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In my last post, I discussed lymph node dissection for men undergoing prostatectomy.  Specifically, I focused on who does and does not need a lymph node dissection based on the risk of lymph node involvement by prostate cancer.  But what happens when prostate cancer is actually identified in the lymph nodes?  In the past, managing men with lymph node positive prostate cancer was not very complicated.  Most men were monitored until symptomatic spread of the cancer was noted.  After symptoms of metastatic disease emerged, palliative therapy with hormones was initiated.  The prognosis was always poor.  Today, however, the situation is quite different.  First, the prognosis is not the same for all men with lymph node positive disease but, rather, varies with the extent of lymph node involvement.  Also, therapy is usually initiated very soon after lymph node disease is diagnosed.  Finally, different treatment modalities are being implemented beyond just hormonal therapy.   In this post, I will describe these new approaches to treating men with prostate cancer in the lymph nodes.

When I was training to be an urologist, all men with prostate cancer found in the lymph nodes were lumped into one category.  These men were generally given a relatively poor prognosis with a 10 year survival rate ranging from 50-80% depending on whether or not they received hormonal therapy.  Recently, however, studies have demonstrated that not all lymph node disease is the same.  Men with greater than 2 lymph nodes involved by prostate cancer, for example, have been shown to have more than twice the likelihood of dying from prostate cancer as compared to those men with 2 or fewer positive lymph nodes.  After 10 years of follow up, the cancer-specific survival rates (chances of surviving prostate cancer) for these two groups were reported to be 33% and 79%, respectively.  Similar differences were noted based on the density of positive lymph nodes.  One study, for example, compared the outcomes of men in whom less than 20% of the lymph nodes removed (during a dissection) were found to harbor cancer with those of men in whom greater than or equal to 20% of the lymph nodes removed were cancerous.  The study reported that those men with the lower percentage of positive lymph nodes (<20%) enjoyed a 72% chance of living free of metastatic disease after 10 years as compared to only 47% of men with the greater density of positive lymph nodes. 

When prostate cancer invades the lymph nodes, it is considered to be metastatic.  As a result, as I mentioned previously, treatment for men with lymph node positive disease in the past was often delayed until symptoms were noted.  The reasoning for this treatment approach was that, because the cancer is already metastatic and hormonal therapy is palliative as opposed to curative, there is no compelling reason to start treatment right away. After all, what is the rush in treating a cancer that you cannot cure, right?  In 1999, however, a study was published in the New England Journal of Medicine, which completely refuted this line of thinking.  The study evaluated a group of about 100 men diagnosed with lymph node positive prostate cancer.  About half of these men received hormonal therapy immediately after diagnosis, while the other half did not receive treatment until they developed symptomatic metastatases.  The study reported that after 7 years, 85% of men undergoing immediate hormonal therapy were alive as opposed to only 64% of men receiving delayed therapy.  This study led to a paradigm shift in treatment.  Since that time, most men with positive lymph nodes will undergo immediate hormonal therapy.  Interestingly, however, the recent data suggesting significantly better prognoses for men with a small number of positive lymph nodes has led many experts to rethink the need for immediate hormonal therapy in all men.  Some have argued that men with minimal lymph node spread may be better served with observation rather than immediate hormonal therapy, particularly in the context of the side effects and dangers of hormonal therapy.  Unfortunately, no good data yet exists to support or refute this approach.

Until recently, the answer was a resounding yes.  As I mentioned above, lymph node involvement by prostate cancer has always been considered to be metastatic disease.  As such, it has not been considered curable and any treatment has been considered palliative.  The mainstay of treatment for metastatic disease has been hormonal therapy, which works to prevent the prostate cancer from spreading further by restricting the fuel for its growth, the male hormone Testosterone. 

Recently, however, studies out of Europe have demonstrated that, when added in combination with hormonal therapy, radiation therapy can substantially increase survival in men with lymph node positive disease.  A study published just this year, for example, evaluated approximately 360 men with prostate cancer found in their lymph nodes.  Of these men, 117 underwent a combination of hormonal therapy and radiation while 247 underwent hormonal therapy alone.  The study reported that , after 10 years of follow up, men undergoing the combination therapy enjoyed a cancer specific survival rate of 86% versus only 70% for those men undergoing hormonal therapy alone.  Similarly, the overall survival rate of men undergoing the combination therapy was also higher at 10 years as compared to those undergoing hormonal therapy alone (74% versus 55%, respectively).  I should stress that the results of this study, while impressive, are by no means definitive and have not yet changed the standard treatment protocol for men with lymph node positive disease.  Nonetheless, the data provides food for thought and a topic for discussion between men with lymph node positive prostate cancer and their urologists/oncologists. 

The treatment of men with prostate cancer found in their lymph nodes has undergone significant changes.  Lymph node positive disease is no longer one entity but, rather, a spectrum of diseases with varying severities and prognoses depending on the number of positive lymph nodes.  While considered metastatic disease, lymph node positive prostate cancer should still be managed early as such expedient treatment has been demonstrated to improve survival. Similarly, early data seems to support the combination of radiation with hormonal therapy in order to optimize survival outcomes for men with lymph node positive prostate cancer.  As always, men should thoroughly discuss these and other issues pertaining to the management of prostate cancer with an urologist and/or oncologist prior to making any decisions about their care.

When I was undergoing my training in urology, the approach to managing lymph nodes for patients with prostate cancer was pretty simple.  First, everyone undergoing a prostatectomy would also undergo a lymph node dissection. Second, anyone with proven metastases to the lymph nodes would be given a horrible prognosis and be treated with hormonal therapy.  Since that time, however, the management of lymph nodes has become much more complicated and controversial for men with prostate cancer.  Far fewer men are undergoing lymph node dissection.  Also, the management of men found to have prostate cancer in their lymph nodes is not quite as clear-cut.  In my next two posts, I will attempt to shed a little light on the controversies surrounding the evaluation and management of lymph nodes in men with prostate cancer.  In this first post, I will explain what the lymph nodes are, why they deserve our attention, and who actually needs a lymph node dissection during a prostatectomy.  In the second post, I will elaborate on the prognosis and treatment for men found to have prostate cancer in their lymph nodes.

The lymphatic system is a transport network for our immune system. It is a way for immune cells to move throughout the body.  When an infection occurs in a part of the body, immune cells attack the infection and then travel to local hubs called lymph nodes where they can reproduce and further target the foreign invaders.  As more immune cells travel to and reproduce in these hubs, the lymph nodes enlarge.  This is why we can actually feel tender lymph nodes around an area of infection.  For example, the lymph nodes of the neck can get swollen during an infection of the throat.  

In cases of cancer, the lymph nodes are also involved.  Cancer that spreads from its location of origin can move through either the blood vessels or the lymphatic system.  For prostate cancer, spread through the blood vessels leads to metastatic deposits in the bones while lymphatic spread leads to cancer in the lymph nodes.  These nodes are located on either side of the prostate within the pelvic cavity. 

A lymph node dissection is a surgical procedure usually performed at the start of a radical prostatectomy, which involves removing all of the lymph nodes surrounding the prostate.  This can be performed through either an open or laparoscopic (robotic) approach with equivalent success.  After removal, the lymph nodes are sent for pathologic evaluation.  The number of lymph nodes removed is quantified and the contents of the lymph nodes are inspected under a microscopic to look for the presence of metastatic prostate cancer.

One would think that by removing lymph nodes that harbor metastatic prostate cancer, a lymph node dissection could improve outcomes in the treatment of prostate cancer.  To date, however, there has been no significant evidence demonstrating that the removal of pelvic lymph nodes changes the prognosis for men undergoing treatment for prostate cancer, whether or not prostate cancer is found in the nodes.  If lymph node dissection provides no therapeutic benefit, why go through the trouble of performing it?

When prostate cancer spreads to the lymph nodes, the entire approach to treatment changes.  First, the presence of prostate cancer in the lymph nodes means that the prostate cancer is no longer curable.  The prognosis is significantly worse for men with positive lymph nodes.  As a shall describe in the next post, the prognosis varies considerably depending on how many lymph nodes are involved as well as the density of positive lymph nodes.  This information is critical in counseling and in medical decision making.   In addition, as I shall also discuss in the next post, the presence of positive lymph nodes calls for the early administration of hormonal therapy.  If such treatment is not promptly initiated because the presence of prostate cancer within the lymph nodes is not revealed, the prognosis can be substantially worse.

At this point you are probably asking yourself a very logical question.  If the lymph node dissection is only valuable from a diagnostic perspective, aren’t there less invasive ways to find out if prostate cancer has spread to the lymph nodes?  The answer is not really.  Mainstream imaging modalities such as CT scans and MRIs are only able to detect prostate cancer in the lymph nodes in approximately 20-30% of cases.  The reason for this is the fact that the resolution of these techniques is around 1cm.  That means that unless a cancerous lymph node has reached 1 cm in size, a CT scan or MRI cannot detect it.  As a result, most lymph nodes, which are often less than 1cm in size, go undetected.  PET scans, as well, have not been very helpful in detecting occult prostate cancer in lymph nodes for this and other reasons.  New technology has been developed which can increase the ability to detect cancerous lymph nodes with an accuracy of 80-90%.  This technique uses a special contrast medium composed of nanoparticles that have an affinity for lymph nodes.  Called Combidex in the United States and Sinerem in Europe, this contrast medium has demonstrated amazing success in detecting prostate cancer within the pelvic lymph nodes when used in conjunction with standard imaging techniques.  For reasons that I have not yet unearthed, however, this new technique has not been approved for use in the United States and, I believe, the manufacturer may have even stopped producing it.  

If non-invasive imaging techniques are not sensitive enough to detect most cancerous lymph nodes, shouldn’t every man undergoing a prostatectomy also undergo a lymph node dissection.  After all, if the surgeon is working in that area already and the dissection can provide important information that can change the treatment plan, it only makes sense to perform a lymph node dissection on everyone, right?  In medicine, like in all other aspects of life, there is no free lunch.  A lymph node dissection, like any other surgery, has potential serious complications that need to be weighed against the potential benefits of the dissection.  The reported complication rates for pelvic lymph node dissections have ranged from 2-20% depending on the extent of the dissection performed.  The most common complications include:

1. Lymphocele formation:  during a lymph node dissection, numerous little lymphatic channels are clipped off and cut.  Occasionally these channels are not appropriately sealed and can leak lymphatic fluid into the pelvis.  This fluid can accumulate and form a collection called a lymphocele.  These collections of lymphatic fluid can grow quite large, compressing nearby structures like blood vessels (which can cause swelling of the legs), the bladder (causing trouble with urination) and the intestines (causing bloating).  Lymphoceles are treated by placing a temporary drain which allows the fluid to leave the pelvis.  Occasionally, more invasive surgical intervention is required as well.

2. Nerve injury: one of the boundaries of a lymph node dissection is the Obturator nerve.  This nerve provides impulses to the leg, which causes it to move inward or towards the midline of the body.  During a lymph node dissection, this nerve can be inadvertently injured or cut.  Such damage can impair the movement of the leg on that side of the body, which can significantly affect the ability to walk or drive a car.  Some sensation is also affected by damage to this nerve.

3. Blood vessel injury:  another boundary of a pelvic lymph node dissection is the external iliac vein.  This is one of the main veins of the body, which drains blood from the legs and feet back to the heart.  Occasionally a tear in this vein can occur which can lead to significant loss of blood during surgery.  In addition, compression of the vein during the procedure can lead to a large blood clot called a deep vein thrombosis or DVT.  Such a clot can cause swelling of the leg and foot and severe pain.  Occasionally, the clot can even travel to the lungs and cause a life threatening condition called a pulmonary embolism.

Understanding these potential complications, one can see why lymph node dissections should not be taken lightly and should certainly be performed only when necessary.  The question, of course, becomes when is the dissection necessary?

To answer this question we must first determine who is at greatest risk of harboring occult, metastatic prostate cancer within their lymph nodes. Overall, only about 4-5% of men with prostate cancer have lymph node positive disease.  However, this rate greatly depends on other characteristics of a given prostate cancer.  Men with low risk prostate cancer, for example, have rarely been found to have lymph node disease.  As I described in a previous post, low risk disease is characterized by a Gleason score of 6 or less, a PSA less than 10 and no to minimal cancer felt on rectal exam.  Studies have shown that men with prostate cancer meeting these criteria  harbored occult lymph node disease in less than 1% of cases, on average.  Men with more extensive prostate cancer are much more likely to have positive lymph nodes.  For example, men with a PSA score greater than 10 have been found to have lymph node involvement in 7-29% of cases, depending on the Gleason score and rectal exam findings.  Similarly, a man with a PSA of 7 or greater has a significantly higher chance of lymph node involvement, even when the PSA is less than 10. One study of men with prostate cancer and a PSA <10, for example, reported lymph node involvement in 3% of men with a Gleason score of 6 as opposed to 25% for those men with a Gleason score of 7 or higher.  Several tools have been developed to help determine a particular man’s chance of harboring lymph node metastasis.  One such tool, called the Partin Tables, uses a patient’s PSA, Gleason score, and rectal exam findings to make this determination.  This tool is available to the public through the Johns Hopkins website at:

Using such tools, patients and urologists can understand the risk of lymph node metastases and, with this knowledge, make the determination of whether or not to proceed with lymph node dissection.  While no hard and fast rules exist as to when lymph node dissection should be performed, most urologists use similar criteria.  Low risk patients, for example, rarely if ever undergo the dissection.  In contrast, men with a Gleason score above 6 and/or a PSA above 10 almost always have their lymph nodes removed.  Some urologists also rely on a cutoff risk of 7% (as predicted by the tools described above) of lymph node metastasis, above which they routinely perform a lymph node dissection.  

The lymph node dissection can provide important information that can lead to significant changes in the management of prostate cancer.  Removal of the pelvic lymph nodes, however, is not risk free and should not be routinely performed in all men treated for prostate cancer.  Rather, the decision of whether or not to perform a lymph node dissection should be determined based on the risk of lymph node metastasis as ascertained from a prediction tool.