Biochemical outcome after radical prostatectomy, external beam radiation therapy, or interstitial radiation therapy for clinically localized prostate cancer

CONTEXT: Interstitial radiation (implant) therapy is used to treat clinically localized adenocarcinoma of the prostate, but how it compares with other treatments is not known. OBJECTIVE: To estimate control of prostate-specific antigen (PSA) after radical prostatectomy (RP), external beam radiation (RT), or implant with or without neoadjuvant androgen deprivation therapy in patients with clinically localized prostate cancer. DESIGN: Retrospective cohort study of outcome data compared using Cox regression multivariable analyses. SETTING AND PATIENTS: A total of 1872 men treated between January 1989 and October 1997 with an RP (n = 888) or implant with or without neoadjuvant androgen deprivation therapy (n = 218) at the Hospital of the University of Pennsylvania, Philadelphia, or RT (n = 766) at the Joint Center for Radiation Therapy, Boston, Mass, were enrolled. MAIN OUTCOME MEASURE: Actuarial freedom from PSA failure (defined as PSA outcome). RESULTS: The relative risk (RR) of PSA failure in low-risk patients (stage T1c, T2a and PSA level < or =10 ng/mL and Gleason score < or =6) treated using RT, implant plus androgen deprivation therapy, or implant therapy was 1.1 (95% confidence interval [CI], 0.5-2.7), 0.5 (95% CI, 0.1-1.9), and 1.1 (95% CI, 0.3-3.6), respectively, compared with those patients treated with RP. The RRs of PSA failure in the intermediate-risk patients (stage T2b or Gleason score of 7 or PSA level >10 and < or =20 ng/mL) and high-risk patients (stage T2c or PSA level >20 ng/mL or Gleason score > or =8) treated with implant compared with RP were 3.1 (95% CI, 1.5-6.1) and 3.0 (95% CI, 1.8-5.0), respectively. The addition of androgen deprivation to implant therapy did not improve PSA outcome in high-risk patients but resulted in a PSA outcome that was not statistically different compared with the results obtained using RP or RT in intermediate-risk patients. These results were unchanged when patients were stratified using the traditional rankings of biopsy Gleason scores of 2 through 4 vs 5 through 6 vs 7 vs 8 through 10. CONCLUSIONS: Low-risk patients had estimates of 5-year PSA outcome after treatment with RP, RT, or implant with or without neoadjuvant androgen deprivation that were not statistically different, whereas intermediate- and high-risk patients treated with RP or RT did better then those treated by implant. Prospective randomized trials are needed to verify these findings.     

Randomized, prospective, controlled study comparing radical prostatectomy alone and neoadjuvant androgen withdrawal in the treatment of localized prostate cancer. Canadian Urologic Oncology Group

PURPOSE: A prospective, multicenter, randomized study was done to test the hypothesis that neoadjuvant androgen withdrawal decreases the incidence of positive margins following radical prostatectomy for localized prostate cancer. MATERIALS AND METHODS: Observations were made of 213 patients randomized to undergo radical prostatectomy alone (101) or to receive a 12-week course of 300 mg. cyproterone acetate daily followed by surgery (112). Groups were similar at baseline in terms of clinical stage, serum prostate specific antigen and Gleason score. Of 192 patients available for efficacy analysis 9 had stage T1b, 8 stage T1c, 63 stage T2a, 36 stage T2b and 76 stage T2c disease. RESULTS: One or more positive surgical margins were found in 59 of 91 patients (64.8%) in the surgery only group compared to 28 of 101 (27.7%) in the cyproterone acetate group (p = 0.001). Patients who received preoperative therapy had a statistically significantly lower rate of apical margin involvement than those who did not (17.8 versus 47.8%, respectively, p < 0.0001). There was no statistically significant difference in surgical (p = 0.8645) or postoperative (p = 0.173) complications between the 2 groups. CONCLUSIONS: Neoadjuvant androgen withdrawal with a 12-week course of 300 mg. cyproterone acetate daily results in a lower rate of positive margins without adversely affecting postoperative recovery. The impact on patient survival will be determined by long-term followup.     

Impact of androgen deprivation prior to radical prostatectomy for T1, T2 prostate cancer on the likelihood of curative surgery

BACKGROUND: Extracapsular extension is commonly seen in patients undergoing radical prostatectomy for localized prostate cancer due to understaging of disease. One possible approach to reduce the likelihood of extracapsular disease is androgen deprivation prior to radical prostatectomy, neoadjuvant therapy. However, adequate application is not clear. We analyzed the outcome of neoadjuvant therapy and radical prostatectomy in an attempt to expand our understanding on indications of neoadjuvant therapy. METHODS: Forty-six selected patients with clinical T1 or T2 prostate cancer were retrospectively reviewed. Twenty-two patients underwent neoadjuvant therapy (group N) that mainly consists of LH-RH agonist. The duration of neoadjuvant therapy, varied from 1 to 12 months with the mean being 4 months. Twenty-four underwent radical prostatectomy alone (group S). RESULTS: In the group N and group S, 59% and 33% had either organ confined disease (OCD) or specimen confined disease (SCD) respectively. When the patients had OCD or SCD, they were defined as surgically cured patients. In the patients with clinical stage T1b, T1c, and T2 disease, likelihood of surgical cure were 100%, 50%, 46.7% in group N, 100%, 20%, 11%, in group S respectively. In the patients with initial serum PSA less than 10 ng/ml and more than 10.1 ng/ml, likelihood of surgical cure were 83.3% and 50% in group N, 63.6% and 15.4% in group S, respectively. Likelihood of surgical cure was higher in the patients with well differentiated carcinoma both in group N and group S. All the patients with serum PSA less than 0.1 ng/ml after neoadjuvant therapy had OCD. CONCLUSION: Neoadjuvent therapy could be beneficial either in the patients with moderately or in the poorly differentiated adenocarcinoma of prostate especially in the group with initial serum PSA more than 10.1 ng/ml. However, in patients both with well differentiated adenocarcinoma and the initial serum PSA less than 10 ng/ml, no evidence of beneficial effect on the likelihood of OCD or SCD was observed. PSA after neoadjuvant therapy could be useful predictor for the pathological outcome.     

The regulation of L-proline transport by insulin-like growth factor-I in human osteoblast-like SaOS-2 cells

OBJECTIVE: To examine the usefulness of clinical stage, tumour differentiation and prostate-specific antigen (PSA) level, alone and in combination, to predict regional nodal metastases in individual patients with localized prostate cancer. PATIENTS AND METHODS: The usefulness of digital rectal examination (DRE), biopsy Gleason sum and PSA, alone and in combination, to predict nodal metastases in an individual patient was examined. The study included 689 patients who had laparoscopic or open pelvic lymph node dissection for clinical stage T1-3 prostate cancer. The Kruskal-Wallis test, Mantel-Haenszel test, chi-squared test and logistic regression were used for continuous, ordinal, categorical, and multivariate analysis, respectively. RESULTS: Of the 689 patients who underwent radical prostatectomy, 52 (8%) had nodal metastases. Although clinical stage, DRE, pre-operative PSA level and biopsy Gleason sum were significantly related in the univariate analysis, only pre-operative PSA level and biopsy Gleason sum were significant predictors of lymph node status in a multivariate analysis. However, based on a receiver operating characteristic curve, a model with satisfactory sensitivity and specificity could not be obtained. CONCLUSION: Current estimations of primary prostate cancer biology using pre-operative PSA level, clinical stage and biopsy Gleason sum are not sufficiently sensitive to predict nodal metastases, and pelvic lymphadenectomy remains the definitive method of detection.     

Outcome based staging for clinically localized adenocarcinoma of the prostate

PURPOSE: Some patients with clinically localized prostate cancer are not cured after radical prostatectomy because of the presence of occult systemic disease. The American Joint Commission on Cancer staging classification for prostate cancer does not reliably distinguish between clinically localized patients who are likely or unlikely to be cured after local therapy. This project was undertaken to develop a staging system capable of predicting long-term outcome after radical prostatectomy on the basis of the clinical parameters obtained routinely during the standard workup for patients with adenocarcinoma of the prostate. MATERIALS AND METHODS: A total of 688 clinically localized prostate cancer patients managed with a radical retropubic prostatectomy for adenocarcinoma of the prostate between 1989 and 1996 was evaluated for clinical features predictive of time to prostate specific antigen (PSA) failure using a Cox regression multivariate analysis. A recently defined clinical factor called the calculated prostate cancer volume and its ability to predict time to PSA failure in conjunction with PSA, biopsy Gleason score and clinical stage were evaluated. RESULTS: The calculated prostate cancer volume (p <0.0001) and the pretreatment PSA (p <0.001) provided the optimal staging system for predicting freedom from PSA failure after radical prostatectomy. CONCLUSIONS: The calculated prostate cancer volume and PSA may provide clinically useful information regarding outcome after radical prostatectomy, enabling the selection of a therapeutic approach for an individual patient with clinically localized disease. Validation of this staging system is needed.     

Is there a role for induction androgen deprivation prior to radical prostatectomy?

The potential advantages of neoadjuvant androgen deprivation include decreased prostatic size, reduced vasculature, and reduced incidence of positive margins. The potential disadvantages are the side effects of hormonal medication, cost, tissue reaction, treatment "delay," and progression of androgen-independent clones. Many theories have been postulated to explain the observed reduction in the incidence of positive margins with neoadjuvant hormonal treatment. It is possible that the reduced prostate size and the frequently found periprostatic tissue reaction facilitate dissection, allowing better cancer clearance. It is possible, however, that the fibrosis may also increase the surgical difficulty, which critics argue may increase the risk of a positive margin. It is difficult to conceive of a research methodology that could resolve this issue. The occurrence of tumor cell death is likely a more significant explanation for the improved results. Whether tumor cells beyond the prostatic capsule are consistently affected to pathologically downstage the disease is unknown. The careful pathologic assessment in the randomized trials discussed previously suggests that pathologic downstaging is not as common as earlier reports have suggested. Difficulty in interpreting pathologic specimens after neoadjuvant treatment must be considered. At this point, neoadjuvant hormonal treatment prior to surgery would appear appropriate for those patients at high risk of having a positive surgical margin. Specifically, this includes clinical stage T2b, PSA elevation greater than 10 to 20 ng/mL, and a high Gleason score on the prostatic biopsy. Research to date suggests that neoadjuvant hormonal therapy prior to radical prostatectomy has a significant effect in reducing the incidence of positive surgical margins. The treatment is well tolerated with minimal side effects. Whether this will translate into improved disease-free survival remains to be determined. Fortunately, the randomized trials have been completed and follow-up data will be forthcoming.     

The contemporary value of pretreatment prostatic acid phosphatase to predict pathological stage and recurrence in radical prostatectomy cases

PURPOSE: We examine the clinical prognostic value of the currently available simple and inexpensive immunoenzymatic prostatic acid phosphatase (PAP) assay for the staging and prognosis of radical prostatectomy cases. MATERIALS AND METHODS: Between February 1, 1990 and May 3, 1996 pretreatment PAP was measured in 295 patients who underwent radical prostatectomy. From February 1, 1990 to May 17, 1992 the Hybritech Tandem-E assay was used in 75 cases, from May 18, 1992 to February 28, 1993 the Abbott EIA assay was used in 49 and from March 1, 1993 to May 3, 1996 the Abbott IMx assay was used in 171. PAP assays were analyzed individually and the results were combined with pretreatment prostate specific antigen (PSA) values to assess the ability to predict organ confined prostate cancer and serological recurrence after radical prostatectomy. RESULTS: PAP testing was not of value for predicting organ confined disease or positive margins. However, this test was useful for predicting the first serological PSA recurrence in the 3 periods (77 to 85% correct) and overall (82% correct, p < 0.001, odds ratio 6.06). The Kaplan-Meier disease-free survival rate at 4 years was 78.8% for men with PAP less than 3 ng./ml. and 38.8% for those with PAP 3 ng./ml. or greater, which was significant when pretreatment PSA was less than 10 ng./ml. (p = 0.047), 10 ng./ml. or greater (p = 0.012) and overall (p < 0.001). PAP testing added prognostic information to pretreatment PSA values and it was an independent predictor of recurrence. CONCLUSIONS: The widely available and inexpensive PAP assays of the 1990s are predictors of recurrence after radical prostatectomy. They should be included in future studies of prostate cancer recurrence modeling. However, they do not predict pathological stage or margin status.     

Distinguishing clinically important from unimportant prostate cancers before treatment: value of systematic biopsies

PURPOSE: We assessed the ability of diagnostic tests to distinguish clinically unimportant cancers. MATERIALS AND METHODS: We correlated T stage (based on digital examination and ultrasound), prostate specific antigen (PSA), PSA density and pathological features of cancer in systematic biopsy specimens with features of cancer in 170 radical prostatectomy specimens. Clinically unimportant cancers were defined as small (0.5 cm.3 or less), well or moderately differentiated and confined to the prostate. RESULTS: Of the patients 10% had an unimportant cancer. On logistic regression analysis the 2 significant predictors were maximum length of cancer in any core and PSA density. Of 12 patients with maximum cancer length 2 mm. or less and PSA density less than 0.1., 75% had an unimportant cancer compared to 5% of the remaining 158 (p < 0.0005). CONCLUSIONS: Quantitative analysis of systematic biopsy specimens combined with PSA density provides valuable staging information and helps to identify cancers of low biological potential.     

Induction androgen deprivation plus prostatectomy for stage T3 disease: failure to achieve prostate-specific antigen-based freedom from disease status in a phase II trial

OBJECTIVES: There is interest in treating prostate cancer with induction androgen deprivation prior to radical prostatectomy. Data on long-term prostate-specific antigen (PSA)-based survival analyses among patients treated with neoadjuvant hormonal therapy (NHT) and prostatectomy are limited. In 1991 we instituted a pilot study for T3 disease based on endorectal coil magnetic resonance imaging (eMRI), mandatory negative laparoscopic nodal dissection prior to hormonal manipulation, and prostatectomy followed by pathologic and PSA-based outcome determinations. METHODS: Of 26 patients, 21 had negative laparoscopic lymphadenectomy followed by 4 months of NHT (leuprolide +/- flutamide) prior to radical prostatectomy. eMRI was performed at the time of diagnosis and following hormonal treatment. Serum PSA was determined at 3-month intervals. Prostatectomy specimens were evaluated by 3-mm whole-mount step sections. RESULTS: Prior to prostatectomy, biochemical response was documented in all patients and downsizing was observed by eMRI in 57%. Pathologic downstaging to a lower stage (T2c or lower) was achieved in 48%. However, the actuarial 3-year freedom from biochemical relapse rate was only 24%. CONCLUSIONS: Using laparoscopy to exclude node-positive patients and 4 months of NHT appears to result in pathologic and initial biochemical evidence of regression. These factors have not translated into improved freedom from biochemical relapse among patients with Stage T3 disease treated with NHT and prostatectomy. Recent data strongly suggest a beneficial effect in patients with clinical T2 disease treated with NHT and radical prostatectomy. The NGT and radical prostatectomy approach appeared to offer no clear advantage when compared with PSA-based benchmarks achieved with conformal irradiation or NHT followed by external beam treatment among patients with clinical T3 disease.     

Incidence, etiology, location, prevention and treatment of positive surgical margins after radical prostatectomy for prostate cancer

PURPOSE: During radical prostatectomy for prostate cancer tumor at the surgical margin is a relatively frequent finding. We summarize the literature on the incidence, etiology, location, prevention and treatment of positive surgical margins after radical prostatectomy. MATERIALS AND METHODS: The literature was reviewed for data on positive margins during radical prostatectomy for prostate cancer. RESULTS: Positive surgical margins may result from artifacts induced by tissue processing, incising inadvertently into the prostate or incising into extraprostatic tumor that has extended beyond the limits of resection. Patients with 10 ng./ml. or greater preoperative prostate specific antigen, biopsy Gleason score 7, multiple positive biopsies, or clinical stage T2b, T2c or T3 cancer have a higher risk of positive margins. Preoperative endorectal magnetic resonance imaging may be useful in staging a select group of patients. Neoadjuvant androgen deprivation reduces the incidence of positive margins but does not appear to delay progression or improve survival. The surgical approach, retropubic or perineal, may influence the location and etiology of positive margins. In general, nerve and bladder neck sparing procedures do not compromise tumor removal in appropriately selected patients. Positive margins increase the risk of progression and correlate with decreased cancer specific and overall survival. There is no consensus on the management of positive margins. External beam radiation and androgen deprivation may be administered as adjuvant therapy or at the time of recurrence. CONCLUSIONS: Tumor at the specimen edge is an adverse prognostic factor. With appropriate patient selection and meticulous surgical technique some positive margins can be prevented. Controlled prospective randomized studies of postoperative therapy are needed before definitive recommendations can be made for treating positive margins.     

Intrathecal clonidine alleviates allodynia in neuropathic rats: interaction with spinal muscarinic and nicotinic receptors

PURPOSE: There has been a significant shift toward multimodality therapy to try to eradicate extracapsular disease better in patients with locally advanced prostate cancer. We assess the feasibility and complications of initial cryotherapy followed by radical prostatectomy, and evaluate the frequency and location of viable benign and malignant prostate tissue and positive surgical margins after this treatment combination. MATERIALS AND METHODS: A total of 12 patients with clinical stage T3 cancer or clinical stages T1c to T2, Gleason score 8 to 10 cancer on the initial biopsy were treated with initial cryotherapy followed by open surgical exploration 2 to 8 days later. If pelvic lymph nodes were negative, radical prostatectomy was performed. Prostate specific antigen was measured approximately every 3 months postoperatively, and complications were assessed by retrospective chart review and a quality of life survey. RESULTS: Radical prostatectomy was aborted in 5 patients with positive pelvic lymph nodes. Of the 7 patients who underwent prostatectomy 4 had no residual prostate cancer in the specimen (pathological stage pT0 disease). All 7 of these patients had focal areas of viable normal prostate glands. Only 1 of the 7 patients had a positive surgical margin and biochemical failure (mean followup 22.6 months). The main complications of cryotherapy followed by radical prostatectomy were urinary incontinence and impotence. CONCLUSIONS: Neoadjuvant cryotherapy achieved complete tumor destruction in 4 of 7 patients with locally advanced prostate cancer. Cryotherapy followed by radical prostatectomy was associated with substantial morbidity, mainly in terms of urinary incontinence.     

Reduced space hidden Markov model training

OBJECTIVE: To analyze trends in the clinical stage and pathologic outcome of patients with prostate cancer who underwent radical prostatectomy at a large referral practice during the prostate-specific antigen (PSA) testing era. MATERIAL AND METHODS: Between January 1987 and June 1995, 5,568 patients with prostate cancer (4,774 with clinically localized disease of stage T2c or less) underwent pelvic lymphadenectomy and radical retropubic prostatectomy at our institution. Patient age, preoperative serum PSA level, clinical stage, pathologic stage, Gleason score, and tumor ploidy were assessed. Outcome was based on clinical and PSA (increases in PSA level of 0.2 ng/mL or more) progression-free survival. RESULTS: Patient age (65 to 63 years old; P<0.001) and serum PSA level (median, 8.4 to 6.8 ng/mL; P<0.001) decreased during the study period. The percentage of patients with clinical stage T1c prostate cancer increased from 2.1% in 1987 to 36.4% in 1995 (P<0.001), and clinical stage T3 cancer decreased from 25.3% to 6.5% (P<0.001). Nondiploid tumors decreased from 38.3% to 24.6% (P<0.001), and the proportion of patients with pathologically organ-confined disease increased from 54.9% to 74.3% (P<0.001). More cT1c than cT2 tumors were diploid (80% versus 72%; P<0.001), had a Gleason score of 7 or less (75% versus 65%; P<0.001), and were confined to the prostate (75% versus 57%; P<0.001). Five-year progression-free survival was 85% and 76% for patients with clinical stage T1c and T2, respectively (P<0.001). CONCLUSION: Since the advent of PSA testing, patients referred to our institution for radical prostatectomy have shown a significant migration to lower-stage, less-nondiploid, more often organ-confined prostate cancer at the time of initial assessment. Cancer-free survival associated with PSA-detected cancer (cT1c) is superior to that with palpable tumors (cT2). Whether these trends translate into improved long-term cancer-specific survival remains to be confirmed with longer follow-up.     

Novel staging tool for localized prostate cancer: a pilot study using genetic adaptive neural networks

PURPOSE: An estimated $1.5 billion is spent annually for direct medical expenses and an additional $2.5 billion for indirect costs for the management of prostate cancer. Today there are several procedures for staging prostate cancer, including lymph node dissection. Despite these procedures, the accuracy of predicting extracapsular disease remains low (range 37 to 63, mean 45%). Use of multiple staging procedures adds significantly to the costs of managing prostate cancer. Recently artificial intelligence based neural networks have become available for medical applications. Unlike traditional statistical methods, these networks do not assume linearity or homogeneity of variance and, thus, they are more accurate for clinical data. We applied this concept to staging localized prostate cancer and devised an algorithm that can be used for prostate cancer staging. MATERIALS AND METHODS: Our study comprised 1,200 men with clinically organ confined prostate cancer who underwent preoperative staging using serum prostate specific antigen, systematic biopsy and Gleason scoring before radical prostatectomy and lymphadenectomy. The performance of the neural network was validated for a subset of patients and network predictions were compared with actual pathological stage. Mean patient age was 62.9 years, mean serum prostate specific antigen 8.1 ng./ml. and mean biopsy Gleason 6. Of the patients 55% had organ confined disease, 27% positive margins, 8% seminal vesicle involvement and 7% lymph node disease. Of margin positive patients 30% also had seminal vesicle involvement, while of seminal vesicle positive patients 50% also had positive margins. RESULTS: The sensitivity of the network was 81 to 100%, and specificity was 72 to 75% for various predictions of margin, seminal vesicle and lymph node involvement. The negative predictive values tended to be relatively high for all 3 features (range 92 to 100%). The neural network missed only 8% of patients with margin positive disease, and 2% with lymph node and 0% with seminal vesicle involvement. CONCLUSIONS: Our study suggests that neural networks may be useful as an initial staging tool for detection of extracapsular extension in patients with clinically organ confined prostate cancer. These networks preclude unnecessary staging tests for 63% of patients with clinically organ confined prostate cancer.     

Response to recombinant human erythropoietin in patients with myelodysplastic syndromes

OBJECTIVES: The impact of a positive surgical margin in otherwise confined prostate cancer after radical prostatectomy remains unclear. We analyzed the outcome of a large number of patients with organ-confined prostate cancer according to the presence and anatomic site of margin positivity. METHODS: We evaluated 2712 prostatectomy patients with Stage pT2N0 cancer (ie, no evidence of extra-prostatic disease, seminal vesicle or regional node involvement) and no prior therapy who were treated by radical prostatectomy between 1987 and 1995 at Mayo Clinic. A total of 697 patients (26%) had positive margins. To assess the effect of margin status in the absence of treatment, 378 patients with postoperative adjuvant therapy were not considered for the study group: the final group consisted of 2334 patients. RESULTS: Overall, 253 (58%) tumors were positive at the apex and/or urethra, 85 (19%) at the prostate base, 11 (2.5%) at the anterior prostate, and 174 (40%) at the posterior prostate; 89 (20%) had at least two margins involved and 21 (8.3%) had more than two involved. The apex/urethra was the only positive anatomic site in 183 (42%). Five-year survival free of clinical recurrence or prostate-specific antigen (PSA) biochemical failure (postoperative serum PSA of 0.2 ng/mL or more) for patients with a single positive margin was 79% for apex or urethra, 78% for anterior/posterior, and 56% for prostate base. Five-year survival free of clinical recurrence or PSA (biochemical) failure was slightly higher for those with one versus two margin-positive regions (77% versus 68%, respectively). Multivariate analysis revealed that positive surgical margins were a significant predictor of clinical recurrence and PSA (biochemical) failure (relative risk [95% confidence interval]: 1.65 [1.24, 2.18]) after controlling for Gleason grade, preoperative PSA, and deoxyribonucleic acid (DNA) ploidy. The effect of margin positivity on recurrence at a specific anatomic site (versus negative margins or positive at a different anatomic site) revealed the prostate base to be the only significant anatomic site when adjusted for grade, PSA, and ploidy. Five-year survival free of the combined clinical or PSA failure end point for those with versus those without positive margins at the prostate base was 56% versus 85%, respectively (P < 0.0001). CONCLUSIONS: Positive surgical margins are a significant predictor of recurrence in Stage pT2N0 cancer, which is independent of grade, PSA, and DNA ploidy. The impact of positive margin status on recurrence-free survival appears to be anatomic and site-specific, with prostate base positivity significantly associated with poor outcome. The benefit of adjuvant therapy based on anatomic site-specific margin positivity remains to be tested in order to optimize recurrence-free survival.     

Selection of patients for laparoscopic pelvic lymphadenectomy prior to radical prostatectomy: a decision analysis

Indications for laparoscopic pelvic lymphadenectomy prior to radical prostatectomy have not been established. Criteria to predict lymph node metastases were derived from the preoperative evaluations of 164 prostate cancer patients undergoing pelvic lymphadenectomy. Decision analysis was used to determine which criteria would be optimal indicators for laparoscopic pelvic lymphadenectomy prior to intended radical prostatectomy. Besides a digital rectal examination suggesting uncontained tumor, which was the best indication for laparoscopic pelvic lymphadenectomy, the most useful criteria were sonographic tumor volume > or = 3 cc and prostate-specific antigen (PSA) > or = 20 ng/mL. If either parameter was met, the sensitivity for identifying patients with pelvic lymph node metastases was 88 percent and the positive predictive value was 42 percent. When both were met, the sensitivity fell to 47 percent but the positive predictive value increased to 67 percent. A combination of Gleason biopsy score and PSA was the best criterion that was independent of transrectal ultrasonography. Using a PSA > or = 15 ng/mL for tumors with Gleason biopsy score > or = 7 or a PSA > or = 25 ng/mL for tumors with a Gleason biopsy score of 5-6 had a sensitivity of 71 percent and positive predictive value of 48 percent for identifying patients with pelvic lymph node metastases. In selecting patients for laparoscopic pelvic lymphadenectomy prior to radical retropubic prostatectomy, criteria with a positive predictive value greater than 39 percent maximize the utility of laparoscopic pelvic lymphadenectomy. Prior to radical perineal prostatectomy, laparoscopic pelvic lymphadenectomy will identify pelvic lymph node metastases that would otherwise be undetected by prostatectomy alone. The sensitivity of selection criteria, therefore, should be increased, as long as the positive predictive value remains above 20 percent.     

Disease progression following radical prostatectomy in men with Gleason score 7 tumor

PURPOSE: The long-term prognosis of men with Gleason score 7 adenocarcinoma of the prostate is uncertain. MATERIALS AND METHODS: We studied 488 men whose radical prostatectomy specimen showed Gleason score 7 tumor without involvement of the seminal vesicles or lymph nodes. Of the 400 men without progression 318 had been followed for 2 years or more and 93 for 7 years or more. RESULTS: Cases of organ confined disease and negative margins regardless of extent of extraprostatic extension had roughly similar and better prognoses than cases of focal and established extraprostatic extension with positive margins. The greater influence of margin status on progression (p <0.0001) compared to extent of extraprostatic extension (p = 0.023) was evidenced in the multivariate analysis. Of 30 men with established extraprostatic extension and positive margins 6 (20%) had progression to distant metastases, which was similar to 14 of 58 (24%) without established extraprostatic extension and positive margins. There was no difference in response to radiotherapy between men with established extraprostatic extension and positive margins compared to the other cases. CONCLUSIONS: Margins status greatly influences the risk of progression in men with Gleason score 7 tumors. Among men with Gleason score 7 tumors, except for those with established extraprostatic extension and positive margins, more than 50% appear to be cured at long-term followup. Because of the high risk of progression in patients with positive margins, clinical studies of adjuvant therapy in this population appear warranted.     

Stage T1-2 prostate cancer: a multivariate analysis of factors affecting biochemical and clinical failures after radical prostatectomy

PURPOSE: Prostate-specific antigen (PSA) is extensively used in case selection and outcome evaluation after treatment of clinically localized prostate cancer. Careful case selection can have a profound impact on pathologic findings and ultimate outcome. In addition, salvage treatment is frequently initiated at the time of biochemical relapse rather than clinical recurrence. Consequently, patterns of failure can be significantly altered compared to previous times when PSA was not available. To better understand the impact of PSA on pathologic findings, outcome, and salvage treatment, we reviewed our experience in the PSA era with clinical Stage T1-2 prostate cancer treated with radical prostatectomy. METHODS AND MATERIALS: Between 1987 and 1993, 423 cases could be identified with clinical Stage T1-2 prostate cancer treated with radical prostatectomy. The distribution of cases by pretreatment PSA levels was as follows: < or = 4 ng/ml (18%), 4-10 ng/ml (42%), 10-20 ng/ml (21%), > 20 ng/ml (14%), and unknown (5%). The median pretreatment PSA level for the entire group was 8.0 ng/ml. Sixteen patients received adjuvant or neoadjuvant androgen suppression and 13 received postoperative radiotherapy. Only 31 patients (7%) had pathologically positive pelvic lymph nodes. The overall margin involvement rate was 46%. Fifty-three percent of patients had surgical Gleason scores > or = 7, and 65% had extracapsular extension. The median follow-up time was 41 months. RESULTS: The projected overall survival at 7 years after surgery was 90%. The 5-year clinical relapse-free survival rate was 84%. At 5 years, the local control and distant failure rates were 92% and 91%, respectively. Biochemical relapse was defined as a detectable or rising PSA level after prostatectomy. The 5-year biochemical relapse-free survival (bRFS) rate was 59%. The 5-year RFS was 88% in patients with preoperative PSA levels < or = 4, 62% for 4-10, 48% for 10-20, and 31% for > 20. Combining the two independent preoperative variables, iPSA and biopsy GS (bGS), two risks groups were defined: low risk [initial PSA (iPSA) levels < or = 10.0 and bGS < or = 6] and high risk (iPSA levels > 10.0 ng/ml or bGS > or = 7). The 5-year bRFS rate for the low-risk cases was 81% vs. 40% for high-risk cases (p < 0.001). On multivariate analysis, three factors independently predicted biochemical relapse: iPSA levels (p = 0.005), Gleason score from the surgical specimen (sGS) (p = 0.002), and positive surgical margins (p < or = 0.001). The 5-year bRFS rates for margin positive vs. margin negative patients were 37% vs. 78%, respectively. The 5-year bRFS rates for GS > or = 7 vs. GS > or = 6 were 42% vs. 80%, respectively. All clinical relapses were accompanied by a rise in PSA. In patients who manifested biochemical failure followed by a clinical failure, the median interval between the PSA rise and clinical failure was 19 months (range 7-71). Margin involvement was the only independent predictor of local failure (p = 0.019). The 5-year local failure-free survival for negative margin cases was 96% vs. 87% for positive margin cases (p = 0.012). Lymph node (LN) involvement and high-risk group were the two independent predictors of distant failure. The 5-year distant failure-free survival for negative LN cases was 94% vs. 67% for positive LN cases (p < 0.001). The 5-year distant failure-free survival for low-risk cases was 97% vs. 85% for high-risk cases (p = 0.005). For the 124 patients failing biochemically, 85 were observed and 39 were treated either with radiation or androgen deprivation. With a median follow-up of 32 months, the clinical disease relapse-free survival was 79% for the treated patients vs. only 32% for the patients observed (p < 0.001). CONCLUSION: Pretreatment PSA is the most potent clinical factor independently predicting biochemical relapse, thereby allowing markedly better case selection. Achieving negative margins, even in relatively advanced disease, provides excellent lon