Triple Play: Ordering Tumor Markers Appropriately

Researchers have identified gene expression patterns and DNA changes that can also be used as tumor markers if present in tumor biopsies.

Cancer creates a need for surgery for many patients and in almost every physiologic system. Only the heart and the retina seem to thwart cancerous growths. More than 20 different tumor markers — most of them proteins produced in excess by a malignant neoplasm — are in clinical use. Though many use blood or urine samples, researchers recently identified gene expression patterns and DNA changes that can also be used as tumor markers if present in tumor biopsies.

Although some tumor markers indicate a specific cancer, others are common to multiple cancers and indicate that more testing is needed. Tumor markers are limited in other ways, as benign conditions can elevate tumor markers, and tumor markers are not uniformly elevated in all associated cancer patients. Thus, their specificity is inexact.

The media often heralds tumor markers as remarkable achievements — which they are — but the attention often motivates patients to ask for lab work to screen for cancer-using markers. However, studies show that tumor markers have the most clinical utility in monitoring treatment and detecting disease recurrence.

Surgeons may be interested in these three items recently published on the topic:

  • The prostate-specific antigen (PSA) is arguably the most commonly ordered tumor marker, as most patients recognize it as an indicator of prostate cancer. As one urologist has said, “Patients who have prostate cancer know their PSAs and ask for frequent retesting.” Four years ago, the American Urological Association (AUA) recommended initiating PSA testing to screen for prostate cancer in all men with an estimated life expectancy of more than 10 years, beginning at age 40. That recommendation was based on consensus. In its now-evidenced-based clinical practice guideline released May 3, 2013, the AUA looked at data that indicates for every 1,000 men screened, only one death has been prevented. Thus, the AUA now advises a more selective approach, as it does not recommend PSA screening for men aged 70 years or older, or any man with less than a 10- to 15-year life expectancy, and the association only suggests screening in men aged 55 to 69 if benefits outweigh risk, which is in line with what other major medical authorities suggest.
  • Most of the current guidelines encourage physicians to order organ-appropriate single tumor marker lab work and advise against screening for the multiple tumor markers in patients who have non-specific symptoms. Despite those recommendations, inappropriate use is common. Many laboratories have reported that their workload for tumor markers has doubled in the last 10 years, citing many requests for multiple tumor markers in an individual patient. Ordering tumor markers can be a sort of fishing expedition for possible cancer. Recognizing that inappropriate requests for tumor markers can be misleading and alarming for patients, a team of researchers in Wales audited 1,878 requests for tumor markers in 727 patients. Thirty-eight percent of those requests were for panels of four or more tumor markers, and most of them were ordered because the patients had lost weight or were fatigued. One-third of requests for cancer antigen 125 (CA-125) were ordered for men, despite the fact that the marker is most useful to detect ovarian cancer and rarely useful in males. When the researchers implemented local guidelines, inappropriate requests dropped by 41 percent.
  • Fallopian tube and ovarian cancers remain difficult to diagnose at early stages, so even though cure rates have somewhat improved, they remain unacceptably low. The largest barrier to progress is the cancers’ vague symptoms. In the diseases, early use of transvaginal ultrasounds and available tumor markers improve the diagnosis rate. Though serum CA-125 has been the sole available serum marker, it unfortunately stays within normal limits in up to 50 percent of Stage I ovarian cancers and it can be elevated in benign conditions. However, Simmons and colleagues published a review in Oncology describing a new serum marker, human epididymis protein 4 (HE4), that is more likely to be elevated early in the disease process, so when combined with CA-125, HE4 may improve early diagnosis. With more data, this test may become commercially available as a needed and useful diagnostic tool.