Men Who Receive Androgen Deprivation Therapy for Prostate Cancer Have Higher Risk of Cardiovascular Disease

“For men with prostate cancer (PCa), the risk for incident cardiovascular disease (CVD) is increased with androgen deprivation therapy (ADT), according to a study published online March 2 in the Journal of Clinical Oncology.

“Sean O’Farrell, from King’s College London, and colleagues used data on filled drug prescriptions in Swedish national health care registers to examine the risk of CVD associated with ADT in men with PCa. Data were collected in a cohort of 41,362 men with PCa on ADT and an age-matched PCa-free comparison cohort of 187,875 men. Overall, 10,656 men were on antiandrogens (AAs); 26,959 were on gonadotropin-releasing hormone (GnRH) agonists; and 3,747 underwent surgical orchiectomy from 2006 to 2012.

“Compared to the comparison cohort, the researchers found that the risk of CVD was increased in men on GnRH agonists (hazard ratio for incident CVD, 1.21) and in those who underwent orchiectomy (hazard ratio, 1.16). The risk of incident CVD was decreased for men on AAs (hazard ratio, 0.87). Men who experienced two or more cardiovascular events before therapy had the highest CVD risk during the first six months of ADT versus the comparison cohort, with hazard ratios of 1.91 for GnRH agonist therapy; 1.60 for AAs; and 1.79 for orchiectomy.”

ADT Increases Risk for Cardiovascular Disease in Men with Prostate Cancer

“Patients with prostate cancer who received androgen-deprivation therapy demonstrated an increased risk for cardiovascular disease, according to study results.

“Men with a previous history of cardiovascular events were at a particularly increased risk for cardiovascular disease (CVD) with androgen-deprivation therapy (ADT), results showed.

“Sean O’Farrell, BSc, MRes,of the division of cancer studies at King’s College London School of Medicine, and colleagues used the Swedish national health care registries to identify 41,362 patients who received ADT for prostate cancer. The analysis also included a control group of 187,785 age-matched, cancer-free men…

“ ‘Our study suggests an increased risk of CVD within the first year from starting GnRH agonist therapy or orchiectomy, especially in men with history of a CVD event within 1 year before ADT,’ O’Farrell and colleagues concluded. ‘There should be solid indication of use of ADT so that the perceived benefit outweighs possible harm. This is particularly important in men with a recent history of CVD.’ “

Phase III Trial Shows Improved Survival With Long‑Term Androgen-Deprivation Therapy Plus High-Dose Radiotherapy in Localized Prostate Cancer

“In the Spanish phase III DART01/05 GICOR trial reported in Lancet Oncology, Zapatero and colleagues found that long-term androgen-deprivation therapy (ADT) increased biochemical disease-free survival and overall survival vs short-term ADT when combined with high-dose radiotherapy in men with localized prostate cancer.

“In this open-label trial, 355 patients were randomly assigned between November 2005 and December  2010 to receive 4 months of ADT (n = 178) or 24 months of ADT (n = 177) following three-dimensional conformal radiotherapy at a minimum dose of 76 Gy (range, 76–82 Gy). Patients had to have clinical stage T1c–T3b, N0, M0 prostate adenocarcinoma with intermediate or high risk based on 2005 National Comprehensive Cancer Network criteria.

“The short-term ADT group received 4 months of neoadjuvant and concomitant androgen deprivation with subcutaenous goserelin (Zoladex) 2 months before and 2 months in combination with high-dose radiotherapy, with flutamide at 750 mg/d or bicalutamide at 50 mg/d added during the first 2 months of treatment. Patients in the long-term ADT group continued with the same luteinizing hormone–releasing hormone analog every 3 months for 24 months. The primary endpoint was biochemical disease-free survival on intention-to-treat analysis.”

Seeds Top EBRT as Boost Tx in Prostate Cancer

“Low-dose brachytherapy boosts held prostate cancer in check significantly better than dose-escalated external-beam radiation therapy (EBRT) in men with unfavorable-risk disease, a randomized trial showed.

“Patients treated with brachytherapy after androgen deprivation therapy (ADT) and whole-pelvis EBRT had an estimated 9-year relapse-free survival (RFS) of 83% compared with 63% for patients who received a conformal EBRT boost. The difference in favor of brachytherapy emerged after 5 years of follow-up, Scott Tyldesley, MD, of the British Columbia Cancer Agency in Vancouver, reported here at the Genitourinary Cancers Symposium.

” ‘In the context of 12 months of androgen deprivation therapy and whole pelvis external beam radiotherapy, treatment with a low-dose pelvic brachytherapy boost results in a 50% reduction in biochemical relapse compared to dose-escalated EBRT to 78 Gray,’ Tyldesley said. ‘At 6.5 years of follow-up, there was no difference in overall survival, prostate cancer specific survival, or metastasis-free survival.’

“However, ‘there was increased late grade 3 or higher GU toxicity with the low-dose rate boost, a 5% to 6% increase in the prevalence of late GU toxicity,’ he said.”

ADT Plus Docetaxel for Prostate Ca: Home Run or Foul Ball?

“A ‘home run’ in advanced prostate cancer did not clear the fence in a second evaluation of androgen deprivation therapy (ADT) with docetaxel, according to a study reported here.

“An updated analysis of a French study showed that adding chemotherapy to ADT did not significantly improve overall survival for men with hormone-sensitive, metastatic prostate cancer. However, the 13-month difference in favor of the docetaxel arm was comparable to the statistically significant 14-month improvement observed in a larger U.S. trial reported last year.

“The French study also failed to show a survival benefit in patients with high-volume disease, which accounted for two-thirds of the patients in the U.S. trial.

” ‘We are awaiting the analysis of [a third randomized trial], and we hope to come up with a common analysis of the three studies altogether in order to give the good [best] treatment for the good [best] patient,’ Gwenaelle Gravis, MD, of Institut Paoli-Calmettes in Marseilles, France, said here at the Genitourinary Cancers Symposium.

“For more than 40 years, ADT has represented standard of care for metastatic hormone-sensitive advanced prostate cancer. The emergence of effective chemotherapy for castration-resistant prostate cancer led to speculation that use of cytotoxic therapy in hormone-sensitive advanced prostate cancer might improve outcomes as compared with ADT alone.”

Provenge Induces Sustained Immune Response Even at 2 Years after Treatment

“Preliminary results from the phase II STAND trial have demonstrated a robust immune response with sipuleucel-T (Provenge) that continues 2 years after completing treatment in men with biochemically recurrent prostate cancer. The findings, along with data from an ongoing phase IV registry related to increasing enrollment of African Americans in prostate cancer trials, are being presented at the 2015 Genitourinary Cancers Symposium, held February 26 to 28 in Orlando…

“The STAND study (Abstract 171) is a randomized, phase II trial that consisted of two patient study groups. One group completed sipuleucel-T 2 weeks before initiation of androgen-deprivation therapy, and the second received the drug 3 months after the start of androgen-deprivation therapy. Preliminary results from STAND indicate that immune responses were observed in both study arms and suggest there may be a greater cellular immune response in patients who received sipuleucel-T prior to androgen-deprivation therapy. Humoral immune responses were observed and similar between both treatment arms.

“ ‘It is very encouraging to observe that [sipuleucel-T] provides an immune response in men with biochemical-recurrent prostate cancer long after the course of androgen deprivation therapy has ended,’ said Neal Shore, MD, Medical Director at the Carolina Urologic Research Center. ‘This study may also provide guidance on the optimal sequencing of immunotherapy and androgen-deprivation therapy in biochemical-recurrent prostate cancer.’ ”

Adding Radiotherapy to Androgen Deprivation in Advanced Prostate Cancer Prolongs Survival by More than One Year

“An 8-year analysis confirmed that adding radiotherapy to androgen deprivation therapy (ADT) in men with locally advanced prostate cancer improved overall survival and reduced the risk of prostate cancer–specific death. The median overall survival was 10.9 years in the combination arm compared with 9.7 years in the ADT-alone arm.

“This final analysis is published in the Journal of Clinical Oncology.

“The original results of this international NCIC Clinical Trials Group PR.3 trial were published in the Lancet  in 2011. This prior interim analysis showed a significant improvement in overall survival for those in the ADT plus radiotherapy treatment arm (hazard ratio [HR] = 0.77; P = .033). Based on the results, radiotherapy was recommended as part of the standard therapy for prostate cancer.

“The NCIC trial is the largest study investigating the addition of radiotherapy to ADT.”

Now BATting: A New Treatment Approach That Uses Testosterone First, Then ADT

Androgen deprivation therapy (ADT) has long been a mainstay in the management of prostate cancer. Indeed, the vast majority of prostate cancers depend on androgens (hormones like testosterone) for their growth. Lowering testosterone levels with ADT is a reasonable approach. But it comes with two sets of problems. Continue reading…

ADT Before or After Surgery Gives Similar Survival Rates in Prostate Cancer

The gist: Recent research found that prostate cancer patients have similar survival rates whether they have androgen deprivation therapy (ADT) before or after tumor-removal surgery. The study focused on men with intermediate- or high-risk prostate cancer who were treated between 1995 and 2002.

“Patients with intermediate- or high-risk prostate cancer demonstrated similar biochemical relapse-free survival, distant metastasis-free survival and OS regardless of whether they received androgen deprivation in the neoadjuvant or adjuvant settings, according to study results.

“Patients with localized prostate cancer typically undergo androgen deprivation therapy (ADT) in the neoadjuvant setting, concurrent with radiation therapy.

“Michael A. Weller, MD,of Cleveland Clinic, and colleagues assessed whether patients who underwent ADT in the adjuvant setting experienced different outcomes.

“The analysis included 515 patients treated with radiation therapy and ADT from 1995 to 2002. Of these patients, 311 underwent ADT in the neoadjuvant setting, beginning 2 to 3 months before the start of radiation therapy. The other 204 patients underwent ADT in the adjuvant setting, immediately after the completion of radiation therapy.”