The researchers took a cohort of 430 men with a biochemical recurrence (PSA increase only) after failed prostatectomy. The men underwent observation until they experienced metastatic disease as determined by CT or bone scan. The researchers then evaluated the PSA at the time the men developed metastasis for those patients who developed metastatic disease.

PSA at metastasis was defined as the PSA value at the time of the first occurrence of metastasis. The median PSA at metastasis was calculated and the interquartile range (IQR) for the entire cohort of men with metastatic progression as well as across different strata of PSADT (?3 vs 3-9 vs 9-15 vs ?15 mo) and Gleason score (?7 vs 8-10). They then used Pearson’s correlation coefficient (r) to examine the relationship between PSADT or Gleason score and PSA at metastasis.

Results:

1- With a median follow-up of 4 years after biochemical recurrence, 126/430 men (29.3%) had developed metastases. Sites of first metastasis included bone in 114 men (90.5%), extra-pelvic lymph nodes in 5 men (4.0%), lung in 3 men (2.4%), liver in 3 men (2.4%), and brain in 1 man (0.8%).

2- The median PSA at the time of initial metastasis was 31.4 ng/mL (IQR, 8.8-87.5). Median PSA at metastasis across different PSADT strata is shown below (Table).

3- There was a weak but statistically significant correlation between PSADT and PSA at metastasis (r=0.20, P=0.02).

4- There was no correlation between Gleason score and PSA at metastasis (r=0.01, P=0.83). Median PSA at metastasis was 30.3 ng/mL (IQR, 8.6-74.9) for men with Gleason ?7 (n=69) and 34 ng/mL (IQR, 7.9-115) for men with Gleason 8-10 (n=57).

Conclusions:

1- In men with biochemical recurrence after prostatectomy, there is an inverse correlation between PSADT and PSA at metastasis, while Gleason sum has no effect on PSA at metastasis. These data may be used by clinicians to estimate at what PSA level metastases are likely to first develop across different strata of PSADT, helping to determine when/if to initiate therapy.

Effect of PSADT on PSA at metastasis
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PSADT group PSA at metastasis (ng/mL)
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Lower quartile                               Median                         Upper quartile

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* 3 mo (n = 29)                 10.0                                            40.4                                     170.0
3-9 mo (n = 52)                  9.3                                            35.4                                      86.1

9-15 mo (n = 20)               7.0                                            26.4                                      78.8

+ 15 mo (n = 25)                6.7                                            19.3                                       52.8

*= less than or equal   += equal or greater than

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Take Homes:

1- As we have discussed the most likely site for initial metastases is the bone. In this cohort over 90% of men first signs of metastatic disease were in their bones. This drives home the significant need to pay attention to general bone health.
2- The longer the PSADT the lower the PSA was to develop metastasizes. This means that men with longer PSADT need to start treatment even with lower PSA numbers.

From the 2011 Genitourinary Cancers Symposium
General Poster Session A: Prostate Cancer: J Clin Oncol 29: 2011 (suppl 7; abstr 16); E. S. Antonarakis, D. Keizman, M. A. Carducci, M. A. Eisenberger; Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD

Joel T Nowak, M.A., M.S.W.