Monday, October 6, 2014

Active surveillance for prostate cancer: What is it and is it right for me?


All cancers are not created equal

Prostate cancer is the most commonly diagnosed non-skin malignancy and the second most common cause of cancer death in American men. It is generally accepted that the introduction of PSA screening in the early 1990s led to increased detection of prostate cancer (Figure). While improved detection has been associated with a subsequent decline in prostate cancer death rates (-4.1% annually from 1994 to 2001), the majority of men diagnosed with prostate cancer will ultimately not die of the disease. In fact, there is increasing evidence that many men are diagnosed with low-risk prostate cancers that would not have impacted their quantity or quality-of-life if never detected. Such "overdiagnosis" is problematic because prostate cancer treatments are associated with side effects including erectile dysfunction and urinary issues – which can have a significant impact on quality of life.

The changing landscape of prostate cancer

In light of this, the landscape of diagnosing and treating prostate cancer has shifted dramatically over the past two decades. While physicians previously sought to diagnose all men harboring prostate cancer so that potentially life-sparing treatment could be offered, we now know that most of these men are diagnosed with indolent (or benign-behaving) cancers which will not require treatment at all. Thus, the burden now lies in identifying and treating men with life-threatening cancers -- while sparing men with indolent disease the side effects associated with unnecessary treatment. Given the number of men and families affected by prostate cancer every year, this has appropriately become a major focus of our efforts against the disease.


Separating the good from the bad

As described above, prostate cancer presents physicians with quite the dilemma. While prostate cancer is the 2nd leading cause of cancer death in this country (just behind lung cancer), the fact remains that the majority of prostate cancers diagnosed will never become harmful to a man during his lifetime. How, then, can we distinguish the dangerous cancers from the others? As it turns out, years of research have taught us that there are clinical (i.e. patient-related) and pathological (i.e. tumor-related) factors that help a great deal in doing so. While this process of dividing cancers based on the threat they pose, termed "risk-stratification," is the subject of many conferences and careers, a few of the most pertinent questions used to stratify prostate cancers are listed below:
  • Was an abnormality of the prostate (e.g. nodule, firmness) detected during digital rectal exam?
  • What was the level of prostate-specific antigen (PSA) detected on a routine blood test?
  • How much cancer was identified on prostate biopsy?
  • How disorganized did the cancer cells appear on the pathologist's microscopic examination?
Using detailed answers to these questions, the National Comprehensive Cancer Network (NCCN) has developed prostate cancer risk levels that patients and physicians can use to help guide management decisions. Men with localized prostate cancer (i.e. no evidence of cancer outside the prostate) will fall into one of the following risk categories: very low risk (VLR), low risk (LR), intermediate risk, or high risk. This is all to say that men in the more favorable risk groups are the same men discussed above – many of whom may not benefit from undergoing treatment. Identifying the men who will benefit from treatment, however, requires watching these men closely for any evidence that their cancer is more dangerous than we originally thought. This practice is known as "active surveillance" (AS) and is described in greater detail below.


What is active surveillance?

Active surveillance is a management strategy that consists of carefully monitoring men with favorable-risk prostate cancer using repeat PSA values, biopsies, and other tests such as MRI. If higher-risk features appear during follow up, curative treatment (e.g. surgery or radiation) is recommended on the presumption that treatment can still occur within the window of opportunity for cure. Given this, the basic tenet of AS rests upon our knowledge that most prostate cancers are slow-growing and a delay in treatment does not compromise the chance to cure.


Which men are candidates for active surveillance?

While the exact criteria used to select candidates for AS vary among institutions, the majority of programs offer surveillance to men with VLR and LR cancer, and in some cases it may be appropriate to consider in men with intermediate risk disease as well. Another important consideration is a man's overall life expectancy. Men who are otherwise healthy and expected to live for another 10 years or longer are more likely to be harmed even by lower-risk cancers; these men are usually recommended to undergo treatment. At Johns Hopkins, we initially offered AS to men with VLR disease, although certain men with LR disease are good candidates as well. Men with intermediate risk cancers are in rare instances considered as well (see table). Regardless, all men considering AS should have an in-depth discussion with their urologist regarding its risks and benefits. Specific entry criteria and considerations at the time of entry are listed in the table below, followed by a tool which can provide an estimate of life expectancy (Cho et al.).

Very low
Gleason Score <7 and stage T1c and PSA density <0.15 and unilateral disease with <3 cores containing cancer regardless of percent core involvement
·         Any age if patient prefers surveillance
·         Preferred if life expectancy is less than 20 years
Gleason Score <7 and stage T1c and PSA density <0.10 and unilateral disease with <3 cores containing cancer regardless of percent core involvement
·         Any age if patient prefers surveillance
·         Preferred if life expectancy is less than 20 years
Stage T1c or T2a and Gleason score <7 and PSA <10
·         Age >65 years
·         Preferred if life expectancy is less than 10 years
Stage T2b or T2c or Gleason score 3+4 or PSA 10-20 (not very low risk)
·         Life expectancy is less than 10 years
Stage T3 or Gleason score >3+4 or PSA >20
·         Not recommended

Gleason refers to Gleason scores. PSA density is PSA divided by prostate volume determined by ultrasound or MRI.

As we will discuss further, participation in active surveillance requires a patient committed to repeat tests and examinations. In our next entry, we will discuss the basic follow-up protocol for AS, why some men ultimately undergo treatment, and what we know about the safety of our surveillance program and others.

Stay tuned to read Part Two. 
For a more detailed explanation of the pathology used to grade prostate cancer, and additional information regarding active surveillance, visit the Johns Hopkins Active Surveillance Program website:

The Blog was written by Jeffrey Tosoian, MD (@UroDocJT). Dr. Tosoian is a PGY3 (Post-Graduate Year 3) urology resident at the Brady Urological Institute at Johns Hopkins.

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