Risks of surveillance, focal therapy, androgen deprivation therapy defined

Key Points

Active surveillance is safe, but some patients will progress. In one study of patients with low-risk disease, 40% met the criteria for active surveillance, and 30% of them agreed to it. In 10 years, 77% of the patients were still alive, and none had died of prostate cancer. However, in another study, among patients who met low-risk criteria, 25% of the patients had fully progressed at 5 years.

Active surveillance is a newer concept that combines the elements of "watchful waiting;" ie, routine monitoring by digital rectal exam and PSA, with judicious use of repeat biopsy in patients appropriately selected on the basis of prostate cancer risk features, chronologic age, and comorbidities. It is an excellent concept because, with screening, an increasing number of men are being diagnosed with prostate cancer. Yet many have tumors that will not progress; thus, they can be followed closely and can receive potentially curable treatment if local progression occurs, Dr. Williams said.

"These data on outcomes of active surveillance add validity to the concept, while definitive data on the efficacy of screening in decreasing prostate cancer-related mortality are awaited."

Of 100 radical prostatectomy cases with reasonable criteria for active surveillance, two-thirds had contralateral disease that was pathologically significant in 20%. In another study of contralateral disease, when surgeons performed a hemi-ablation, 83% had residual tumor that was pathologically significant 30% of the time. After three-quarter ablation, 50% had residual tumor, 10% of which was pathologically significant. Surgeons performed a 3-D mapping biopsy on patients who met criteria for focal ablation and found that 20% were upgraded to Gleason 8 and two-thirds were up-staged.

There is increasing interest in subtotal focal treatment of prostate cancer using multiple different approaches, and it is being espoused by some as excellent treatment. However, three studies investigating its potential role suggest it is a flawed concept because results show that a substantial percentage of patients have higher-volume and some higher-grade disease than expected at original biopsy, indicating subtotal treatment will be inadequate in these patients, Dr. Williams said.

He acknowledged that focal treatment has proven benefits in many diseases. However, its role in prostate cancer is uncertain, due to the absence of adequate, prospective controlled studies demonstrating efficacy. There are also no data on local recurrence/progression following partial surgical resection, which is important, considering a theoretical risk that surgical manipulation could induce local tumor spread.

"The primary issue in determining the role of partial treatment is whether prostate cancer is unifocal," Dr. Williams said. "In fact, it rarely is. Therefore, I believe prostate cancer is not amenable to partial treatment, except in patients who don't require treatment in the first place."

Patients with focal positive margins are less likely to recur, but are more likely to recur than are patients with negative margins. The difference remains in patients with T2 disease.

This take-home message highlights what has been a major step forward in open and minimally invasive approaches to radical prostatectomy; ie, an emphasis on the importance of positive margin status and methods to decrease positive margin rates. Previous data have shown that recurrence risk associated with positive margins depends on extent and location. This report corroborates that information in showing that a focal positive margin is less likely to be associated with recurrence than an extensive positive margin is.

"However, the bottom line is to reinforce the necessity of vigilance on the part of the surgeon to prevent positive margins and of pathologists to accurately define positive margins when performing their histologic review," Dr. Williams said.

In patients with high-risk disease who were randomized to either radiation therapy or radiation therapy plus androgen deprivation therapy (ADT), those receiving combined therapy lived longer. However, when stratified to include comorbidity, patients with high comorbidity were more likely to die if they had received ADT.

While the addition of ADT to radiation therapy in men with high-risk disease may result in a survival benefit overall, this information underscores the need to consider the individual patient, since there is a risk that ADT may hasten his demise, rather than prevent it. Osteoporosis-related fractures long have been recognized as a risk of ADT. More recently, higher risks of cardiovascular disease and diabetes mellitus have been documented among men receiving ADT.

"Whenever therapeutic intervention is contemplated, it is incumbent on the physician to fit the treatment appropriately to the patient. In the case of ADT, that means evaluating a man's overall medical status to determine if he is an appropriate candidate for ADT and, if this treatment is initiated, providing close follow-up to detect heart disease and adverse metabolic effects. The importance of this monitoring is something relatively new to urologists," Dr. Williams said.