For patients with high-risk metastatic castration-sensitive prostate cancer who have completed upfront ADT + docetaxel, would you consider starting abiraterone or enzalutamide in addition to ADT while the disease is still castration-sensitive?

No. In patients with castration-sensitive disease on ADT who have completed six cycles of docetaxel as per the CHAARTED data (Sweeney et al. NEJM 2015), there is no good evidence that adding abiraterone after docetaxel while still castration-sensitive is warranted. Abiraterone has potential harm and we don’t have data to know if it would improve outcomes further in this setting. Thus, at this time, with no known benefit and the potential for harm, I do not recommend this be done. Perhaps future studies will help answer this question with data.

Presently there is no data to support the practice of potent AR blockade with docetaxel/ADT in men with mHSPC. Ongoing studies will address this, including ENZAMET, ARCHES, and PEACE1, and STAMPEDE is testing the addition of a range of novel therapies to ADT/abiraterone or ADT/docetaxel including metformin, estradiol, rucaparib for men with HRD mutations, radiation to the primary, and enzalutamide plus abiraterone. At this time, all we can say is that abiraterone for men with mHSPC who have completed docetaxel increases the costs and toxicities and limits available options down the road. However, there may be benefit to two life-prolonging agents simultaneously or sequentially in men with mHSPC which is why clinical trials are being done.

Separate studies have investigated the role of upfront docetaxel, and abiraterone plus prednisone in addition to standard androgen deprivation therapy (ADT) in the new hormone sensitive metastatic prostate cancer (mHSPC) setting, and have shown improved survival outcomes with these interventions. Given these data, each of these interventions can be considered standard of care of these patients.

However, there has NOT been a study establishing the role of upfront docetaxel followed by abiraterone plus prednisone in addition to ADT in this population. Although, this strategy seems appealing, we need to keep treatment related toxicities and cost in mind. Given lack of evidence for this approach, I would NOT recommend upfront docetaxel, followe...

I don't use abiraterone or other next-generation hormonal therapies (NHTs) immediately following docetaxel in HSPC and acknowledge that enzalutamide did not benefit the subset of patients in ENZAMET with HSPC who received docetaxel. However, I have considered adding a next-generation hormonal therapy after docetaxel x6 has been completed in patients with particularly high-risk HSPC disease (symptomatic high volume, Grade Group 5, and/or PSA > 0.2 after 6 months of Rx (esp those with PSA > 4) (Hussain et al., PMID 16921051). I acknowledge there are no data that this approach is superior to adding an NHT at the time of progression (and there are trials for patients starting an NHT for newly castration-resistant PC).

While I completely agree that data are lacking to support ADT+docetaxel+abiraterone in high risk mPC, the question was “ would you consider”. Given benefits of ADT+docetaxel and ADT+abiraterone it is hard (in my view) NOT to “consider“ ADT+docetaxel+abiraterone. No doubt the trial must be done...and extrapolations from existing data are extremely risky...mHSPC is also lethal. Risk of long term irreversible toxicity is likely very small (I recognize I said “likely”).

For an otherwise healthy young informed patient with mHRPC I do consider and discuss ...and have used....ADT+docetaxel+abiraterone

The possibility is certainly interesting, but I must agree with my esteemed colleague, @Dr. First Last. In the absence of information on safety and efficacy, AND with considering the potential costs of care (both for drug and accompanying supportive care), it would not be appropriate to recommend this form of therapy as a standard approach. What is most interesting about the docetaxel and the abiraterone studies is the similarity in the OS benefit. It would not be, however, easy to assume that the effects are additive.