scholarly journals Metastatic progression following multimodal therapy for unfavorable-risk prostate cancer

2021 ◽  
Vol 16 (4) ◽  
Author(s):  
David Guy ◽  
Rachel Glicksman ◽  
Roger Buckley ◽  
Patrick Cheung ◽  
Hans Chung ◽  
...  

Introduction: Identifying the optimal management of unfavorable-risk (ProCaRS high intermediate-, high-, and very high-risk categories) non-metastatic prostate cancer is an important public health concern given the large burden of this disease. We compared the rate of metastatic progression-free survival among men diagnosed with unfavorable-risk non-metastatic prostate cancer who were initially treated with radiation therapy or radical prostatectomy. Methods: Information was obtained from medical records at two academic centers in Canada from 333 men diagnosed with unfavorable-risk non-metastatic prostate cancer between 2007 and 2012. Median followup was 90.4 months. Men were eligible for study if they received either primary radiation therapy (n=164) or radical prostatectomy (n=169), in addition to various adjuvant and salvage therapies when deemed clinically appropriate. Patients were matched on prognostic covariates using two matching techniques. Multivariable Cox proportional hazards models were used to estimate the hazard ratios (HR) and confidence intervals (CI) for metastatic progression-free survival between groups. Results: After matching, treatment groups were balanced on prognostic variables except for percent core positivity. Hazard ratios from all Cox proportional hazards models (i.e., before and after matching, and with and without multivariable adjustment) showed no difference in the rate of metastatic progression-free survival between groups (adjusted unmatched HR 1.16, 95% CI 0.63, 2.13, p=0.64). Conclusions: Metastatic progression-free survival did not differ between men diagnosed with unfavorable risk non-metastatic prostate cancer who were treated with either radiation therapy or radical prostatectomy.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 59-59
Author(s):  
Umang Swami ◽  
Taylor Ryan McFarland ◽  
Benjamin Haaland ◽  
Adam Kessel ◽  
Roberto Nussenzveig ◽  
...  

59 Background: In mCSPC, baseline CTC counts have been shown to correlate with PSA responses and progression free survival (PFS) in small studies in the context of androgen deprivation therapy (ADT) without modern intensification with docetaxel or novel hormonal therapy. Similar correlation of CTC count with PSA responses and PFS was recently reported from an ongoing phase 3 trial in mCSPC setting (SWOG1216) without reporting the association in the context of ADT intensification. Furthermore, none of these studies correlated CTCs with overall survival (OS). Herein we evaluated whether CTCs were associated with outcomes including OS in a real world mCPSC population treated with intensified as well as non-intensified ADT. Methods: Eligibility criteria: new mCSPC receiving ADT with or without intensification and enumeration of baseline CTCs by FDA cleared Cell Search CTC assay. The relationship between CTC counts (categorized as: 0, 1-4, and ≥5/7.5 ml) and both PFS and OS was assessed in the context of Cox proportional hazards models, both unadjusted and adjusted for age, Gleason, PSA at ADT initiation, de novo vs. non-de novo status, and ADT intensification vs. non-intensification therapy. Results: Overall 99 pts were identified. Baseline characteristics are summarized in Table. In unadjusted analyses, CTC counts of ≥5 as compared to 0 were strongly associated with inferior PFS (hazard ratio [HR] 3.38, 95% CI 1.85-6.18; p < 0.001) and OS (HR 4.44 95% CI 1.63-12.10; p = 0.004). In multivariate analyses, CTC counts of ≥5 as compared to 0 continued to be associated with inferior PFS (HR 5.49, 95% CI 2.64-11.43; p < 0.001) and OS (HR 4.00, 95% CI 1.31-12.23; p = 0.015). Within the ADT intensification subgroup also, high CTC counts were associated with poor PFS and OS. For PFS, the univariate HR for CTC ≥5 vs. 0 was 4.87 (95% CI 1.66-14.30; p = 0.004) and multivariate HR for CTC ≥5 vs. 0 was 7.43 (95% CI 1.92-28.82; p = 0.004). For OS, the univariate HR for CTC ≥5 vs. 0 was 15.88 (95% CI 1.93-130.58; p = 0.010) and multivariate HR for CTC ≥5 vs. 0 was 24.86 (95% CI 2.03-304.45; p = 0.012). Conclusions: To best of our knowledge this is the first study to show that high baseline CTC counts are strongly associated with inferior PFS as well as OS in pts with newly diagnosed mCSPC, even in those who received intensified ADT therapy. Identifying these pts at highest risk of progression and death can help with counselling and prognostication in clinics as well as design and enrollment in future clinical trials. [Table: see text]


2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 240-240
Author(s):  
Sina Vatandoust ◽  
Ganessan Kichenadasse ◽  
Michael E O'Callaghan ◽  
Tina Kopsaftis ◽  
Scott Walsh ◽  
...  

240 Background: In 15-30% of pts with metastatic PCa who progress on Maximal Androgen Blockade (MAB), withdrawal of the antiandrogen agent (AAWD) and continuing the LHRH agonist alone, leads to PSA decreases of ≥50% and prolonged progression free survival. Here we describe patient and disease characteristics, treatment history and outcomes of pts who have been managed with AAWD. Methods: Data were obtained from SA-PCCOC (a longitudinal, observational registry of biopsy-proven PCa cases, throughout the Australian state of South Australia since 1998). Proportions were compared using a Chi squared test. A multivariable model used competing risks (Fine and Gray) and Cox proportional Hazards models to assess overall survival and Prostate cancer specific mortality (PCSM). Survival was calculated from the date of rising PSA for patients on LHRH and AA. Results: 140 pts were found to have MAB. Of these, 31(22.1%) had AAWD. In the AAWD group, median age was 81y (51-95). Age at diagnosis, Gleason score at biopsy and diagnostic PSA were not significantly different amongst the two groups. Treatment PSA was significantly lower in the AAWD group (20.55 (range 0.6-9,995) vs 50.50 (range 0.95-4378) p= 0.02). There was a significant association of AAWD with PCSM (sHR 0.35, 95% CI 0.16-0.76; p = 0.008). Also significant in the model was prior time on hormones (sHR [per month increase] 0.96 95% CI 0.95-0.98, p<0.001). There was also a significant association of AAWD with overall survival (HR 0.22, 95% CI 0.10-0.46; p <0.001). Again, prior time on hormones was also significant (HR [per month increase] 0.96 95% CI 0.95-0.98, p<0.001). Multivariate analysis was performed on data from 80 pts (60 pts omitted due to missing data). Conclusions: Pts in whom AAWD was used were older and had lower treatment PSA. In this small cohort, AAWD was associated with both reduced PCSM and overall risk of death. The time spent on MAB also appeared to be significant. This retrospective observational study may be subject to confounding, however the observation warrants further investigation in larger cohorts and in a prospective setting.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5023-5023 ◽  
Author(s):  
Eric Jay Small ◽  
Fred Saad ◽  
Simon Chowdhury ◽  
Stephane Oudard ◽  
Boris A. Hadaschik ◽  
...  

5023 Background: The addition of APA to ongoing ADT in pts with nmCRPC significantly prolonged metastasis-free survival (MFS), time to symptomatic progression (SymProg), and second progression-free survival (PFS2) in SPARTAN. We assessed the impact of APA on these end points in pts with or without BL CM. Methods: Using Cox proportional hazards models, treatment effect of APA was evaluated in SPARTAN pts with CM at BL, stratifying by the presence of BL diabetes/hyperglycemia (D/H), cardiovascular disease (CVD), hypertension (HTN), and renal insufficiency (RI). Results: Of 1207 SPARTAN pts, 1062 (88%) had ≥ 1 BL CM, including 703/806 (87%) APA pts and 359/401 (90%) PBO pts. A total of 226 (19%), 398 (33%), 798 (66%), and 774 (64%) pts had D/H, CVD, HTN, and RI, respectively; 323 (27%), 412 (34%), 259 (21%), and 68 (6%) pts had 1, 2, 3, and 4 CM, respectively. Incidence of CM was balanced between arms. Pts with CM were older than pts with no CM (median age, 75 vs 69 yrs, APA; 74 vs 69 yrs, PBO). MFS, SymProg, and PFS2 benefit with APA was significant in all CM subgroups, except PFS2 for pts with D/H (Table) and regardless of the number of CM. The incidence of any treatment-emergent AE was balanced between pts with and without CM. AEs with APA were not affected by any CM. Clinical trial information: NCT01946204. Conclusions: The benefit of APA + ongoing ADT in pts with nmCRPC was maintained in pts with D/H, CVD, HTN, and RI. The safety profile of APA was not affected by any CM.[Table: see text]


2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 32-32 ◽  
Author(s):  
Olusola Olusesan Faluyi ◽  
Lawson Eng ◽  
Xin Qui ◽  
Dangxiao Cheng ◽  
Daniel John Renouf ◽  
...  

32 Background: Better understanding of the biology of esophageal cancer may help improve its treatment. MicroRNAs (miRs) regulate mRNA and can exert some influence on carcinogenesis. Identification of the microRNAs which regulate esophageal cancer development could potentially yield alternative therapeutic options. Objectives: We evaluated polymorphisms in miRs, miR biogenesis, binding sites of miR and their role in the survival of esophageal cancer patients. Methods: 324 esophageal cancer patients of all stages and histological subtypes were evaluated. Using Illumina Custom GoldenGate, 43 polymorphisms in miR pathways were evaluated. Cox proportional hazards models adjusted for clinical prognostic variables and determined the association of polymorphisms with overall survival (OS) and progression free survival (PFS). Adjusted hazard ratio (aHR) and 95% confidence intervals (CI) were calculated. Results: Among our patients, 83% were male while the mean age was 65 years. 73% had adenocarcinomas while 33.6% had advanced tumors (Stage IV). The median PFS was 1.20 years, while median OS was 2.17 years. After adjustment for clinical variables, a 5’UTR polymorphism in pri-mir26a-1 (rs7372209) was significantly associated with reduced PFS [aHR=0.78, CI:0.62-0.98, p=0.04] and OS [aHR 0.71 (0.56-0.89), p=0.003]. Three other polymorphisms were significantly associated with OS but not PFS: these included two polymorphisms of miR processing genes, DDX20 (rs197412) [aHR 1.31 (1.04-1.64), p=0.02] and EIF2C1 (rs595961) [aHR 0.76 (0.60-0.97), p=0.03] as well as the CD86 3’UTR C>G (rs17281995) polymorphism, which has been predicted to affect the binding of miR337, miR582, miR200a, miR184, and miR212 [aHR 1.38 (1.03-1.85), p=0.03]. Conclusions: We report the initial association of miR related polymorphisms with survival in esophageal cancer. We plan to explore additional relationships and validate these findings in other datasets.


2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 37-37
Author(s):  
Christopher David Kosarek ◽  
Stephen Bentley Williams ◽  
Jinhai Huo ◽  
Karim Chamie ◽  
Marc C. Smaldone ◽  
...  

37 Background: To compare overall survival of patients who underwent radical prostatectomy or radiotherapy versus non-cancer controls in order to discern if there is a survival advantage according to prostate cancer treatment. Methods: A matched cohort study was performedusingthe Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database. We identified 34,473 patients age 66 to 75 years without significant comorbidity from who were diagnosed with localized prostate cancer treated with surgery or radiotherapy between 2004 and 2011. These patients were matched to a non-cancer control cohort. We compared the rates of all-cause mortality that occurred within the study period. We used Cox Proportional Hazards Regression analysis to identify determinants associated with overall survival. Results: Of the total 34,473 patients who were included in the analysis, 21,740 (63%) received radiation therapy and 12,733 (37%) received surgery. When compared to the non-cancer control, there was no significant difference between the prostate cancer cohort and the non-cancer control group with exception of race/ethnicity (p < 0.001). There was improved survival in patients treated with surgery (hazard ratio [HR], 0.35; 95% CI, 0.32-0.38) as well as with radiotherapy (HR, 0.72; 95% CI, 0.68-0.75) when compared to non-cancer controls. There was significantly improved overall survival among both treatment groups with most benefit observed among patients who underwent surgery ( log rank p < 0.001). Conclusions: Using population based data, treatment with either surgery or radiotherapy demonstrated improved overall survival when compared to a cohort of matched non-cancer controls. Treatment with surgery resulted in longer overall survival compared to those receiving radiation therapy. These results suggest inherent selection-bias due to unmeasured confounding variables when using cancer registry data.


2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 14-14 ◽  
Author(s):  
Cameron Ghaffary ◽  
Tamer Dafashy ◽  
Christopher David Kosarek ◽  
Zhigang Duan ◽  
Brian F. Chapin ◽  
...  

14 Background: National Cancer Institute (NCI) and National Comprehensive Cancer Network (NCCN)-designated cancer centers (CCs) offer patients state-of-the-art treatment. We sought to identify whether proximity to NCI/NCCN CCs was associated with survival outcomes for prostate cancer patients who undergo radical prostatectomy (RP). Methods: A total of 12,478 total patients diagnosed with clinical stage T1 or T2 prostate cancer between 2004–2011 using linked Surveillance, Epidemiology, and End Results (SEER)-Medicare data were included. Multivariable regression analyses were used to quantify overall survival and use of secondary therapies for RP patients according to proximity to NCI/NCCN CCs. Cox proportional hazards models were used to quantify the association between survival outcomes and access to NCI/NCCN CCs. Results: Patients with proximity to ≥ 2 NCI centers and those diagnosed in 2011 enjoyed a statistically significant overall survival advantage when compared to no access to an NCI center (Hazard Ratio (HR) 0.72; 95% confidence interval (CI) 0.57–0.92, p < 0.01). Proximity to an NCCN CC, when compared with men who did not have access, was associated with improved overall survival (HR 0.76; 95% CI 0.61–0.95, p = 0.015). There was no significant difference in use of secondary therapies according to NCI or NCCN access. Conclusions: Patients who undergo RP with access to an NCI/NCCN CCs experienced improved overall survival with no significant difference in utilization of secondary therapies. Given the need for improved health quality measures in cancer care, these findings may support health policy implementation and regionalization of care to these centers.


2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 9-9
Author(s):  
Shree Agrawal ◽  
Jason A. Efstathiou ◽  
Jeff M. Michalski ◽  
Thomas Michael Pisansky ◽  
Bridget F. Koontz ◽  
...  

9 Background: Early salvage radiation therapy (SRT) following radical prostatectomy (RP) has been shown to reduce biochemical recurrence and distant metastases. We aim to identify factors predictive of prostate cancer-specific mortality (PCSM) and all-cause mortality (ACM) from a consortium database from 10 academic institutions. Methods: 2,454 node-negative patients (pts) with detectable post-prostatectomy PSA ( ≥ 0.01 ng/mL) treated with SRT ± neoadjuvant/concurrent androgen deprivation therapy (N/C ADT) were included. Cumulative incidence and Kaplan-Meier methods were used to estimate rates of PCSM and ACM, respectively. Univariate and multivariable analyses (MVA) were performed by competing risks regression and Cox proportional hazards methods for PCSM and ACM. Results: Median follow-up was 5 years from SRT completion and 8 years from date of RP; 24% had pathologic Gleason score (GS) of ≤ 6, 56% GS 7, and 19% GS ≥ 8; 56% extraprostatic extension (EPE), 18% seminal vesicle invasion (SVI), 58% positive surgical margins, and 16% received N/C ADT. Median age at RP and SRT were 62 years (IQR 56-66) and 64 years (59-69), respectively. Median SRT dose was 66 Gy (IQR 65-68) and median pre-SRT PSA was 0.5 ng/mL (IQR 0.3-1.1). MVA performed from SRT completion date demonstrated higher pre-SRT PSA (HR = 2.1), higher GS (GS 7 vs. ≤ 6: HR 2.0; GS ≥ 8 vs. 6: HR 3.3) , SVI (HR 2.5), year of SRT (2000-2004, 1995-1999, 1985-1994 vs. 2005-2012; HR 2.9, HR 2.5, HR 3.6, respectively) were significantly associated with higher PCSM. These same variables were all significantly associated with higher PCSM and ACM rates calculated from both SRT completion date and date of RP. Conclusions: Initiation of early SRT at lower post-operative PSA levels following RP is associated with reduced risk of PCSM and ACM, even when calculated from RP date to account for lead time bias. Other factors significantly associated with PCSM include higher GS, SVI, and earlier year of SRT. [Table: see text]


2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 67-67
Author(s):  
Daphna Spiegel ◽  
Julian C. Hong ◽  
W. Robert Lee ◽  
Joseph Kamel Salama

67 Background: Combined androgen deprivation therapy (ADT) and radiation therapy (RT) is a frequently used localized prostate cancer (PC) treatment. Testosterone recovery (TR) after combined ADT-RT is not well-characterized. We studied TR in men who received RT and either short-term (ST) ADT or long-term (LT) ADT with LHRH agonists. Methods: We identified consecutive localized PC patients treated with ADT-RT at the Durham VA Medical Center (DVAMC) from 1/2011-10/2016. All patients had a documented baseline testosterone (T) level. Individual patient records were reviewed. TR was defined as time from last ADT injection to T normalization ( > 240 ng/dL). The Kaplan-Meier method was used to estimate time to TR. Cox proportional hazards models were generated to identify TR predictors with a nomogram built based on a parsimonious multivariate model. Results: 252 patients were identified. Median follow-up was 26.7 months. Median age was 65. Prior to treatment, 69% had a normal baseline T. 67% were treated with STADT, median duration 6 months. 33% were treated with LTADT, median duration 18 months. Median time for TR was 22.6 months for all patients (19.5 months for STADT and 25.6 months for LTADT). At 1 and 2 years post ADT, estimated TR was 13% and 53% (17% and 57% for STADT and 3% and 42% for LTADT). 2-year biochemical control was 99.2% and 97.6% for STADT and LTADT, respectively; 98.9% and 98.6% for those with and without TR, respectively. On multivariate analysis, higher pre-treatment T (HR = 1.004 95% CI 1.003-1.006, p < 0.001), use of STADT (HR = 2.48 95% CI 1.45-4.25, p = 0.001), and lower BMI (HR = 0.95 95% CI 0.91-0.98, p = 0.001) were associated with shorter time to TR. White race was a negative TR predictor (HR = 0.65 95% CI 0.43-0.9992, p = 0.049). Age, smoking, and Charlson Comorbidity Index were not significant independent TR predictors. A nomogram was generated to predict probability of TR at 1, 2, and 3 years. Conclusions: In this VA population of localized PC patients treated from 2011-2016, TR following the use of ADT-RT was variable. Using pre-treatment T levels, ADT duration, BMI, and race, a predictive nomogram can estimate the likelihood of TR.


2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 37-37 ◽  
Author(s):  
Michael A. Weller ◽  
Rahul D. Tendulkar ◽  
Chandana A. Reddy ◽  
Kevin L. Stephans ◽  
Patrick Kupelian

37 Background: Androgen deprivation therapy (ADT) is typically given neoadjuvantly and concurrently with radiation therapy (RT) rather than adjuvantly in the management of intermediate and high risk prostate cancer. Our objective is to compare outcomes between patients who receive adjuvant ADT (ADJ), i.e. immediately after the completion of RT, with those who receive a neoadjuvant and concurrent regimen (NEO). Methods: From 1995-2002, 515 patients with CaP were definitively treated with RT and ADT. ADT was given for a duration of 6 months in all cases. NEO was given 2-3 months prior to the start of RT. ADJ was initiated immediately following the completion of RT. ADT sequencing was NEO in 311 (60%) and ADJ in 204 (40%). The distribution by NCCN risk classification for NEO was high in 67%, intermediate in 26%, and low in 7%. The risk group distribution for ADJ was high in 69%, and intermediate in 31%. RT dose was either 78 Gy at 2 Gy/fx (n=168) or 70 Gy at 2.5 Gy/fx (n=347). Kaplan-Meier analysis was used to calculate biochemical relapse free survival (bRFS, Phoenix definition), distant metastasis free survival (DMFS) and overall survival (OS). Cox proportional hazards regression was used to examine the impact of ADT timing on outcomes. Results: The median follow up for all patients was 8 years. For the entire cohort, the 10-yr bRFS, DMFS and OS rates were 61%, 80% and 66%, respectively. The 10-yr bRFS rates for ADJ vs. NEO were 63% vs. 60% (p=0.98). The 10-yr DMFS rates for ADJ vs. NEO were both 80% (p=0.60). The 10-yr OS rates for ADJ vs. NEO were 65% vs. 67% (p=0.98). There were no statistically significant differences in bRFS, DMFS or OS between the two groups after accounting for patient, tumor and treatment characteristics on both univariate and multivariate analyses. Conclusions: There is no difference between neoadjuvant vs. adjuvant ADT in the setting of dose-escalated RT for localized prostate cancer. This suggests that the synergy between radiation therapy and androgen deprivation is independent of the sequencing of both modalities and that the initiation of RT does not need to be delayed for a course of neoadjuvant ADT.


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