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P C Walsh

Publications and source records attributed to P C Walsh.

At least 19 recordsLinked to original sources

Combination of prostate-specific antigen, clinical stage, and Gleason score to predict pathological stage of localized prostate cancer. A multi-institutional update.

OBJECTIVE: To combine the clinical data from 3 academic institutions that serve as centers of excellence for the surgical treatment of clinically localized prostate cancer and develop a multi-institutional model combining serum prostate-specific antigen (PSA) level, clinical stage, and Gleason score to predict pathological stage for men with clinically localized prostate cancer. DESIGN: In this update, we have combined clinical and pathological data for a group of 4133 men treated by several surgeons from 3 major academic urologic centers within the United States. Multinomial log-linear regression was performed for the simultaneous prediction of organ-confined disease, isolated capsular penetration, seminal vesicle involvement, or pelvic lymph node involvement. Bootstrap estimates of the predicted probabilities were used to develop nomograms to predict pathological stage. Additional bootstrap analyses were then obtained to validate the performance of the nomograms. PATIENTS AND SETTINGS: A total of 4133 men who had undergone radical retropubic prostatectomy for clinically localized prostate cancer at The Johns Hopkins Hospital (n=3116), Baylor College of Medicine (n=782), and the University of Michigan School of Medicine (n=235) were enrolled into this study. None of the patients had received preoperative hormonal or radiation therapy. OUTCOME MEASURES: Simultaneous prediction of organ-confined disease, isolated capsular penetration, seminal vesicle involvement, or pelvic lymph node involvement using updated nomograms. RESULTS: Prostate-specific antigen level, TNM clinical stage, and Gleason score contributed significantly to the prediction of pathological stage (P<.001). Bootstrap estimates of the median and 95% confidence interval of the predicted probabilities are presented in the nomograms. For most cells in the nomograms, there is a greater than 25% probability of qualifying for more than one of the pathological stages. In the validation analyses, 72.4% of the time the nomograms correctly predicted the probability of a pathological stage to within 10% (organ-confined disease, 67.3%; isolated capsular penetration, 59.6%; seminal vesicle involvement, 79.6%; pelvic lymph node involvement, 82.9%). CONCLUSIONS: The data represent a multi-institutional modeling and validation of the clinical utility of combining PSA level measurement, clinical stage, and Gleason score to predict pathological stage for a group of men with localized prostate cancer. Clinicians can use these nomograms when counseling individual patients regarding the probability of their tumor being a specific pathological stage; this will enable patients and physicians to make more informed treatment decisions based on the probability of a pathological stage, as well as risk tolerance and the values they place on various potential outcomes.

Decision Support Techniques

Role of prostate-specific antigen velocity in prediction of final pathologic stage in men with localized prostate cancer.

OBJECTIVES: Prostate-specific antigen (PSA) velocity prior to radical retropubic prostatectomy was evaluated to determine if men with a faster rate of rise in PSA have locally more extensive prostate cancer. METHODS: Of 368 men who underwent radical retropubic prostatectomy, 82 had two to seven PSA measurements between 1.3 and 6.7 years before prostate biopsy for evaluation of PSA velocity. PSA velocity and the pretreatment parameters of PSA, Gleason score, and T stage were evaluated as predictive parameters of pathologic stage. RESULTS: In men with pathologically organ-confined disease, PSA velocity was 1.12 ng/mL/yr; in non-organ-confined cases, it was 1.88 ng/mL/yr. There was a statistically significant relationship between a Gleason score of 7 and above and the pathologic extent of disease. There was no statistically significant relationship between T stage, the PSA at diagnosis, and PSA velocity with respect to final pathologic stage. CONCLUSIONS: PSA velocity is not a strong predictor of pathologic stage in men with localized prostate cancer.

Adult

Stage D1 (T1-3, N1-3, M0) prostate cancer: a case-controlled comparison of conservative treatment versus radical prostatectomy.

OBJECTIVES: There is no consensus on the management of Stage D1 prostate cancer. The literature suggests that radical prostatectomy, as compared with pelvic lymphadenectomy (PLND) alone, may extend survival, Despite evidence that lymph node tumor burden influences cancer survival, few groups of researchers have controlled for this variable when comparing management strategies. We performed a study that was case-controlled for nodal tumor burden to determine if a survival advantage exists for radical prostatectomy. METHODS: Of 168 men with Stage D1 disease diagnosed between 1983 and 1995, 127 underwent pelvic lymphadenectomy and radical retropubic prostatectomy (PLND/RRP) and 41 underwent PLND alone. Clinical charts were reviewed for follow-up, and lymph node tumor burden was assessed by volume of nodal metastases and the percentage of positive nodes sampled. Adjuvant treatment was based on the surgeon's preference and clinical situation. Nineteen patients from each group were matched for age, PSA, Gleason score, clinical stage, follow-up, and nodal tumor burden. RESULTS: Comparison of the non-case-controlled PLND/RRP and PLND groups showed no differences in age, prostate-specific antigen level, Gleason score, clinical stage, or follow-up. The nodal tumor burden was greater for the PLND group (P = 0.001). The 10-year cancer-specific survival rates for the PLND/RRP and PLND groups were statistically different (P = 0.006). In the case-controlled group, the results were similar for cancer-specific survival at 10 years (56% and 34%, respectively; P = 0.09). CONCLUSIONS: These data suggest that in Stage D1 prostate cancer, a trend toward a statistical difference in survival may exist for radical prostatectomy as compared with conservative treatment. Further case-controlled and prospective randomized studies are needed to verify these results.

Actuarial Analysis

Prostate-specific antigen after anatomic radical retropubic prostatectomy. Patterns of recurrence and cancer control.

In a series of 1623 men with a follow-up of 5 +/- 3 years (range 1-13) after anatomic RRP for clinically localized prostate cancer, 17% (276/1623) have shown recurrence. A detectable PSA was the only evidence of recurrence in 7.9%, whereas 2.5% have recurred locally and 5.4% have developed distant metastases. The overall actuarial progression-free rate for these men at 10 years was 68%. Actuarial rates at 10 years were 18% for development of an isolated PSA recurrence, 8% for local recurrence, and 9% for distant recurrence. The actuarial likelihood of a postoperative recurrence increased with increasing clinical stage, Gleason score, preoperative PSA level, and pathologic stage. Although not shown in our previous report, the actuarial rate of recurrence of tumors with a Gleason score of 7 was statistically different from that of tumors of higher Gleason score (8-10). As well, men with preoperative PSA levels of 10.1 to 20 ng/mL experienced recurrence at a significantly lower rate than did men with preoperative PSA levels greater than 20 ng/mL. By using a combination of Gleason score, pathologic stage, and surgical margin status, we demonstrated that the presence of a positive surgical margin did not dramatically affect recurrence in tumors of Gleason scores 2 to 6 with capsular penetration. Surgical margin status was important in high-grade tumors with capsular penetration. In fact, tumors with capsular penetration, Gleason score of at least 7, and a positive surgical margin behaved similarly to tumors with invasion of the seminal vesicles. Preservation of potency did not adversely influence cancer control. The Gleason score, presence or absence of seminal vesicle or lymph node involvement, and the timing of PSA recurrence are all important variables in predicting eventual local versus distant failure associated with an isolated rise in serum PSA. Overall actuarial cause-specific survival at 5 and 10 years was 99% and 93%. Although there was no difference in survival among men grouped by TNM stage or preoperative PSA, advancing histologic grade and pathologic stage did have an effect on actuarial cause-specific survival. Men undergoing RRP for clinically localized prostate cancer showed a 16% actuarial rate of development of metastatic disease at 10 years. This is considerably better than conservative therapy and justifies RRP as the treatment of choice for men with clinically localized disease who are otherwise healthy and have a greater than 10-year life expectancy.

Disease Progression

Clinical and biological characteristics of familial benign prostatic hyperplasia.

PURPOSE: We attempted to determine the clinical and biological characteristics of familial benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: Urinary flow rate, prostate size, symptom score, serum prostate specific antigen, testosterone and dihydrotestosterone were measured in subjects who participated in the nationwide Merck phase III finasteride clinical trial. Findings in the 69 men with familial BPH (3 or more family members with BPH, including the proband) were compared to those in the 345 with no family history of BPH. Logistic regression was used to detect relationships between familial BPH, and these variables before and after 5 alpha-reductase inhibition with finasteride. RESULTS: Familial BPH was characterized by large prostate size. Mean prostate volume in men with familial and sporadic BPH was 82.7 and 55.5 ml., respectively (p < 0.001). Other clinical findings, including serum androgen levels and response to finasteride, were similar in familial and sporadic BPH. The frequency of familial BPH in patients with prostate size in the largest and smallest deciles was 46 and 13%, respectively. CONCLUSIONS: Familial BPH in this group of patients was associated with large prostate size, normal serum androgen levels and normal response to 5 alpha-reductase inhibition. A genetic factor responsible for familial BPH may exert its influence through androgen independent control of prostatic growth.

5-alpha Reductase Inhibitors

Prospective evaluation of men with stage T1C adenocarcinoma of the prostate.

PURPOSE: The pathological characteristics of stage T1c cancers in the era of widespread prostate specific antigen (PSA) testing were determined, and the ability of pretreatment parameters to predict tumor significance in men with stage T1c disease was evaluated. MATERIALS AND METHODS: Of 336 men with stage T1c prostate cancer seen between 1994 and 1996, 240 (71.4%) were treated with radical prostatectomy, 20 (6%) with radiation therapy and 76 (22.6%) expectantly. Recommendations for treatment were based on previously determined criteria predictive of a significant stage T1c cancer (more than 0.2 cm.3): 1) PSA density 0.15 ng./ml./gm. or more, 2) Gleason score 7 or greater, 3) 3 or more cores involved with cancer, or 4) 50% or more involvement of any core with cancer. Pathological evaluation of prostatectomy specimens allowed classification of tumors as insignificant (confined tumor smaller than 0.2 cm.3 with a Gleason score of less than 7), minimal (confined tumor 0.2 to less than 0.5 cm.3 with a Gleason score of less than 7), moderate (0.5 cm.3 or larger disease, or capsular penetration with a Gleason score of less than 7) and advanced (capsular penetration with a Gleason score of 7 or more, or positive margins, seminal vesicles or lymph nodes). Pathological characteristics of tumors in this series were compared to a previous series of 157 men with stage T1c cancers who underwent radical prostatectomy between 1988 and 1992. RESULTS: Of 240 men who underwent radical prostatectomy tumors were insignificant in 40 (17%), minimal in 29 (12%), moderate in 124 (52%) and advanced in 47 (19%). An increase in organ confined cancers (51 to 72%) and a decrease in positive margins (17 to 8%) were noted when comparing stage T1c series (1988 to 1992 versus 1994 to 1996) but the percentage of insignificant tumors remained stable (16 versus 17%) between series. Ultrasound and sextant biopsies were available for review in 72 cases (current series). If the pretreatment criteria used to recommend therapy suggested significant tumor (64 cases) then insignificant tumor was present in only 10 (16%). If pretreatment criteria suggested insignificant tumor (8 cases), insignificant or minimal tumor was present in 6 (75%) and moderate organ confined disease was present in 2 (25%). The absence of a lesion on ultrasound and measurement of total length of cancer within the biopsy specimen were not predictive of an insignificant tumor. CONCLUSIONS: In a nonscreened population stage T1c cancers are being discovered earlier with widespread PSA testing. Even with the detection of earlier cancers we demonstrated that it is possible to minimize the number of patients with small tumors who will undergo radical prostatectomy using pretreatment criteria to counsel men regarding appropriate management options.

Adenocarcinoma

Major susceptibility locus for prostate cancer on chromosome 1 suggested by a genome-wide search.

Despite its high prevalence, very little is known regarding genetic predisposition to prostate cancer. A genome-wide scan performed in 66 high-risk prostate cancer families has provided evidence of linkage to the long arm of chromosome 1 (1q24-25). Analysis of an additional set of 25 North American and Swedish families with markers in this region resulted in significant evidence of linkage in the combined set of 91 families. The data provide strong evidence of a major prostate cancer susceptibility locus on chromosome 1.

Adult