Prostate Cancer Management

Clinically localized prostate cancer poses a future risk. So long as the cancer appears to be confined to the prostate, it generally does not cause any symptoms and there is never a risk of impending death - no one ever dies within the first 5 years of diagnosis and death directly attributable to prostate cancer is very uncommon even 10 years after a diagnosis. Therefore, a man must live long enough to suffer any consequences from prostate cancer.

As a result of the typically slow progression of prostate cancer, neither radiation or surgery show virtually any survival benefit within the first 10 years after diagnosis. It isn’t that the treatments are ineffective, it is just that most prostate cancers don’t cause death until 10-15 years after the time of diagnosis. Make no mistake that some men with prostate cancer have progressive disease, sometimes to an incurable state, in the first 10 years and that many prostate cancers are lethal. Radiation and surgery can not only slow progression of disease and death but this is highly time dependent.

Therefore, assessment of longevity is the first consideration. This takes into account age, how active and functional one is and other health issues. Patients with other types of cancers, smokers, poorly controlled diabetes or serious heart disease are less likely to live long enough derive benefit from surgery or radiation.

A recommendation against surgery or radiation is an acknowledgement of futility of treatment in some circumstances and for patients with limited life expectancy will spare them the sometimes serious consequences of the treatment itself.

Men with life expectancies below 10 years are often observed using a strategy called watchful waiting.

Disease considerations include all of the results that allow us to characterize the cancer. This includes the PSA, imaging studies, prostate exam and biopsy results. While the details can be confusing, never forget that this all comes down to the risk that a cancer might cause problems (including both symptoms and death) at some time in the future.

Patients often make the errors of focusing on only one disease characteristic at the expense of others or failure to weight the different factors appropriately. Remember that not all information should be equally weighted and everything must be taken in the context of the entire clinical picture.

Rather than dwell on the details (though one may do so if they like and explanations follow), it is usually more helpful to think about the consequences of that risk.

1. Risk that the tumor will progress and cause symptoms and necessitate treatment at any particular time point in the future.

2. Risk that that the tumor will result in death at any particular time point in the future.

Risk stratification is the most commonly used way to put all of the disease characteristics together. Patients are determined to be in one of the following groups:

1. Very low risk.

2. Low risk

3. Intermediate risk (favorable and unfavorable).

4. High risk.

5. Very high risk.

Men with very low risk disease can be considered for either active surveillance or watchful waiting. Men with low or intermediate risk disease may also be candidates for similar approaches if the life expectancy is reduced or if there is a strong aversion to surgery or radiation. Almost all men with high risk disease or able will merit some form of treatment even if they do not have symptoms.

Most urologists do NOT use the AJCC/UIC staging system in routine practice (i.e. the Stage I, II, III, IV system) and more commonly use the NCCN guidelines staging system.

As a general rule, men with intermediate or higher risk disease combined with a life expectancy of at least 10-15 years are likely to benefit from surgery or radiation. There will be other permutations where treatment should also be considered - very young men even with low risk disease or older men with very high risk disesae.

The integration of patient and disease characteristics is the starting point to quantify the risk that tumor poses to a patient. One then determines if treatment can bend the arc of a patient’s life in a favorable way (i.e. the benefits) and if the costs/side-effects of treatment (i.e. the harms) are on balance acceptable to the individual.

A basic property of prostate cancer is that disease progression usually occurs over years. We usually find prostate cancers 5-10+ years before they might cause symptoms (there are always exceptions). and where treatment is necessary (not optional) to minimize pain and suffering Therefore, a patient must live long enough either develop symptoms or die after a diagnosis of localized prostate cancer is made.

Since humans are mortal, every patient, to varying degrees, may not live long enough for prostate cancer to progress to the point where treatment is non-negotiable.

The vast majority of men with a new diagnosis of prostate cancer do not have any symptoms from the cancer. Even symptoms which one might be fearful are from the cancer (e.g. problems with urination, aches in bones) are usually not from the cancer.

The absence of symptoms does not, however, mean that the one can ignore the issue until symptoms are present. Once one has symptoms that are actually a result of prostate cancer the cancer is usually incurable and one is left with palliative (non-curative) treatments as the only option. Advanced prostate cancer is a terrible disease, especially once the cancer becomes unresponsive to palliative treatments.

Therefore, we are often forced to take action in the present to reduce the risk that the cancer will cause problems in the future.

Making a decision is almost always challenging because the future is uncertain and one has to think in years and decades. This also forces men to think about their own mortality. Fortunately, there is a large body of clinical information that can help with the assessment of risk over time and life-expectancy after which a patient can bring their own values and goals into the calculus of how they want to proceed.

Not all prostate cancers actually cause problems. Some men may “die with prostate cancer rather than because of it” but in those patients in whom the cancer progresses, there may be serious consequences.

Note that radiation and surgery reduce the risk of cancer progression, sometimes by curing the cancer and other times by slowing its progress. Cancer may still progress to advanced disease despite treatment.

Some facts:

• Most men diagnosed with clinically localized prostate cancer will die of another cause rather than from prostate cancer.

• The risk of prostate cancer-specific death depends on life-expectancy and disease characteristics.

• Cancer characteristics associated with an increased risk of tumor progression include higher grade, higher volume, higher PSA, higher stage. Men with longer life-expectancies have greater risk exposure.

• The risk of progression to metastatic disease increases over time and is dependent on tumor characteristics. The risk at 15 years ranges between 10% and 100%.

• The development of metastases (bone and lymph node) is a pre-requisite to death from prostate cancer and usually occurs 3-7 years prior to death.

• Approximately 1 in 30 of all men die of prostate cancer. Men with a diagnosis of prostate cancer have a higher risk of death but that risk may be as low as 3% over 15 years and as high as 70% over 15 years.

• Metastatic prostate cancer is incurable. Palliative treatments (hormones, chemotherapy, palliative radiation or surgery) are available.

• Quality of life in men with advanced prostate cancer and those requiring palliative treatments tends to be very poor.

• Loss of function as a direct result of advanced prostate cancer includes but is not limited to: obstruction of the urinary tract (kidneys, bladder resulting in urinary retention or renal failure - surgery, urinary diversion, catheters), urinary incontinence, bleeding or development of fistulae (bladder, rectum - fulguration, hyperbaric oxygen, laser therapy, salvage cystectomy, urinary or fecal diversion), local invasion (pelvic floor, penis, testicles), bone metastases (fractures, spinal cord compression with paralysis), fatigue, weight loss.

• Loss of function as a direct result of treatment for advanced prostate cancer includes but is not limited to: symptoms of medical castration (erectile dysfunction, loss of libido), osteoporosis (bone fractures), hot flushes, weight gain, breast enlargement, fatigue.

• There will always be exceptions.

Quality of life and length of life is why we treat prostate cancer. Untreated cancer can be devastating but the treatments also carry risk, sometimes significant.

For clinically localized prostate cancer we do not have reliable data comparing radiation to surgery but we do have reliable data on treatment-related side effects. Consider those differences carefully - and understand how additional treatments, if necessary, might affect your quality of life.

The management options available to treat prostate cancer will depend on a large number of factors. Be clear on what your ‘disease state’. Most me are clinically localized and in some cases, observation may be an option. Men with advanced states of prostate cancer a very different set of options available.

There are 4 general groups of physicians who have different ‘tools’ to manage prostate cancer.

1. Urologists: surgery, medication

2. Radiation oncologists: various forms of radiation and medication.

3. Medical oncologists: more complex medications.

4. Other: your family physician, pain specialists, palliative care physicians, endocrinologists, affiliated health professionals etc.)

The type(s) of services you need and specialists you see will depend on the status of your disease. Sometimes we will ‘mix and match’ these tools and services.

Radiation and medical oncologists provide care at the BC Cancer Agency and/or local hospital. Surgeons provide care in local hospitals and offices.

There will be certain instances where some types of care are not applicable. For example, localized prostate cancer falls under the purview of surgeons and radiation oncologists - medical oncologists are not involved in care for this disease state and you would not be referred to one for an opinion.

By necessity, in the absence of perfect knowledge we must predict or forecast the future.

Just as there are no certainties or guarantees in life, there are no certainties in the management of prostate cancer. We are trying to forecast how the cancer might behave and how our treatments might improve or worsen the outcome.

This goes hand in hand with considering risks and benefits. Patients should not think about risk and benefits in absolutes. Black and white’ thinking is not appropriate when considering options since outcomes cannot be guaranteed and the future in inherently uncertain. Professional insight allows your physicians to provide more accurate predictions to allow you to make better decisions.

Therefore, think of possible future events (outcomes) as more or less likely to occur and recognize that any intervention (e.g. surgery, radiation, medication) may increase or decrease the chances of that event occurring. Never think that any intervention is guaranteed to have the desired effect.

For example, neither surgery or radiation are guaranteed to cause a cure when used to treat prostate cancer because (1) it is always possible that the cancer has spread beyond the reach of those treatments without our knowledge prior to treatment rendering it incurable or (2) the treatment did not eradicate the tumor because, for example, tumor was left behind at surgery or the dose of radiation was too low. We make decisions to proceed with the surgery or the radiation because at the when we are required to make a decision and with the available information there was a chance of cure that was acceptable in light of the potential side-effects of treatment and the patients quality and length of life are, on balance, more likely to be improved. Hindsight is usually much better than foresight but by making good decision there is less chance of regret.

Technically, this type of thinking is called probabilistic reasoning and will be understood by anyone who plays games where chance and skill are involved (e.g. poker). The true nature of prostate cancer may take years to become apparent. Prostate cancer can be a formidable opponent and we’re always striving to gain the upper hand. We have limited control over the hand that has been dealt but strive to make the most of those cards (or any that we might have up our sleeve). The stakes involved will depend on the specific nature of the cancer and the tools that are used to treat it.

Every single course of action has the potential for risk and reward. Consider these carefully and think about the nature of those risks and benefits .

1. How often a complication is expected to arise.

2. Spectrum of severity of a complication. If a rate (e.g. 5%) is quoted, consider what severity of complication this refers to and if that risk changes (increases or decreases with time). Many complications will have a spectrum of severity and you may only be receiving a quote on a particular severity of complications.

3. Timing of the complication. For any particular complication, does that risk increase or decrease with time?

4. How is the complication treated? What is involved, how difficult is the treatment, will it come back

5. What would be the impact on my quality of life.

Management of prostate cancer comes with unavoidable comprommises.

Recognizing the limits of medical knowledge is important. We rely on clinical experience and judgement in these situations.

One common example of limited knowledge comes in the setting of clinically localized prostate cancer. We do not have the data that could allow us to state if radiation or surgery is a superior treatment for cancer control. The gold standard would be a randomized controlled trial (RCT) comparing radiation to surgery but this has not happened and is unlikely to happen in the near future. There have been serious attempts to answer this question with an RCT but the clinical trials could not get off the ground (difficulties with enrollment and the 10+ years of necessary follow-up scuttled those trials). Observational trials, which are notoriously unreliable, have unsurprisingly shown a mixed bag of results when analyzing hundreds of thousands of patients and should not be relied upon. Reference: Wallis et al. European Urology 73 (2018) 11-20.

Caution is advised if you are provided certain advice on a subject that has inescapable uncertainty.