Linear regressive analysis using prostate-specific antigen doubling time for predicting tumor biology and clinical outcome in prostate cancer

Abstract

Background. This study was undertaken to calculate the prostate‐specific antigen doubling time (PSA‐DT) of prostate cancers recurrent after external beam radiation therapy and to investigate if a correlation exists between the PSA‐DT and the clinical behavior of prostate cancer as a possible reflection of the tumor doubling time. Methods. Twenty‐two patients treated with external beam radiation between October 1985 and October 1990 for clinical stages B1, B2, and C (T2a, T2b, T3) prostate cancer experienced PSA elevation as their only sign of failure. Serial PSA determinations are available before initiation of any secondary treatment and these have been used to calculate PSA‐DT. Results. The results of this study reveal that the PSA‐DT is a constant (r ± 0.98). Mathematically, this means the PSA value is growing exponentially and may represent tumor growth in the exponential phase. Second, the PSA‐DT was found to be linearly correlated (r = 0.86) with the interval to clinical relapse after PSA failure. Graphically, the slope of this correlation is equal to the number of PSA‐DT (4.5 with 95% confidence interval [3.6]) required before clinical disease manifests after PSA failure. Using this relationship, one can delineate those patients with aggressive tumor biology (PSA‐DT < 3.8 months) who require immediate therapeutic intervention versus a relatively indolent tumor biology (PSA‐DT ± 3.8 months) who can be spared the morbidity and expense of androgen deprivation therapy until clinical recurrence manifests. Furthermore, in the pretreatment setting, observation rather than treatment may be indicated for patients with PSA‐DT for 18 months or more, because the disease may not become clinically apparent during the patient's lifetime. Conclusion. PSA‐DT after radiation therapy may reflect the tumor doubling time and has implications in the posttherapy setting regarding the optimal time of intervention with androgen deprivation and in the pretreatment setting regarding the necessity for treatment rather than observation.

Anatomic distribution and pathologic characterization of small-volume prostate cancer (<0.5 ml) in whole-mount prostatectomy specimens

“…Several studies have suggested that it is between several months and 4 years. 27,28 If the tumor volume doubling time were three years, patients 60 years or younger with tumor volumes of 0.5 ml might be likely to develop clinically significant prostate cancer based on the average life expectancy. If tumors have higher Gleason scores, the potential for metastasis may increase and these patients may present with clinically significant prostate cancer sooner.…”

Validation of a treatment policy for patients with prostate specific antigen failure after three‐dimensional conformal prostate radiation therapy

“…D'Amico and Hanks, evaluating the same 22 patients who demonstrated PSA failure after receiving RT at FCCC, described a linear correlation between the PSADT and the clinical disease free interval after PSA failure. 15 Using linear regression analysis techniques, it was noted that clinical failure should manifest on average 4.5 times the PSADT. Lee et al subsequently described the natural history of a large group of patients with an increasing PSA profile after receiving definitive RT at FCCC.…”

Use of pretreatment prostate-specific antigen doubling time to predict outcome after radical prostatectomy

“…1,4,5 D'Amico and Hanks found that, following radiation therapy for prostate cancer, PSA doubling time was linearly correlated with the interval to clinical relapse after PSA failure. 5 They recommended observation rather than treatment for patients with PSA doubling times of ! 18 months, because the disease may not become clinically apparent during the patient's life time.…”