Positive Margins After Surgery for Prostate Cancer

The anatomical location of the prostate gland, situated within millimeters of the bladder and rectum, means that urologists are simply unable to cut a wide margin around the gland. Slicing into the bladder or rectum is not an option. Unfortunately, if a patient’s cancer grows through the capsule, rather than cutting around the cancer, the surgeon will be forced to cut through the cancer during the attempt to remove the gland. When this occurs, it is called a “positive margin.”

Leaving cancer behind is certainly a dismal failure. After all, if the cancer can’t be completely removed, why do the operation? The reality is that, prior to the operation, there is always uncertainty about the extent of the cancer. During the operation, microscopic disease that is outside the prostate is invisible to the naked eye. Remember, the art of surgical prostate removal was developed in a previous era, when all cancers were perceived as life-threatening and surgery was the only option available. Back then, radiation technology was decidedly inferior. Cure rates were much lower with radiation, and toxic side effects were worse.

Modern imaging with 3T multiparametric MRI performed prior to surgery, while not perfect, has the potential to greatly enhance surgical planning. Unfortunately, only a minority of the 70,000 men undergoing surgery every year benefit by having a scan for surgical planning prior to doing an operation. Hopefully, this policy will change.

Due to the anatomical circumstances outlined above, cancer, on average, is left behind in the patient’s body anywhere from 10% to 50% of the time. A positive margin may first come to a patient’s attention a few days after the operation. After removal, the prostate is analyzed in the laboratory by a specialized physician called a pathologist. The prostate is prepared for microscopic evaluation first by dropping it into a bottle of ink so that the whole outer layer of the gland is covered. Then the gland is sliced horizontally into thin areas, with special attention be paid to the area of the gland where the cancer is located. If the tumor is observed “butting up” against an inked area, that means the surgeon’s scalpel cut through tumor during the operation, leaving tumor behind in the patient’s body.

The presence of a positive margin can be more or less serious depending on the Gleason score and the extent of the margins. Recent data from France suggest that the risk of future cancer relapse in men who had prostatectomies with positive margins depends on the extent of the margins, with recurrence ranging from approximately 12% for less than 3 mm margins to 54% for larger than 3 mm margins. However, when the Gleason score is higher, or if the positive margins are extensive, the risk of future relapse may approach 100%.

Further Treatment When Margins Are Positive

Deciding on further treatment after surgery when margins are positive can be challenging. One option is to simply observe the situation while monitoring PSA levels closely. This approach is more attractive when the Gleason score is lower and less extensive positive margins are present. Men who remain in remission can avoid the treatment-related side effects from radiation altogether. In this era of rapidly advancing technology, men who undergo delayed treatment for a rising PSA years down the road may also "grandfather" into an era of improved therapy that is less toxic and more effective.

For men who decide to pursue observation, PSA monitoring should be performed with ultrasensitive technology. Then, if the PSA rises, treatment can be initiated at a very early stage, when the PSA is still less than 0.1. Cure rates are best when treatment is started at a lower level of PSA.

When surgical margins are positive, several studies show that immediate radiation to the prostate fossa will lower relapse rates and may slightly improve 10-year survival rates. However, since only 50% of men will relapse, waiting for evidence of a PSA rise before starting radiation may be a reasonable alternative. Generally, the monitoring process consists of checking PSA every 3 months. Radiation is initiated if the PSA rises above 0.2.

Radiation is the most common treatment for management of a local relapse after surgery. While radiation is often effective, the possibility of microscopic metastases outside the prostate fossa in another area of the body needs to be considered. Radiation to the fossa alone will not be curative if the disease has spread. Unfortunately, a final determination about the presence or absence of microscopic metastasis can never certain. No current technology consistently detects microscopic disease with 100% accuracy.

Experienced professionals have learned through experience that microscopic metastases are more likely to be present when the Gleason score is high and when the positive surgical margins are more extensive. In these situations, the radiation field should probably be expanded to cover the lymph nodes. Hormone therapy with Lupron is also commonly recommended.

Multiple Positive Margins

Monitoring prostate cancer without immediate treatment is not appropriate for men who have multiple positive margins. Multiple margins usually mean that the original cancer was large and high grade. A monitoring program in this situation is inappropriate because aggressive cancers will almost always recur at some point. Delaying treatment simply allows more time for the cancer to grow and spread.

Men with multiple positive margins after surgery should be managed with a multimodality treatment approach that includes radiation, hormone therapy, and possibly even chemotherapy. Basically, it’s time to make an aggressive, final effort to cure the disease. There is substantial variation among experts as to the exact protocol to be recommended. However, in general, treatment programs tend to mimic the way that high-risk, newly diagnosed disease is managed (see below). Investigational programs are also looking into the addition of more powerful hormonal agents, such as Xtandi or Zytiga, or the addition of four to six cycles of chemotherapy with Taxotere to see if cure rates can be further improved.

It is a good idea to wait a few months after the operation before starting treatment. This provides some healing time, and hopefully will allow for the restoration of urinary control before starting treatment. Further delay, in the hope that erectile function will resume—a process that may require up to two years—is usually not prudent. Assuming there have been no unanticipated complications, hormone therapy with Lupron and Casodex is initiated and continued for 12-18 months. (Hormone therapy is associated with a number of potential side effects, some of which can be diminished with medications, diet, and exercise.) A consultation with an experienced radiation therapist, one who has experience with treating the pelvic lymph nodes, should also be obtained.

The usual advice for men with multiple positive margins is to start radiation therapy that is directed at the prostate fossa and the pelvic lymph nodes. The pelvic nodes are the first jumping-off point for the cancer if it is going to spread. The radiation starts about 60 days after the initiation of the Lupron and Casodex.

After the completion of radiation and hormone therapy, ongoing surveillance is necessary. Testosterone and PSA levels are monitored every three months for two years, then every six months for the next three years. Testosterone monitoring can stop once normal levels return. All men who have had radiation, even those who have been cured, will need lifelong annual monitoring due to the risk of radiation-induced secondary tumors of the bladder or rectum. While these types of tumors are rare, early detection leads to less-toxic, more effective therapy.