Prostate Cancer: Determining When to Treat

New data suggest that some carefully selected men who are diagnosed with low-risk prostate cancer can have favorable short-term clinical outcomes without undergoing immediate treatment by electing for active surveillance.

Physicians Weekly | 08.31.2009

Since the discovery and widespread use of PSA screenings, more men are being diagnosed each year with prostate cancer. However, nearly half of these cancers have characteristics associated with a low risk of cancer progression. Moreover, up to 30% of patients electing for surgery to remove the prostate—radical prostatectomy—have pathologic features consistent with an exceedingly low risk of disease recurrence. Although radiation therapy and surgery are effective treatments with a long-standing track record of cancer control, they can result in serious long-term side effects such as incontinence and erectile dysfunction.

Clinicians have increasingly become interested in establishing management strategies that offer the possibility of delaying, obviating, or minimizing the impact of treatment for prostate cancer to avoid subjecting patients to unnecessary treatment and reduce the risk of treatment-related morbidity. One such strategy is active surveillance (AS) with selective delayed intervention (Table 1). “Decisions on when or if to treat men with low-risk prostate cancer have always been challenging,” says Scott E. Eggener, MD. “Some men elect for a treatment that won’t necessarily help them. Close observation of patients with well-specified disease characteristics may allow them to maintain their quality of life without increasing the chance of having their cancer spread.”

Addressing a Critical Question

There are currently no widely-accepted recommendations on which patients are appropriate candidates for AS or when to perform restaging biopsies. Recent investigations suggest that a trial of AS for select patients can help them maintain urinary and sexual function while not compromising disease-specific outcomes or the success of a delayed curative intervention. In the April 2009 Journal of Urology, Dr. Eggener and colleagues compiled a multi-institutional cohort of patients who—based on age and a strict definition of low-risk cancer—were offered multiple options but ultimately elected for AS. “The study addresses when to actively treat versus when to observe and closely monitor the disease,” says Dr. Eggener. “This is an important question for newly diagnosed men who are at minimal risk of prostate cancer progression or metastases.”

In the investigation, AS was defined as commencing on the date of a second biopsy. Follow-up consisted of office visits, reviews of general health and urinary symptoms, digital rectal examinations, and PSA screenings every 6 to 12 months. Biopsies were routinely recommended within 18 months of starting AS and subsequently every 1 to 3 years or as prompted by changes in clinical status that indicated potential disease progression.

With a median follow-up of 29 months, Dr. Eggener’s study demonstrated that active surveillance for select patients with prostate cancer appeared to be safe and was associated with a low risk of systemic progression (Table 2). “Importantly,” adds Dr. Eggener, “two factors—cancer at restaging biopsy and a higher total number of cancerous cores—were associated with a lower likelihood of remaining on AS. Considering these findings, our study team strongly recommends a restaging biopsy prior to commencing AS.”

Developing a Successful AS Program

For any AS program to be successful, Dr. Eggener says that accurate disease characterization at diagnosis is critical. “In our study,” he says, “we specified strict clinical and pathological inclusion criteria and required a second restaging biopsy before commencing AS. This enabled us to identify men with a very low risk of cancer progression. The rate of discontinuing AS was low (about 5% per year). In addition, it’s imperative that all men partaking in an AS program be counseled on the low but real risk of potentially life-threatening cancer progression, which happened to 1% of our patients at short follow-up. To minimize this risk, a restaging biopsy before initiating AS should be mandatory. Findings on the second biopsy can exclude about 30% of patients who originally considered AS based on their initial diagnostic biopsy.” It also minimizes the risk of a Gleason grade sampling error and predicts the likelihood of patients remaining on AS.

Studies indicate that just 10% of patients with newly diagnosed prostate cancer elect for AS. “Our data indicate that AS should be considered more often in appropriately selected patients,” Dr. Eggener says. “Our view on AS is not a disregard for low-risk cancer features. Instead, AS should be seen as a strategy that encourages initial observation, frequent monitoring (including serial prostate biopsies), and, if needed, the implementation of active therapy while the disease is still at a highly curable stage. The bottom line is most men will not require an intervention, but those who do can benefit from a period when quality of life and cancer-related outcomes do not appear to be compromised.”

Scott E. Eggener, MD, has indicated to Physician’s Weekly that he has no financial disclosures to report.

Copyright Physicians Weekly 2009