Ann. Oncol.
Addition of docetaxel to hormonal therapy in low- and high-burden metastatic hormone sensitive prostate cancer: long-term survival results from the STAMPEDE trial.
Abstract
Background
STAMPEDE has previously reported that the use of upfront docetaxel improved overall survival (OS) for metastatic hormone naïve prostate cancer patients starting long-term androgen deprivation therapy. We report on long-term outcomes stratified by metastatic burden for M1 patients.
Methods
We randomly allocated patients in 2 : 1 ratio to standard-of-care (SOC; control group) or SOC + docetaxel. Metastatic disease burden was categorised using retrospectively-collected baseline staging scans where available. Analysis used Cox regression models, adjusted for stratification factors, with emphasis on restricted mean survival time where hazards were non-proportional.
Results
Between 05 October 2005 and 31 March 2013, 1086 M1 patients were randomised to receive SOC (n = 724) or SOC + docetaxel (n = 362). Metastatic burden was assessable for 830/1086 (76%) patients; 362 (44%) had low and 468 (56%) high metastatic burden. Median follow-up was 78.2 months. There were 494 deaths on SOC (41% more than the previous report). There was good evidence of benefit of docetaxel over SOC on OS (HR = 0.81, 95% CI 0.69-0.95, P = 0.009) with no evidence of heterogeneity of docetaxel effect between metastatic burden sub-groups (interaction P = 0.827). Analysis of other outcomes found evidence of benefit for docetaxel over SOC in failure-free survival (HR = 0.66, 95% CI 0.57-0.76, P < 0.001) and progression-free survival (HR = 0.69, 95% CI 0.59-0.81, P < 0.001) with no evidence of heterogeneity of docetaxel effect between metastatic burden sub-groups (interaction P > 0.5 in each case). There was no evidence that docetaxel resulted in late toxicity compared with SOC: after 1 year, G3-5 toxicity was reported for 28% SOC and 27% docetaxel (in patients still on follow-up at 1 year without prior progression).
Conclusions
The clinically significant benefit in survival for upfront docetaxel persists at longer follow-up, with no evidence that benefit differed by metastatic burden. We advocate that upfront docetaxel is considered for metastatic hormone naïve prostate cancer patients regardless of metastatic burden.
Related Questions
Are there any clinical scenarios where you would recommend adjuvant docetaxel for localized prostate cancer?
This is quite a controversial topic and good for a tumor board discussion! The RTOG 0521 trial is the only trial to demonstrate a potential survival benefit with docetaxel in the adjuvant setting following radiation and in the setting of long term ADT. The absolute difference in OS at 4 years was 4%...
What duration of ADT do you recommend for a patient with locally treated prostate cancer who undergoes metastasis-directed radiation therapy to a single oligometastatic bone lesion?
While I agree with @Dr. First Last that very small studies like STOMP and ORIOLE suggest that a small subset of men can delay the need for ADT by 1-3 years, this is not level 1 evidence. Most men with oligometastatic HSPC will still progress with metastasis directed therapy alone over a short time h...
How would you manage a patient with localized prostate cancer treated with radical prostatectomy and found to have a single involved pelvic lymph node on final pathology and a detectable postoperative PSA?
This patient is now in the salvage setting with PSA recurrence after RP and with PSA persistence and node-positive disease. This is a grey area of medicine without level 1 evidence from RCTs but there are some sources of data to help guide optimal outcomes. This patient is at high risk for further m...
Would you consider applying the principles of STAMPEDE with <5 oligometastatic non-regional lymph nodes from prostate cancer?
About 25% in STAMPEDE had low volume metastatic disease with no bone Mets, with most having a non-regional node in that category to qualify as low volume Mets.That being said, common iliac could be the primary drainage of prostate cancer based on SNLN studies and I would favor treating like node-pos...
If a patient with low metastatic burden has bulky retroperitoneal adenopathy without osseous metastasis, would you recommend prostatic radiation?
We could debate whether "bulky" retroperitoneal adenopathy is a truly low volume metastatic disease, but technically it would fit the definition used in the STAMPEDE Trial. In addition, patients presenting with nodal metastatic disease may have a more indolent course than those presenting de novo wi...
How do you decide between abiraterone or docetaxel for first line treatment of newly diagnosed metastatic prostate cancer?
Abiraterone (LATITUDE and STAMPEDE trials) and docetaxel (CHAARTED and STAMPEDE trials) both have level 1 evidence supporting their use in men with metastatic hormone-sensitive prostate cancer. However, a pre-planned subset analysis from the CHAARTED study demonstrated that docetaxel only appeared t...