The level of testosterone (T) in the blood of men with riskier, localized prostate cancers who undergo hormone therapy should be suppressed to a level lower than currently accepted to achieve optimal outcomes, suggests a new retrospective study.
Androgen deprivation therapy (ADT) is a standard treatment for some men with intermediate- and high-risk prostate cancer that has not yet spread outside of the gland, point out the study authors, led by Brent Rose, MD, a radiation oncologist at the University of California, San Diego.
The goal of ADT is to reduce T levels to a "castrate" level, which is historically defined as <50 and="" cancer.="" dl="" hormonal="" ng="" of="" p="" slow="" stimulation="" the="" thereby="">
However, other research has suggested that, in the setting of metastatic disease, patients with "nadir" T levels from 20 - 50 ng/dL have poorer outcomes compared to men who achieve even lower levels of T, namely, <20 be.="" better="" dl.="" in="" level="" lower="" ng="" outcome="" p="" short="" tends="" testosterone="" the="" to="">
So Rose and colleagues decided to study this issue in men with earlier-stage disease and add to the small body of related literature.
Their study was published online December 10, 2018, in the International Journal of Radiation Oncology - Biology - Physics.
Using a Veteran's Administration database, the investigators identified 764 men with with intermediate- or high-risk localized prostate cancer who underwent treatment with ADT and definitive radiotherapy from 2000 to 2015.
The men were divided into two groups on the basis of their minimum T level during continuous gonadotropic-releasing hormone agonist therapy: <20 -="" 20="" 49="" and="" dl.="" dl="" ng="" p="">
Rose and colleagues report that for men with T levels from 20 - 49 ng/dL, 10-year biochemical recurrence rates were higher (28.1% vs 18.3%), as were metastasis rates (12.9% vs 7.8%), compared to the patients with T levels <20 dl.="" ng="" p="">
The difference in rates persisted when the investigator performed multivariable analyses.
Also, shorter-term measures favored the group with lower T levels.
Specifically, the T nadir of 20 - 49 ng/dL was associated with higher 3-month postradiotherapy prostate-specific antigen (PSA) levels compared to a T nadir <20 0.16="" dl="" i="" nbsp="" ng="" style="max-width: 100%;">P
Higher PSA levels are undesirable and are a sign of more active disease.
There was also a trend toward inferior prostate cancer–specific mortality for the 20 - 49 ng/dL group.
"Our study suggests that there are clinically significant differences in early PSA response and long-term clinical outcomes among patients who achieve differing levels of testosterone suppression below the historical 50 ng/dL castrate level," summarize the authors.
Inadequate Testosterone Suppression?
The new results raise questions about current practice and castrate levels of serum T, suggested David Wise, MD, PhD, a medical oncologist at New York University (NYU) Langone Health in New York City.
"The NCCN [National Comprehensive Cancer Network] guidelines recommend <50 accepted="" an="" and="" dl="" he="" i="" is="" nbsp="" ng="" standard="" style="max-width: 100%;" this="" told="">Medscape Medical News
in an email.
"This study provides an intriguing pilot dataset that calls into question the reliance on this standard <50 added.="" dl="" he="" ng="" p="" threshold="">
The new findings need further validation in an independent cohort, Wise advised.
The NYU physician also said that it is standard to check the serum T level after initiation of androgen suppression to ensure appropriate suppression. "Inadequate testosterone suppression can happen and is a preventable cause of poor outcome," he reminded.
Wise said the new findings are consistent with previous studies that suggest a link between the depth of testosterone suppression and clinical outcome.
According to the study authors, the new results also prompt the question, what do you do clinically when T levels cannot be satisfactorily suppressed?
"Newer therapies such as abiraterone [multiple brands] and enzalutamide [Xtandi,Astellas] may suppress serum testosterone more effectively in many patients and thus hold promise as adjunct therapies in patients with insufficient testosterone suppression," they propose.
Again, Wise said use of these agents needed confirmation: "Further prospective studies will be needed to validate this approach for this highly curable disease."
The study was supported by the National Institutes of Health. The authors and Dr Wise have disclosed no relevant financial relationships.
Int J Radiat Oncol Biol Phys. Published online December 10, 2018. Abstract
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