5.01.07 Lymph Nodes & Surgery, Prostate Cancer Metastasis, Prostate Cancer Surgery

Many surgeons won’t do a radical prostatectomy when they find there’s cancer in a man’s lymph nodes. They assume that surgery isn’t a viable choice because there’s no longer a chance that the operation can remove all of the prostate cancer. Radiation therapists have similar concerns. There was a period of time when I also agreed with this viewpoint. But a number of studies have changed my opinion.

In 1994, Zagars, et al. from MD Anderson Cancer Center published treatment results for a group of men with cancerous lymph nodes but no detectable cancer in their bone. The men received hormonal therapy rather than surgery or radiation. After ten years, most of the men had failed hormonal therapy. Investigators then took the important step of finding out where in the body hormone-resistance first appeared. In more than half the cases, hormone resistance appeared first in the prostate gland. In somewhat more than 40% of the cases, hormone resistance appeared in the bone and in less than 5% of cases in the lymph nodes. The implications of this study are very provocative: even after lymph node metastases developed, the cancer remaining in the prostate gland is still the biggest threat to the patient’s continued health.

So then what happens if we operate on men with lymph node involvement? The largest series of patients treated in this fashion are those from the Mayo Clinic under the care of Dr. Zincke. For more than 20 years, Dr. Zincke has treated such men with radical prostatectomy followed by hormonal therapy. And over the years, he’s written many papers detailing his results. Overall, his patients do extremely well. Since he treated a large number of patients, he can provide a great deal of detail on how the lymph node involvement affects his results. At one extreme, men with only one node have a 95% chance of being in remission at ten years. As the number of abnormal nodes and amount of cancer increases, the chance of being in remission drops to almost 50%. Other factors also alter success rates. If the cancer has a normal number of chromosomes (diploid), hormone resistance is quite uncommon regardless of the extent of lymph node spread. A cancer with an abnormal number of chromosomes (aneuploid) tends to do much worse.

One randomized controlled trial (published in 1999) tested Dr. Zincke’s approach. In this study, surgeons operated on all men with known lymph node metastases. Within three months after surgery, half of the men started hormonal therapy with Zoladex alone. After a median of seven years, close to 80% of men on combined treatment were in remission compared with 18% of those who’d only had surgery. And less than 10% of those on combined treatment died compared with more than 30% of those treated with surgery alone. This trial has been criticized because it was terminated early for the difficulty researchers had getting the ideal number of patients into the trial. I think this criticism misses the point: the differences were astoundingly positive for combined treatment and are consistent with the MD Anderson paper we mentioned in Vol 8 # 12. It represents a dramatic confirmation of Dr. Zincke’s claims. Furthermore, these results are consistent with laboratory studies of prostate cancer in animal models and make sense in terms of what we know about prostate cancer biology.

So, at this point, I think there’s a strong case for using radical prostatectomy to treat men with lymph node—but not bone—metastases if you follow surgery with adjuvant hormonal therapy. Of course, controversy remains about the best way to administer hormonal therapy. In particular, it may well be that intermittent hormonal therapy will prove to be both more effective at cancer control and less toxic to the patient.

To read more about Managing Lymph Node Metastases, click here to purchase Vol 9 # 01.