active surveillance/watchful waiting

Watchful Waiting / Active Surveillance
for Prostate Cancer


Leonard S. Marks, M.D.
Medical Director, USRF
Clinical Professor of Urology, UCLA
Kattan Nomogram to Evaluate
Risk of Treatment Deferral

Dall'Era Review of
Current Literature



February, 2008---Many cases of prostate cancer do not need treatment, because they are harmless, so indolent they do not threaten the individual. For men who harbor tiny, slow-growing lesions, watchful waiting or active surveillance (preferred term) is often preferable to treatment with surgery or radiation. Because of widespread PSA testing and ease of biopsy, non-threatening prostate cancers are now found with increasing frequency. Currently, candidates for active surveillance constitute approximately half of all men with newly diagnosed prostate cancer.

The Over-Treatment Concern
Prostate cancer increases with age; it is not often diagnosed before age 50 y.o.; and typically, it exhibits a long latency period. A pathologist at Wayne State University, Dr. Wael Sakr performed careful sectioning of prostate glands removed from 525 men dying after trauma in Detroit, MI. Sakr found that spots of cancer were present in 8% of men in their 20s, 31% of men in their 30s, and a further increase with each decade up to 80% of men in their 70s. These cancers were incidental, ie, they had not presented with clinical manifestations. Thus, incidental prostate cancer is extremely common in aging men, but may also be found in young men.

As a result of widespread PSA testing, many prostate biopsies---as many as one million annually in the U.S.--- are now performed. Consequently, many incidental cancers, which would have remained undetected and clinically irrelevant in the pre-PSA era, are now being brought to light. Most prostate cancers diagnosed today are classified as Stage T1c, meaning the biopsy was driven purely on the basis of a PSA elevation and no palpable abnormality is present. While many important cancers are detected at this stage (T1c), over-treatment of non-important T1c prostate cancers is now a concern.


Epstein
Recognition of the Problem
Dr. Jonathan Epstein, who has studied prostates removed by Dr. Patrick Walsh and colleagues at Johns Hopkins University, was among the first to recognize that many radical prostatectomy specimens contained very small cancers. Small well-differentiated tumors, i.e., those less than 0.5 cc in volume, are very unlikely to ever become clinically manifest, according to work from Professor Stamey at Stanford University in the 1980s. Thus, several investigators have followed Epstein’s lead in correlating clinical findings with pathologic findings in the whole-prostate, aiming to avoid surgery for unimportant cancers.

Establishing an Active Surveillance Program

Carter
Among the pioneers of the active surveillance movement was H. Ballentine Carter, M.D., Professor of Urology at Hopkins. In 1997, Carter reported that men appearing to have unimportant cancers (20-30% of a non-screened population), according to the 1994 criteria of Epstein and Walsh, could safely watch and wait. In 2002, Carter expanded his work, showing that although 30% of his watchful waiting group progressed under the surveillance, when they came to operation, more than 90% of them were still curable. By 2007, Carter’s active surveillance group had grown to more than 400 men, with 59% continuing in the ‘Expectant Management’ program at a median follow-up of 3.4 years (range 0.4 – 12.5 years). Under Carter’s protocol, PSA and digital rectal exam are performed every 6 months and biopsy is performed annually.

Listen as Dr. Carter explains ‘Expectant Management’ of Prostate Cancer.
Criteria for Active Surveillance
According to the most recent information from Johns Hopkins University, the criteria for active surveillance of a prostate cancer are as follows:

Gleason Score < 6
PSA Density < 0.15
< 3 biopsy cores containing cancer
No core showing more than 50% cancer
When initial or follow-up data show an adverse change from these criteria, the patient is advised that his tumor may be progressing and active intervention must then be considered. Progression of a cancer may also be detected by following the PSA doubling time; according to Professor Klotz of Toronto, a PSADT < 3 years may warrant active intervention. In the Toronto experience, approximately 20% of men would move to active intervention because of a PSADT < 3 years. PSA Doubling Time (PSADT) can be determined using the handy and free calculator described here.


Kattan
Kattan's Nomogram
Dr. Michael Kattan now of Memorial/Sloan-Kettering Cancer Center in New York recently published a nomogram to help men with small foci of prostate cancer determine their risk. Data to create the nomogram were taken from a large sample of British men with prostate cancer diagnosed in the early 1990s, who were followed for many years without treatment. While the database is not perfectly applicable to U.S. men diagnosed nowadays, it is a generally helpful instrument providing an analytic approach to this problem. Specific patient examples, where the Kattan nomogram is applied to predict risk, are given here.

Patient Anxiety and the Decision for Active Intervention
Despite attempts at applying science to the “latent cancer quandary,” an individual’s decision to have active intervention is often made on the basis of fear. Cancer phobia is common, even among well-educated people, and is often the primary motivating factor in a man’s decision to have treatment. Latini and co-workers have shown, in a study of 124 men with prostate cancer in active surveillance across the U.S., that anxiety is an independent predictor of treatment. The implication is that a program of psychosocial support, yet to be defined, should be incorporated into the overall aspects of active surveillance.

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Key References
Kattan MW, Cuzick J, Fisher G, Berney DM, Oliver T, Foster CS, Møller H, Reuter V, Fearn P, Eastham J, Scardino PT. Nomogram Incorporating PSA Level to Predict Cancer-Specific Survival for Men With Clinically Localized Prostate Cancer Managed Without Curative Intent. Cancer 2008 Jan;112(1):69-74

Latini DM, Hart SL, Knight SJ, Cowan JE, Ross PL, DuChane J, Carroll PR and the CaPSURE™ Investigators. The Relationship Between Anxiety and Time to Treatment for Patients With Prostate Cancer on Surveillance. J Urol. 2007 Sept;178:826-32

Carter HB, Kettermann A, Warlick C, Metter EJ, Landis P, Walsh PC, Epstein JI. Expectant Management of Prostate Cancer With Curative Intent: An Update of The Johns Hopkins Experience.
J Urol. 2007 Apr;178:2359-65

Roemeling S, et al., Active Surveillance for Prostate Cancers Detected in Three Subsequent Rounds of a Screening Trial: Characteristics, PSA Doubling Times, and Outcome, Eur Urol (2006), doi:10.1016/j.eururo.2006.11.053

Klotz L. Active Surveillance with Selective Delayed Intervention Using PSA Doubling Time for Good Risk Prostate Cancer. European Urology 47 (2005) 16-21

Cooperberg MR, Lubeck DP, Meng MV, Mehta SS, Carroll PR. The Changing Face of Low-Risk Prostate Cancer: Trends in Clinical Presentation and Primary Management. JCO 04 Jun;22(11):2141-49

Carter HB, Walsh PC, Landis P, Epstein JI. Expectent Management Of Nonpalpable Prostate Cancer With Curative Intent: Preliminary Results. J Urol. 2002 Mar;167:1231-34.

Epstein JI, Walsh PC, Carmichael M, Brendler CB. Pathologic and clinical findings to predict tumor extent of nonpalpable (stage T1c) prostate cancer. JAMA 1994 Feb;271(5):368

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