Meta-analysis may help guide treatment planning for patients with high-
risk prostate cancer

Date:
January 20, 2022
Source:
University of California - Los Angeles Health Sciences
Summary:
Results of a large study could help guide treatment planning for
patients with high-risk prostate cancer.



FULL STORY ========================================================================== Results of a large study led by UCLA Jonsson Comprehensive Cancer
Center researchers could help guide treatment planning for patients with high-risk prostate cancer.


==========================================================================
An international effort consisting of a consortium of 16 research centers
in collaboration with two international cooperative trial groups found
that patients receiving high-dose external beam radiation therapy alone
may benefit from androgen deprivation therapy (ADT) lasting longer
than 18 months, while those with external beam radiation therapy and a brachytherapy boost -- the implantation of radioactive seeds to deliver
a higher total dose to the prostate -- may be optimally managed with 18
months of ADT or possibly less.

Results are published in the Jan. 20 issue of JAMA Oncology.

"Adding androgen deprivation therapy to radiation therapy has been
consistently shown to improve survival when treating men with high-risk prostate cancer.

However, lowering testosterone levels is associated with a number of side effects, including not only a decrement in quality of life, but possibly
more serious adverse events when longer durations are used. While it
has long been hypothesized that by delivering extremely high doses of radiation, one might be able to shorten the required duration of ADT,
this has never been proven," said lead author Amar Kishan, MD, associate professor and vice chair of clinical and translational research in the Department of Radiation Oncology at UCLA and a researcher at the UCLA
Jonsson Comprehensive Cancer Center.

The researchers analyzed individual patient data from three cohorts of patients: a retrospective cohort of patients from 16 cancer treatment
referral centers between 2000 and 2014 who received either high-dose
external beam radiotherapy or external beam radiotherapy with a
brachytherapy boost; a cohort of patients enrolled in a randomized phase
3 trial that included patients from 23 treatment centers in Australia
and New Zealand; and a cohort of patients enrolled in a randomized phase
3 trial conducted across 10 treatment centers in Spain. This is the only analysis to include both retrospective and prospective data in evaluating optimal ADT duration in high-risk prostate patients receiving these two
forms of radiation therapy.

"Because of androgen deprivation therapy's unpleasant side effects,
it is often underutilized, with men receiving considerably shorter
durations of ADT than might be recommended. To discern the ADT duration thresholds that provide the greatest metastasis-free survival benefit for
these patients, we analyzed a multi-institutional database of patients, developed hypotheses, and then evaluated our findings by analyzing
individual patient data from randomized trials," said Kishan.

"The consistency of our results across multiple different patient
cohorts greatly strengthens our findings," said Tahmineh Romero, senior statistician in the UCLA Department of Medicine Statistics Core and the
senior author of the article.

In the retrospective cohort -- looking at ADT durations of less than six months, six to 18 months, and greater than 18 months -- a significant interaction was seen between treatment type and ADT duration. A
duration of 18 months or more was associated with improved outcomes,
relative to shorter durations, for patients receiving high-dose external
beam radiation therapy without a brachytherapy boost. In contrast,
among patients receiving radiation therapy and brachytherapy, an ADT
duration of at least six months but less than 18 months was associated
with improved metastasis-free survival and overall survival, compared
to receipt of less than six months of ADT. But there appeared to be no improvement in metastasis-free survival for those receiving both forms
of radiation therapy and more than 18 months of ADT.

With further analysis, the researchers determined that for patients
receiving radiation therapy without brachytherapy, the optimal ADT
duration was 26.3 months; for those treated with radiation therapy
and a brachytherapy boost, the minimum threshold was 12 months. Their hypotheses drawn from the retrospective study appeared to be supported
by effects observed in the randomized clinical trials.

"Contrary to findings in a previous study, our results suggest that
optimal duration of ADT for patients receiving high-dose radiation therapy
may be more than 18 months. This is implied by findings from all the
cohorts we analyzed. A secondary conclusion, based on the retrospective dataset, is that ADT duration shorter than 18 months may be sufficient for patients undergoing both radiation therapy and brachytherapy. Although
current and future studies will continue to offer clarification,
individual patient meta-analyses incorporating data from various trials
may provide the best current guidance for doctors and patients.

We have additional studies underway to explore this concept further,"
said Kishan.

========================================================================== Story Source: Materials provided by University_of_California_-_Los_Angeles_Health_Sciences.

Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Amar U. Kishan, Alison Steigler, James W. Denham, Almudena Zapatero,
Araceli Guerrero, David Joseph, Xavier Maldonado, Jessica K. Wong,
Bradley J. Stish, Robert T. Dess, Avinash Pilar, Chandana Reddy,
Trude B.

Wedde, Wolfgang A. Lilleby, Ryan Fiano, Gregory S. Merrick,
Richard G.

Stock, D. Jeffrey Demanes, Brian J. Moran, Phuoc T. Tran, Santiago
Martin, Rafael Martinez-Monge, Daniel J. Krauss, Eyad I. Abu-Isa,
Thomas M. Pisansky, C. Richard Choo, Daniel Y. Song, Stephen
Greco, Curtiland Deville, Todd McNutt, Theodore L. DeWeese,
Ashley E. Ross, Jay P. Ciezki, Derya Tilki, R. Jeffrey Karnes,
Jeffrey J. Tosoian, Nicholas G. Nickols, Prashant Bhat, David
Shabsovich, Jesus E. Juarez, Tommy Jiang, T. Martin Ma, Michael
Xiang, Rebecca Philipson, Albert Chang, Patrick A. Kupelian, Matthew
B. Rettig, Felix Y. Feng, Alejandro Berlin, Jonathan D. Tward, Brian
J. Davis, Robert E. Reiter, Michael L. Steinberg, David Elashoff,
Paul C. Boutros, Eric M. Horwitz, Rahul D. Tendulkar, Daniel
E. Spratt, Tahmineh Romero. Interplay Between Duration of Androgen
Deprivation Therapy and External Beam Radiotherapy With or Without
a Brachytherapy Boost for Optimal Treatment of High-risk Prostate
Cancer. JAMA Oncology, 2022; DOI: 10.1001/jamaoncol.2021.6871 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/01/220120125350.htm

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