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Brachy boost therapy and surgery extend survival about the same in high risk patients, but brachy boost does more
Posted: 08 Mar 2018 09:04 AM PST
Two retrospective studies were published in the last week, and they had some similar findings, but some dissimilar things to say about which treatment is best for high risk prostate cancer. The three therapies they looked at were the combination of brachytherapy and external beam radiation (brachy boost therapy - BBT), external beam therapy alone (EBRT), and surgery (RP).
Kishan et al. reported on 1,809 men with Gleason score of 9 or 10 who were treated between 2000 and 2013 at 12 tertiary cancer care institutions (UCLA, Los Angeles VA, California Endocurie Therapy Center, Fox Chase, Mt. Sinai, Cleveland Clinic, Wheeling Jesuit University, University of Michigan, Johns Hopkins, Oslo University, William Beaumont Hospital, and Dana-Farber).
Patient characteristics:
- 639 were treated with radical prostatectomy (RP).
- 734 were treated with EBRT only.
- 436 were treated with BBT (BT was either low dose rate in 62% or high dose rate in 38%).
- All patients were Gleason 9 or 10 on biopsy.
- Pelvic LN involvement was discovered in 17% of RP patients ; 40% had positive surgical margins.
- RP patients were younger (61 years of age) compared to EBRT or BBT patients (68 years of age)
- RP patients were lower stage ( 87% clinical stage T1/T2) compared to EBRT (70% clinical stage T1/T2 ) or BBT patients (79% clinical stage T1/T2)
- RP patients had lower pre-therapy PSA (7 ng/ml) compared to EBRT or BBT patients (10 ng/ml)
- RP patients had lower percentage of Gleason score 10 (4%) compared to EBRT (6%) or BBT patients (9%)
Treatment specs
- Among the RP patients, 43% had adjuvant or salvage radiation therapy (68 Gy).
- Among radiation patients, about 90% had adjuvant ADT
- Median dose of EBRT was 74 Gy.
- adjuvant ADT continued for 22 months, median.
- Median equivalent dose of EBRT+BT was 92 Gy
- adjuvant ADT continued for 12 months.
Oncological outcomes
After a median follow-up of 4.2, 5.1 and 6.3 years for RP, EBRT, and BBT, respectively, the oncological outcomes (adjusted for age and disease characteristics) were as follows:
- The 10-year rates of distant metastases were
- 46% for RP
- 44% for EBRT
- 13% for BBT
- Differences between BBT and the two others were statistically significant.
- The 10-year rates of prostate cancer-specific mortality (PCSM) were
- 23% for RP
- 26% for EBRT
- 13% for EBRT + BT
- Differences between BBT and the two others were statistically significant.
- The 10-year rates of all-cause mortality (ACM) were
- 32% for RP
- 39% for EBRT
- 31% for BBT
- None of the differences were statistically significant.
- There was a difference at 7.5 years in favor of BBT that vanished by 10 years.
In additional analyses, the authors looked at outcomes by duration of androgen deprivation for those receiving any kind of radiation. They found that ADT duration made no significant difference in detected metastases or PCSM within EBRT or BBT, and did not account for the difference between them. They also looked at radiation doses. EBRT patients who received <70 Gy had PCSM significantly worse than those who received ≥ 78 Gy. The rates of metastases did not differ. Notably, very few (11%) of the EBRT patients had both ≥ 78 Gy and ≥2 years of ADT, a combination that is now considered standard of care. Those that did had superior outcomes compared to RP. The use of LDR-BT or HDR-BT as part of BBT made no difference.
The authors conclude:
Among patients with Gleason score 9-10 prostate cancer, treatment with EBRT+BT with androgen deprivation therapy was associated with significantly better prostate cancer–specific mortality and longer time to distant metastasis compared with EBRT with androgen deprivation therapy or with RP.
In an analysis of the National Cancer Database, Ennis et al. reported on the overall survival of patients who were treated with RP, EBRT, and BBT for high-risk PC from 2004 to 2013. The database covers about 70% of all new prostate cancer patients treated in the US. The patient profile was:
- 24,688 patients treated with RP, at least at first
- 15,435 patients treated with EBRT
- 2,642 patients treated with BBT.
- All EBRT patients also had adjuvant ADT
- BBT patients may or may not have had ADT
- All were high risk by the NCCN definition: Either Gleason score 8-10, stage T3/4, or PSA≥20 ng/ml
- RP patients were younger (62 years of age) compared to EBRT (70 years of age) or BBT patients (67 years of age)
- RP patients were lower stage ( 89% clinical stage T1/T2) compared to EBRT (84% clinical stage T1/T2 ) or BBT patients (85% clinical stage T1/T2)
- RP patients had lower pre-therapy mean PSA (19 ng/ml) compared to EBRT (23 ng/ml) but the same as BBT patients (19 ng/ml)
- RP patients had lower percentage of Gleason score 8-10 (70%) compared to EBRT (78%) or BBT patients (73%)
- Comorbidities were similar among groups.
- The above risk factors as well as socioeconomic factors and year of diagnosis were used to adjust the raw data.
- It is unknown what percent of RP patients had adjuvant or salvage radiation.
- There was no data available on post-reatment metastases or prostate cancer-specific survival
Because surgery is sometimes aborted when pelvic LN cancer is discovered, they estimated the probability that patients had positive nodes, and included it as a risk factor. This would seem to double count those risk factors, but the authors say it had little effect. Based on their model, they estimated that the percent who had positive nodes was 10% of RP patients, 34% of EBRT patients, and 23% of BBT patients.
After a median follow-up of 36 months, the relative oncological outcomes (adjusted for age and other patient and disease characteristics), expressed as hazard ratios were as follows:
- RP: 1.0
- EBRT: 1.53 (i.e., 53% worse survival vs. RP)
- EBRT with < 79.2 Gy: 1.68
- EBRT with ≥79.2 Gy: 1.33
- BBT: 1.17 (not significantly different from RP)
- not different if ADT included
- no interaction between comorbidities and treatment effects
The authors conclude:
This analysis showed no statistical difference in survival between patients treated with RP versus EBRT plus brachytherapy with or without AD. EBRT plus AD was associated with lower survival.
- with thanks to Amar Kishan for allowing me to see the full text.
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