Prostate cancer spans a spectrum like all cancers, ranging from localized disease to metastatic disease. As with breast cancer, prostate cancer is exquisitely sensitive to hormonal manipulation, and from a practical point of view is divided into hormone-naïve versus castrate-resistant disease.
Recurrent Prostate Cancer Post-localized Disease
Recurrent post-localized prostate cancer is usually manifested by a climbing serum prostate-specific antigen (PSA) after therapy for localized disease. Typically, I stage patients with a CT scan and bone imaging, either with a bone scan or a F18 PET scan. When PSA doubling time (PSA DT) becomes less than six months, androgen-deprivation therapy (ADT) is initiated.
In general, if scans show no metastases, I start patients on LHRH analogs such as leuprolide or gosserlin. There are LHRH antagonists commercially available that can be used as well. I tend to offer patients intermittent ADT as long as patients appear to be reliable and motivated for follow-ups.
I do not use a specific PSA level to reinitiate therapy but rather look at the rate at which the PSA rises. Every time it takes a sharp rise, I tend to reimage, and do not do scans on a set schedule.
Metastatic Prostate Cancer
Due to the current controversies about PSA screening, we are seeing more patients with newly diagnosed metastatic prostate cancer now than five years ago. Based on the CHARTERED trial, which showed a significant survival advantage to the use of chemotherapy along with ADT, I do offer docetaxel x 6 cycles in addition to ADT for these patients with bone or visceral metastases.
For patients with recurrent prostate cancer following localized disease, I start them on ADT. I offer intermittent ADT even in patients with metastatic disease after having a discussion with patients regarding their goals and tolerability to ADT.
Ultimately, castrate resistance—defined as a rising serum PSA despite low testosterone—develops in almost all patients starting ADT. I will reimage them to set a new baseline, and if the patient remains non-metastatic, I would use drugs such as bicalutamide first.
In general responses are variable, and if serum PSA rises, I will initiate anti-androgen withdrawal and then reimage again. If patients are non-metastatic, I would pursue older drugs such as nilutamide or even ketoconazole/hydrocortisone—surveillance alone may also be appropriate in certain cases.
Metastatic Castrate-Resistant Prostate Cancer
Management of patients with metastatic castrate-resistant prostate cancer has become challenging, as there are several FDA-approved drugs for this group of patients. These include sipuleucel-T, abiraterone, enzlautamide, radium 223, as well as chemotherapy. I use Provenge or sipuleucel-T when patients have slow-rising PSA with long PSA DT and when they are asymptomatic and not too concerned about PSA values.
I use enzalutamide if patients have issues with diabetes or poorly controlled hypertension and abiraterone with prednisone if they have pain and would benefit from the prednisone use. Typically I do not use these drugs back to back, as there is a very low chance of response.
After failure of either enzalutamide or abiraterone, I re-scan. If patients have bone-only disease, I would recommend alpharadin (radium-223, Xofigo) for six cycles. If patients have bulky nodal disease or visceral disease, I would recommend chemotherapy with docetaxel.
I typically stop chemotherapy after six to eight cycles and give patients a chemotherapy holiday. I will treat with additional hormonal agents such as abiraterone or enzalutamide if patients have never received that drug. For patients progressing after this, I will re-treat with docetaxel if it has been more than a year since the last treatment; otherwise I recommend cabazitaxel.
While mitoxantrone is an old drug, I still use it in patients who have progressed on taxanes or those who have had an allergic reaction to taxanes.
Bone health is a vital part of the care of patients with prostate cancer. I use bone-modifying drugs in patients with castrate metastatic prostate cancer but not in those with newly diagnosed bone metastases. A randomized trial from CALGB did not support the use of zoledronic acid in newly diagnosed metastatic prostate cancer patients. I will use zoledronic acid or denosumab every three months along with a GNRH analog, which I continue as well.
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