A nomogram for testosterone recovery following combined androgen deprivation therapy and radiation therapy for prostate cancer.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 67-67
Author(s):  
Daphna Spiegel ◽  
Julian C. Hong ◽  
W. Robert Lee ◽  
Joseph Kamel Salama
Keyword(s):  
Prostate Cancer ◽  
Radiation Therapy ◽  
Androgen Deprivation Therapy ◽  
Median Duration ◽  
Proportional Hazards ◽  
Medical Center ◽  
Cox Proportional Hazards ◽  
Androgen Deprivation ◽  
Cox Proportional Hazards Models ◽  
Pre Treatment

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.

scholarly journals Risk and Timing of Cardiovascular Disease After Androgen-Deprivation Therapy in Men With Prostate Cancer

2015 ◽  
Vol 33 (11) ◽  
pp. 1243-1251 ◽  
Author(s):  
Sean O'Farrell ◽  
Hans Garmo ◽  
Lars Holmberg ◽  
Jan Adolfsson ◽  
Pär Stattin ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cardiovascular Disease ◽  
Androgen Deprivation Therapy ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Androgen Deprivation ◽  
Gnrh Agonists ◽  
Cvd Risk ◽  
Comparison Cohort ◽  
Using Data

Purpose Findings on the association between risk of cardiovascular disease (CVD) and the duration and type of androgen-deprivation therapy (ADT) in men with prostate cancer (PCa) are inconsistent. Methods By using data on filled drug prescriptions in Swedish national health care registers, we investigated the risk of CVD in a cohort of 41,362 men with PCa on ADT compared with an age-matched, PCa-free comparison cohort (n = 187,785) by use of multivariable Cox proportional hazards regression models. Results From 2006 to 2012, 10,656 men were on antiandrogens (AA), 26,959 were on gonadotropin-releasing hormone (GnRH) agonists, and 3,747 underwent surgical orchiectomy. CVD risk was increased in men on GnRH agonists compared with the comparison cohort (hazard ratio [HR] of incident CVD, 1.21; 95% CI, 1.18 to 1.25; and orchiectomy: HR, 1.16; 95% CI, 1.08 to 1.25). Men with PCa on AA were at decreased risk (HR of incident CVD, 0.87; 95% CI, 0.82 to 0.91). CVD risk was highest during the first 6 months of ADT in men who experienced two or more cardiovascular events before therapy, with an HR of CVD during the first 6 months of GnRH agonist therapy of 1.91 (95% CI, 1.66 to 2.20), an HR of CVD with AA of 1.60 (95% CI, 1.24 to 2.06), and an HR of CVD with orchiectomy of 1.79 (95% CI, 1.16 to 2.76) versus the comparison cohort. Conclusion Our results support that there should be a solid indication for ADT in men with PCa so that benefit outweighs potential harm; this is of particular importance among men with a recent history of CVD.

Outcomes of men with recurrent M0 prostate cancer who defer androgen deprivation therapy until metastasis.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 5016-5016
Author(s):  
Catherine Handy Marshall ◽  
Wei Fu ◽  
Hao Wang ◽  
Bruce J. Trock ◽  
Mario A. Eisenberger
Keyword(s):  
Prostate Cancer ◽  
Androgen Deprivation Therapy ◽  
Proportional Hazards ◽  
Local Treatment ◽  
Drug Approval ◽  
Cox Proportional Hazards ◽  
Androgen Deprivation ◽  
Clinical State ◽  
Optimal Timing ◽  
Kaplan Meier

5016 Background: Optimal timing and criteria for implementation of androgen deprivation therapy (ADT) in men with relapsed M0 prostate cancer (PCa) remains undefined. Early ADT induces the non-metastatic castration resistant PCa (nmCRPC) clinical state. FDA approved apalutamide (SPARTAN) and enzalutamide (PROSPER) for nmCRPC based on prolongation of metastasis free survival (MFS) which is now considered a valid endpoint for drug approval. Because overall survival (OS) in PCa is usually long and long-term ADT is associated with irreversible adverse events and high costs, we sought to evaluate OS and other outcomes of men with relapsed PCa and ADT deferred until metastasis. Methods: Retrospective review of 2,636 men who had radical prostatectomy (RP) between 1981-2017 and developed biochemically recurrent PCa from a single-institution. Patients who received ADT prior to metastasis were excluded. Kaplan-Meier survival estimates of MFS and OS were defined from RP to event or censor. Multivariable Cox proportional hazards regression was used to identify prognostic factors. Results: 1,686 men treated with deferred ADT until metastasis or censored metastasis-free were eligible. Medians: follow up 10 years (IQR5-16), age 60 years, PSADT 33 months, Gleason < 7 (24%), Gleason 7 (55%), Gleason > 7 (21%). 688 (41%) received salvage radiotherapy. Median MFS and OS were 21 and 22 years, respectively (Table). In multivariable models, age (HR 1.06, 95% CI 1.04-1.1), Gleason < 8 vs ≥8 (HR 0.4; 0.3-0.5) , RP stage (organ confined vs not 0.6; 0.5-0.8), PSADT (0.995, 0.993-0.997) and salvage RT (0.88; 0.81, 0.96) were associated with OS. Conclusions: Deferred ADT in relapsing M0 patients is associated with long OS measured from time of local treatment, comparable to OS with salvage ADT in contemporary experience. Drug approval trials in nmCRPC should focus on patients at high risk for metastasis and death prior to ADT, and determine standardized criteria for initiation of ADT. Prolongation of MFS in nmCRPC requires further validation and may not necessarily reflect a net OS benefit. [Table: see text]

scholarly journals Associations between Peripheral Thromboembolic Vascular Disease and Androgen Deprivation Therapy in Asian Prostate Cancer Patients

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Yu-Chuan Lu ◽  
Chao-Yuan Huang ◽  
Huei-Ming Yeh ◽  
Jian-Hua Hong ◽  
Chao-Hsiang Chang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Vascular Disease ◽  
Androgen Deprivation Therapy ◽  
Proportional Hazards ◽  
Day Treatment ◽  
Arterial Occlusion ◽  
Incidence Rates ◽  
Cox Proportional Hazards ◽  
Androgen Deprivation ◽  
Chemical Castration

Abstract This study aimed to investigate the risks of thromboembolic vascular disease following androgen deprivation therapy (ADT) administered to prostate cancer (PCa) patients. A total of 24,464 men with newly diagnosed PCa during 2000–2008 were recruited through a longitudinal health insurance database in Taiwan. All PCa patients were stratified into two: ADT and non-ADT groups. Patients with ADT treatment were grouped into three: surgical castration, chemical castration, and anti-androgen alone. The risks of pulmonary embolism (PE), peripheral arterial occlusion disease (PAOD), and deep vein thrombosis (DVT) were assessed in multiple Cox proportional-hazards regression with time-dependent covariates. During the 12-year follow-up period, incidence rates per 1000 person-years in ADT and non-ADT groups were 2.87 and 1.62 for DVT, 1.00 and 0.52 for PE, and 1.03 and 0.70 for PAOD, respectively. The DVT and PE risks were significantly increased in patients receiving combined androgen blockade (CAB) compared with the counterpart ADT non-recipients. After adjusting for potential risk factors, PCa patients receiving CAB had the highest PE risk (HR = 3.11), followed by DVT risk (HR = 2.53). The DVT risk remained elevated throughout the entire duration of chemical castration. However, high PE risk was observed in patients with ≤720-day treatment duration. No association was found between ADT and PAOD risks. Overall, the risks of PE and DVT were considerably heightened in Asian men subjected to CAB for PCa, whereas PAOD risk was unrelated to such treatments.

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 ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Radiation Therapy ◽  
Radical Prostatectomy ◽  
Metastatic Prostate Cancer ◽  
Proportional Hazards ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Metastatic Progression ◽  
Free Survival ◽  
Cox Proportional Hazards Models

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.

scholarly journals Association of Androgen Deprivation Therapy With Depression in Localized Prostate Cancer

2016 ◽  
Vol 34 (16) ◽  
pp. 1905-1912 ◽  
Author(s):  
Kathryn T. Dinh ◽  
Gally Reznor ◽  
Vinayak Muralidhar ◽  
Brandon A. Mahal ◽  
Michelle D. Nezolosky ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Deprivation Therapy ◽  
Proportional Hazards ◽  
Psychiatric Treatment ◽  
Secondary Analysis ◽  
Cox Proportional Hazards ◽  
Androgen Deprivation ◽  
Primary Analysis ◽  
Increased Risk ◽  
Inpatient Psychiatric Treatment

Purpose Androgen deprivation therapy (ADT) may contribute to depression, yet several studies have not demonstrated a link. We aimed to determine whether receipt of any ADT or longer duration of ADT for prostate cancer (PCa) is associated with an increased risk of depression. Methods We identified 78,552 men older than age 65 years with stage I to III PCa using the SEER-Medicare–linked database from 1992 to 2006, excluding patients with psychiatric diagnoses within the prior year. Our primary analysis was the association between pharmacologic ADT and the diagnosis of depression or receipt of inpatient or outpatient psychiatric treatment using Cox proportional hazards regression. Drug data for treatment of depression were not available. Our secondary analysis investigated the association between duration of ADT and each end point. Results Overall, 43% of patients (n = 33,882) who received ADT, compared with patients who did not receive ADT, had higher 3-year cumulative incidences of depression (7.1% v 5.2%, respectively), inpatient psychiatric treatment (2.8% v 1.9%, respectively), and outpatient psychiatric treatment (3.4% v 2.5%, respectively; all P < .001). Adjusted Cox analyses demonstrated that patients with ADT had a 23% increased risk of depression (adjusted hazard ratio [AHR], 1.23; 95% CI, 1.15 to 1.31), 29% increased risk of inpatient psychiatric treatment (AHR, 1.29; 95% CI, 1.17 to 1.41), and a nonsignificant 7% increased risk of outpatient psychiatric treatment (AHR, 1.07; 95% CI, 0.97 to 1.17) compared with patients without ADT. The risk of depression increased with duration of ADT, from 12% with ≤ 6 months of treatment, 26% with 7 to 11 months of treatment, to 37% with ≥ 12 months of treatment (P trend < .001). A similar duration effect was seen for inpatient (P trend < .001) and outpatient psychiatric treatment (P trend < .001). Conclusion Pharmacologic ADT increased the risk of depression and inpatient psychiatric treatment in this large study of elderly men with localized PCa. This risk increased with longer duration of ADT. The possible psychiatric effects of ADT should be recognized by physicians and discussed with patients before initiating treatment.

Adjuvant versus neoadjuvant androgen deprivation with radiation therapy for prostate cancer: Does sequencing matter?

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 37-37 ◽  
Author(s):  
Michael A. Weller ◽  
Rahul D. Tendulkar ◽  
Chandana A. Reddy ◽  
Kevin L. Stephans ◽  
Patrick Kupelian
Keyword(s):  
Prostate Cancer ◽  
Radiation Therapy ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Androgen Deprivation ◽  
Free Survival ◽  
Entire Cohort ◽  
High Risk Prostate Cancer ◽  
Risk Prostate Cancer ◽  
The Impact

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.

scholarly journals Radiation therapy dose and androgen deprivation therapy in localized prostate cancer: a meta-regression of 5-year outcomes in phase III randomized controlled trials

2021 ◽  
Author(s):  
Tommy Jiang ◽  
Daniela Markovic ◽  
Jay Patel ◽  
Jesus E. Juarez ◽  
Ting Martin Ma ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Radiation Therapy ◽  
Androgen Deprivation Therapy ◽  
Dose Escalation ◽  
Low Dose ◽  
Androgen Deprivation ◽  
Phase Iii ◽  
Localized Prostate Cancer ◽  
Treatment Intensification ◽  
Meta Regression

Abstract Background While multiple randomized trials have evaluated the benefit of radiation therapy (RT) dose escalation and the use and prolongation of androgen deprivation therapy (ADT) in the treatment of prostate cancer, few studies have evaluated the relative benefit of either form of treatment intensification with each other. Many trials have included treatment strategies that incorporate either high or low dose RT, or short-term or long-term ADT (STADT or LTADT), in one or more trial arms. We sought to compare different forms of treatment intensification of RT in the context of localized prostate cancer. Methods Using preferred reporting items for systemic reviews and meta-analyses (PRISMA) guidelines, we collected over 40 phases III clinical trials comparing different forms of RT for localized prostate cancer. We performed a meta-regression of 40 individual trials with 21,429 total patients to allow a comparison of the rates and cumulative proportions of 5-year overall survival (OS), prostate cancer-specific mortality (PCSM), and distant metastasis (DM) for each treatment arm of every trial. Results Dose-escalation either in the absence or presence of STADT failed to significantly improve any 5-year outcome. In contrast, adding LTADT to low dose RT significantly improved 5-year PCSM (Odds ratio [OR] 0.34, 95% confidence interval [CI] 0.22–0.54, p < 0.001) and DM (OR 0.35, 95% CI 0.20–0.63. p < 0.001) over low dose RT alone. Adding STADT also significantly improved 5-year PCSM over low dose RT alone (OR 0.55, 95% CI 0.41–0.75, p < 0.001). Conclusion While limited by between-study heterogeneity and a lack of individual patient data, this meta-analysis suggests that adding ADT, versus increasing RT dose alone, offers a more consistent improvement in clinical endpoints.

Patterns of Care and Outcomes of Primary Adenoid Cystic Carcinoma of the Trachea

2021 ◽  
pp. 000348942110081
Author(s):  
Sara Behbahani ◽  
Gregory L. Barinsky ◽  
David Wassef ◽  
Boris Paskhover ◽  
Rachel Kaye
Keyword(s):  
Radiation Therapy ◽  
Adenoid Cystic Carcinoma ◽  
Surgical Resection ◽  
Proportional Hazards ◽  
Invasive Disease ◽  
Cox Proportional Hazards ◽  
Tumor Diameter ◽  
Adenoid Cystic ◽  
Cox Proportional Hazards Models ◽  
Age Of Diagnosis

Objective: Primary tracheal malignancies are relatively rare cancers, representing 0.1% to 0.4% of all malignancies. Adenoid cystic carcinoma (ACC) is the second most common histology of primary tracheal malignancy, after squamous cell carcinoma. This study aims to analyze demographic characteristics and potential influencing factors on survival of tracheal ACC (TACC). Methods: This was a retrospective cohort study utilizing the National Cancer Database (NCDB). The NCDB was queried for all cases of TACC diagnosed from 2004 to 2016 (n = 394). Kaplan-Meier (KM) and Cox proportional-hazards models were used to determine clinicopathological and treatment factors associated with survival outcomes. Results: Median age of diagnosis was 56 (IQR: 44.75-66.00). Females were affected slightly more than males (53.8% vs 46.2%). The most prevalent tumor diameter range was 20 to 39 mm (34.8%) followed by greater than 40 mm in diameter (17.8%). Median overall survival (OS) was 9.72 years with a 5- and 10-year OS of 70% and 47.5%, respectively. Localized disease was not associated with a survival benefit over invasive disease ( P = .388). The most common intervention was surgery combined with radiation therapy (RT) at 46.2%, followed by surgery alone (16.8%), and standalone RT (8.9%). When adjusting for confounders, surgical resection was independently associated with improved OS (HR 0.461, 95% CI 0.225-0.946). Tumor size greater than 40 mm was independently associated with worse OS (HR 2.808; 95% CI 1.096-7.194). Conclusion: Our data suggests that surgical resection, possibly in conjunction with radiation therapy, is associated with improved survival, and tumor larger than 40 mm are associated with worse survival.

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