Basel, Switzerland (UroToday.com) Dr. Clarke gave a summary talk on the topic of optimization of the treatment of newly diagnosed metastatic prostate cancer.
The discussion began on the STAMPEDE biomedical imaging group (BIG) and STAMPEDE biomedical research group (BRG) which have incorporated 5,000 CT and bone scans with a target of more than 10,000. The scans are linked to outcome and pathology and annotated for metastasis type, location, and size. One of the reasons for collecting this data is because the bone scan has been shown to be predictive of response to radiotherapy to the primary site when the bone metastasis number is 4 or less. Therefore, at low-volume disease burden, there appears to be a volume threshold effect whereby treatment of the primary with radiotherapy is beneficial.
Next, Dr. Clarke moved on to discuss the various disease volume/risk definitions (Table 1). Unfortunately, none are validated, but all of them agree that non-regional lymph node disease is regarded as low volume disease while visceral disease is regarded as high-volume disease. When assessing the LATITUDE study, examining the role of abiraterone + prednisone + androgen deprivation therapy (ADT) in hormone-sensitive metastatic prostate cancer (mHSPC) patients compared to ADT alone, there was a clear overall survival benefit for the abiraterone treated patients1. However, when stratifying by disease volume, the benefit was significantly more substantial for the high-volume disease. In the CHAARTED study the docetaxel benefit for high-volume disease was substantially higher than for low-volume disease in patients who presented with de novo metastatic disease. This difference was not apparent in patients with prior local therapy.
In an abstract that will be presented at the ESMO 2019 meeting (#8440), the effect of docetaxel in hormone-sensitive metastatic prostate cancer (mHSPC) in the STAMPEDE trial will be assessed, including a subgroup analysis by metastatic burden. The cohort selection for this study is shown in Figure 1. The results showed that there was no benefit for docetaxel in overall survival for low-burden metastatic disease. Therefore, there is no dichotomized volume/burden related effect relating to docetaxel.
Dr. Clarke concluded his brief talk with two important conclusions:
- At low disease burden, there is a volume threshold effect whereby treatment of the primary tumor with radiotherapy is beneficial. This threshold is predicted by the conventional bone scan.
- Prostate cancer patients presenting with de novo mHSPC should all be considered for combined systemic treatment with docetaxel or novel ADT combined with standard of care ADT.
Table 1 – The various disease volume definitions used
Figure 1 – Cohort selection for abstract 8440 at ESMO 2019 assessing the effect of docetaxel in mHSPC patients in the STAMPEDE trial
Presented by: Noel William Clarke, MD, Consultant Urologist at Salford Royal Hospital and The Christie, Manchester, UK
Written by: Hanan Goldberg, MD, Urology Department, SUNY Upstate Medical University, Syracuse, New York, USA, Twitter: @GoldbergHanan at the 2019 Advanced Prostate Cancer Consensus Conference (APCCC) #APCCC19, Aug 29 – 31, 2019 in Basel, Switzerland
1. Fizazi, Karim, NamPhuong Tran, Luis Fein, Nobuaki Matsubara, Alfredo Rodriguez-Antolin, Boris Y. Alekseev, Mustafa Özgüroğlu et al. “Abiraterone plus prednisone in metastatic, castration-sensitive prostate cancer.” New England Journal of Medicine 377, no. 4 (2017): 352-360.