Salvage Androgen Deprivation Therapy Research Articles

Positron emission tomography with 18F-fluciclovine to predict recurrence in post-treatment recurrent prostate cancer and its role in altering treatment plans.

214 Background: 18F-fluciclovine PET/CT can improve the detection of post-treatment recurrent prostate cancer (PCa). We quantified factors which increase the likelihood of a positive scan, assessed the ability of 18F-fluciclovine to alter treatment plans and identified an optimal PSA cut-off to identify radiographic recurrence. Methods: Patients who received 18F-fluciclovine PET/CT for recurrent PCa (n=78) were analyzed. Treatment changes based on positive scans were tracked. A receiver-operator characteristic (ROC) curve was used to estimate the optimal PSA cut-off for a positive scan. Results: 18F-fluciclovine predicted radiographic recurrence in 67.9% of patients. PSA at scan (p = 0.010), salvage therapy (p = 0.03), any use of ADT (p = 0.016) and number of studies (p = 0.042) were all associated with a positive scan. Alteration of treatment plans occurred in 34/58 (58.6%) patients. Recurrence sites are: 79/120 (65.8%) lymph nodes, 27/120 (22.5%) bone, 11/120 (9.2%) prostatic bed, and 3/120 (2.5%) elsewhere. The most common treatment alteration was directed stereotactic body radiation therapy (SBRT) (16/34, 47%), followed by salvage surgical therapy (4/34, 11.7%) and ADT (3/34, 8.7%).The optimal PSA cut-off was 0.5 with sensitivity of 81.13% and specificity of 78.38% (ROC=0.7880). Conclusions: 18F-fluciclovine PET/CT detected radiographic disease in 67.9% of patients, resulting in alterations in treatment plans in 58.6% of cases. SBRT was the most common alteration in treatment plan. Previous use of salvage therapy or ADT are risk factors and when combined with a PSA >0.5, may be associated with radiographic recurrence. [Table: see text]

Phase II trial enzalutamide and androgen deprivation therapy (ADT) with salvage radiation in men with high-risk PSA recurrent prostate cancer (PC): The STREAM trial.

29 Background: Salvage external beam radiotherapy (RT) and hormonal therapy improves survival over RT alone in men with non-metastatic hormone naïve PC and PSA recurrence after radical prostatectomy (RP). We investigated the safety/efficacy of enzalutamide with salvage RT and ADT in this setting. Methods: This was a 3 center prospective phase 2 single arm clinical trial in the Dept of Defense Prostate Cancer Clinical Trials Consortium. Eligibility: Gleason 7-10 PC and PSA recurrence within 4 years (yrs) of RP, PSA 0.2-4.0, no prior hormonal therapy, and no metastases on CT/Bone Scan imaging. Men received 6 months (mos) of ADT with 160 mg/d enzalutamide and 66 Gy RT to the prostate bed. Primary endpoint was 2 yr PFS with testosterone (T) recovery to >100 ng/dl. Secondary objectives included PSA nadir, 3 yr PFS, safety and patient reported quality-of-life over time. This trial was designed with 84% power to detect a 20% improvement in 2 yr PFS vs historic data and a 1-sided alpha of 0.05. Results: We enrolled 38 men (90% white, 8% black, 2% Asian); 37 (97%) completed therapy and were evaluable with T recovery at 2 yrs. Median age was 64 yrs; 47% Gleason 8-10, 79% T3/T4 disease, 21% had resected N+ PC; median PSA was 0.4 (0.19-4.19). Median follow-up is 29.5 mo. Treatment was well tolerated with 11 patients (29%) experiencing G3 toxicities (including 4 HTN, 2 urinary retention, 2 CV events); no G4-5 or unexpected toxicities were observed. T recovery occurred in 35 (95%) at 12 mos. The primary endpoint of 2 yr PFS was 65% (95% CI: 47%-78% vs. historic controls with 51% 2 yr PFS rate) among the 37 patients with T recovery. PSA remained at undetectable levels in 69% at 2 yrs. The 3 yr PFS was 53% (95% CI: 36%, 68%). QOL data over time suggest short term reductions in urinary and sexual function with recovery by 12-24 mo in most men. Conclusions: Salvage enzalutamide and ADT for 6 months with RT following RP for men with PSA recurrent high risk PC is safe, and demonstrates encouraging efficacy at 2 and 3 years. Most men have testosterone recovery at 1 year. These data warrant prospective controlled phase 3 trials to assess the impact of potent AR inhibition in this curative intent setting. Clinical trial information: NCT02057939.

Preliminary results of a two stage phase II study of 18F-DCFPyL PET-MR for enabling oligometastases ablative therapy in subclinical prostate cancer.

250 Background: Despite maximal local therapies (MLT) (radical prostatectomy followed by radiotherapy [RT]), 20-30% of men will have incurable progression of prostate cancer (PC). Most recurrences in this scenario are characterized by continuous PSA rises and failure of standard imaging (bone scan [BS] and computed tomography [CT]) to detect recurrence sites. We conducted a phase II trial for men with rising PSA after MLT using 18F-DCFPyL PET-MR followed by targeted ablation of PET positive foci. We report the results of our pre-defined analysis. Methods: Patients with rising PSA (0.43.0 ng/mL) after MLT, negative BS/CT and no prior salvage ADT were eligible. All patients underwent 18F-DCFPyL PET-MR followed by immediate PET-CT acquisition. Those with limited disease, where possible, underwent stereotactic ablative RT (SABR) or surgery. No ADT was used. The primary endpoint was biochemical response rate (complete [undetectable PSA] or partial [PSA decline ≥50% compared to baseline]). A Simon’s two stage study design was employed. Stage 1 included 12 response evaluable patients, requiring 1 or more responses in the absence of grade 3+ toxicities to proceed to stage 2 (additional 25 response evaluable patients). Results: After a median of 58 months (range 29-120) post MLT, 20 patients underwent PET-MR/CT to have 12 response evaluable patients. Median PSA at enrollment was 1.3 ng/mL (range 0.4-2.8). Three patients had negative PET-MR/CT, while 17 had positive scans, of which 12 (60%) were amenable to response evaluable ablation. The median number of detected lesions in those treated was 2 (range 1-5). Ten patients underwent SABR (27-30 Gy/3 fractions) and 2 had surgery. One patient (8%) had complete and 4 (33%) had partial PSA responses at a median of 3.3 months (range 2.8-6.0) after ablation, while the remaining 7 (59%) did not have biochemical response. No grade 3+ toxicities were observed. Conclusions: 18F-DCFPyL PET/MR has high detection rates in men with rising PSA after MLT. We observed favorable early results with SABR or surgery (41% RR). Trial completion will inform if this approach offers potential for cure in an early molecularly-defined PC oligometastatic state. Clinical trial information: NCT03160794.

Pathologically Node-Positive Prostate Carcinoma – Prevalence, Pattern of Care and Outcome From a Population-Based Study

AimsTo evaluate the prevalence, patterns of care and outcome of pathologically node-positive (pN+) prostate cancer (P-Ca) after radical prostatectomy from a provincial population database. Patients and methodsPatients were identified from a provincial cancer registry and a genitourinary cancer outcomes unit (2005–2014). Of a total of 4723 patients who underwent radical prostatectomy, 167 patients with pN+ P-Ca were identified (28/2181 from 2005–2007 and 139/2542 from 2010–2014). Persistently elevated postoperative prostate-specific antigen (PSA) ≥ 0.2 ng/ml was noted in 52 (31%) patients, 23 (44.2%) of whom had salvage androgen deprivation therapy plus radiotherapy (ADT + RT), 25 (48%) were managed with ADT alone and four (7.8%) had no treatment. Of 115 patients with postoperative PSA <0.2 ng/ml, 47 (41%) had ADT alone and 50 (43.5%) had ADT + RT. Survival estimation was carried out using the Kaplan–Meier method. The association of prognostic factors with survival was evaluated using univariate and multivariate analysis and was limited to the newer cohort (2010–2014). ResultsThe median age was 64 years; the median baseline PSA was 12.5 ng/mL (range 2.5–108.4). After a median follow-up of 48 months, overall survival at 5 and 10 years for the entire cohort were 89% and 81%, respectively, and distant metastasis-free survival (DMFS) at the same time points were 77% and 58%, respectively. For the newer cohort, 5-year overall survival and DMFS were 91.5% and 76%, respectively. On univariate analysis, persistently elevated postoperative PSA ≥0.2 ng/ml (P = 0.0003), seminal vesicle involvement (P = 0.027), ≥2 nodes (P = 0.035) and ADT alone (P = 0.054) had a poor prognostic impact on DMFS, whereas margin involvement had a marginally negative influence on overall survival (P = 0.06). On multivariate analysis, postoperative PSA ≥0.2 ng/ml (hazard ratio 4.4, 95% confidence interval 1.7–11.4; P = 0.002) continued to have a significant association with DMFS. On a sensitivity analysis, postoperative PSA ≥0.1 also had a significant association with DMFS on univariate and multivariate analysis (hazard ratio 3.69, 95% confidence interval 1.32–10.29; P = 0.01). Similarly, postoperative PSA ≥0.4 ng/ml had a significant association with DMFS (hazard ratio 3.87, 95% confidence interval 1.58–9.46, P = 0.003). ConclusionThis study showed a notable difference in the proportion of pN+ P-Ca patients between two different time cohorts. A significant association of persistently elevated postoperative PSA with DMFS was noted in our study. This must be accounted for while tailoring postoperative treatment in pN+ P-Ca.

Early Versus Delayed Initiation of Salvage Androgen Deprivation Therapy and Risk of Prostate Cancer-Specific Mortality.

Background: This study sought to ascertain whether there is an association between prostate cancer (PC)-specific mortality (PCSM) and timing of salvage androgen deprivation therapy (ADT) among men with short versus long prostate-specific antigen doubling times (PSA-DTs). Methods: The study cohort was selected from 206 men with localized unfavorable-risk PC randomized to radiation therapy (RT) or RT plus 6 months of ADT between 1995 and 2001. A total of 54 men who received salvage ADT for PSA failure after a median follow-up of 18.72 years following randomization defined the study cohort. The Fine-Gray competing risks regression model was used to analyze whether the timing of salvage ADT was associated with an increased risk of PCSM after adjusting for age, comorbidity, known PC prognostic factors, and previously identified interactions. Results: After a median follow-up of 5.68 years (interquartile range, 3.05-9.56) following salvage ADT, 49 of the 54 men (91%) died, of which 27 from PC (54% of deaths). Increasing PSA-DT as a continuous covariate (per month increase) was associated with a decreasing risk of PCSM (adjusted hazard ratio [HR], 0.33; 95% CI, 0.13-0.82; P=.02). Among men with a long PSA-DT (≥6 months), initiating salvage ADT later (PSA level >12 ng/mL, upper quartile) versus earlier was associated with an increased risk of PCSM (adjusted HR, 8.84; 95% CI, 1.99-39.27; P=.004), whereas for those with a short PSA-DT (<6 months; adjusted HR, 1.16; 95% CI, 0.38-3.54; P=.79) this was not true. Conclusions: Early initiation of salvage ADT for post-RT PSA failure in men with a PSA-DT of ≥6 months may reduce the risk of PCSM.

The impact of the definition of biochemical recurrence following salvage radiotherapy on outcomes and prognostication in patients with recurrent prostate cancer after radical prostatectomy: a comparative study of three definitions.

PurposeThe clinical management and follow-up of patients with recurrent prostate cancer after salvage radiotherapy (SRT) has not yet been established, and no standardized definition of biochemical recurrence (BCR) after SRT exists. We compared the impact of applying three different definitions of BCR following SRT on patient outcomes and prognostication.SubjectsPatients who received salvage androgen-deprivation therapy before the completion of SRT were excluded. The data of 118 men who had undergone salvage radiation as monotherapy for BCR after radical prostatectomy were reviewed. In all patients, SRT comprised irradiation to the prostatic bed (70 Gy) using three-dimensional conformal radiotherapy techniques. Treatment outcomes, including BCR-free survival and prognostic factors, were analyzed and compared among three definitions: The Nara, Radiation Therapy Oncology Group (RTOG) 9601, and GETUG-AFU 16 definitions.ResultsThe BCR rate differed significantly among the applied definitions. Multivariate analyses identified the same four independent prognostic factors, including primary Gleason pattern 4 or 5, negative resection margin, prostate-specific antigen (PSA) level before SRT 0.5 or more, and PSA doubling time before SRT <6 months, using the RTOG 9601 and GETUG-AFU 16 definitions, whereas only two of the four factors were identified using the Nara definition. Although the results obtained using the RTOG 9601 and GETUG-AFU 16 definitions were similar, the prognostic value of the four factors differed. According to the RTOG 9601 definition of BCR, a negative resection margin on prostatectomy specimens and short PSA doubling time before SRT were associated with no subsequent response in PSA level.ConclusionsThe applied definition of BCR after SRT can influence the reported BCR-free rate and the potential prognostic factors. Establishment of the standardized definition is needed for the optimal management of patients with recurrent prostate cancer undergoing SRT.

Could 68-Ga PSMA PET/CT become a new tool in the decision-making strategy of prostate cancer patients with biochemical recurrence of PSA after radical prostatectomy? A preliminary, monocentric series.

To evaluate the impact of gallium68PSMA-11 (HBED-CC)-PET/CT on decision-making strategy of patients with relapsing prostate cancer (PC) presenting a second biochemical relapse after radical prostatectomy (RP) and salvage RT or salvage androgen deprivation therapy (ADT). 40 patients were retrospectively analyzed. All of them had received prostatectomy. Thirteen out of 40 were addressed to gallium68PSMA-11 (HBED-CC)-PET/CT for a biochemical relapse after RP, 14/40 after a salvage RT and 13/40 after salvage or adjuvant ADT. The PSA level ranged between 0.1 and 1.62ng/ml (median value: 0.51ng/ml). We studied the impact on the decision-making process of a multidisciplinary tumor board of additional data obtained from gallium68PSMA-11 (HBED-CC)-PET/CT. Thirty-one out of 40 evaluated patients showed positive findings at gallium68PSMA-11 (HBED-CC)-PET/CT (77.5%). Of them, five were positive in the prostatic bed, nine in the pelvic nodes, twelve in nodes outside the pelvis and eight at bone level. Nine patients presented two different sites of relapse (22.5%). Gallium68PSMA-11 (HBED-CC)-PET/CT data changed the therapeutic approach in 28 patients (70%). Gallium68PSMA-11 (HBED-CC)-PET/CT can be a useful tool in the restaging of post-RP, RT or ADT patients presenting biochemical relapse of PC and it could change the decision-making process in up of 70% of these patients. Prospective, larger series are needed to establish the correct role of this very promising tool in the staging and therapeutic approach of PC patients.

Lymph node yield during radical prostatectomy does not impact rate of biochemical recurrence in patients with seminal vesicle invasion and node-negative disease

ObjectivesSeminal vesicle invasion (SVI) is a risk factor for poor oncologic outcome in patients with prostate cancer. Modifications to the pelvic lymph node dissection (PLND) during radical prostatectomy (RP) have been reported to have a therapeutic benefit. The present study is the first to determine if lymph node yield (LNY) is associated with a lower risk of biochemical recurrence (BCR) for men with SVI. MethodsA total of 220 patients from 2 high-volume institutions who underwent RP without adjuvant treatment between 1990 and 2015 and had prostate cancer with SVI (i.e., pT3b) were identified, and 21 patients did not undergo lymph node dissection. BCR was defined as a postoperative PSA>0.2ng/mL, or use of salvage androgen deprivation therapy (ADT) or radiation. Multivariable Cox proportional hazards models were used to determine whether LNY was predictive of BCR, controlling for PSA, pathologic Gleason Score, pathologic lymph node status, NCCN risk category, etc. The Kaplan-Meier method was used to determine 3-year freedom from BCR. ResultsMedian number of lymph nodes sampled were 7 (IQR: 3–12; range: 0–35) and 90.5% underwent PLND. The estimated 3-year BCR rate was 43.9%. Results from multivariable analysis demonstrated that LNY was not significantly associated with risk of BCR overall (HR = 1.00, 95% CI: 0.98–1.03; P = 0.848) for pN0 (HR = 0.99, 95% CI: 0.97–1.03; P = 0.916) or pN1 patients (HR = 0.96, 95% CI: 0.88–1.06; P = 0.468). Overall, PSA (HR = 1.02, P<0.001) and biopsy Gleason sum ≥ 8 (HR = 1.81, P = 0.001) were associated with an increased risk of BCR, and increasing LNY increased the likelihood of detecting>2 positive lymph nodes (OR = 1.27, 95% CI: 1.06–1.65, P = 0.023). ConclusionSeminal vesicle invasion is associated with an increased risk of BCR at 3 years, primarily due to pathologic Gleason score and PSA. Although greater lymph node yield is diagnostic and facilitates more accurate pathologic staging, our data do not show a therapeutic benefit in reducing BCR.

MP34-15 PROSTATE CANCER QUALITY OF CARE DISPARITIES AND THEIR IMPACT ON PATIENT OUTCOMES

You have accessJournal of UrologyProstate Cancer: Epidemiology & Natural History II1 Apr 2018MP34-15 PROSTATE CANCER QUALITY OF CARE DISPARITIES AND THEIR IMPACT ON PATIENT OUTCOMES Keith Lawson, Katherine Daignault, Olli Saarela, Robert Abouassaly, and Antonio Finelli Keith LawsonKeith Lawson More articles by this author , Katherine DaignaultKatherine Daignault More articles by this author , Olli SaarelaOlli Saarela More articles by this author , Robert AbouassalyRobert Abouassaly More articles by this author , and Antonio FinelliAntonio Finelli More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.1107AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The ability to rigorously measure disparities in care that drive poor patient outcomes is essential for developing effective strategies for quality improvement. As real-world case-mix adjusted quality variations have yet to be reported in prostate cancer, our objective was to apply a data-driven analytical framework to determine the validity of expert-defined quality indicators (QIs) in order to reveal true disparities in prostate cancer care and their impact on patient outcomes. METHODS Hospital-level quality of care was assessed according to 10 published, expert-defined QIs utilizing data derived from the United States National Cancer Database (NCDB). Case-mix adjusted hospital benchmarking was performed using indirect standardization methodology and multivariable regression models as previously described by our group [1]. In a training set of hospitals, a composite measure of hospital quality, the Prostate Cancer Quality Score (PC-QS), was derived from those individual QIs that discriminated hospital performance in a manner associated with poor patient outcomes; including the need for salvage therapy, initiation of androgen deprivation therapy, 30- and 90-day mortality, and overall mortality. Subsequently, associations between the PC-QS and hospital volume, academic affiliation, and patient outcomes (as above) were determined in a separate validation set of hospitals. RESULTS Collectively, data from over 1100 hospitals were analyzed, with widespread variation observed across all QIs. In the training set, between 3-36% of hospitals were identified as poor outliers compared to the national average level of care for a given QI. Based on associations between outlier status and the aforementioned patient outcomes, 5 individual QIs were incorporated into the PC-QS. In the validation set, lower PC-QS hospitals displayed smaller referral volumes and were less likely to be academic hospitals than those with higher PC-QS (p < 0.001). Higher PC-QS was associated with lower rates of salvage therapy, ADT initiation and 30-day mortality (adjusted hazard ratio [confidence interval]: 0.85 [0.79-0.91], 0.94 [0.91-0.98], adjusted odds ratio 0.92 [0.87-0.97] per PC-QS unit increase, respectively). CONCLUSIONS Data-driven benchmarking of hospital-level quality performance reveals the widespread disparities that exist in prostate cancer care. This data supports the use of our novel PC-QS composite metric as a benchmarking tool for quality improvement. 1. Lawson KA et. al. Eur Urol 2017; 72: 379-386. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e443 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Keith Lawson More articles by this author Katherine Daignault More articles by this author Olli Saarela More articles by this author Robert Abouassaly More articles by this author Antonio Finelli More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Androgen deprivation therapy during and after post-prostatectomy radiotherapy in patients with prostate cancer: a case control study

BackgroundHere we assessed the influence of androgen deprivation therapy (ADT) during and/or after post-prostatectomy radiotherapy (RT) on biochemical recurrence (BCR) and radiographic progression in patients with prostate cancer.MethodsPatients with prostate cancer who underwent post-prostatectomy RT were analyzed. BCR and radiographic progression after RT were compared according to the concurrent or salvage ADT. Cox regression analyses were used to identify risk factors for BCR and radiographic progression.ResultsOf the 227 patients who underwent post-prostatectomy RT, 95 (41.9%) received concurrent ADT for a median of 17.0 months. Despite more aggressive disease characteristics in the concurrent ADT group than in the RT-only group, the former had a better 5-year BCR-free survival rate than the latter (66.1 vs. 53.9%; p = 0.016), whereas the radiographic progression rate was not significantly different between two groups. On the other hand, salvage ADT after post-RT BCR significantly delayed radiographic progression (5-year radiographic progression-free survival; 75.2 vs. 44.5%; p = 0.002).ConclusionsConcurrent ADT improved BCR-free survival, and salvage ADT after post-RT BCR improved radiographic progression-free survival. To maximize the oncological benefit, ADT of sufficient duration should be implemented.

Early versus delayed initiation of salvage androgen deprivation therapy and the risk of prostate cancer-specific mortality.

189 Background: We sought to ascertain whether there is an association between prostate cancer (PC)-specific mortality (PCSM) and salvage androgen deprivation therapy (ADT) timing amongst men with short versus long prostate-specific antigen doubling times (PSA-DT)s. Methods: The study cohort was selected from 206 men with localized unfavorable-risk PC who were randomized to radiation therapy (RT) or RT plus 6 months of ADT between 1995 and 2001. Fifty-four men who received salvage ADT for PSA failure after a median follow up of 18.72 years following randomization defined the study cohort. Fine-Gray competing risks regression analyzed whether the timing of salvage ADT was associated with an increased risk of PCSM after adjusting for age, comorbidity, known PC prognostic factors, and previously identified interactions. Results: After a median follow-up of 5.68 years (IQR 3.05 - 9.56) following salvage ADT 49 of the 54 men (91%) died, 27 from PC (54% of deaths). Increasing PSA-DT as a continuous covariate was associated with a decreasing risk of PCSM (adjusted hazard ratio [AHR] 0.33, 95% CI 0.13, 0.82; P=0.02). Amongst men with a long PSA-DT (≥6 months), initiating salvage ADT later (PSA&gt;12ng/mL, upper quartile) versus earlier was associated with an increased risk of PCSM (AHR 8.84, 95% CI 1.99-39.27; P=0.004); whereas for men with a short (&lt;6 months) PSA-DT (AHR 1.16, 95% CI 0.38-3.54; P=0.79) this was not true. Conclusions: Early initiation of salvage ADT for post-RT PSA recurrence in men with a PSA-DT of 6 months or more may reduce the risk of PCSM, arguing against the unproven assumption that patients with a short PSA-DT are those most likely to benefit from early initiation of salvage ADT. Clinical trial information: NCT00116220.

Low testosterone at first PSA failure and assessment of the risk of death in men with unfavorable-risk prostate cancer treated on prospective clinical trials.

45 Background: Low testosterone at prostate cancer diagnosis has been associated with a worse prognosis. Whether this is true and how to define the best treatment approach at first PSA failure following definitive therapy and prior to the documentation of metastatic disease has not been elucidated and was studied. Methods: Between 1995 to 2001, 58 men with unfavorable-risk prostate cancer treated on clinical trials with radiation and androgen deprivation therapy (ADT) had testosterone levels at PSA failure available. Cox and Fine and Gray regressions were performed to ascertain whether low versus normal testosterone at PSA failure was associated with the risk of prostate cancer-specific, other-cause and all-cause mortality (PCSM, OCM, ACM) adjusting for age, salvage ADT use and known prostate cancer prognostic factors. Results: After a median follow-up of 6.68 years following first PSA failure, 31 men (53.4%) died; 10 from prostate cancer (32.3%), of which 8/11 (72.7%) versus 2/47 (4.3%) occurred in men with low versus normal testosterone at PSA failure, respectively. A significant increase in the risk of ACM (adjusted hazard ratio, AHR [2.54, 95% CI 1.04-6.21]; P = 0.04) and PCSM (AHR [13.71, 95% CI 2.4-78.16]; P = 0.003), with a reciprocal trend toward decreased risk of OCM (AHR [0.18, 95% CI 0.02-1.55]; P = 0.12) was observed in men with low versus normal testosterone at first PSA failure. Conclusions: Low testosterone at first PSA failure confers a very poor prognosis. Given prolonged survival when abiraterone or docetaxel is added to ADT in men with castrate-sensitive metastatic prostate cancer and possibly in men with localized high-risk prostate cancer provides rationale to support their use with ADT in men with low testosterone at PSA failure in the setting of a phase II trial.

Costs and of treating Gleason score 9 and 10 prostate cancer vary widely based on need for adjuvant therapy: A critical assessment into the long-term cost implications of additional treatment modalities.

53 Background: The costs of treating localized, Gleason score 9 and 10 prostate cancer remain poorly described, especially when the particularly aggressive nature of the disease often requires a multimodal approach. We report the results of time-driven activity-based costing to assess the long-term costs of treating this subset of patients with either RALP, high-dose EBRT, or EBRT with a high-dose rate brachytherapy (BT) boost. Methods: Based on a multi-institutional cohort of 487 patients with Gleason score 9-10 prostate cancer, we generated process maps for each phase of care from the initial urologic visit through a median follow-up of 3.76 years, incorporating all prostate cancer treatment over this horizon. Costs were calculated per unit time, and the proportion of capacity for each step was determined. TDABC was defined as the sum of its resources. Results: Substantial cost variation was demonstrated between treatment modalities with an estimated median cost of $49,681 for EBRT, $35,140 for RALP, and $31,647 for EBRT + BT at 3.76 years. The primary driver in cost variation was the use of ADT. RALP (170 pts) ranged from $18,896 (29.5%) for no postoperative therapy to $63,270 for immediate long-term ADT (5.3%). EBRT (230 pts) had the greatest cost variation [Table 1]. Finally, EBRT + BT (336 pts) ranged from $26,522 for EBRT + BT alone (12.6%) to $37,834 for EBRT + BT + salvage ADT + HIFU (1.2%). Conclusions: Characterizing the costs associated with the distribution of treatments for men with high-risk prostate cancer is essential as we move towards health care accountability. There is substantial long-term cost variation between treatments in this subset of patients, and understanding these differences may affect treatment implications as we shift toward accountable payment models.[Table: see text]

Extended radical prostatectomy following neoadjuvant chemohormononal therapy (low dose estrmustine + LHRH agonist/antagonist) contributes to good cancer control for patients with high risk localized prostate cancer.

185 Background: Patients with high-risk prostate cancer (PCa) according to D’Amico risk categories are prone to a pathological diagnosis of positive margins or lymph node invasion and biochemical recurrence, despite having undergone radical prostatectomy (RP). Therefore, it is controversial whether RP should be done for high risk PC patients. Methods: 87 high-risk PCa patients prospectively underwent ‘extended’ RP following neoadjuvant chemohormonal therapy (NAC); primarily 6 months of estramustine phosphate 280 mg bid, along with a LH-RH agonist/antagonist. Our surgical technique was developed to reduce the rates of positive surgical margins. The goal is to approach the muscle layer of the rectum by dissecting the mesorectal fascia and continuing the dissection through the mesorectum until the muscle layer of the rectum is exposed. The procedure was safely performed as a result of good recognition of the structure between the perineal body and the rectal surface. We also performed extended lymphadenectomy if the patients meet two or more of D’Amico risk categories Results: More than 1 year had elapsed after surgery in 69 of the 87 patients with the median follow-up period of 36.2 months. Among those 69 patients, 18 (26.1%) experienced PSA failure. Kaplan-Meier analyses revealed that significant poorer PSA progression-free survival were observed in patients with higher positive biopsy core ratio, lymph node metastasis, and higher pathological stage (pT3a/b). Multivariate Cox-regression analysis revealed that higher pathological stage (pT3a/b) was the only independent valuable for predicting PSA progression failure. These 18 cases received salvage androgen deprivation therapy followed-by external beam radiotherapy and showed no progression after the salvage therapies (median follow-up period, 34.6 months after PSA progression). Conclusions: NAC concordant with extended RP is feasible and contributes to negative surgical margins that might provide good cancer control for patients with high-risk PCa.

Prognostic factors in men receiving androgen deprivation therapy (ADT) for recurrent prostate cancer: Using absolute PSA and PSA doubling time (DT) to guide timing of ADT initiation.

129 Background: ADT is the first-line treatment for men experiencing recurrence after undergoing radical therapy for prostate cancer. However, timing of ADT initiation is controversial and there are limited data on prognostic factors in patients starting ADT. Methods: We identified consecutive men who underwent radical prostatectomy (RP) for localized prostate cancer at our institution between 1987 and 2007 and who subsequently received salvage ADT. Early progression on ADT was defined as development of metastatic disease within 2yrs of initiation. The primary outcomes of interest were cancer-specific (CSS) and overall survival (OS). Results: A total of 2418 men were included. Median age at RP was 64yrs and median follow-up was 13.9yrs. 48% and 20% of men had pathologic Gleason scores of 7 and 8-10 respectively. The median PSA was 2.6ng/ml, while 385 men (16%) had metastatic disease at receipt of ADT. Overall, 1060 men (44%) developed clinical metastases, with 625 (59%) of these doing so within 2yrs of starting ADT. On multivariable analysis, longer PSA DT before ADT was associated with lower odds of early progression on ADT (DT 3-9mths, OR = 0.19; DT ≥9mths, OR = 0.10, both p &lt; 0.001). 10- and 20-year CSS were 89% and 70%, and 10- and 20-year OS were 82% and 40% respectively. Independent predictors of lower CSS included metastatic disease at time of ADT (HR = 2.60), PSA at ADT of 5-50ng/ml (HR = 2.68) and &gt; 50ng/ml (HR = 4.33, all p &lt; 0.001), while longer PSA DT was associated with higher CSS (DT 3-9mths, HR = 0.54; DT ≥9mths, HR = 0.45, both p &lt; 0.001). PSA at ADT of 5-50ng/ml (HR = 3.10) and &gt; 50ng/ml (HR = 5.20, both p &lt; 0.001) were independent predictors of OS. Conclusions: PSA DT &lt; 3mths and absolute PSA at ADT initiation of ≥ 5ng/ml are adverse prognostic indicators in men receiving salvage ADT for relapse after RP. For patients with these features, their risk of early progression and death should be part of a discussion about the timing of ADT and consideration given to more aggressive treatment strategies. Conversely, men with biochemical relapse who have longer DT and PSA &lt; 5ng/ml are at lower risk and could make an informed decision to defer ADT initiation.

Impact of Early Salvage Androgen Deprivation Therapy in Localized Prostate Cancer after Radical Prostatectomy: A Propensity Score Matched Analysis.

PurposeAndrogen deprivation therapy (ADT) is used as a salvage treatment for men with biochemical recurrence (BCR) of prostate cancer (PCa) following initial radical prostatectomy (RP). The optimal time at which to begin salvage ADT (sADT) remains controversial. In this retrospective study, we evaluated the efficacy of initiating sADT in patients before prostate-specific antigen (PSA) values met the clinical definition of BCR.Materials and MethodsWe identified 484 PCa patients who received sADT for BCR after RP. Median follow-up was 82 months. Propensity score matching was performed based on preoperative PSA level, pathologic T stage, and Gleason score. Patients were assigned to two groups of 169 patients each, based on PSA levels at the time of sADT: Group A (without meeting of the definition of BCR) and Group B (after BCR). Kaplan-Meier survival analyses and Cox regression analyses were performed.ResultsThe median PSA level at sADT initiation was 0.12 ng/mL in group A and 0.42 ng/mL in group B. Kaplan-Meier analyses showed that group A had favorable disease progression-free survival (DPFS) and distant metastasis-free survival (DMFS), but did not have better cancer-specific survival (CSS) than group B. In subgroup analyses, group A showed better CSS rates in the non-organ confined PCa group. In Cox regression analyses, early sADT was associated significantly with DPFS and DMFS rates, however, did not correlate with CSS (p=0.107).ConclusionEarly sADT after RP improved DPFS and DMFS. Furthermore, early sADT patients demonstrated better CSS in non-organ confined PCa.

Low testosterone at first prostate-specific antigen failure and assessment of risk of death in men with unfavorable-risk prostate cancer treated on prospective clinical trials.

Low testosterone at the time of diagnosis of prostate cancer has been associated with a worse prognosis. Whether this is true and how to define the best treatment approach at the time of first prostate-specific antigen (PSA) failure to the authors' knowledge has not been elucidated to date and was studied herein. Between 1995 and 2001, a total of 58 men with unfavorable-risk PC who were treated on clinical trials with radiotherapy and androgen deprivation therapy (ADT) had available testosterone levels at the time of PSA failure. Cox and Fine and Gray regressions were performed to ascertain whether low versus normal testosterone was associated with the risk of PC-specific mortality, other-cause mortality, and all-cause mortality adjusting for age, salvage ADT, and known PC prognostic factors. After a median follow-up of 6.68 years after PSA failure, 31 men (53.4%) had died; 10 of PC (32.3%), of which 8 of 11 (72.7%) versus 2 of 47 (4.3%) deaths occurred in men with low versus normal testosterone at the time of PSA failure, respectively. A significant increase in the risk of all-cause mortality (adjusted hazard ratio [AHR], 2.54; 95% confidence interval [95% CI], 1.04-6.21 [P = .04]) and PC-specific mortality (AHR, 13.71; 95% CI, 2.4-78.16 [P = .003]), with a reciprocal trend toward a decreased risk of other-cause mortality (AHR, 0.18; 95% CI, 0.02-1.55 [P = .12]) was observed in men with low versus normal testosterone. Low, but not necessarily castrate, testosterone levels at the time of PSA failure confer a very poor prognosis. These observations provide evidence to support testosterone testing at the time of PSA failure. Given prolonged survival when abiraterone or docetaxel is added to ADT in men with castrate-sensitive metastatic PC and possibly localized high-risk PC provides a rationale supporting their use with ADT in men with low testosterone in the setting of a phase 2 trial. Cancer 2018;124:1383-90. © 2017 American Cancer Society.

Does surgical delay for radical prostatectomy affect biochemical recurrence? A retrospective analysis from a Canadian cohort.

We sought to explore the impact of surgical wait time (SWT) to robot-assisted radical prostatectomy (RARP) on biochemical recurrence (BCR). Retrospective review of a prospectively collected database between 2006 and 2015 was conducted on all RARP cases. SWT was defined as period from prostate biopsy to surgery. Primary outcome was the impact on BCR, which was defined as two consecutive PSA ≥0.2ng/dl, or salvage external beam radiation therapy and/or salvage androgen deprivation therapy. Patients were stratified according to D'Amico risk categories. Univariable analysis (UVA) and multivariable analyses (MVA) with a Cox proportional hazards regression model were used to evaluate the effect of SWT and other predictive factors on BCR, in each D'Amico risk group and on the overall collective sample. Patients eligible for analysis were 619. Mean SWT was 153, 169, 150, and 125days, for overall, low-, intermediate-, and high-risk patients, respectively. Multivariate analysis on the overall cohort did not show a significant relation between SWT and BCR. On subgroup analysis of D'Amico risk group, SWT was positively correlated to BCR for high-risk group (p=0.001). On threshold analysis, cut-off was found to be 90days. SWT did not significantly affect BCR on UVA and MVA in the low- and intermediate-risk groups. Increased delay to surgery could affect the BCR, as there was a positive association in high-risk group. Further studies with longer follow-up are necessary to assess the impact of wait time on BCR, cancer specific survival and overall survival.

MP64-15 ROBOTIC ASSISTED LAPAROSCOPIC RADICAL PROSTATECTOMY IN ISUP GRADE 5 PROSTATE CANCER: ONCOLOGICAL OUTCOMES

You have accessJournal of UrologyProstate Cancer: Localized: Surgical Therapy V1 Apr 2017MP64-15 ROBOTIC ASSISTED LAPAROSCOPIC RADICAL PROSTATECTOMY IN ISUP GRADE 5 PROSTATE CANCER: ONCOLOGICAL OUTCOMES Itay Sagy, Charles Nottingham, Shay Golan, Matt Galocy, and Arieh Shalhav Itay SagyItay Sagy More articles by this author , Charles NottinghamCharles Nottingham More articles by this author , Shay GolanShay Golan More articles by this author , Matt GalocyMatt Galocy More articles by this author , and Arieh ShalhavArieh Shalhav More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.1988AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES We present here oncological outcome for patients with International Society of Urological Pathology (ISUP) Grade 5 prostate cancer (PC) who underwent primary treatment with robotic assisted laparoscopic radical prostatectomy (RALP). METHODS Using a prospectively collected institutional registry, we identified patients with clinically organ confined and locally advanced (cT1-T3N0M0) ISUP Grade 5 PC who underwent RALP with bilateral pelvic lymphadenectomy as primary treatment between 2005 and 2013. RESULTS We included 106 patients with median age of 65 years (IQR 58.5-68). The majority of patients had clinically organ-confined disease (90%). Following surgery, 71 patients (67%) were upstaged to pT3 and 40 patients (38%) were downgraded to Gleason score 8 or 7. With median follow-up of 63.5 months (IQR 34-85), 50 patients (48%) had biochemical failure: 24 patients (23%) had PSA persistence and 26 patients (24%) had biochemical recurrence (BCR). Adjuvant and salvage RT were administered to 12 (11%) and 34 (32%) patients, respectively; adjuvant and salvage ADT were given to two (2%) and 31 (29%) patients, respectively; 9 patients (8%) received subsequent therapies. Eleven patients (10%) had systemic failure and 10 patients (9.5%) died: 3 (3%) from prostate cancer and 7 (7%) from other causes. Using Kaplan-Meier estimate, the 5-year overall, disease specific, metastasis-free and disease-free survivals are 91%, 96%, 88%, and 59% respectively. Using univariate analysis, pre-operative PSA, number of cores involved with ISUP grade 5 PC on biopsy, percentage of positive cores on biopsy, and pathological T stage were all correlated with both biochemical and systemic failure. CONCLUSIONS The disease volume on pre-operative biopsy and specifically the amount of Gleason 5 pattern predicted both biochemical and systemic failure. RALP in ISUP grade 5 PC is a viable treatment option in the multimodality management of PC, it affords local control and might improve long-term oncologic outcomes. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e850 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Itay Sagy More articles by this author Charles Nottingham More articles by this author Shay Golan More articles by this author Matt Galocy More articles by this author Arieh Shalhav More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

PD10-03 EXTENDED RADICAL PROSTATECTOMY FOLLOWING NEOADJUVANT CHEMOHORMONONAL THERAPY (LOW DOSE ESTRMUSTINE + LHRH AGONIST/ANTAGONIST) CONTRIBUTES TO GOOD CANCER CONTROL FOR PATIENTS WITH HIGH RISK LOCALIZED PROSTATE CANCER

You have accessJournal of UrologyProstate Cancer: Localized: Surgical Therapy I1 Apr 2017PD10-03 EXTENDED RADICAL PROSTATECTOMY FOLLOWING NEOADJUVANT CHEMOHORMONONAL THERAPY (LOW DOSE ESTRMUSTINE + LHRH AGONIST/ANTAGONIST) CONTRIBUTES TO GOOD CANCER CONTROL FOR PATIENTS WITH HIGH RISK LOCALIZED PROSTATE CANCER Hideki Enokida, Shuichi Tatarano, Hiroaki Nishimura, Akihiko Mitsuke, Hirofumi Yoshino, Ryosuke Matsushita, and Masayuki Nakagawa Hideki EnokidaHideki Enokida More articles by this author , Shuichi TataranoShuichi Tatarano More articles by this author , Hiroaki NishimuraHiroaki Nishimura More articles by this author , Akihiko MitsukeAkihiko Mitsuke More articles by this author , Hirofumi YoshinoHirofumi Yoshino More articles by this author , Ryosuke MatsushitaRyosuke Matsushita More articles by this author , and Masayuki NakagawaMasayuki Nakagawa More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.566AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Patients with high-risk prostate cancer (PCa) according to D′Amico risk categories are prone to a pathological diagnosis of positive margins or lymph node invasion and biochemical recurrence, despite having undergone radical prostatectomy (RP). METHODS 84 high-risk PCa patients prospectively underwent ′extended′ RP following neoadjuvant chemohormonal therapy (NCH); primarily 6 months of estramustine phosphate 280 mg bid, along with a LH-RH agonist/antagonist. Our surgical technique was developed to reduce the rates of positive surgical margins. The goal is to approach the muscle layer of the rectum by dissecting the mesorectal fascia and continuing the dissection through the mesorectum until the muscle layer of the rectum is exposed. The procedure was safely performed as a result of good recognition of the structure between the perineal body and the rectal surface. We also performed extended lymphadenectomy if the patients meet two or more of D′Amico risk categories RESULTS Pathological analysis revealed that positive surgical margins were found in only two patients. More than 1 year had elapsed after surgery in 64 of the 84 patients with the median follow-up period of 36.1 months. Among those 64 patients, 12 (18.8%) experienced PSA recurrence (Table 1). Kaplan-Meier analyses revealed that significant poorer PSA progression-free survival were observed in patients with younger age, higher positive biopsy core ratio, positive extra-prostate extension (EPE), lymph node metastasis, and higher pathological stage (pT3a/b). Multivariate Cox-regression analysis revealed that higher pathological stage (pT3a/b) was the only independent valuable for predicting PSA progression failure (Table 2). These 12 cases received salvage androgen deprivation therapy followed-by external beam radiotherapy and showed no progression after the salvage therapies (median follow-up period, 22.9 months after PSA progression). CONCLUSIONS NCH concordant with extended RP is feasible and contributes to negative surgical margins that might provide good cancer control for patients with high-risk PCa. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e199-e200 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Hideki Enokida More articles by this author Shuichi Tatarano More articles by this author Hiroaki Nishimura More articles by this author Akihiko Mitsuke More articles by this author Hirofumi Yoshino More articles by this author Ryosuke Matsushita More articles by this author Masayuki Nakagawa More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...