CaP wysokiego ryzyka - dł. adj. HT - EBRT vs EBRT+HDR BT

[zosia bluszcz]

Optymalne leczenie raka prostaty wysokiego ryzyka - czas trwania adjuwantowej ADT u pacjentow leczonych samą EBRT lub EBRT w połączeniu z HDR BT
Analiza danych z 3 kohort pacjentów (badania kliniczne DART i RADAR oraz jedno badanie retrospektywne)


Pytanie
Jaki jest optymalny minimalny czas trwania terapii deprywacji androgenowej (ADT) podczas leczenia raka prostaty wysokiego ryzyka za pomocą radioterapii wysokodawkowej?


Wyniki
Badanie obejmujące 3 kohorty wykazało istotną interakcję między rodzajem wysokodawkowej radioterapii (EBRT solo lub EBRT + boost HDR BT) a optymalnym czasem trwania ADT.
DT trwająca od 18 do 28 miesięcy wiązała się z 63% redukcją zgonów lub przerzutów po EBRT;
po dodaniu boostu do brachyterapii związek między ADT a przeżyciem bez przerzutów odległych obejmował 12 miesięcy.


Znaczenie
Wyniki tego badania sugerują, że pacjenci otrzymujący samą EBRT mogą odnieść korzyść z HT trwającej 18 miesięcy lub dłużej;
ADT trwająca 18 miesięcy, a być może nawet krócej, może być optymalna.



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.
A Patient-Level Data Analysis of 3 Cohorts

Published online January 20, 2022. doi:10.1001/jamaoncol.2021.6871


Key Points

Question
What is the optimal minimum duration of androgen deprivation therapy (ADT) when treating high-risk prostate cancer with high-dose radiotherapy?


Findings
This patient-level cohort study of 3 cohorts found a significant interaction between the type of high-dose radiotherapy (external beam radiotherapy with or without a brachytherapy boost) and optimal duration.
Prolonging ADT for 18 to 28 months was associated with a 63% reduction in death or metastasis with external beam radiotherapy;
when a brachytherapy boost was added, the nonlinear association between ADT and distant metastasis-free survival was broad and spanned 12 months.


Meaning
The findings of this cohort study suggest that patients receiving external beam radiotherapy alone may benefit from ADT durations of 18 months or more;
if a brachytherapy boost is added, a duration of 18 months or possibly less may be optimal.



Abstract
Importance Radiotherapy combined with androgen deprivation therapy (ADT) is a standard of care for high-risk prostate cancer. However, the interplay between radiotherapy dose and the required minimum duration of ADT is uncertain.

Objective
To determine the specific ADT duration threshold that provides a distant metastasis-free survival (DMFS) benefit in patients with high-risk prostate cancer receiving external beam radiotherapy (EBRT) or EBRT with a brachytherapy boost (EBRT+BT).

Design, Settings, and Participants
This was a cohort study of 3 cohorts assembled from
- a multicenter retrospective study (2000-2013);
- a post hoc analysis of the Randomized Androgen Deprivation and Radiotherapy 03/04 (RADAR 2003-2007) randomized clinical trial (RCT); and
- a cross-trial comparison of the RADAR vs the Deprivación Androgénica y Radio Terapía (Androgen Deprivation and Radiation Therapy; DART) 01/05 RCT (2005-2010).
In all, the study analyzed
1827 patients treated with EBRT and 1108 patients treated with EBRT+BT from the retrospective cohort,
181 treated with EBRT and 203 with EBRT+BT from RADAR; and
91 patients treated with EBRT from DART.

The study was conducted from October 15, 2020, to July 1, 2021, and the data analyses, from January 5 to June 15, 2021.

Exposures
High-dose EBRT or EBRT+BT for an ADT duration determined by patient-physician choice (retrospective) or by randomization (RCTs).

Main Outcomes and Measures
The primary outcome was DMFS; secondary outcome was overall survival (OS). Natural cubic spline analysis identified minimum thresholds (months).


Results
This cohort study of 3 studies totaling 3410 men (mean age [SD], 68 [62-74] years; race and ethnicity not collected) with high-risk prostate cancer found a significant interaction between the treatment type (EBRT vs EBRT+BT) and ADT duration (binned to <6, 6 to <18, and ≥18 months). Natural cubic spline analysis identified minimum duration thresholds of 26.3 months (95% CI, 25.4-36.0 months) for EBRT and 12 months (95% CI, 4.9-36.0 months) for EBRT+BT for optimal effect on DMFS.
In RADAR, the prolongation of ADT for patients receiving only EBRT was not associated with significant improvements in DMFS (hazard ratio

---

,1.01; 95% CI, 0.65-1.57);
however, for patients receiving EBRT+BT, a longer duration was associated with improved DMFS (DMFS HR, 0.56; 95% CI, 0.36-0.87; P = .01).
For patients receiving EBRT alone (DART), 28 months of ADT was associated with improved DMFS compared with 18 months (RADAR HR, 0.37; 95% CI, 0.17-0.80; P = .01).


Conclusions and Relevance
These cohort study findings suggest that the optimal minimum ADT duration for treatment with high-dose EBRT alone is more than 18 months; and for EBRT+BT, it is 18 months or possibly less. Additional studies are needed to determine more precise minimum durations.


https://jamanetwork.com/journals/jamaon ... le/2788324

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.pdf