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The STAMPEDE trial promises to change how and when chemotherapy is administered for high-risk patients with prostate cancer. However, there are still questions regarding patient selection for docetaxel and whether the treatment can be reintroduction later in the disease course.
To explore this topic further, Daniel P. Petrylak, MD, provides an example focused on a 55-year-old male who had a radical prostatectomy and an initial prostate-specific antigen (PSA) level of 4. The patient had very high risk pathology, a Gleason score of 9, extracapsular extension, and his PSA never normalized after surgery.
This is an example of a patient with poor prognosis, says Petrylak. Based on the STAMPEDE data that are emerging, there should be a discussion with this patient about delaying progression and potentially improving survival with early chemotherapy. Although this approach may not become a standard of care, physicians owe it their patients to have this discussion, particularly with younger patients, where there may be the possibility of improved survival, stresses Petrylak.
While surgery is not ideal for grossly positive nodal disease (N2, N3 disease), explains Christopher P. Evans, MD, FACS, the subset analyses from the TAX trial and other studies suggest that local control (eg, prostatectomy) may provide a true benefit, even in the face of metastatic disease. Surgery can potentially help patients avoid later complications, such as colostomy and incontinence, adds Petrylak.
Many questions remain about subsequent treatment approaches in patients with hormone-sensitive disease who are treated with docetaxel and then progress to mCRPC, explains Celestia S. Higano, MD, FACP. As a general rule, if a patient was responsive to docetaxel earlier, she will retreat with docetaxel at a later point, even years later.
It is unclear whether patients will respond to docetaxel once it is reintroduced, explains Petrylak. For the most part; however, if there was a response to docetaxel initially, it is likely that there will be a response again, as the tumor will probably still be just as sensitive. However, the upfront synergy of androgen deprivation and docetaxel is going to be different mechanistically than when reintroduced in a castrate-resistant tumor with much lower levels of testosterone, warns Evans.
Side effects should also be considered. If docetaxel is readministered, the patient will likely see a worsening of neuropathy, if this side effect was also experienced initially, the panelists concur. Between treatments of docetaxel, the neuropathy may improve but not completely resolve, explains Higano. Once docetaxel has been restarted, neuropathy will again be a problem. Neuropathy with cabazitaxel is not as bad as it is with docetaxel, states Petrylak; thus, in this situation, cabazitaxel maybe the better choice when considering the reintroduction of chemotherapy.