UROLOGICAL ONCOLOGY

The natural history of noncastrate metastatic prostate cancer after radical prostatectomy
Yossepowitch O, Bianco FJ Jr, Eggener SE, Eastham JA, Scher HI, Scardino PT
Department of Urology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA
Eur Urol. 2007; 51: 940-7; discussion 947-8

• Objectives: To characterise the natural history of metastatic prostate cancer after radical prostatectomy (RP) in patients followed expectantly for rising prostate-specific antigen (PSA) (noncastrate metastases).
• Methods: Cox proportional hazards analyses were used to assess predictors of survival among 95 patients who developed clinically detectable noncastrate metastases after RP. The initial metastatic phenotype was characterised as minimal (nodal or axial skeletal involvement) or extensive (appendicular skeletal involvement or visceral metastases). Estimates of survival after diagnosis of metastases were generated with the Kaplan-Meier method.
• Results: Median disease-specific survival from diagnosis of noncastrate metastases was 6.6 yr (95% confidence interval [CI], 5.2, 7.9). The initial site of metastatic disease was bone, lymph node, and viscera in 63%, 36%, and 6% of patients, respectively. Thirteen patients (14%) had extensive disease at their first metastatic manifestation. Longer PSA doubling time in the rising PSA state (hazard ratio [HR] 0.8 for each month increase in doubling time; 95% CI, 0.67-0.94) and the initial metastatic phenotype (HR 0.3 for minimal vs. extensive disease; 95% CI, 0.1-0.6) were associated with improved survival. The prostatectomy Gleason score, lymph node status at RP, PSA level at diagnosis of metastases, and interval from surgery to diagnosis of metastases did not correlate with outcome.
• Conclusion: Men who develop noncastrate metastases after RP may have a durable survival. Favourable prognostic indicators include longer PSA doubling time preceding diagnosis of metastases and initial involvement of axial skeleton or lymph nodes.
  
  
• Editorial Comment
  What happens to patients with metastatic prostate cancer without hormonal deprivation (noncastrate metastases)? These patients nowadays are quite rare and it is very interesting to read this article on 95 patients who developed metastases after radical prostatectomy (RP) and were not castrated.
  The time from operation to development of metastases was 3.2 years median, and the median cancer-specific survival thereafter was 6.6 years.
  Interestingly, in these patients neither Gleason sum score nor lymph node status at RP, PSA level at diagnosis of metastases correlated to outcome. In contrast, fast premetastatic PSA doubling time and extensive (that is, fast) development of metastases were indicators of poor survival.
  The authors propose a flow diagram which may be helpful to identify patients with high risk for the development of metastases in which the first identifier of poor outcome is PSA doubling time < 3 months.

Dr. Andreas Bohle
Professor of Urology
HELIOS Agnes Karll Hospital
Bad Schwartau, Germany
E-mail: boehle@urologie-bad-schwartau.de