JAMA Oncol 2021 Feb 18
Association of Bone Metastatic Burden With Survival Benefit From Prostate Radiotherapy in Patients With Newly Diagnosed Metastatic Prostate Cancer: A Secondary Analysis of a Randomized Clinical Trial.
Abstract
Importance
Prostate radiotherapy (RT) improves survival in men with low-burden metastatic prostate cancer. However, owing to the dichotomized nature of metastatic burden criteria, it is not clear how this benefit varies with bone metastasis counts and metastatic site.
Objective
To evaluate the association of bone metastasis count and location with survival benefit from prostate RT.
Design, setting, and participants
This exploratory analysis of treatment outcomes based on metastatic site and extent as determined by conventional imaging (computed tomography/magnetic resonance imaging and bone scan) evaluated patients with newly diagnosed metastatic prostate cancer randomized within the STAMPEDE trial's metastasis M1 RT comparison. The association of baseline bone metastasis counts with overall survival (OS) and failure-free survival (FFS) was assessed using a multivariable fractional polynomial interaction procedure. Further analysis was conducted in subgroups.
Interventions
Patients were randomized to receive either standard of care (androgen deprivation therapy with or without docetaxel) or standard of care and prostate RT.
Main outcomes and measures
The primary outcomes were OS and FFS.
Results
A total of 1939 of 2061 men were included (median [interquartile range] age, 68 [63-73] years); 1732 (89%) had bone metastases. Bone metastasis counts were associated with OS and FFS benefit from prostate RT. Survival benefit decreased continuously as the number of bone metastases increased, with benefit most pronounced up to 3 bone metastases. A plot of estimated treatment effect indicated that the upper 95% CI crossed the line of equivalence (hazard ratio [HR], 1) above 3 bone metastases without a detectable change point. Further analysis based on subgroups showed that the magnitude of benefit from the addition of prostate RT was greater in patients with low metastatic burden with only nonregional lymph nodes (M1a) or 3 or fewer bone metastases without visceral metastasis (HR for OS, 0.62; 95% CI, 0.46-0.83; HR for FFS, 0.57; 95% CI, 0.47-0.70) than among patients with 4 or more bone metastases or any visceral/other metastasis (HR for OS, 1.08; 95% CI, 0.91-1.28; interaction P = .003; HR for FFS, 0.87; 95% CI, 0.76-0.99; interaction P = .002).
Conclusions and relevance
In this exploratory analysis of a randomized clinical trial, bone metastasis count and metastasis location based on conventional imaging were associated with OS and FFS benefit from prostate RT in M1 disease.
Trial registration
ClinicalTrials.gov Identifier: NCT00268476; ISRCTN.com Identifier: ISRCTN78818544.
Related Questions
How would you treat a newly diagnosed hormone sensitive high risk prostate cancer with one small lung metastasis and no other evidence of metastatic disease per PSMA PET?
I think there is no solid answer to this. De-novo visceral metastases are very rare in mHSPC, and lung-only oligometastases on PSMA-PET are even more rare. Since lung metastases is expected to be visible on CT, this is undeniably a high-volume disease based on the CHAARTED criteria. Patients with vi...
In what situations would a standard FDG PET/CT be useful in the evaluation of high risk prostate cancer?
Overall, my impression is that the use of FDG PET for this purpose is limited. If interested, below is my rationale as summarized in the Conclusion.As mentioned, PSMA PET/CT is considered by many to be the current best standard of care for the staging evaluation of high-risk prostate cancer, and it ...
How do you approach a prostate cancer patient with oligomet disease on PSMA PET?
I think there is a spectrum of 'PSMA-PET Avid lesion suspicious for metastasis'. In some locations, such as ribs, I worry more about false positives. For lesions with PET avidity without CT correlate, I worry about false positives and may advocate for a biopsy if it will change the treatment plan. S...
How would you work up a patient with prostate cancer with bone scan suspicious for metastatic disease and a negative PSMA PET/CT?
While some bone metastases are 99mTc-positive and PSMA-negative, this circumstance is quite rare (< 2%). Based on this alone, in cases like this, I typically conclude that the patient is clinically M0. However, I do consider 3 other factors: the prevalence of bone metastases within the patient’s par...
Is there evidence that radiotherapy to less than all sites of oligometastatic prostate cancer is beneficial?
The ORIOLE trial referenced above helps to answer this question. Within the SBRT arm (n=36), patients received PSMA PET, however, the treating rad oncs were blinded to the result and patients were "consolidated" based on conventional imaging. Treatment plans were then reviewed and compared to PSMA, ...
Would you treat the prostate in a case of oligometastatic disease with well-controlled UC?
Yes, I would with a clear discussion of risks and benefits. While there is not extensive data, the retrospective literature and my personal experience are that men with well controlled inflammatory bowel disease are at little additional risk. Some studies show an increased acute toxicity risk and ot...
For persistent PSA elevation after prostatectomy, would you recommend salvage radiation if pathologically negative nodes, but regional and non-regional lymphadenopathy on PSMA PET?
While based on classical staging methods, it appears that he would fulfill the criteria for salvage RT with a persistent PSA, it sounds like this patient has M1a disease by advanced imaging (possibly at presentation). I think that it is very unlikely that he would gain any meaningful benefit from ad...
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...