Prostate cancer - Philippe Sebe, md, phd

Hello,

My name is Philippe Sebe.  I am a surgeon and urologist at  Diaconesses-Croix Saint-Simon Hospital group where I work in the urology unit led by Doctor Bertrand Guillonneau.  The unit is primarily devoted to the treatment of genitourinary tract tumors.

I am a member of the Scientific Board of APREC, and it is in that capacity that I will describe the current advances in the treatment of prostate cancer.

Prostate cancer is clearly an important issue in public health since it is the most common cancer in men, and the second cause of death by cancer, just behind lung cancer.  But the words “prostate cancer” include diseases that are extremely varied and which present different challenges in terms of research and therapies.

Localized prostate cancer is the form that is concentrated in the prostate.  In general it causes very few symptoms, and can be detected with the help of two tools: clinical examination and a rectal probe, which are currently too often replaced by echography and measuring PSA levels in the blood.  PSA measuring is unfortunately a very imprecise indicator today, because the level is quite variable.  It can vary depending on the age of the patient, the volume of his prostate, his ethnicity, and his sexual activity, or any medication he may be taking, and there is currently a great amount of research involving the development of new markers, both in the urine and in the blood, which would enable an early and more precise diagnosis of prostate cancer.  Unfortunately, such tools are not currently available, but it is obvious that they would represent an enormous progress in detection.  Today, the main argument for thinking that a cancer is growing is when the PSA increases abnormally.  This is all that we can say, but interpretation remains complex.

When PSA levels and a clinical exam lead to a suspicion of cancer, there must be a biopsy of the prostate.  Currently, the tendency is to develop increasingly precise imaging techniques, to fuse the images that had been done earlier, notably with MRI.  And because we are today able through echography to visualize the suspect areas in an MRI on a screen, we can indeed do targeted   biopsies that are no longer blind biopsies.  This is truly a great step forward in the diagnosis of prostate cancer.

Once localized prostate cancer has been diagnosed, there is no emergency to adopt an immediate treatment.  It is important to consider all options, and this is truly very, very important, because the first question that must be asked is: should we or shouldn’t we treat a localized prostate cancer. If the PSA is low, and the clinical exam is normal, and the biopsies have revealed a small, non-aggressive cancer, then the first option we currently recommend is to watch the disease to determine over time its potential to progress.  This ultimately very modern approach is being increasingly adopted these days.

Obviously, if the above criteria, notably the biopsy, indicate that the cancer has potential to progress, then we must immediately plan for curative treatment.  It is often a difficult choice to make together with the patients because there are several treatment possibilities.  The treatments can all be equally effective, but, unfortunately, they can have negative urinary and sexual side-effects.

There are currently three treatments that have been validated, which also are constantly evolving with the progress that has been made in the past few years.

For example, treatment by curietherapy is one of these options.  Curietherapy consists of implanting radioactive particles inside the prostate.  Current research is leading to the use of needles that allow delivery of higher doses into the prostate with less toxic effects on the surrounding tissues. And so we speak of high-dose curietherapy, which is a very interesting evolution in curietherapy research.

The second possible treatment is external radiotherapy which is also currently undergoing great transformations, since the evolution of radiotherapy techniques is also ongoing, using new computing tools and multi-directional beams of radiation that revolve around the patient, are adapted to the respiratory movements,  have a modulated intensity, and allow us to target precisely the prostate while preserving the surrounding organs, which is very important in terms of the patient’s tolerance for the treatment.

The third treatment is surgical intervention, which has also undergone enormous changes in the past few years.  Initially, traditional open surgery for radical prostatectomy was the treatment of reference.  It remains so today, but other techniques have appeared, more recently robotic laparoscopic techniques that today enable us to obtain equivalent results while being less aggressive. But, and this is an important point, the success of a surgical intervention continues to be related to the experience of the surgeon, regardless of the technique that is employed.

The second type of prostate cancer is the metastatic form which, understandably, is the potentially most deadly form of this cancer.  Thus a great amount of research has been undertaken in this area in the past few years.

Metastatic prostate cancer is a form of prostate cancer in which the cancer cells have left the prostate and have migrated toward other organs such as the lymph nodes, or more frequently bones, and consequently can, this time, produce symptoms such as back or pelvic pain, or trouble urinating related to the pressure by the tumor on the prostate if its volume is important.

The first treatment is generally hormonal therapy.  The goal of these initial treatment is to block the patient’s own production of testosterone.  Testosterone is a sex hormone that is produced by the testicles and upon which the cancer feeds in order to develop.  The primary role of this treatment is to suppress the stimulation of the cancer by testosterone.  The result is generally spectacular with a PSA that very quickly decreases, pain that disappears, general status which rapidly improves. Unfortunately, this initial hormonal treatment, which is called castration therapy, is not indefinitely effective.  When the prostate cancer is not very aggressive, duration of efficacy may be for several years.  However, when the prostate cancer is aggressive, the therapy can be immediately either ineffective, or work for only a few months, and then the cancer turns into “castration-resistant” prostate cancer. It is that form of cancer that today is potentially fatal.

It is in the treatment of this disease that much effort has been made during the past few years.  The goal today is not only to block the production of testosterone by testicles, but we have also discovered new targeted ways that enable us to isolate the cancer cells from any hormonal influence.

The first means is to block all production of sex hormones in the patient, because tumors adapt and use pathways other than just those of testosterone.  And so we developed treatments that consist of blocking the production of all sex hormones, notably by the adrenal glands, and these treatments are available today, and are proving to be quite effective.

Other possibilities consist of blocking the receptors of sex hormones that are located on the cancer cells.  These receptors activate the growth of cancer cells, and so we no longer block the production of hormones, but we block their stimulation on the cancer cell.  New treatments have appeared that block these receptors, again with much success.

The third therapeutic approach is the direct destruction of cells.  Up to now I have spoken of treatments that have indirect effectiveness.  Here we have the possibility through treatments of directly killing the cancer cell, which is the very principle of chemotherapy.  New chemotherapy drugs are appearing, just as effective as previous ones, but which have enlarged the scope of direct destruction of the tumor.

To conclude this description of developments in the treatment of  metastatic cancer, I will mention the treatment of bone metastasis which, here, too, are part of the treatment, since the most frequent secondary sites and the principal source of symptoms are bone metastasis.  Thus today there are treatments that prevent tumor cells from destroying bone, which enable bone to be regenerated, and which successfully fight against the proliferation of tumor cells in the bones, thereby diminishing the risk of fractures, of pain, of neural compression, notably of the spinal cord, which could lead to paralysis.

Another current field of research is that we call immunotherapy.  This involves the ability to isolate cells from the patient’s immune system, and to re-inject them in order to effectively destroy the tumor.  This is a truly new line of research that is different from others and which enables us to have a broader range of therapeutic weapons at our disposal.

And so you can see that in the past few years we have been developing a therapeutic arsenal that has grown considerably.  The challenge today is in knowing which sequence of treatments should be followed, and how to combine