Proton Radiation Therapy for Prostate Cancer

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Proton radiation is an enhanced type of radiation gaining in popularity for the treatment of prostate cancer. Men who are contemplating proton radiation need to compare and contrast it with all the other types of radiation to determine if proton therapy is advantageous for them in view of their specific circumstances.

A full course of proton radiation requires five treatments per week continued for eight or nine consecutive weeks.

During each visit, patients are positioned in front of an invisible beam of protons that target the prostate gland.

Proton vs. Photon Radiation

Proton radiation is different from other types of radiation, which rely on photons. Photon radiation comes in three types: intensity modulated radiation therapy (IMRT), radioactive seed radiation (brachytherapy), and stereotactic body radiation therapy (SBRT). Sometimes a combination of brachytherapy in conjunction with one of the other types of beam radiation is used.

All types of radiation are effective, resulting in the death of cancer cells. All can potentially cause side effects, if the radiation touches adjacent normal organs, such as the bladder, rectum, and urethra.

The Risk of Erectile Dysfunction

So far experts are unable to agree that one type of radiation consistently outshines all the others. However, depending on the various types of situations that patients face, one form of therapy may have advantages over the others.

All the options, when delivered by experienced physicians, achieve good cure rates and have relatively few permanent side effects—except for the risk of erectile dysfunction (ED).

The risk of permanent ED—defined as ED unresponsive to Viagra or similar drugs—is about 50 percent with all types of radiation.

 The risk is higher in older men and in men with preexisting sexual impairment. The risk is lower in younger men and when preexisting sexual function is good. Treatment for radiation-induced ED is effective but unnatural, and requires either an injection of prostaglandins into the penis or a surgically-placed prosthetic implant.

Bottom line, though ED after radiation is common, it is not considered a determining factor in the selection of one type of radiation over another. This is because the risk of ED is the same with all types of radiation. Comparing radiation options, therefore, depends on other factors such as cure rates and the incidence of bladder or rectal problems.

Risk of Rectal Burns

Historically, using older radiation technology, rectal burns from radiation were common and potentially devastating. Now in this modern era, due to better methods of targeting, serious rectal burns have become very uncommon. Presently, all four types of radiation (proton radiation, IMRT, brachytherapy and SBRT) have a relatively similar (1 to 2 percent) risk of long term rectal problems.

There are two exceptions to this assertion. First, some but not all studies of SBRT suggest it may have a slightly higher risk of rectal burns than with the other three options, a risk in the 3 percent to 4 percent range.

The second exception is “old-fashioned” proton radiation. Older proton equipment delivers a wider beam of radiation, which is more likely to result in radiation “overspray” into the rectum. Modern proton radiation, called intensity modulated proton therapy (IMPT) is delivered using small pencil beams, very similar to the type of technology used in the delivery of IMRT. Both IMPT and IMRT can create a “curved” radiation field that can be shaped to adhere more closely to the spherical borders of the prostate gland. This results in much less radiation overspray and therefore a lower risk of rectal damage.

A Gel to Prevent Rectal Burns

A lifelong rectal burn is rare, but it can be very debilitating, resulting in pain, bleeding, and loss of rectal control. A revolutionary technology called SpaceOAR greatly reduces the risk of a serious burn to the rectum. SpaceOAR hydrogel is injected between the prostate gland and rectal wall and remains in place throughout the period of radiation. The hydrogel moves the rectal wall away from the prostate gland and out of the radiation field. Thus, the risk of a radiation burn to the rectum is almost eliminated.

The Risk of Radiation-Induced Urinary Problems

Urinary problems after radiation include pain during urination, urinary urgency, and waking up at night frequently to urinate. The risk of symptoms after radiation is increased in men with preexisting urinary problems and in men who have particularly large prostate glands.

The risk of urinary problems is also increased when seed implants are used. This is because the total dose of radiation delivered by seeds is higher. The urethra, the urinary passage that carries urine from the the bladder to the outside via the penis, runs straight through the middle of the prostate. Therefore, temporary irritation during radiation and immediately after radiation is common amongst all the options.

Long term urinary symptoms occur in 10 percent or so of men who have seed implants. Long term urinary symptoms can also occur with the other options, but in fewer than 5 percent of the patients, assuming they don’t have excessively large glands or a notable degree of preexisting urinary problems. Medications to counteract these long term urinary symptoms are only partially effective. There is a tendency for the long-term symptoms to slowly improve, although significant improvement may not occur for several years.

Overall, apart from the minor exceptions noted above, the risk of urinary and rectal side effects is fairly similar with all the options. This leads us to addressing cure rates, which vary depending on a patient’s cancer stage. In men who are candidates for radiation, two broad stages of prostate cancer have been described, “high-risk and “intermediate-risk.”

Radiation for High-Risk Prostate Cancer

Since better studies exist for high-risk, treatment selection is less controversial than it is for intermediate-risk. Men with high-risk are characterized by at least one of the following:

•    A Gleason grade of 8 or higher
•    A PSA blood level over 20
•    A digital rectal exam that shows a large tumor or cancer outside the prostate

With high-risk disease, experts recommend an “all out” therapeutic approach. As was noted above, seed radiation delivers a higher dose of radiation compared to the other options. A higher dose improves cure rates. A large study called the ASCENDE-RT clinical trial validates this premise. The study prospectively compared IMRT alone with IMRT plus a seed implant. The combination of seeds plus IMRT resulted in a 20 percent higher cure rate compared to treatment with IMRT alone. As such, the consensus is that seed radiation in combination with IMRT is the best type of radiation for men with high-risk disease.

Since there are many similarities between modern proton therapy (IMPT) and IMRT, it is probably reasonable to substitute IMPT (plus seeds) for IMRT plus seeds in men with high-risk disease. However, such interchangeability has never been validated in a clinical trial. Perhaps this shortcoming is partially offset by certain physical advantages known to be associated with protons compared to photons. The anticancer energy delivered via a proton beam stops at the prostate, reducing radiation exposure to normal tissue on the far side of the gland.

In contrast, photon radiation passes straight through the body, exposing a larger amount of the body to radiation. The main argument for using proton radiation rather than IMRT is based on this premise, that there is a reduction in the amount of normal body tissues exposed to radiation.

Radiation for Intermediate-Risk Prostate Cancer

There is far more flexibility of choice with intermediate-risk disease. Good results have been documented with all the options. However, many experts are beginning to divide intermediate-risk into favorable and unfavorable subtypes. Using this system, men with the favorable subtype must meet all the following criteria:

•    Gleason 3 + 4 (instead of Gleason 4 + 3)
•    Only two or three of the biopsy cores total that contain cancer
•    A PSA blood level of less than ten
•    If the doctor feels a nodule, it is small and contained

With favorable intermediate-risk, all the options—seeds, SBRT, IMRT, and proton (IMPT) radiation—would be reasonable. Men with very large prostate glands, over 60 cc to 80 cc for example, or men who have an excessive degree of preexisting urinary symptoms, face a higher risk of long term urinary problems with seed radiation and should probably opt for SBRT, IMRT or IMPT. If SpaceOAR hydrogel is utilized to protect rectal damage risks, SBRT is an attractive choice over IMRT and proton radiation, since the number of required treatment visits is far less with SBRT compared to IMRT and proton therapy.

Unfavorable intermediate-risk prostate cancer retains the characteristics of intermediate-risk (Gleason 7, PSA from 10 to 20 or a moderate prostate nodule) but fails to meet the stringent criteria outlined above for favorable intermediate-risk. Examples are: Gleason 4 + 3, men with more than one intermediate-risk factor and men with multiple biopsy cores containing cancer. These factors indicate a type of disease that is potentially aggressive. Therefore, treatment should be a combination of IMRT (or IMPT) plus a seed implant. This approach may seem identical to what was recommended above for high-risk disease. There is, however, a major difference—the way hormonal therapy is utilized.

Hormonal therapy is required for all men getting radiation except for men with favorable intermediate-risk. Typically, a Lupron or a Lupron-like medication is started two months before radiation and continued during radiation. Men with unfavorable intermediate-risk continue hormonal therapy for a total of 6 months. Men with high-risk continue longer, stopping after 18 months. A compelling study published in the New England Journal of Medicine also indicates that a stronger type of hormone therapy called Zytiga should be administered in conjunction with the Lupron for men with high-risk.

Proton Therapy Advantages and Disadvantages

Proton radiation may represent an incremental improvement over IMRT due to the reduced exposure of surrounding normal body tissues to radiation. Therefore, in the situations outlined above where IMRT would normally be considered, men may prefer to choose proton radiation over IMRT. The purported advantages of proton radiation over IMRT remain theoretical and clinically unproven. No head to head studies comparing the IMRT and proton radiation exist.

Disadvantages associated with proton radiation are related to its high cost and the fact that not all insurance programs cover proton radiation. In addition, there are relatively few centers doing proton radiation, so geographic inconvenience can be a major factor considering that numerous visits are required over a 5 to 9-week period.

Men considering treatment for prostate cancer need to do their homework.  Side effects from radiation can be irreversible.  The selection of optimal radiation varies with patient circumstances. Many factors need to be considered when radiation is contemplated.

Sources:

James, ND., et al. "Abiraterone for prostate cancer not previously treated with hormone therapy." New England Journal of Medicine (2017).

Morris, JW, et al. "Androgen Suppression Combined with Elective Nodal and Dose Escalated Radiation Therapy (the ASCENDE-RT Trial): An analysis of survival endpoints for a randomized trial comparing a low-dose-rate brachytherapy boost to a dose-escalated external beam boost for high-and intermediate-risk prostate cancer." International Journal of Radiation Oncology* Biology* Physics 98.2 (2017): 275-285.

Zelefsky, MJ., et al. "Efficacy of oral sildenafil in patients with erectile dysfunction after radiotherapy for carcinoma of the prostate." Urology 53.4 (1999): 775-778.

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