Role of microvessel density in predicting recurrence in pathologic stage T3 prostatic adenocarcinoma

doi:10.1016/S0090-4295(99)00202-2

Urology

Volume 54, Issue 3, September 1999, Pages 479-485

https://doi.org/10.1016/S0090-4295(99)00202-2 Get rights and content

Abstract

Objectives. Extraprostatic extension of prostatic adenocarcinoma (pathologic Stage T3) increases the risk of recurrence after radical prostatectomy compared with organ-confined prostate cancer. Use of microvessel density in predicting cancer recurrence in Stage pT3 cancer is poorly understood. We evaluated known predictors of recurrence, including Gleason grade, preoperative serum prostate-specific antigen (PSA), DNA ploidy, seminal vesicle involvement, and surgical margin status in comparison with optimized microvessel density (OMVD) and area-weighted microvessel density (AWMVD) in patients with Stage pT3 prostate cancer.

Methods. Between 1987 and 1989, 290 previously untreated patients underwent radical prostatectomy and were found to have pathologic Stage T3 adenocarcinoma. No patient received adjuvant therapy. Embedded prostatectomy specimens from 211 patients with sufficient tissue for immunohistochemical staining with factor VIII-related antigen were studied by computer-assisted digital image analysis for OMVD and AWMVD. The correlation of Gleason grade, preoperative PSA, DNA ploidy, seminal vesicle involvement, surgical margin positivity, OMVD, and AWMVD with clinical or biochemical failure was assessed using the Cox proportional hazards model. Biochemical failure was defined as a postoperative increase in PSA greater than 0.2 ng/mL, and clinical failure was defined as a positive biopsy or metastasis on bone scan.

Results. The mean follow-up ± SD for all patients was 7.1 ± 1.8 years, with 43 deaths (9 due to prostate cancer) and 124 cases of clinical and/or biochemical recurrence. The mean OMVD was 65.0 ± 17.3, and the mean AWMVD was 8.2 ± 5.3. OMVD and AWMVD were not predictors of cancer recurrence or significantly associated with DNA ploidy or preoperative PSA. AWMVD was associated with Gleason grade (P = 0.003). The estimated relative risk (adjusted for other cancer variables) of clinical and biochemical recurrence associated with a change in OMVD from the 25th percentile (53.5) to the 75th percentile (75.4) was 1.14 (95% confidence interval 0.92 to 1.42). The estimated relative risk (adjusted) of clinical and biochemical recurrence associated with a change in AWMVD from the 25th percentile (4.8) to the 75th percentile (10.4) was 1.17 (95% confidence interval 0.97 to 1.42). Gleason grade, preoperative PSA, DNA ploidy, and seminal vesicle involvement were predictors of clinical and/or biochemical recurrence in univariate and multivariate analyses.

Conclusions. Microvessel density, assessed by OMVD and AWMVD, did not predict recurrence in patients with pathologic Stage T3 adenocarcinoma of the prostate (TNM Stage T3N0M0). DNA ploidy, Gleason grade, preoperative PSA, and seminal vesicle involvement remained the best predictors of clinical and/or biochemical recurrence in this group of patients.

Section snippets

Patients

The study cohort was selected from a group of 290 patients with pathologic Stage T3 prostate cancer treated with bilateral pelvic lymphadenectomy and radical retropubic prostatectomy between 1987 and 1989 at Mayo Clinic, Rochester, Minn. This interval was selected to include only patients with preoperative serum PSA determination (begun in 1987 at Mayo Clinic) and extended follow-up. Preoperative TNM clinical stage was assigned for all patients on the basis of the results of bone scan, digital

Patient characteristics

The mean patient age at prostatectomy was 67.3 years (range 40 to 79). The median preoperative PSA was 10.0 ng/mL (range 0.7 to 105.0) (Table I). The mean patient follow-up after surgery was 7.1 years (± 1.8 years SD). At the close of the study, 43 patients had died, including 9 of prostate cancer.

Correlation of OMVD with other prognostic factors

The mean OMVD was 65.0 (range 31.6 to 154.6), and the median AWMVD was 8.2 (range 0.6 to 46.0). OMVD and AWMVD were not significantly associated with DNA ploidy, preoperative PSA, seminal vesicle

Comment

Although the goal of radical prostatectomy is complete eradication of prostate cancer, 33% to 42% of clinically organ-confined cancers have pathologic evidence of extraprostatic disease.1, 2, 3, 4, 6 Extraprostatic extension of cancer after radical prostatectomy increases the risk of recurrence, although some patients have a better postoperative course than others,1, 2, 6 and the prediction of outcome is often difficult in this group of patients. Adjuvant therapy in these patients is

Conclusions

Microvessel density analysis, assessed by OMVD and AWMVD, did not improve prediction of cancer recurrence in our cohort of patients with pT3 prostate cancer. OMVD and AWMVD were not significantly associated with DNA ploidy, preoperative PSA, seminal vesicle involvement, or surgical margin status; however, AWMVD was significantly associated with Gleason grade. Cancer recurrence in our cohort of patients with pathologic Stage T3 (TNM staging system, 1997 revision) adenocarcinoma of the prostate

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Our data suggest angiogenic and hypoxia biomarkers may predict outcome and benefit of dose escalation, however further validation in prospective studies including hypoxia modification is needed.
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Adult UrologyRole of microvessel density in predicting recurrence in pathologic stage T3 prostatic adenocarcinoma

Abstract

Section snippets

Patients

Patient characteristics

Correlation of OMVD with other prognostic factors

Comment

Conclusions

J Urol

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Adult Urology
Role of microvessel density in predicting recurrence in pathologic stage T3 prostatic adenocarcinoma