Androgen Blockade and Salvage ­Radiation Therapy in Prostate Cancer: Cautious Optimism Amid Unanswered Questions


“The recent report of results of RTOG 9601 by Shipley et al in The New England Journal of Medicine—reviewed in this issue of The ASCO Post—strongly supports the variably used practice of adding ‘androgen blockade’ to salvage radiation therapy in men with a rising prostate-specific antigen (PSA) after radical prostatectomy. The findings show a clear reduction in prostate cancer–specific and overall mortality with the addition of 2 years of bicalutamide to salvage radiation therapy. Another likely (although not demonstrated) benefit is the reduction in the need to treat patients with subsequent life-long continuous or intermittent androgen blockade at the expense of treating all men with 2 years of bicalutamide.”

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Patients with Detectable PSA Post-Prostatectomy Should Receive More Aggressive Radiation Therapy

“Prostate cancer patients with detectable prostate specific antigen (PSA) following radical prostatectomy should receive earlier, more aggressive radiation therapy treatment, according to a study published in the February 1, 2015 issue of the International Journal of Radiation Oncology • Biology • Physics (Red Journal), the official scientific journal of the American Society for Radiation Oncology (ASTRO). This study is a 10-year post-treatment analysis of the German ARO 96-02 trial, a prospective clinical trial that compared a wait-and-see approach versus an adjuvant radiation therapy approach for patients with node negative prostate cancer who had a prostatectomy.

“ARO 96-02 accrued 388 patients from 1997 to 2004 with pT3-4pN0 prostate cancer with positive or negative margins who had already undergone radical prostatectomy. Twenty-two centers in Germany participated in the trial. Three patients were excluded from the study because they received immediate hormonal treatment. Prior to reaching an undetectable PSA post-prostatectomy, 159 patients were randomized to a wait-and-see approach (Arm A) and 148 patients were randomized to receive adjuvant radiation therapy (Arm B). Seventy-eight patients who did not achieve an undetectable PSA were moved to Arm C. Four of the patients in Arm C refused treatment, and 74 patients were treated with salvage radiation therapy in Arm C.

“All patients in the study had a pre- and post-operative PSA test, a bone scan and chest radiography. Patients in Arm B received 60 Gy of 3-D conformal radiation therapy. Patients in Arm C received 66 Gy of 3-D conformal radiation therapy. Follow-up was conducted for all eligible patients in the trial quarterly for the first two years, twice a year from three to six years post-treatment, and annually thereafter. The median follow-up time was 112 months (9.3 years).”

Clues Found to Prostate Cancer Upgrading

During median follow-up of 6.4 years, 31.3% of the localized cancers were upgraded. The proportion of men with upgraded tumors increased over time, D. Andrew Loblaw, MD, reported here at the ASCO GU symposium. “This increase over time was not statistically significant, but it allows for some hypothesis generation.” A panel of experts debated the result and the future of active surveillance for low-risk prostate cancer patients.

Phase I Data of a New Androgen Receptor (AR) Inhibitor, ODM- 201

Phase I and pre-clinical results with ODM-201, the ARADES trial show the drug is well tolerated, with no significant treatment-related adverse events. Prostate specific antigen (PSA) response was seen in 81% of 21 treatmnent naive patients and 92% achieved a greater than 50% PSA decrease. For post-abiraterone, post-chemo patients this decrease was seen in 67% of patients.

Researchers Study Role of Radical Prostatectomy for Prostate Cancer Patients

There is benefit to radical prostatectomy (RP) in prostate cancer patients, evenin the presence of screening. But, the benefit is limited to a subgroup of patients and can take years to become evident according to the study which analyzed the results of the Scandinavian Prostate Cancer Group Study Number 4 (SPCG-4) and the U.S. Prostate Cancer Intervention Versus Observation Trial (PIVOT) trials.

Targeting Constitutively Activated β1 Integrin Could Be a New Target for Prevention of Metastasis of Prostate Cancer

Researchers from the MD Anderson Cancer Center in Houston show that β1 integrin activation occurs in metastatic progression of prostate cancer and is constitutively active in late state prostate cancer cells. The study shows the integrin palys a reole in survival of metastatic prostate cancer cells in circulation. Inhibition of β1 integrin activity by antibody or knockdown results in increased apoptosis.

Prostate cancer risk reduction in men taking dutasteride, but some concerns remain

Nearly 2,800 men participated in the four-year REDUCE (REduction by DUtasteride of prostate Cancer Events) observational clinical study evaluated prostate cancer risk reduction in men taking dutasteride, a 5-alpha-reductase inhibitor (5ARI) typically used to treat enlarged prostate. Results showed that few new prostate cancers were detected during the two-year follow-up in either treatment group and no deaths were reported. However, the former dutasteride group produced double the number of cancers than the former placebo group (14 vs. 7).

Consistent epigenetic ‘signatures’ found in prostate cancer patients’ metastatic tumors

Researchers at Johns Hopkins analyzed 13 metastatic prostate tumors, finding a a consistent epigenetic signature among the samples. The discovery of the stable, epigenetic “marks” that sit on the nuclear DNA of cancer cells and alter gene expression, defies a prevailing belief that the marks vary so much within each individual’s widespread cancers that they have little or no value as targets for therapy or as biomarkers for treatment response and predicting disease severity.

Behavioral stress accelerates prostate cancer development in mice, new study shows

We know stress is bad for cancer patients in general. Now, a new study shows mouse prostate cancer models under stress (they can smell a predator) had lower responses to cancer drug compared to non-stressed counterparts. A linked commentary suggests drugs such as beta-blockers that affect adrenaline could boost efficacy of anti-cancer treatments.