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Two different perspectives in the management of pT3 and/or margin-positive prostate cancer after radical prostatectomy

Created: 5/10/2006
Updated: 4/11/2006

 
Two different perspectives in the management of pT3 and/or margin-positive prostate cancer after radical prostatectomy
Choo R, Kawakami J, Siemens R, Davis BJ, Brundage M, Pisansky TM.
BJU Int. 2006 Oct;98(4):773-6

Introduction
Two perspectives exist on the optimum management of pT3 and/or positive resection margins with undetectable PSA after radical prostatectomy (RP):

  • Should a blanket policy of adjuvant RT be applied to all patients with pT3 and/or a positive resection margin?
  • Or can a strategy of surveillance with timely implementation of salvage RT limited to only those with PSA relapse be equally effective?
  • pT3 and/or positive surgical margins are associated with a greater risk of PSA relapse, local recurrence, distant metastasis, and death from prostate cancer 
  • Patients with pT3 disease have a 68% 15-year local failure rate with RP alone
  • 75% of patients with pT3 and/or margin-positive disease can develop a PSA relapse
  • Patients with pT3 and/or margin-positive disease can be subdivided into those without or with detectable PSA levels after RP
  • Current review concerns pT3 and/or positive resection margins with undetectable PSA levels after RP
Phase III studies comparing RT with observation

1 EORTC 22911
  • 1005 patients between 1992 and 2001, randomized to observation (503) alone and adjuvant RT (502)
  • Median follow-up of 5 years
  • RT arm had significantly better PSA progression-free (74.0% vs 52.6%) and clinical progression-free survival (85.1% vs 77.5%)
  • No difference in overall survival (92.3% vs 93.1%) and incidence of distant metastasis (6.1% vs 6.3%) between the arms
2 SWOG-coordinated Intergroup study 8794
  • 473 patients between 1988 and 1995
  • Median follow-up of 9.7 years
  • RT significantly improved the PSA progression-free and clinical progression-free survival rates
  • Advantages with adjuvant RT did not translate into improvements in metastasis-free or overall survival rates at 5 and 10 years
3 ARO 9602
  • Targeted patients with undetectable PSA levels after RP in the setting of pT3 disease
  • 108 men treated with RT and 153 managed with observation
  • At 4 years the PSA progression-free rate was significantly better in the RT arm (81% vs 60%)
NB EORTC and the SWOG studies did not recognize the clinical significance of 'undetectable' vs 'detectable' PSA levels after RP in relation to the efficacy of RT and failed to stratify patients according to PSA level after RP
Timing and type of therapeutic intervention for those with PSA relapse was left at the discretion of the attending physician
Studies not aimed at answering current review question

Adjuvant RT vs surveillance with timely salvage RT

Level 1 evidence exists for the benefit of adjuvant RT on PSA progression-free survival, but has not been unanimously accepted 

FOR AGAINST
A significant proportion of patients with pT3 and/or positive resection margins will eventually develop PSA relapse. Without being able to accurately predict the future course of the disease, it is prudent to consider adjuvant RT after RP

PSA relapse at 4 years rate in patients with pT3 and/or positive resection margins with undetectable PSA levels is 40%. Thus a blanket policy of adjuvant RT for all is over-treatment
Level 1 evidence exists to support adjuvant RT in terms of PSA progression-free survival and local control. This may translate into a gain in metastasis-free, disease-specific, and overall survival There is no evidence for adjuvant RT improving metastasis-free, disease-specific, or overall survival. The natural history of untreated PSA relapse can be long, and n such patients, the likelihood of dying from other causes might be greater

It is possible that by the time a patient develops a clinical local recurrence or rising PSA level, occult distant metastasis might have already developed. Studies have shown PSA progression-free survival from the time of surgery is better for patients receiving adjuvant RT than for those undergoing salvage RT

Salvage RT might be as effective as adjuvant RT if delivered as soon as there is a sign of PSA relapse. E.g. Studies have shown if the PSA level is <1 ng/mL before RT the probability of 5-year PSA relapse-free survival after salvage RT was not statistically different from that after adjuvant RT
Adjuvant RT after RP is generally associated with a small risk of serious radiation morbidity Although grade = 3 radiation toxicity might not be common, the incidence of grade =2 radiation morbidity can be much more prevalent

The addition of adjuvant RT is consistent with the initial management intent of curative approach Careful surveillance with timely salvage RT limited to only those with PSA relapse is not necessarily contradictory to the initial curative intent


Conclusion

  • The optimum management of patients with pT3 and/or positive resection margins with undetectable PSA levels after RP remains controversial
  • Despite phase III studies, showing benefit of adjuvant RT in terms of PSA relapse-free survival
  • Further study is needed to address the following question
  • Can a strategy of careful surveillance with timely implementation of salvage RT limited to only those with PSA relapse be as effective as a blanket policy of adjuvant RT for all? 






     


ArticleDate:20061005
SiteSection: Article
 
   
    
                                            



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