Biochemical failure does not predict overall survival after radical prostatectomy for localized prostate cancer: 10-year results

doi:10.1016/S0090-4295(99)00252-6

Urology

Volume 54, Issue 5, November 1999, Pages 884-890

https://doi.org/10.1016/S0090-4295(99)00252-6 Get rights and content

Abstract

Objectives. To compare rates of overall survival in men with biochemical failure (bF) to those with no bF after radical prostatectomy for localized prostate cancer.

Methods. Radical prostatectomy was performed in 1132 consecutive patients between June 1986 and September 1998, and bF (prostate-specific antigen [PSA] 0.2 ng/mL or greater) was documented in 213 patients (19%), with a mean follow-up of 56 months (range 1 to 125). Ninety-nine patients were treated with androgen ablation and/or radiation therapy at the time of bF. Kaplan-Meier estimates of bF, metastasis-free survival, and overall survival were generated and compared using the log-rank test.

Results. The 10-year overall survival rates for patients with bF (88%) versus no bF (93%) were similar (P = 0.94). The survival rates of patients with bF were not statistically different than those of patients without bF when compared by age older than 65 years, preoperative PSA greater than 10 ng/mL, biopsy or specimen Gleason score 7 or greater, clinical Stage T2b-3, presence of extracapsular extension, positive surgical margins, and seminal vesicle invasion. Patients who received second-line treatment also had a similar 10-year overall survival rate (86%, P = 0.97). For the 213 patients with bF, the metastasis-free survival rate at 10 years was 74%. The overall survival rate for patients with distant metastasis (56%) was markedly lower (P <0.001) than for those without distant metastasis.

Conclusions. At 10 years, patients with a PSA recurrence after radical prostatectomy for localized disease have an excellent overall survival equivalent to those without a detectable PSA. Within this period, the clinical significance of a detectable PSA needs to be further evaluated.

Section snippets

Patients

RP was performed in 1132 consecutive patients between June 1986 and September 1998 at the Cleveland Clinic Foundation. Excluded from the analysis were all patients who received adjuvant therapy other than for a rise in PSA. bF was defined as a serum PSA of 0.2 ng/mL or greater (Abbot IMX or TOSOH assays) and was documented in 213 patients (19%). Ninety-nine of these patients received second-line treatment with androgen ablation (n = 48) or radiation therapy (n = 30), or both (n = 21).

Tumor stage and grade

The

Results

The characteristics of patients with and without bF are shown in Table I. The proportion of patients older than 65 years was similar between the two groups. Patients in the bF group had a higher proportion of initial PSA greater than 10 ng/mL, biopsy and specimen Gleason score 7 or greater, clinical Stage T2b or greater, extracapsular extension, seminal vesicle invasion, lymph node metastasis, and positive margin(s). The average time to bF was 22.2 months. The characteristics of patients

Comment

Our bF rate of 19% is consistent with data from many series that suggest that 10% to 40% of men who undergo RP for localized prostate cancer will develop a detectable PSA level within 5 years.8, 13, 16, 17, 18 Even though tumor progression rarely occurs in the absence of an elevated PSA,7 most of these patients remain asymptomatic, with a detectable PSA the only evidence of failure, especially if the PSA doubling time is 6 months or longer.19 Pound et al.8 showed that 103 (34%) of 304 men with

Conclusions

At 10 years, patients with a PSA recurrence after RP for localized disease have an excellent overall survival, equivalent to those without a detectable PSA. Although PSA-free survival is widely used as an end point and indicator of the success or failure of surgery, the clinical significance of bF needs to be evaluated with longer follow-up of these patients. These observations illustrate the long natural history of prostate cancer treated by RP and emphasize the need for long-term follow-up in

References (36)

J.E Oesterling
Prostate specific antigena critical assessment of the most useful tumor marker for adenocarcinoma of the prostate
J Urol
(1991)
P.H Lange et al.
The value of serum prostate specific antigen determinations before and after radical prostatectomy
J Urol
(1989)
T.A Stamey et al.
Prostate specific antigen in the diagnosis and treatment of adenocarcinoma of the prostate IIradical prostatectomy treated patients
J Urol
(1989)
A Stein et al.
Prostate specific antigen levels after radical prostatectomy in patients with organ confined and locally extensive prostate cancer
J Urol
(1992)
A.W Partin et al.
Serum PSA after anatomic radical prostatectomythe Johns Hopkins experience after 10 years
Urol Clin North Am
(1993)
M.G Oefelein et al.
The incidence of prostate cancer progression with undetectable serum prostate specific antigen in a series of 394 radical prostatectomies
J Urol
(1995)
O Dillioglugil et al.
Hazard rates for progression after radical prostatectomy for clinically localized prostate cancer
Urology
(1997)
H Zincke et al.
Long-term (15 years) results after radical prostatectomy for clinically localized (stage T2c or lower) prostate cancer
J Urol
(1994)
P Kupelian et al.
Correlation of clinical and pathological factors with rising prostate-specific antigen profiles after radical prostatectomy alone for clinically localized prostate cancer
Urology
(1996)
W.J Catalona et al.
Cancer recurrence and survival rates after anatomic radical retropubic prostatectomy for prostate cancerintermediate-term results
J Urol
(1998)

H.A Frazier et al.

Is prostate specific antigen of clinical importance in evaluating outcome after radical prostatectomy?

J Urol

(1993)

W.R Morgan et al.

Long-term evaluation of radical prostatectomy as treatment for clinical stage C (T3) prostate cancer

Urology

(1993)

D.F Paulson

Impact of radical prostatectomy in the management of clinically localized disease

J Urol

(1994)

A Patel et al.

Recurrence patterns after radical prostatectomyclinical usefulness of prostate specific antigen doubling times and log slope prostate specific antigen

J Urol

(1997)

J.G Trapasso et al.

The incidence and significance of detectable levels of serum PSA after radical prostatectomy

J Urol

(1994)

G.L Lu-Yao et al.

Population-based study of long-term survival in patients with clinically localised prostate cancer

Lancet

(1997)

A.W Partin et al.

Radical prostatectomy for high grade diseasea reevaluation 1994

J Urol

(1994)

M.G Oefelein et al.

Long-term results of radical retropubic prostatectomy in men with high grade carcinoma of the prostate

J Urol

(1997)

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Adult UrologyBiochemical failure does not predict overall survival after radical prostatectomy for localized prostate cancer: 10-year results

Abstract

Section snippets

Patients

Tumor stage and grade

Results

Comment

Conclusions

J Urol

J Urol

J Urol

J Urol

Urol Clin North Am

J Urol

Urology

J Urol

Urology

J Urol

J Urol

Urology

J Urol

J Urol

J Urol

Lancet

J Urol

J Urol

Adult Urology
Biochemical failure does not predict overall survival after radical prostatectomy for localized prostate cancer: 10-year results