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Protons, Surgery, X-rays

Cancer is a big business in the United States. More people make a living from it than die from it. It comes as no surprise that medical specialists protect and promote their own turf. Surgeons think surgery is the best. Radiologists think x-rays are the best. Proton therapy centers love proton therapy. And hammers see everything as if it were a nail. My purpose here is to compare proton therapy with surgery and x-rays.

Many of my illustrations will be for prostate cancer, my personal area of experience. The principles, however, apply to most types of cancer. Let me start with two important declarations. First, you are not likely to get an unbiased opinion from a doctor whose specialty is under consideration. Perhaps your family doc will do better, but probably not. Mostly, with proton therapy, you are on your own. Second, I am not a doctor and I am not giving medical advice. If I succeed in my mission to get you curious about proton therapy, please peruse the websites of proton therapy centers (see CHOOSE A CENTER) or contact them directly for a consultation or to ask questions.

ALL TREATMENTS NOT ARE EQUAL

A common myth is that all treatments kill cancer equally well, and therefore, are essentially interchangeable. But what about the treatment itself, the experience, the quality of life, side effects, longevity, recurrence, and many other considerations? At the end of this essay I include an article that I find is more balanced than many. Even so, the author makes this comment (my bolding):

The American Urologic Association periodically reviews all the published series reporting treatment results for prostate cancer and always comes to the same conclusion - Taken as a whole, there is no difference in the likelihood of cure whether one has surgery or radiation therapy. If one method of treatment were clearly superior, it would make life easy. We as physicians would just tell everyone to have that treatment. Since cure rates are equivalent, however, men have to consider their options and decide which treatment they want (or more realistically, which treatment they would least mind having).

This kind of statement concentrates solely on the endpoint, killing the cancer. This is like many drugs, which gain approval by successfully eliminating a specific set of symptoms, but in so doing, create others, some of which can be fatal. Killing cancer is not the only criterion. Patients want the complete picture.

I have a friend who, as a nurse, worked in cancer research decades ago. One modality they tested, microwaves, killed the cancer but caused such devastation and suffering they had to halt their trials. Microwaves would fit under the general statement above as killing cancer, but at what human cost?

While surgery and x-rays do indeed address the cancer, I feel they do not measure up to proton therapy when everything is considered. Therefore, I will discuss each of these modalities. The bottom line: which one would you choose?

Of all the books I read, the best was: An ABC of Prostate Cancer Today by Alan G. Lawrenson. (See: https://www.amazon.com/ABC-Prostate-Cancer-Today-Solutions/dp/1695696395) The author lives in Australia where he works as a medical researcher. When diagnosed with prostate cancer, he had the tools, experience, and knowledge to look into every viable treatment, which he describes in his book. In the end, he chose proton therapy. That got my attention. 

Wow, are you still with me? As your reward I have included a relatively balanced discussion of cancer modalities. (See the original here: https://www.medicaldaily.com/prostate-cancer-treatment-vs-removal-surgery-side-effects-and-prognosis-each-404675)

Prostate Cancer Treatment Vs. Removal Surgery: Side Effects And Prognosis Of Each  

As far as curing the cancer, there are several options with an equally good probability of doing this, so each patient's decision comes down to "Which set of side effects would I least mind going through?"

The American Urologic Association periodically reviews all the published series reporting treatment results for prostate cancer and always comes to the same conclusion - Taken as a whole, there is no difference in the likelihood of cure whether one has surgery or radiation therapy. If one method of treatment were clearly superior, it would make life easy. We as physicians would just tell everyone to have that treatment. Since cure rates are equivalent, however, men have to consider their options and decide which treatment they want (or more realistically, which treatment they would least mind having).

Before going any further, there are a few things to keep in mind.

Not everyone with prostate cancer needs to be treated - active surveillance is appropriate for many men - at least for a short time and perhaps for a lifetime.

There are only two methods of curing prostate cancer - surgery and radiation therapy. Things like cryotherapy, High Intensity Focused Ultrasound, microwave heating, laser ablation and a few other methods may be appropriate for prostate cancer that recurs after primary treatment, but these are not curative by themselves.

Androgen suppression (hormone therapy) will stop the progression of most prostate cancers, make the PSA drop to (essentially) zero and make masses or bone metastasis shrink away - but its effect is only temporary - lasting a few months to a few years. Like the methods listed above, is not a curative treatment by itself (although it may be combined with radiation therapy to increase its likelihood of cure). Androgen suppression has its own set of side effects including fatigue, loss of muscle mass, weight gain, loss of libido, impotence, osteoporosis and depression.

Urologists are fond of telling patients that "If you have surgery, you can always have radiation afterward, but if you have radiation, you can't have surgery afterward" which is, for the most part, a true statement, but this generalization omits some important facts.

First, It is rarely necessary to have surgery on one's prostate after radiation therapy, since most men who are not cured of their disease don't have recurrence in their prostate gland. Instead, most men who are not ultimately cured of their cancer had subclinical disease beyond the prostate that could not be detected prior to starting treatment. It just takes some time for these undetectable deposits of cancer cells to grow enough so that they eventually cause an elevation of the PSA, independent of any PSA being produced in the prostate.

If someone does have a persistently elevated PSA following treatment with radiation therapy - and if repeat biopsies of their gland are positive (oh, and by the way, post-irradiation biopsies are only reliable starting about two years after the completion of radiation therapy, since it takes time for cancer cells to die after being treated), then there is only a 50:50 chance that their recurrence is only in the gland.

Salvage prostatectomy can be performed after radiation therapy, although it is a difficult operation due to the intense fibrosis around the gland and the decreased blood supply - both of which are as a result of the prior radiation therapy. These operations are best performed at a major urologic center where they do quite a few of them, as opposed to being done by a community urologist. Even in the best of hands, there is a high risk of incontinence following a prostatectomy performed after radiation therapy.

Since there is only a fifty/fifty chance that the recurrent cancer is only in the prostate, there is only a fifty/fifty chance that the surgery will result in a cure.

Not only can you have radiation therapy after surgery, but 20 to 30 percent of the time, you must have radiation after surgery (since that is how often the pathologist finds cancer that has been cut through at the edge of the specimen) in order to be cured. Post-operative radiation therapy results in a ninety percent chance of sterilizing any residual cancer found by the pathologist. And, by the way, when surgeons report their overall cure rates, they include the patients that were only cured due to having post-op radiation therapy (although they seldom mention this in their publications).

Prostate cancer is generally slow growing.

Don't let anyone rush you into making a decision that will have consequences for the rest of your life.

The term "Early Stage" prostate cancer refers to the fact that it is still localized to the prostate or at least in the immediate peri-prostatic tissue. Early stage cancer can still be low, intermediate of high risk based on its Gleason score (assigned by the pathologist after examining the biopsy material), the PSA level and to some extent, the number of positive biopsy cores.

There are basically two methods of performing a prostatectomy:

Open - where the surgeon makes an incision from just above the pubic bone to the belly button and dissects out the prostate (and some lymph nodes), then connects the neck of the bladder to the remaining urethra (since the intervening prostatic urethra is no longer there), and leaves a catheter in place for a few weeks to allow everything to heal back together.

Robotic - which is basically the same operation, but is performed through small incisions using remotely controlled robotic arms and stereoscopic visualization. Dissection is more precise (in experienced hands) and in-hospital stays are shorter. Publications report the potential for a reduced incidence of side effects like infection and bleeding, but it's difficult to tell if the major long term complications like impotence and incontinence are any less.

The major side effect that surgery has that radiation therapy doesn't is incontinence. Most men require one to two months to regain continence after surgery and overall, about five percent never regain urine control (wearing a diaper the rest of their lives).

Impotence is more common with surgery than with radiation therapy. Although surgical series frequently report potency preservation rates above 50 percent, they define potency as the "ability to obtain an erection sufficient for vaginal penetration". So if you can have sex for 30 seconds, you are counted as being potent by the urologists.

I had surveyed the first 150 men on whom I had performed brachytherapy (back in the mid-nineties) and and simply asked the question "Are you satisfied with your sex life?" and left room on the survey form for them to elaborate. Over 60 percent said that they were satisfied with their function (and no one who said they could only achieve penetration said that they were).

At our Proton Center, we survey every man we have treated with two Quality of Life measurement tools on each follow-up visit. One is the "Expanded Prostate Cancer Index Composite" or EPIC questionnaire and the other is the SHIM (Sexual Health Inventory for Men). We have over 2,600 patients in our database so far and over 70 percent have scores indicating satisfaction with their function.

So - overall, men do vastly better with sexual function and infinitely better with continence (since we end up dividing essentially by zero - incontinence almost never occurs with radiation therapy) if they are treated with radiation therapy as opposed to surgery.

So what's the down side of radiation therapy? I'll address these as they relate to each of the various ways in which radiation therapy may be given.

For patients with low risk, localized disease (Gleason 6 histology with a PSA less than 10 and fewer than 4 positive biopsy cores), brachytherapy can be used as monotherapy. Patients come for a mapping procedure where the exact contour of the prostate is outlined every 5 mm from top to bottom using trans-rectal ultrasound and then a three dimensional reconstruction is created in the computer treatment planning system. An optimal arrangement of radioactive seeds is calculated and pre-loaded into needles for placement in the gland. The day of the procedure, the patient is placed under general anesthesia and 20 to 40 needles are used to place 60 to 120 seeds in the prostate under trans-rectal ultrasound guidance.

The patient usually goes home in a few hours and may have a catheter over night (since the gland may swell somewhat and it's better to have the catheter already in place, than to come to the ER in the middle of the night when you can't pee). Men usually have pretty severe irritative voiding symptoms (frequency, urgency, nocturia, decreased stream force) for the next month which resolve over the following month.

They may have some irritative rectal symptoms for a few weeks and can develop a rectal ulcer one to two years after the procedure if some of the seeds end up being right next to the rectal wall. This rectal ulcer always heals up with time as long as a gastroenterologist doesn't biopsy it (thinking it is suspicious for cancer), in which case it may never heal and the patient ends up needing a colostomy.

If someone has risk factors beyond those described above, then brachytherapy alone (brachytherapy as monotherapy) does not result in a sufficiently high cure rate (due to the involvement of periprostatic tissues beyond where the seed irradiation can reach) and must be supplemented by twenty-five external beam radiation therapy treatments (to increase the dose to the periprostatic tissues).

Since the main advantage of brachytherapy is to shorten the length of time it takes to get the treatment, once you add five weeks to get the external beam component, much of that advantage is lost. In the case of higher risk disease, the brachytherapy basically replaces the final nineteen external treatments one would have if they had external beam radiation therapy definitively (which usually consists of 44 treatments over nine weeks).

So if someone has intermediate to high risk disease, they would probably opt for definitive external beam radiation therapy as opposed to going through the procedure for brachytherapy in addition to twenty-five of the external treatments. So what is the procedure for, and what are the side effects of, definitive external beam radiation therapy for prostate cancer. External beam treatment can be given with high energy x-rays (using a technique knows as Intensity Modulated Radiation Therapy or IMRT) or with Proton Therapy and I'll discuss the differences in these two modalities momentarily. By the way, the Cyberknife, tomotherapy and a variety of linear accelerators deliver IMRT treatment with x-rays - there is no difference in the end result, just the machines being used to deliver it. You may also hear the term IGRT which stands for Image Guided Radiation Therapy, which simply means that some sort of imaging (CT, portal imaging, stereoscopic x-rays, etc.) are performed with the patient on the treatment table just before the treatment is delivered. IGRT is used with all forms of IMRT as well as with Proton Beam Treatment.

For either method of treatment (Protons or x-rays) treatment planning begins with a thin slice CT scan which is fused with a highly detailed MRI. The CT is necessary to tell the treatment planning computer what the tissue density is at all points through which the radiation beams will pass. The MRI gives better anatomic detail for contouring the prostate, seminal vesicles, bladder, rectum, etc.

After several days of contouring structures and running multiple trials of beam arrangements, beam modulation, etc., an optimal treatment plan is developed. Then, the physicists run quality assurance tests to verify that the computer predictions achieve the planned dose distribution in tissue. Finally, the patient returns for the initial "Image Guidance" and the first of 44 treatments.

The radiation oncologist sees each patient weekly and manages any side effects they may have. For x-ray (IMRT) treatments side effects may include fatigue, sometimes to the point that they need to go home and take a two hour nap in the afternoon.

A few weeks into treatment, rectal irritation may begin which can range from mild diarrhea to pain, bleeding and a continual feeling of needing to have a bowel movement, even though there may be nothing besides a little mucous in the stool.

Also, a few weeks into treatment, urinary irritative symptoms such as frequency, urgency, slow bladder emptying, and nocturia (getting up several times at night to urinate) may begin and last until a few weeks after the treatment is over.

Long term risks include the development of radiation induced cancers.

Other than the long term risk of developing a secondary cancer, most side effects resolve within a few months to a year after the radiation therapy is over.

For Proton Treatment

Fatigue is minimal or non-existent. (I treated an avid cyclist a few years back who rode his bicycle over a thousand miles during the nine weeks he was receiving treatment).

Rectal symptoms are almost unheard of (since such a small volume of the rectum is receiving radiation - basically just the part immediately adjacent to the prostate). Urinary irritative symptoms may occur over the same time course as they do with x-ray treatment, although they are generally less severe than with x-rays.

Multiple epidemiologic studies have shown that there is only a minimal increase in the risk of radiation induced cancers with protons as opposed to x-rays - likely due to the much smaller volume of tissue receiving any radiation dose. The few side effects men do have, usually resolve within a few weeks after proton irradiation is over. 

What about the data on the relative side effects of Proton Therapy vs. IMRT?

We pooled our data with various cancer centers in order to study about 1,000 patients who had been treated for prostate cancer with Proton Beam Therapy and compared their Quality of Life scores (in the domains of urinary and bowel function) with those of a control group of men who had no treatment (because they didn't have prostate cancer).

The EPIC questionnaire was completed by all men every three months from the beginning of treatment until at least one year after treatment. The results showed that men who were treated with proton therapy for prostate cancer had the same urinary and rectal quality of life scores as men who didn't even have prostate cancer.

Don't let anyone rush you into making a decision that will have consequences for the rest of your life. 


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