Readers of this column may realize that I seldom write about prostate cancer despite its enormous incidence and consequences in men. In part, this stems from the fact that, in my view, it has been shamefully understudied compared to breast cancer, its analogue in women. Thus, while we are overwhelmed with information on every aspect of breast cancer from its genetics, etiology, screening, treatment and follow-up, we face a comparative dearth of information on all of these issues with regard to prostate cancer.
A key factor in our bewilderment at how to deal with prostate cancer is its omnipresence. Autopsy studies from some decades ago tell us that prostate cancer is present in approximately 60% of the prostates of men of middle or older age. Consequently, the positive predictive value of an elevated prostate-specific antigen (PSA), an excellent biomarker for prostate cancer, is very high, i.e., for men with elevated PSA levels, the probability of a positive prostate biopsy for cancer is very high. But is that a surprise when older men have 60% or higher rates of prostate cancer in their prostates? One fascinating study that explored the impact of PSA for screening was wise enough to biopsy also those men whose PSA levels were normal (under 4). While the prostate cancer positivity rates were significantly higher in those with elevated PSA levels, the cancer detection levels even in those with normal PSA levels was still in the 15% range. That level argues to me that we could almost dispense with PSA screening and just biopsy everyone’s prostate on some regular basis.
But that brings us to the real issue in the management of prostate cancer—distinguishing clinically meaningful from clinically indolent and unaggressive prostate cancer. The former would require therapy with surgery or radiation therapy while the latter could be safely monitored and followed. Most will never make serious clinical problems for the patient. In the past, these distinctions were not attempted, but rather all men diagnosed with prostate cancer underwent some form of ablative treatment (surgery or radiotherapy). But now serious efforts are in place to limit treatment for less serious prostate cancer.
So how do we recognize or define a “safe” prostate cancer? Our traditional tool has been staging—generally speaking, we are talking about a small prostate cancer limited to the prostate, but to that we certainly have to add grade. Grade is a measure of how aggressive the tumor appears to be under the microscope to the pathologist. It is measured by the degree of dedifferentiation. And in prostate cancer nowadays, we use a scoring system known as the Gleason score, named after Donald Gleason, a Minnesota pathologist from the 1960s. The scores range from 2 to 10. Scores of 2-4 are low-grade and portend an excellent prognosis. Most of the diagnosed prostate cancers are Gleason’s 5-7, and are intermediate in risk, while scores of 8-10 are high-grade and poor prognosis; many systems will include Gleason 7 as high-grade as well.
In recent years, multiple studies have shown convincingly that we can define low-risk prostate cancers that do not require surgery or radiotherapy, but which can be safely monitored and followed. These patients would have a relatively low risk for progressive or metastatic disease and could reasonably expect to avoid the consequences of surgery or radiation therapy, both of which engender high rates of urinary incontinence and erectile dysfunction.
The precise guidelines for the utilization of active surveillance vary a bit among organizations, but a reasonable set of characteristics is provided by the European Society for Medical Oncology (ESMO):
- PSA less than 10 ng/ml
- Gleason score up to 6
- A primary tumor that is small—T1 or T2a (the tumor is either clinically not apparent nor palpable, or it is palpable but involves less than one-half of one side of the prostate).
As an example, one randomized trial conducted in the U.K. randomized 1,643 men with low-risk disease to one of three arms: active monitoring, radical prostatectomy or radiation therapy. Active monitoring consisted of serum PSA levels every three months in the first year and then every six to 12 months thereafter. Prostate biopsies and MRIs were not utilized in this study, as are now recommended as part of active surveillance. By 15 years, prostate cancer death rates were similar across the three groups—3.1%, 2.2% and 2.9%, respectively. The occurrence of bone metastases was 9.4%, 4.7% and 5.0%.
Current guidelines do recommend active surveillance for the large number of patients with low-risk prostate cancer. There are certainly those for whom it may not be appropriate even if they fulfill the low-risk criteria—those with very high anxiety about their disease, those unable to return frequently for monitoring and others, and shared decision-making is required between patients and physicians. Recent surveys indicate that for this patient population, the use of active surveillance has reached 60%.
Nonetheless, its use is uneven—there are urology practices which have levels of use at 5-10% while other practices have rates greater than 80%. Some urologists never recommend it. The thinking is that some urologists may conform to traditional modes of cancer management in dealing with such patients. My own cynical view, given our pay-for-service healthcare system, is that financial remuneration may play a significant role in physician recommendations. Thus, as with most scenarios in cancer, this is not an emergency; a second opinion at a second institution and, in addition, with a radiation oncologist is advisable before choosing your path.
Alfred I. Neugut, MD, PhD, is a medical oncologist and cancer epidemiologist at Columbia University Irving Medical Center/New York Presbyterian and Mailman School of Public Health in New York. Email: [email protected].
This article is for educational purposes only and is not intended to be a substitute for professional medical advice, diagnosis, or treatment, and does not constitute medical or other professional advice. Always seek the advice of your qualified health provider with any questions you may have regarding a medical condition or treatment.
