprivation therapy (ADT) following total-gland cryoablation (TGC) in patients with high-risk localized prostate cancer (HRLPC). Materials and MethodsThis open-label randomized trial included 38 HRLPC patients who received TGC between July 2011 and March 2013. Within 4 weeks after TGC, subjects were randomly assigned (1:1) to either the 12-month adjuvant ADT or non-adjuvant ADT group. The primary outcome was biochemical failure measured by the Phoenix definition. Adverse events were measured at month 1, 2, 3, 6, 9 and 12. In addition, a cohort of 145 HRLPC patients was selected retrospectively for outcome validation. ResultsThe adjuvant ADT and non-adjuvant ADT groups did't differ in peri-operative characters, such as age, preoperative PSA, tumor stages, Gleason score, prostate size and cryoprobe number. Four patients with adjuvant ADT withdrew from this trial for personal reasons (N = 2), elevated liver function (N = 1) and poorly controlled hyperglycemia (N = 1). In contrast, none in non-adjuvant ADT group experienced adverse events. Biochemical failures were identified in 5 (26%) patients in each group during a median follow-up duration of 45 months. The median times to biochemical failure were 25 and 5.5 months for adjuvant ADT and non-adjuvant ADT groups, respectively. Biochemical-failure survival curves converged 24 months after TGC. Univariable and multivariable analyses revealed adjuvant ADT was not associated with biochemical recurrences in the validation cohort. ConclusionsAdjuvant ADT does not reduce biochemical failure for HRPLC patients undergoing TGC. It should be further confirmed by a larger cohort.

Predictive factors and the important role of detectable prostate-specific antigen for detection of clinical recurrence and cancer-specific mortality following robot-assisted radical prostatectomy.

To evaluate predictive factors associated with detectable prostate-specific antigen (PSA) and describe clinical recurrence (CR) and cancer-specific mortality (CSM) after robot-assisted radical prostatectomy (RARP). The study included 2500 patients who were treated with RARP at a single institution between 2000 and 2016. All patients had clinically localized PCa. Patients were divided into two groups according to PSA value at 6weeks after surgery: undetectable (n=2271; PSA<0.1ng/dl) and persistently elevated (n=229; PSA≥0.1ng/dl). The association between various covariates and: (1) detectable PSA and (2) CR was evaluated. Kaplan-Meier analyses estimated CR and CSM rates according to PSA persistence. Inside the group of detectable PSA, 146 men (63.75%) received adjuvant treatments, 44 patients (19.21%) salvages therapies and 38 men (16.5%) experienced CR. Factors associated with aggressive disease predicted PSA persistence. Within patients with detectable PSA, pathologic stage ≥pT3a (HR 2.71; p<0.029) and to received adjuvant androgen deprivation therapy (ADT) due to bad prognosis tumors (HR 13.36; p<0.001) were associated with CR. Overall 14 (0.56%) died of PCa. 5 and 10-year CSM rates were higher for patients with CR (9.6 and 23.7%, p<0.001), and Gleason≥8 (5.7 and 6.9%, p=0.003). A detectable PSA is affected by factors associated with aggressive prostate cancer. Within men with persistent PSA, those with higher pathologic stage and who received adjuvant ADT are more likely to have CR. Patients with CR, Gleason≥8, and those who received adjuvant ADT must have a close monitoring due to the high rate of mortality.

Survival Outcomes of Men with Lymph Node-positive Prostate Cancer After Radical Prostatectomy: A Comparative Analysis of Different Postoperative Management Strategies

BackgroundOptimal management of patients with lymph node metastasis (LNM) after radical prostatectomy (RP) remains undefined. ObjectiveWe evaluated the association between three different management strategies and survival in prostate cancer with LNM after RP. Design, setting, and participantsWe analyzed data of 1338 patients with LNM after RP from three tertiary care centers. Three hundred and eighty-seven patients (28%) were observed, 676 (49%) received lifelong adjuvant androgen deprivation therapy (ADT), and 325 (23%) received adjuvant external beam radiation therapy (EBRT) and ADT. Three hundred and sixty-eight men were followed for more than 10 yr. Outcome measurements and statistical analysisPrimary outcome measure was overall survival (OS). Secondary outcomes were cancer-specific survival (CSS) and other-cause mortality. Kaplan-Meier methods were used to visualize OS for the three treatment groups. Cox proportional hazards regression was utilized to compare OS and CSS among the three groups. Results and limitationsADT+EBRT was associated with better OS than ADT alone (hazard ratio [HR]: 0.46, 95% confidence interval [CI]: 0.32–0.66, p<0.0001) or observation (HR: 0.41, 95% CI: 0.27–0.64, p<0.0001). Higher-risk patients benefited more from ADT+EBRT than lower-risk patients. Ten-year mortality risk difference between ADT+EBRT, observation, or ADT alone ranged from 5% in low-risk patients to 40% in high-risk patients. Adjuvant ADT+EBRT was also associated with better CSS than observation or ADT alone (p<0.0001), ADT had better CSS compared to observation (HR: 0.64, 95% CI: 0.43–0.95, p=0.027). However, ADT was associated with an increased risk of other-cause mortality (HR: 3.05, 95% CI: 1.45–6.40, p=0.003) compared with observation, resulting in similar OS between ADT and observation (HR: 0.90, 95% CI: 0.65–1.25, p=0.5). While selection bias might remain, its effect would operate in the opposite direction to our findings. ConclusionsIn men with LNM after RP, ADT+EBRT improved survival over either observation or adjuvant ADT alone. This survival benefit increases with higher-risk disease. Patient summaryLymph node metastasis following radical prostatectomy is associated with poor survival outcomes. However, we found that adjuvant androgen deprivation therapy with external beam radiation therapy improved survival in these patients.

The impact of multifocal perineural invasion on biochemical recurrence and timing of adjuvant androgen-deprivation therapy in high-risk prostate cancer following radical prostatectomy.

Perineural invasion (PNI) is a distinct pathologic entity and a recognized source of tumor spread. However, the role of PNI in high-risk prostate cancer (PCa) has not been explored. The aims of the study were to investigate the impact of PNI on biochemical recurrence (BCR) and optimal timing of adjuvant androgen-deprivation therapy (ADT) after radical prostatectomy (RP). A total of 265 prostatectomies, median follow-up 45 months, were assessed for the presence and intensity of PNI (unifocal and multifocal) in RP specimens. Kaplan-Meier curves were used to estimate BCR probabilities. Cox proportional hazard models were used to address predictors of BCR. Harrell's C-index was conducted to further validate prognostic value of multi-PNI. A total of 123 patients (46.4%) were PNI positive, among which, 91 (74%) and 32 (26%) had unifocal PNI (uni-PNI) and multifocal PNI (multi-PNI), respectively. The presence of multi-PNI was strongly associated with increasing incidence of BCR (HR = 3.87, 95%CI: 1.66-9.01, P = 0.002). Patients with uni-PNI had a similar BCR rate to those without PNI after adjuvant ADT. For men with multi-PNI, immediate ADT was superior to delayed ADT in decreasing biochemical failure. Our findings suggest that detection of multi-PNI in high-risk RP specimens could be a prognosticator for early biochemical relapse post-surgery. Initiation of adjuvant therapy may be appropriate in patients with multi-PNI as soon as possible after surgery.

The impact of multifocal perineural invasion on biochemical recurrence and timing of adjuvant androgen-deprivation therapy in high-risk prostate cancer following radical prostatectomy.

e595 Background: Perineural invasion (PNI) is a distinct pathologic entity and a recognized source of tumor spread. However, the role of PNI in high-risk prostate cancer (PCa) has not been explored. We investigated the impact of the severity of PNI on biochemical recurrence (BCR) and optimal timing of adjuvant androgen deprivation therapy (ADT) post radical prostatectomy (RP). Methods: Of 265 prostatectomies, median follow-up 45 months, were assessed for the presence of PNI and its intensity (unifocal PNI and multifocal PNI) in RP specimen. Kaplan-Merier curves were used to estimate BCR probabilities. Cox proportional hazard models were used to address predictors of BCR. Harrell’s C-index was conducted to further validate prognostic value of multi-PNI. Results: A total of 123 patients (46.4%) were PNI positive, among which, 91 (74%) and 32 (26%) had unifocal PNI (uni-PNI) and multifocal PNI (multi-PNI), respectively. Other than uni-PNI, the presence of multi-PNI was strongly associated with increasing incidence of BCR (HR = 3.87, 95% CI: 1.66-9.01, p = 0.002). Patients with uni-PNI seemed to have a similar BCR rate to those without PNI after adjuvant ADT. For men with multi-PNI, immediate ADT obviously appeared to be superior to delayed ADT in decreasing biochemical failure. Conclusions: Multi-PNI detected in high-risk RP specimens could be a prognosticator for early biochemical relapse post-surgery. Our findings suggest that patients with multi-PNI appear appropriate to choose adjuvant therapy as soon as possible after surgery.

Outcomes of patients with lymph node metastasis treated with radical prostatectomy and adjuvant androgen deprivation therapy in a Chinese population: results from a cohort study.

BackgroundThe aim of this study is to assess the prognosis of prostate cancer (PCa) with lymph node metastases (LNM) detected in pelvic lymph node dissection (PLND) after radical prostatectomy (RP) and adjuvant androgen deprivation therapy (ADT) in a Chinese population.MethodsFrom June 2005 to September 2012, the medical histories of 67 Chinese PCa patients with LNM detected after RP and extended PLND were collected, and all these patients received continuous adjuvant ADT. Postoperative survival was estimated using the Kaplan-Meier method. The impact of various clinicopathological factors on outcome was analyzed using Cox proportional hazard regression models. All tests were two-sided with P < 0.05 considered significant.ResultsMedian follow-up was 46.7 months, and two patients were lost to follow-up. Five-year event-free survival for patients with positive lymph nodes was 93.0%, 83.0%, and 96.0% for local recurrence, systemic progression, and cancer death, respectively. One-year, 2-year, and 3-year biochemical recurrence (BCR)-free survival was 52%, 40%, and 22%, respectively. Postoperative BCR-free survival was 25.7 months. BCR-free survival for patients with a single LNM was longer than those with two or more LNM (median 39.1 months vs. median 17.2 months, P = 0.002). In a multivariate Cox model, only two or more LNM was a significant predictor of BCR (hazard ratio 2.6, P = 0.005).ConclusionsDespite low BCR-free survival, Chinese patients with LNM can benefit from RP and adjuvant ADT. Patients with low nodal metastatic burden had a favorable prognosis.

Robotic-assisted pelvic lymph node dissection for prostate cancer: frequency of nodal metastases and oncological outcomes.

Limited data are available regarding the oncologic efficacy of pelvic lymph node dissection (PLND) performed during robotic-assisted laparoscopic prostatectomy (RALP) for prostate cancer. We aimed to determine the frequency of pelvic lymph node metastasis and oncological outcomes following RALP with PLND in patients who did not receive adjuvant androgen deprivation therapy (ADT). We retrospectively reviewed the records of 1740 consecutive patients who underwent RALP and extended PLND. The primary endpoint was biochemical recurrence (BCR). The estimated BCR probability was obtained using the Kaplan-Meier method. Cox proportional hazard regression models were used to assess for predictors of BCR. One hundred and eight patients (6 %) with positive LNs were identified. The median number of LNs removed was 17 (IQR 11-24), and median follow-up was 26 months (IQR 14-43). Ninety-one (84 %) patients did not receive adjuvant ADT of whom 60 % had BCR with a median time to recurrence of 8 months. The 1- and 3-year BCR-free probability was 42 and 28 %, respectively. Patients with ≤2 LN+ had significantly better biochemical-free estimated probability compared to those with >2 LN+ (p = 0.002). The total number of LN+ (HR = 1.1; 95 % CI 1.01-1.2, p = 0.04) and Gleason 8-10 (HR = 1.96; 95 % CI 1.1-3.4, p = 0.02) were predictors of BCR on multivariate analysis. Among men with positive lymph nodes at time of robotic prostatectomy, those with two or fewer positive nodes and Gleason <8 exhibited favorable biochemical-free survival without adjuvant therapy.

Risk Factors for Clinical Metastasis in Men Undergoing Radical Prostatectomy and Immediate Adjuvant Androgen Deprivation Therapy

Adjuvant androgen deprivation therapy (ADT) is a treatment option for prostate cancer (PC) patients after radical prostatectomy (RP). Although it can achieve a good progression-free survival rate, some patients still develop clinical metastasis. We here investigated risk factors of clinical metastasis in post- prostatectomy patients who received immediate adjuvant ADT. We identified 197 patients with non-metastatic PC who underwent RP at our institution between 2000 and 2012, followed by adjuvant ADT. The associations of various clinicopathologic factors with clinical metastasis (primary endpoint) and cancer-specific survival (secondary endpoint) were assessed. Multivariate analysis was conducted using a Cox proportional hazards model. Median follow-up was 87 months after RP. Nine (4.6%) patients developed clinical metastasis and six (3.0%) died from PC. Eight of nine metastatic patients had a pathologic Gleason score (GS) 9 and developed bone metastasis, while the remaining one had pathologic GS 7 and developed metastasis only to para-aortic lymph nodes. On multivariate analyses, pathologic GS ≥9 and regional lymph node metastasis (pN1) were independent predictors of clinical metastasis and pathologic GS ≥9 was an independent predictor of cancer-specific death. Pathologic GS ≥9 and pN1 were independent predictors of clinical metastasis in post-prostatectomy patients who received immediate adjuvant ADT. Furthermore, pathologic GS ≥9 was an indispensable condition for bone metastasis, which may imply that patients with GS ≤8 on adjuvant ADT are unlikely to develop bone metastasis.

805TiP - Randomised Phase 3 Trial of Enzalutamide in Androgen Deprivation Therapy with Radiation Therapy for High Risk, Clinically Localised, Prostate Cancer: Enzarad (Anzup 1303)

ABSTRACT Background: Background: Adjuvant androgen deprivation therapy (ADT) including a luteinising hormone releasing hormone analogue (LHRHA) is standard of care given before during and after radiotherapy for localised prostate cancer (PC) at high risk of recurrence. Enzalutamide is a new second generation androgen receptor (AR) inhibitor that is more potent and binds with a higher affinity to the AR than conventional non-steroidal anti-androgens (NSAA) and improves survival in metastatic castration-resistant PC. We hypothesise that the incorporation of enzalutamide in adjuvant ADT, given before, during and after radiation therapy for localised PC at high risk of recurrence, will further improve outcomes. Aim: To determine the effectiveness of enzalutamide as part of adjuvant ADT with a LHRHA in men planned for radiotherapy for localised PC at high risk of recurrence. Trial design: Open label, randomised, stratified, 2-arm, phase 3 intergroup trial Eligibility: Localised PC, high risk of recurrence, suitable for EBRT with curative intent Stratification: Gleason 8-10, T3-4, PSA >20, study site Endpoints: Overall survival (Primary), Cause-specific survival, PSA PFS, Clinical PFS, HRQOL, Adverse events, ICER Accrual: 800 participants. 2 yrs accrual + 5.5 years minimum f/up. 80% power to detect a 33% reduction in the hazard of death assuming a 5-year survival rate of 76% amongst controls. Participants will be randomised 1:1 to enzalutamisde 160mg daily for 24 months versus conventional NSAA for first 6 months. Background treatment for all participants: LHRHA for 24 months and EBRT (78Gy/39F) starting after week 16. Study assessments are at baseline, weeks 4, 12, 16, 20 and 24, then 3-4 monthly until year 5, 6-monthly until year 7, then annually. Imaging with CT/MRI and bone scan at baseline and then as clinically indicated. Tertiary correlative objectives include the identification of prognostic / predictive biomarkers from archival tumour tissue, and from fasting bloods collected at baseline, 24 weeks, 5 years, and first evidence of progression. Email: enzarad@ctc.usyd.edu.au Website: http://www.anzup.org.au/ Disclosure: C. Sweeney: Consulting with honoraria to declare with Asetallas, Janssen and Sanofi; P. Nguyen: Consulted for Medivation (

Androgen Deprivation Therapy and Definitive Radiotherapy for Prostate Cancer

Adjuvant androgen deprivation therapy (ADT) improves outcomes of patients receiving definitive radiotherapy (RT) for local-regionally advanced prostate cancer. However, patients in most randomized trials had more advanced disease than observed in many practices and were treated with suboptimal RT doses. Although data are conflicting, long-term ADT likely has adverse side-effects in patients with comorbidities. We recommend 6 months of ADT monotherapy with gonadotropin-releasing hormone agonist and RT for patients with high-risk prostate cancer (≥T2c, Gleason Score 8 to 10, and/or prostate-specific antigen ≥20 ng/mL) with minimal or no comorbidities. Adjuvant ADT for unfavorable intermediate-risk patients with a Gleason Score of 4+3=7 is also reasonable.

The Role of Adjuvant Hormonal Treatment after Surgery for Localized High-Risk Prostate Cancer: Results of a Matched Multiinstitutional Analysis

Introduction. To assess the role of adjuvant androgen deprivation therapy (ADT) in high-risk prostate cancer patients (PCa) after surgery. Materials and Methods. The analysis case matched 172 high-risk PCa patients with positive section margins or non-organ confined disease and negative lymph nodes to receive adjuvant ADT (group 1, n = 86) or no adjuvant ADT (group 2, n = 86). Results. Only 11.6% of the patients died, 2.3% PCa related. Estimated 5–10-year clinical progression-free survival was 96.9% (94.3%) for group 1 and 73.7% (67.0%) for group 2, respectively. Subgroup analysis identified men with T2/T3a tumors at low-risk and T3b margins positive disease at higher risk for progression. Conclusion. Patients with T2/T3a tumors are at low-risk for metastatic disease and cancer-related death and do not need adjuvant ADT. We identified men with T3b margin positive disease at highest risk for clinical progression. These patients benefit from immediate adjuvant ADT.

Seminal vesicle invasion: what is the best adjuvant treatment after radical prostatectomy?

• To evaluate the biochemical-failure free survival according to different adjuvant treatments in patients who underwent radical prostatectomy (RP) with seminal vesicle invasion (SVI). • Between 1994 and 2008, 4090 men underwent RP in nine centres. Of these, 310 men had a SVI. • Exclusion criteria were: detectable postoperative prostate-specific antigen, lymph node metastases and follow-up <18 months. • Therefore, the study group included 199 patients. Of these, 41 received adjuvant radiotherapy (RT) only, 26 received adjuvant androgen deprivation therapy (ADT) only, 50 received adjuvant ADT combined with RT and 82 were monitored. The endpoint for this analysis was biochemical no evidence of disease (bNED). • Preoperative prostate-specific antigen level, specimen Gleason score, age, clinical stage, surgical margin status and adjuvant treatment were evaluated in a multivariable analysis with respect to bNED survival. • After a mean (range) follow-up of 60.3 (18-185) months, 88 (44.2%) patients had a biochemical relapse. • The estimated 5- and 7-year bNED survival were 32.6% and 25.9% for the observation group, 44.4% and 28.6% for the RT only group, 48.4% and 32.3% for the ADT only group and 82.8% and 62.1% for the adjuvant ADT combined with RT group. • On multivariate analysis, only adjuvant ADT combined with RT (P < 0.001) was an independent prognostic factor of biochemical relapse. • RP appeared to be insufficient as a single treatment for patients with SVI. • The findings of the present study suggest that adjuvant ADT combined with RT after RP for patients with SVI confers a substantial benefit on 5-year bNED survival.

Psychological distress in men with prostate cancer receiving adjuvant androgen-deprivation therapy

ObjectivesTo compare the occurrence of depression, anxiety, self body image perception, sleep disturbances, and diminished quality of life in prostate cancer patients undergoing adjuvant androgen-deprivation therapy (ADT) as opposed to patients in follow-up alone. Methods and materialsHospital Anxiety and Depression Scale, Pittsburgh Sleep Quality Index, Restless Legs Syndrome Study Group essential diagnostic criteria, Body Image Scale and Functional Assessment of Cancer Therapy Prostate were administered to consecutive prostate cancer patients who underwent radical prostatectomy or radiation therapy and are presently either under adjuvant ADT or included in a follow-up program. ResultsOf the 103 patients enrolled, 49 (47.6%) were receiving adjuvant ADT and 54 (52.4%) were not. Compared with the controls, the patients undergoing ADT showed higher levels of depression (P = 0.002), worse self body image perception (P = 0.001), worse quality of life (P = 0.0001) and worse sleep quality (P = 0.04). ADT was significantly associated with depression at multivariate analysis after adjustment for age, stage, Gleason score, as well as demographic and social variables (P = 0.001). Depression scores showed a strong inverse correlation with quality of life scores (P < 0.01). ConclusionsAdjuvant ADT is associated with depression, worse quality of life, and altered self body image in prostate cancer patients.

886 LONG-TERM SURVIVAL AFTER SURGERY VERSUS EXTERNAL BEAM RADIOTHERAPY FOR HIGH-RISK PROSTATE CANCER

INTRODUCTION AND OBJECTIVES: The management of patients with high-risk prostate cancer remains in debate, and prospective clinical trials comparing treatment outcomes are lacking. We evaluated the survival of patients with high-risk disease following radical prostatectomy (RP) and external beam radiation therapy (RT) during the PSA era. METHODS: We identified 1,238 men who underwent RP and 609 men treated with RT between 1988–2004 who had a pretreatment prostate specific antigen (PSA) 20 ng/mL, biopsy Gleason score 8–10, or clinical stage T3. The impact of treatment modality on cancer-specific (CSS) and overall survival (OS) was analyzed using Cox proportional hazard regression models controlling for patient age, Charlson comorbidity index (CCI), and clinicopathologic tumor variables. RESULTS: Patients treated with RT were older (p 0.0001), had a greater pretreatment PSA (p 0.02), higher biopsy Gleason score (p 0.0001), and more advanced clinical stage (p 0.0001). In total, 344 (57%) men who underwent RT were treated with adjuvant androgen deprivation therapy (ADT), while 418 (34%) men who underwent RP received adjuvant ADT and 136 (11%) received adjuvant RT. Median follow-up was 10.2, 6.0, and 7.2 years after RP, RT ADT, and RT alone. Estimated 10-year CSS following RP and RT ADT was equivalent (92%), and was modestly better than RT alone (88%; p 0.06). 10-year OS was significantly improved after RP (77%) versus RT ADT (67%) or RT alone (52%; p 0.001). On multivariate analysis (Table), patients who underwent RT alone had a significantly increased risk of death from prostate cancer (p 0.0006) and overall mortality (p 0.0001) compared to patients treated with RP. No significant difference in the risk of cancer death was seen between RT ADT and RP (p 0.90); however, men who received RT ADT had a greater than 50% increased risk of overall mortality versus men who underwent RP (p 0.0005). CONCLUSIONS: RP and RT ADT provide similar long-term cancer control for patients with high-risk disease, although the risk of all-cause mortality was greater after RT ADT. As surgery provides pathologic staging to guide the selected use of secondary therapies, prospective studies evaluating the differing impact of treatments on quality of life and non-cancer mortality are necessary to determine the optimal management approach to these men.