Temporarily Deferred Therapy (watchful waiting) for Men Younger Than 70 Years and With Low-Risk Localized Prostate Cancer in the Prostate-Specific Antigen Era

Reviewer: Jack Wei, MD
The Abramson Cancer Center of the University of Pennsylvania
Ultima Vez Modificado: 31 de marzo del 2004

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Authors: Corey A. Carter, Timothy Donahue, Leon Sun, et al.
Source: Journal of Clinical Oncology 21(21): 4001-4008, 2003

Background

  • Prostate cancer (PC) is the most common solid tumor in men in the United States.
  • The optimal management of clinically localized PC is unclear.
  • Watchful waiting (WW) (a strategy of close observation without active treatment) has been used in these low-risk patients; however, studies of watchful waiting have primarily focused on older men.
  • This study describes a population of younger men with low-grade, low-stage PC who initially pursued WW and details the rate and risk factors for eventual abandonment of WW for other secondary treatments.

Methods

  • Records from 15,063 patients from the Department of Defense Center for Prostate Disease Research Tri-Service Multicenter Prostate Disease Research Database were reviewed.
  • Inclusion criteria included diagnosis between January 1991 and January 2002, age 70 years, Gleason score (GS) 6 with no Gleason pattern 4, clinical stage T2, and PSA 20 ng/ml.
  • From the database, 2,074 patients pursued WW and 313 patients were found to be eligible (most patients were ineligible due to age >70 years).
  • PSA doubling times (DTs) were analyzed for 241 patients.
  • Rates and risk factors for progression to secondary treatment were analyzed.
  • Median follow-up time was 3.8 years

Results

  • Median age of diagnosis was 65.4 years.
  • Median PSA at diagnosis was 5.1 ng/ml.
  • Median GS was 5.
  • At 2 years, 57% of men proceeded to secondary therapy, and at 4 years, the rate was 74%.
  • The decision for repeat biopsy was left to the discretion of the treating physician, and 24.6% of patients underwent repeat biopsy; 24% of repeat biopsies resulted in upgrading of the GS.
  • On univariate analysis, younger age, higher clinical stage, shorter PSA DTs, lack of treatment for BPH, and increased GS on repeat biopsy were all predictive of progression to secondary treatment.
  • On multivariate analysis, only clinical stage and PSA DTs were predictive of progression to secondary treatment.
  • Patients who remained on WW for more than 4 years were very unlikely to progress to secondary therapy
  • No data was given regarding the reason patients abandoned WW.

Author's Conclusions

  • In general, younger patients with low-risk disease are unlikely to pursue WW.
  • PSA DT and clinical stage are the most significant factors associated with progression to secondary treatment.
  • The high rate of progression to secondary treatment suggests a need to redefine the criteria for using WW in this population.
  • An analysis of the outcomes of patients who underwent immediate treatment versus those who underwent secondary treatment after an initial period of WW is currently underway.

Discussion

The current study demonstrates that younger patients with low-risk disease are unlikely to remain on long-term WW. The ongoing study mentioned in the author's conclusions will be important in determining the impact of delaying therapy in these patients. If no detrimental effect is found for delayed therapy, it may be reasonable to pursue WW in these patients to spare them the potential side effects of definitive therapy. Without this information available, patients with higher stage disease and short PSA DTs should strongly be considered for upfront therapy.


News
Extent of disease not worsened in men who defer surgery for surveillance

Sep 27, 2010 - Men with low- to intermediate-risk prostate cancer undergoing prostate-specific antigen surveillance who later have deferred radical prostatectomy do not have significantly worsened pathologic features after surgery than men undergoing primary radical prostatectomy, according to research published in the October issue of The Journal of Urology.



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