Addressing the Dilemma of Prostate Cancer: When to Treat? How to Treat?

Moul, Judd W., M.D.
Director, Duke Prostate Center
Division Chief, Urology
Professor of Surgery
DukeUniversity Medical Center
Durham, North Carolina
Also by this Author 

Widespread screening for prostate cancer over the last thirty years using the prostate-specific antigen (PSA) test has led to a sharp increase in men being diagnosed with and treated for prostate cancer. Yet recent studies have found that for many  men, the cancer would not have been harmful, and that some  men’s lives have not been extended  as a result1.

With the benefits of increased screening in question physicians face the dilemma of when and how frequently to screen and how to proceed once cancer has been detected.As Dr. Judd W. Moul, Director, Duke Prostate Center, Duke University Medical Center, observes: “The challenge we’re facing today with prostate cancer is we’ve gotten almost too good at screening.”

PSA Screening - Opening Up Pandora’s Box

Dr. Moul believes the PSA test can raise as many questions as answers. “Screening is all about early detection,” he says, “but it almost seems that in many men we’re picking up prostate cancer too early, mainly because a lot of prostate cancers are not lethal for a very, very long time.” This ’over-diagnosis‘ and subsequent treatment can present unnecessary risk and may needlessly compromise quality of life.

Since elevated PSA levels do not necessarily indicate the presence of prostate cancer, and because there is as of yet no “male mammogram” to accurately determine the intra-glandular extent of a tumor, a biopsy - with its attendant risks - is needed to confirm diagnosis2. And even then there is uncertainty, since prostate needle biopsy pathology suffers from sampling error, which could underestimate the grade of cancer in 30-40% of cases. 

PSA as a Baseline Test – A Valuable Tool

Where the PSA test certainly plays a valuable role for younger men is as a baseline test at age 40. There is limited awareness and use of the PSA test in this way, points out Dr. Moul, even though it is now part of guidelines for both the National Comprehensive Cancer Network (NCCN) and the American Urological Association (AUA). Obtaining a PSA value at age 40 can help the physician determine an individual’s  future risk for prostate cancer, and how aggressive or nonaggressive to be with screening over the next 10-20 years. 

Treatment vs. Active Surveillance

Once cancer has been detected by biopsy, the choice for physicians and patients is between treatment and active surveillance. If a biopsy detects a very small cancer, or a cancer that is indeterminate, the question Dr. Moul wrestles with is: “What should we do? Are we going to risk reducing his quality of life now, or are we going to let him go for a while before we proceed with a radical prostatectomy?”

There are no clear criteria for decision making, given the lack of robust clinical trial data to determine therapy or identify patients for active surveillance. For Dr Moul, “The decision ultimately rests with the patient and what their gut feeling is.”

With little consensus among physicians on the frequency and intensity of ’active surveillance‘ and patient anxiety over the possible presence of the cancer, it is not nearly as common a path as active treatment. 

For patients with early-stage disease, Dr. Moul sees fine-tuning the process of active surveillance as the way forward. With more robust longitudinal data doctors will be better able to determine when active surveillance is appropriate.  New research would also clarify the optimal frequency for biopsies and how closely to follow a patient following the baseline PSA test.
 

The Promise of Diagnostic Advances

More precise diagnosis is needed to help direct treatment or determine a plan for subsequent biopsies. With no imaging test analogous to those available for breast cancer, Dr. Moul looks forward to the development of a universally accepted test that accurately determines the size and malignancy of prostate tumors.

Improvements in intra-glandular imaging using newer generation ultrasound or MRI could provide a basis for focal-gland therapies, such as focal cryotherapy or high-intensity focused ultrasound (HIFU). But with  no such ’technological breakthrough‘ yet on the horizon, advances in molecular diagnostics hold the most promise. These include active research to identify new biomarkers and developments in genetic testing, such as the PCA3 urine test.  However, the clinical community will need to wait for their validation by clinical trials.

Treating Advanced Disease

Recent developments in the treatment of metastatic disease include the FDA approval of sipuleucel-T, cabzitaxel, abiraterone and denosumab for advanced castrate-resistant prostate cancer. Dr. Moul cautions that the availability of these new therapies - and their associated expense - have fueled debate about their relative cost/benefitand how to appropriately sequence their use

In this respect the FDA-cleared circulating tumor test (CTC) may assist physicians in monitoring and predicting cancer progression and in evaluating response to therapy in patients with metastatic cancer.In patients with metastatic prostate cancer, CTC counts have been shown to be earlier predictors of treatment response than reduction in PSA levels3.

Dr. Moul underlines the need for further research into multi-modality and multi-disciplinary care, combining surgery with radiation or hormonal therapy to help direct appropriate treatment. “For those with life-threatening prostate cancer, we need to use the full toolbox to manage them.”

References

  1. NCI Cancer Bulletin, September 8, 2009.
    http://www.cancer.gov/aboutnci/ncicancerbulletin/archive/2009/090809/page2
  2. American Cancer Society, Prostate Cancer Facts & Figures 2010, pg. 30
  3. CellSearch®Circulating Tumor Cell Kit (Epithelial) [package insert]. Raritan, NJ: Veridex LLC. LBL 50058, Rev. 6, 2009-05. Available at: http://www.veridex.com/pdf/7800047_04.pdf. Accessed August 11, 2009.