William Oh, MD: The Role of Chemotherapy and Local Therapy

Is chemotherapy appropriate in this patient? What about local therapy?

Chemotherapy has been shown, based on the CHAARTED and STAMPEDE Trials, to be associated with a very significant survival benefit. In fact, the hazard ratios suggested at least a 30% to 40% improvement in overall survival with the addition of docetaxel chemotherapy within the first 4 months of starting androgen deprivation therapy in newly-diagnosed metastatic, hormone-sensitive prostate cancer.

This is a paradigm shift in this disease. We used to only use ADT in these patients, and, of course, patients would typically progress after a year or two on average. Now we’re seeing with these two trials that in fact their survival can be extended by as much as 14 to 20 months, which is really profoundly longer. This has changed the way we treat hormone-sensitive metastatic prostate cancer in my practice, and I think it’s really changed the international standard of care. In other words, patients who present, like this case, with newly-diagnosed metastatic prostate cancer should not just receive androgen deprivation therapy (ADT), but they should be offered docetaxel chemotherapy. Six cycles of docetaxel are typically given without prednisone, which is different from the way this drug is used in CRPC, and of course you have to discuss the pros and cons with this patient who’s a very appropriate candidate for that approach.

One of the considerations with a patient with metastatic disease is, should you consider local therapy? Local therapy of course means surgery or radiation therapy. In fact, we have historically not done such a thing because most of the patients in the past were considered to have metastatic disease, and what’s the point of taking out the prostate or radiating the prostate?

I think our thinking on this is evolving. There’s increasing amounts of evidence, although no randomized data, that suggest that treating the primary site is associated with additional benefit. Historically, we would normally do radiation, for example, if the patient had bleeding or excessive pain or obstruction, for example, urinary obstruction. But in truth, the last few years we’ve been thinking maybe we need to take care of the primary site. Maybe the primary site is a source for continued metastasis, and by radiating, or even, in some very functional patients, removing the prostate, we might improve survival.

CASE: Metastatic Prostate Cancer (Part 2)

Mathew J is a 61 year old African American male who presented to his primary care physician with lower urinary tract symptoms, including sporadic hematuria. He complains of abdominal pain and low back pain starting four months ago and increasing in frequency. Prior medical history includes non-insulin dependent diabetes mellitus, well-controlled on metformin since 2006. The patient was referred to urology for further evaluation. ng/ml.

During his most recent follow-up exam, the patient complained of intermittent back pain and increasing fatigue.

• Digital rectum exam revealed nodular prostate /L
• Serum PSA level; 129 ng/ml
• Alkaline phosphatase, 258
• TRUS/prostate biopsy: 53 gram prostate, 12/12 cores (+), Gleason 4 + 5
• CT indicates blastic lesions to lumbar spine and pelvis
• Bone Scan positive for T/L spine, pelvis, right femur, scapula
• ECOG performance status, 1