To Treat or Not To Treat, Early Stage Prostate Cancer

Over 200,000 men will be diagnosed with prostate cancer this year. The majority of these men (90%) will have localized disease. It has been established that early prostate cancer is over diagnosed and over treated. The dilemma for most of these men will be whether to treat or not to treat.

The Scandinavian Prostate Cancer Group Study has provided evidence that after a median follow-up of 12.8 years, patients treated with surgery (prostatectomy) had a greater survival than patients treated with watchful waiting by about 5% (87.5% vs. 82.1%). Metastasis was also less likely to be found in the treated group by 6% (19.3% treated vs. 26% not treated). This survival benefit was restricted to men younger than 65 years of age, Gleason score <7.

This survival benefit may not be relevant in men identified by PSA screening, as in the Scandinavian study 88% of patients had palpable tumors, implying a more advanced stage. In the US the median age at diagnosis of prostate cancer is 67, fewer than 50% have palpable tumors, and the lead time associated with prostate cancer detection from PSA screening has been estimated to be as long as 10 years. The only reason to question therapy is the price one has to pay in side effects and decrease quality of life issues. Prostatectomy is associated with erectile dysfunction and urinary incontinence.

Advancements in the delivery of radiation therapy, including image guided and focusing techniques, have allowed for improvements in the rates of disease control similar to surgery. Large, randomized studies comparing the two modalities in early stage disease are lacking. Radiation therapy is associated with bladder irritability, bowel symptoms and at some point erectile dysfunction as well. Adjuvant hormone therapy, shown to benefit patients receiving radiation therapy, increases the side effect profile with vitality and hormonal function issues.

Treatment-related symptoms are exacerbated by obesity, large prostate size, high PSA score, and older age. These changes influence satisfaction with treatment outcomes in patients and their partners. In the end, the decision to treat or not to treat is a personal one with one’s urologist acting as coach. The question to ask: “…is the promised benefit at the end of the road worth the price paid in decrease quality of life en route?”

“Quality of Life” Trumps Plain Survival

There is a growing consensus among physicians and patients that survival in prostate cancer with quality of life beats plain survival. Prostate cancer comes in basically two patterns of behavior (low-risk and high-risk), and the vast majority diagnosed by screening today (85%) is a low-risk, indolent cancer which takes many years to develop. The problem is that the words “cancer” and “indolent” don’t fit well with most people’s conceptions of cancer as a disease, and this falls into the patterned behavior of urologists who are trained to take “cancers” out. Active surveillance of low-risk prostate cancer has been shown by various studies to be clinically acceptable and maintain quality of life.

There is little probability that a cancer that can be cured will not be cured if active surveillance is carried out. In the words of the late oncologic urologist Dr. Whitmore: “If the prostate cancer is curable is treatment necessary, and if treatment is necessary is cure possible?” The undercurrent of his allusion implies that we are dealing with two different diseases, and we actually don’t know if one morphs into the other. Many men are found to have died with prostate cancer from other causes rather than of it. The concept that low-risk prostate cancer does not kill people is not being taught to patients.

Of course once active surveillance is chosen close follow-up is necessary to avoid the charge, in our litigious environment, that a window of opportunity was missed. The decision of when to turn from surveillance to treatment will always be a point of contention, but this can be reached jointly by patient and physician as they assess the objective findings being followed.

As patients become more educated, they are less likely to go through “knee-jerk” treatment after diagnosis. Over-diagnosis and over-treatment are likely to increase with the American Urological Association recommendation to begin screening at age 40. Autopsy series reveal that 30% of men in their 30′s have histologic evidence of prostate cancer. Treating young people with low risk disease condemns them to a decreased quality of life, when the latency period of their disease could be quite prolonged. There is enough evidence to suggest that active surveillance is a sound initial strategy in low-risk prostate cancer.

The Prostate Story

The prostate has become a common focus of discussion in health related media outlets, but it would not be wrong to assume that most people don’t know what the prostate is. The prostate is a male reproductive organ about the size of a golf ball, growing around the urethra (the urinary channel) as it leaves the bladder. Its function is to make semen, the nutrient fluid in which the sperm lives.

The prostate can be the cause of many problems in men and the consternation is compounded by the confusion surrounding the media cacophony about screening for prostate cancer and the usefulness of PSA (prostate specific antigen) in this regard. Prostate cancer is one of the most commonly diagnosed cancers among men in the United States. Prostate cancer is not only prevalent, but also slow growing. Only 0.6% of diagnosed prostate cancer patients die within 5 years. (NCI SEER data) This makes it difficult to decide how and if to treat the prostate cancer. The main question becomes: is the cancer significant enough to require treatment? Not all prostate cancers are the same. Age, Gleason score, stage, co-morbidities, all contribute to outcomes. The AUA has come out publicly with the statement that prostate cancer is over diagnosed and over treated and active surveillance is an acceptable option.

The main marker used to screen for prostate cancer is the PSA. However this elevated in benign conditions as often as it is in the presence of prostate cancer. The PSA is a protein made by prostate cells, which can be found in increased amounts in the blood in conditions where the vascularity of the prostate increases. This can occur in both malignant as well as inflammatory conditions, as in prostatitis. The PSA is not diagnostic of prostate cancer, but taken in context with other clinical information obtained during evaluation, can help in diagnostic and treatment related decision-making by experienced physicians.

Although there is debate regarding the role of diet in prostate cancer, some clear trends have emerged:

  • Prostate cancer rates vary widely between countries and ethnicities.
  • Prostate cancer rates are higher in societies with “Western” diets and lifestyles.
  • These higher cancer rates follow the adoption of Western eating practices.

Prostate cancer has been shown to have a genetic component with a three-fold increase in incidence in first-degree relatives. However, environmental factors also play an important and possibly a decisive role in the appearance of this disease. There is a three-fold increased incidence in prostate cancer between Asians (88/100,000) and Blacks in the US (233/100,000). What are the main dietary differences between Western and developing countries? The emphasis is on animal-based foods in the former, versus plant-based foods in the latter.

There is a large amount of evidence pointing to animal derived fat as playing a role in the development of prostate cancer. What are the mechanisms for this? The first mechanism involves a hormone that increases cancer cell growth. This is a growth hormone called Insulin-like Growth Factor 1 (IGF-1). It turns out that consuming animal-based foods increases the blood level of this growth hormone.

Vitamin D metabolism has also been implicated in prostate cancer. Our bodies can make all the Vitamin D we need by exposure to the sun. This Vitamin D gets transformed to the active form 1,25 D in the kidney. This active form of Vitamin D is 1,000 times more active than the non-active form, and acts in preventing cells in becoming diseased. Animal protein-containing foods cause a significant decrease in 1,25 D. Another cause of decreased 1,25 D is too much calcium in the diet. All these variable pathways can interact in unexpected ways to lead to adverse effects in these intricate networks. The take home-message regarding diet, to quote Michael Pollan, the healthy food advocate:
“Eat food. Not too much. Mostly plants.”