Page 3 - Metastatic castration-naive and castration-sensitive prostate cancer: CUA/CUOG

guideline: mCnPC & mCSPC

radiotherapy group (15 vs. 12 m, crude HR 0.78; 95% CI ment in treating participants with metastatic PC; https://
0.63–0.97; p=0.02). Subgroup analysis showed that mCNPC www.swog.org/clinical-trials/s1802), and G-RAMPP/AUO
with <5 metastases (HR 0.90; 95% CI 0.70-–1.14; p=NS) and –AP-75/13 (Impact of radical prostatectomy as primary treat-
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no bony pain (HR 0.83; 95% CI 0.69–1.14; p=NS) appeared ment in patients with PC with limited bone metastases).
to have the most impact of EBRT. Until the results of these trials clarify the impact of radical
The STAMPEDE trial, also known as MRC PR08, is a prostatectomy in mCNPC and, more importantly, which
multi-arm, multi-stage (MAMS), randomized trial recruit- patients would benefit the most, surgery of the primary is
ing in the U.K. and Switzerland. It aims to evaluate mul- not recommended in patients with metastatic PC.
tiple therapeutic strategies in the management of high-risk,
locally advanced and mCNPC compared to standard of care Systemic therapies: Chemotherapy, abiraterone acetate,
(androgen deprivation only). In the EBRT component of the enzalutamide, and apalutamide
study, the trial randomized 2061 men with mCNPC to either
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EBRT and ADT or ADT alone. The median PSA was 97 ng/
2
mL; 819 (40%) men had low metastatic burden based on Docetaxel (75 mg/m every three weeks for six cycles) plus
CHAARTED criteria and 1664 (81%) had no pain. 8,15 EBRT ADT is an option for men with mCNPC/mCSPC with good
was given as one of two schedules: either 36 Gy in six con- performance status and high-volume metastatic disease,
secutive weekly fractions of 6 Gy, or 55 Gy in 20 daily frac- defined as: presence of visceral metastases, or four or more
tions of 2.75 Gy over four weeks. Subgroup analyses were bone lesions with at least one beyond the vertebral bodies
prespecified for baseline metastatic burden (low vs. high). and pelvis (Level 1, Strong recommendation).
Similar to the HORRAD trial, EBRT improved failure-free
survival (FFS) (HR 0.76; 95% CI 0.68–0.84; p<0.0001) but Docetaxel plus ADT may also be an option in patients
not OS (HR 0.92; 95% CI 0.80–1.06; p=0.266). Subgroup with mCNPC/mCSPC with good performance status with
analysis by metastatic burden showed FFS was improved in low-volume disease (Level 2, Weak recommendation).
both low and high metastatic burden (low metastatic burden
HR 0.59; 95% CI 0.49–0.72; p<0·0001and metastatic burden, “High risk” mCNPC/mCSPC patients (defined as at least
interaction p=0.002; high metastatic burden HR 0.88; 95% two of: Gleason score of 8–10, visceral metastases, and
CI 0·77–1.01; p=0·059). OS was improved in patients with three or more bone metastases) with good performance
low metastatic burden at baseline who were allocated EBRT status can also be considered for docetaxel chemotherapy
(HR 0.68; 95% CI 0.52–0.90; p=0.007), whereas in patients (Level 1, Strong recommendation).
with a high metastatic burden, there was no impact on OS
(HR 1.07; 95% CI 0.90–1.28; p=0.420). Docetaxel, a taxane derivative that binds to tubulin that
Although both trials showed negative impact of EBRT in inhibits mitosis and tumor proliferation, was the initial chemo-
unselected men in mCNPC, both HORRAD and STAMPEDE therapeutic agent that improved survival in men with mCRPC.
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reveal the benefits of local therapy in those with low-bur- Three different, large, randomized trials assessed the impact
den disease. A recent STOPCAP meta-analysis combining of introducing docetaxel in mCNPC/mCSPC: CHAARTED,
data from the trials confirm the benefits of EBRT in men STAMPEDE, and GETUG-AFU 15. 8,20,21 The CHAARTED
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with fewer than five bone metastases. This meta-analysis trial randomized 790 with mCNPC/mCSPC patients to ADT
showed that there was 7% improvement in three-year sur- plus docetaxel (75 mg/m every three weeks for six cycles) or
2
vival in men with fewer than four bone metastases. ADT alone. Within this trial, 35% (277 patients) had low-
8
volume metastases and 65% (513 patients) had high-volume
Radical prostatectomy in mCNPC should only be per- metastases (high-volume of metastases was defined by the
formed in a clinical trial setting (Expert opinion, Strong presence of visceral metastases or four or more bone lesions
recommendation). with at least one beyond the vertebral bodies and pelvis).
Overall, the median OS was 13.6 months longer with ADT
Currently, there is limited evidence showing the benefit plus docetaxel than with ADT alone (57.6 vs. 44.0 months; HR
of radical prostatectomy in mCNPC. However, the results 0.61; 95% CI 0.47–0.80; p<0.001). Subgroup analysis showed
from HORRAD and STAMPEDE imply that there may also that OS benefits of combination were maintained in the high-
be certain men with mCNPC that may benefit from surgical volume mCNPC/mCSPC (n=513; HR 0.63; 95% CI 0.50–0.79;
extirpation. There are many clinical trials currently assessing p<0.001), whereas survival benefits were lost in low-volume
this question, including TRoMBONE (Testing radical pros- disease (n=277; HR 1.04; 95% CI 0.70–1.55; p=0.86). 22
tatectomy in men with PC and oligometastases to the bone: The GETUG-AFU15 trial randomized 385 mCNPC/
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a randomized, controlled, feasibility trial), SWOG1802 mCSPC patients to receive ADT plus docetaxel or ADT
(Standard systemic therapy with or without definitive treat- alone. Although the dosage of docetaxel was the same as
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CUAJ • February 2020 • Volume 14, Issue 2 19