Evaluation of 6 weeks treatment of terbinafine in tinea unguium in a double-blind trial comparing 6 and 12 weeks therapy. The Lagos V Study Group

OBJECTIVES: This study sought to characterize the postoperative prostate-specific antigen (PSA) doubling time and time to biochemical recurrence in patients who have failed radical prostatectomy. METHODS: Of 539 consecutive patients who underwent radical prostatectomy between 1984 and 1992, postoperative PSA levels in 80 initially became undetectable (less than 0.07 ng/mL) before eventually increasing, as evidenced by rising PSA levels above the residual cancer detection limit of the Tosoh AIA-600 immunoassay run in the ultrasensitive mode (i.e., 0.07 ng/mL or higher). The PSA doubling time and time to biochemical recurrence were calculated for each of the 80 patients and were correlated with the histopathologic variables from the operative specimen. RESULTS: Postoperative PSA doubling times were predicted by the extent of capsular penetration, percent Gleason grade 4 or 5, lymph node involvement, and tumor volume on univariate analysis and by capsular penetration, percent Gleason grade 4 or 5, lymph node involvement, and patient age on multivariate analysis. Times to recurrence were predicted by the presence of positive margins and percent Gleason grade 4 or 5 in both univariate and multivariate regression models. The PSA doubling time did not correlate with recurrence time. The median PSA doubling time for all patients was 284 days, and the median time to recurrence was 648 days. CONCLUSIONS: These results demonstrate that PSA doubling time and recurrence time are indicative of different biologic characteristics of recurrent prostate cancer: Doubling time appears to represent the aggressiveness of the original prostate cancer, whereas time to recurrence reflects the extent of residual postoperative disease. This information should aid in the selection of men who need greater vigilance during postoperative surveillance.     

Tumor volume and prostate specific antigen: implications for early detection and defining a window of curability

PURPOSE: We attempted to determine the relationship between tumor volume and extent of localized prostate cancer, as well as the interrelationships of tumor volume with prostate specific antigen (PSA) level, grade and stage. MATERIALS AND METHODS: Serial whole mount sections from 128 patients who underwent radical prostatectomy were analyzed using a computer assisted volumetric program. Statistical evaluations were performed using logistic and simple regression analyses. RESULTS: The median tumor volume for patients with organ confined disease was significantly lower than for those with extraprostatic extension (1.25 versus 2.94 cc, p < 0.001). A significant incidence (32%) of small volume cancers (0.51 to 1.5 cc) exhibited extraprostatic extension while that of extraprostatic disease increased to 66% for patients with tumor volumes greater than 1.5 cc (p < 0.001). Of men with clinically significant (greater than 0.5 cc, or Gleason score 7 or more) pathological stage B disease 31% had a serum PSA value of 4 ng./ml. or less. Multivariate regression analysis of tumor volume as a function of PSA, grade and stage demonstrated that log PSA had the strongest association with tumor volume. Goodness-of-fit analysis (coefficient of determination) revealed that only 40 to 50% of the PSA levels are explained by tumor volume. CONCLUSIONS: These data suggest that the window of curability for prostate cancer decreases significantly once the tumor grows to a volume greater than 1.5 cc, and that grade and tumor volume are more significantly related to stage than PSA.     

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.     

Prospective characterization of pathological features of prostatic carcinomas detected via serum prostate specific antigen based screening

PURPOSE: Many small (less than 0.5 cc), well differentiated, organ-confined prostate carcinomas remain clinically undetected during the life of the patient and are identified only at postmortem examination. Thus, these cancers are often called latent or autopsy cancers. There is concern that serum prostate specific antigen (PSA) based screening may preferentially detect these cancers. There are limited prospective data concerning the pathological features of carcinomas of the prostate detected in a screening program. We determined if prostatic carcinomas detected via PSA based screening resembled autopsy cancers. MATERIALS AND METHODS: We assessed the pathological features of carcinomas in 100 consecutive, completely embedded radical prostatectomy specimens from men whose cancer was detected in a PSA based screening program. The tumors were evaluated for pathological stage, surgical margin status, Gleason histological grade and intraglandular tumor extent (morphometrically quantified as percentage carcinoma and tumor volume). RESULTS: Of 100 carcinomas 68 (68%) were larger than 0.5 cc in volume (mean 1.7, range 0.1 to 10.7). Mean amount of carcinoma in the surgical specimen was 10.3% (range 0.1 to 41.6). Of the 100 carcinomas 94 had a Gleason score of 5 to 8 (mean 5.7) and only 6 (6%) were well differentiated (Gleason score of 4 or less). Locally advanced disease was noted in 41 cases (41%) as judged by the presence of extracapsular carcinoma and/or cancerous surgical margins. CONCLUSIONS: We concluded that the pathological features of most prostatic carcinomas detected via PSA based screening do not resemble those of autopsy cancers, and that most prostatic cancers detected in screening programs are likely to be clinically important.     

Prostate cancer staging: correlation between ultrasound determined tumor contact length and pathologically confirmed extraprostatic extension

PURPOSE: We determine whether a new parameter, the amount of tumor in contact with the fibromuscular rim (capsule) of the prostate, correlates with extraprostatic extension, and ascertain whether estimating the new parameter using transrectal ultrasonography can predict extraprostatic extension. MATERIALS AND METHODS: We analyzed step sectioned prostatectomy specimens from 189 patients who had had positive peripheral zone biopsies. We measured the contact length, maximum length (mm.) of the portion of the peripheral zone cancer that was in contact with the fibromuscular rim, and determined the contact ratio from the quotient (%) of the contact length divided by the tumor circumference. We evaluated the correlation between the pathological and ultrasound measurements of these parameters, as well as the accuracy of these criteria for predicting microscopic extraprostatic extension. RESULTS: Among the 189 cancers there was a significant difference (p <0.0001) between organ confined tumors and tumors with extraprostatic extension in contact length and contact ratio. There was a positive correlation (r = 0.691) between the contact lengths measured ultrasonically and histologically among 95 patients who had hypoechoic lesions associated with positive biopsies. A receiver operating characteristics curve of the ability of ultrasound estimated contact length to predict extraprostatic extension revealed the best cutoff value to be 23 mm. with 77% accuracy. Logistic regression analysis revealed that pathological contact length correlated better with extraprostatic extension than tumor volume, Gleason score, prostate specific antigen (PSA) level and pathological contact ratio. The best preoperative predictor of extraprostatic extension was the ultrasound contact length, followed by the contact ratio, PSA value, percentage of the biopsy specimen that was cancer and presence of perineural invasion in the biopsy specimen. Multiple logistic regression analysis revealed that the predictability of ultrasound contact length was improved by considering PSA value also. Probability plots for predicting extraprostatic extension were developed by combination of ultrasound contact length with PSA value. CONCLUSIONS: The length of tumor contact with the fibromuscular rim is more significantly related to extraprostatic extension than tumor volume, PSA level and tumor grade. For hypoechoic cancers a new ultrasound staging criterion, contact length, has been defined. For men who are clinically candidates for radical prostatectomy and have peripheral zone hypoechoic cancers the combination of ultrasound contact length and PSA value is the best predictor of extraprostatic extension.     

Predictors of pathological stage before neoadjuvant androgen withdrawal therapy and radical prostatectomy. The Canadian Urologic Oncology Group

PURPOSE: This prospective randomized trial was used to compare predictive factors for organ confined margin negative status after radical prostatectomy with and without a 3-month course of neoadjuvant androgen withdrawal therapy. MATERIALS AND METHODS: A total of 213 patients with localized adenocarcinoma of the prostate were randomized to radical prostatectomy with or without a 3-month course of 300 mg. neoadjuvant cyproterone acetate daily. Multivariate logistic regression analysis was used to determine significant predictors of organ confined margin negative status after radical prostatectomy in both groups. Parameters evaluated included baseline prostate specific antigen (PSA 4 or less, 4.1 to 10, greater than 10 ng./ml.), clinical stage (T2c versus T2b or less), biopsy Gleason score and percentage of surface area of biopsies involved with cancer. The multivariate analysis was repeated with PSA density and the natural logarithm of PSA to optimize the model. RESULTS: In the radical prostatectomy alone arm a model incorporating only PSA density was the best predictor of organ confined margin negative status. In the neoadjuvant androgen withdrawal therapy arm a model incorporating biopsy Gleason score, PSA density and clinical stage was the best predictor. CONCLUSIONS: The conventional predictors of pathology at radical prostatectomy, biopsy Gleason score, PSA density and clinical stage retain significance as predictors in patients treated with a 3-month course of neoadjuvant androgen withdrawal therapy before radical prostatectomy.     

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.     

A multivariable analysis of clinical factors predicting for pathological features associated with local failure after radical prostatectomy for prostate cancer

PURPOSE: A multivariate analysis is used to determine the predictive value of pretreatment clinical indicators on pathologic features associated with local failure after radical prostatectomy in patients with prostate cancer. METHODS AND MATERIALS: A retrospective review of the pathologic findings of 235 patients with adenocarcinoma of the prostate treated between 1990 and 1993 with a radical retropubic prostatectomy was performed. The preoperative clinical data including the serum prostate specific antigen, clinical stage, Gleason sum, and endorectal magnetic resonance scan findings are used to identify patients prior to definitive treatment who would be at high risk for having pathologic features associated with local failure at radical prostatectomy. Outcome prediction curves are constructed from a logistic regression multivariate analysis displaying the probability of pathologic involvement of the seminal vesicle, extracapsular disease, or positive surgical margins as a function of the preoperative prostate specific antigen and Gleason sum for the cases when the endorectal magnetic resonance scan is positive, negative, or not included in the multivariate analysis. RESULTS: Factors identified on multivariate analysis as significant predictors of seminal vesicle invasion include endorectal magnetic resonance scan findings (p < 0.0001), and preoperative prostate specific antigen (p = 0.017). Endorectal magnetic resonance scan findings (p = 0.0016), preoperative prostate specific antigen (p = 0.0002), and Gleason sum (p < 0.0001) were significant predictors of extracapsular extension and preoperative prostate specific antigen (p < 0.0001) and Gleason sum (p = 0.03) were significant predictors of disease extending to the margins of resection. Clinical stage was not a significant predictor (p > 0.05) of pathologic features associated with local failure on multivariate analysis. As a single modality, endorectal surface coil magnetic resonance imaging was accurate 93%, 69%, and 72% of the time for predicting seminal vesicle invasion, transcapsular disease, and final pathologic stage, respectively. Failure to recognize microscopic penetration of the capsule found at the time of pathologic evaluation in a prostate gland with a grossly intact capsule accounts for the majority (70%) of the staging inaccuracies. CONCLUSIONS: The use of the endorectal surface coil magnetic resonance scan findings in conjunction with both the serum prostate specific antigen and Gleason sum improves the clinical accuracy of predicting those patients at high risk for clinically unsuspected extraprostatic disease. In particular, for the subgroup of patients with moderately elevated prostate specific antigen (> 10-20 ng/mL) and intermediate grade clinically organ confined prostate cancer [Gleason sum: 5-7] where the specificity of these tests to predict for occult extraprostatic disease is suboptimal, the additional information obtained from the endorectal coil magnetic resonance scan allows the physician to definitively subgroup these patients into low and high risk for seminal vesicle invasion or transcapsular disease.     

The role of cyclic guanylate monophosphate in nitric oxide-induced injury to rat small intestinal epithelial cells

PURPOSE: Biostatistical models predicting the risk of recurrence after radical prostatectomy for clinically localized prostate cancer are necessary. Identifying these high risk patients shortly after surgery, while tumor burden is minimal, makes them candidates for possible adjuvant therapy and/or investigational phase II clinical trials. This study builds on previously proposed models that predict the likelihood of early recurrence after radical prostatectomy. MATERIALS AND METHODS: In our analysis we evaluate age, race, prostatic acid phosphatase and nuclear grade with the established prognostic variables of pretreatment prostate specific antigen, postoperative Gleason sum and pathological stage. RESULTS: After multivariable Cox regression analysis using only statistically significant variables that predicted recurrence we developed an equation that calculates the relative risk of recurrence (Rr) as: Rr = exp[(0.51 x Race) + (0.12 x PSAST) + (0.25 x Postop Gleason sum) + (0.89 x Organ Conf.). These cases are then categorized into 3 distinct risk groups of relative risk of recurrence of low (< 10.0), intermediate (10.0 to 30.0) and high (> 30.0). Kaplan-Meier survival analysis of these 3 risk groups reveals that each category has significantly different risks of recurrence (p < 0.05). This model is validated with an independent cohort of radical prostatectomy patients treated at a different medical center by multiple primary surgeons. CONCLUSIONS: This model suggests that race, preoperative prostate specific antigen, postoperative Gleason sum and pathological stage are important independent prognosticators of recurrence after radical prostatectomy for clinically localized prostate cancer. Race should be considered in future models that attempt to predict the likelihood of recurrence after surgery.     

Color Doppler imaging in predicting the biologic behavior of prostate cancer: correlation with disease-free survival

OBJECTIVES: We investigated the association of transrectal color Doppler imaging (CDI) signal detection in localized prostate cancer with biologic behavior as assessed by tumor Gleason grade, seminal vesicle invasion, capsular and margin status, and actuarial biochemical freedom from relapse. METHODS: From 1991 to 1996, transrectal ultrasound with CDI and biopsy was performed in 2718 men using a 7.0-MHz probe optimized to detect color-coded blood flow within the gland and along the capsular margin. Color flow was graded on a scale from 0 to 2+, with 0 and 1+ representing no detectable flow and normal flow, and 2+ indicating increased flow. Color flow maps were constructed in 47 men with clinically localized prostate cancer treated by radical prostatectomy (RP) and compared to their whole mount RP specimen step sections. RESULTS: Color flow detected within the index tumor was graded as 2+ in 22 of 47 patients and 0 or 1+ in the remaining 25. Tumors graded 2+ correlated with higher Gleason grade, higher incidence of seminal vesicle invasion, and higher relapse rate, with only 11 of 22 patients disease free based on undetectable prostate-specific antigen (PSA) levels. In contrast, 24 of 25 patients with tumors graded 0 or 1+ are free of biochemical relapse with a median follow-up of 30.9 months. Patients with increased flow were 10.2 times more likely to relapse even after correction for other prognostic variables. In addition, tumors with 2+ capsular flow correlated with a higher incidence of non-organ-confined disease. CONCLUSIONS: Color-coded Doppler flow within the tumor and overlying capsule appears to correlate with both tumor grade and stage, respectively. Detection and grading of color-coded flow within biopsy-proven cancers may identify patients with a high likelihood of biochemical relapse.     

Free-to-total prostate specific antigen ratio as a single test for detection of significant stage T1c prostate cancer

PURPOSE: We investigated whether impalpable, invisible (stage T1c) but significant prostate cancer can be detected better by determining the free-to-total prostate specific antigen (PSA) ratio of equivocal PSA serum levels. MATERIALS AND METHODS: The specificity of free-to-total PSA ratio using research monoclonal enzyme immunoassays was compared to that of PSA greater than 4.0 ng./ml. in 117 consecutive patients with PSA 3 to 15 ng./ml. (Hybritech Tandem-R assay) due to untreated benign prostatic hypertrophy or prostate cancer. Of the patients 77% underwent adenectomy or radical prostatectomy with thorough pathological evaluation of surgical specimens. RESULTS: Benign prostatic hypertrophy had a greater median free-to-total PSA ratio than stages T1c and T2 or greater prostate cancer (0.16 versus 0.09 and 0.11 ng./ml., p = 0.0001 and p = 0.0268, respectively). In stage T1c prostate cancer, areas under receiver operating characteristic curves were 0.58 and 0.84 for PSA and free-to-toal PSA ratio, and free-to-total PSA ratio correlated with prostate volume (r = 0.49, p = 0.005) and Gleason score (r = -0.37, p = 0.036). Pathologically, 84% of stage T1c cancers were significant and comparable to stage T2 or greater cancers. CONCLUSIONS: Free-to-total PSA ratio enhances the efficacy of PSA measurement by improving specificity for detecting impalpable, invisible but significant stage T1c prostate cancer.     

Serum antibodies to diphtheria-tetanus-pertussis vaccine components in Argentine children

In recent years the introduction of serum prostate-specific antigen (PSA) determination as a screening tool for early detection of prostate cancer in asymptomatic men has led to a markedly increased detection of prostate cancers that are neither palpable nor visible with transrectal ultrasonography (stage T1c). In this preliminary study we assessed pathologic features and aspects that are indicative of clinical significance in T1c tumors and tumors with palpable or visible lesions (non-T1c tumors). Between June 1994 and December 1995, 51 consecutive radical prostatectomies were performed on screened participants in the Rotterdam section of the European Randomized Study of Screening for Prostate Cancer (ERSPC). After determination of pathologic stage and Gleason score, morphometric analysis was performed to determine tumor volume. Radical prostatectomy specimens were divided into three mutually exclusive subsets: T1c tumors, non-T1c tumors with preoperative PSA levels below 4 ng/ml, and non-T1c tumors with PSA levels equal to or greater than 4 ng/ml. These subsets were compared for differences in the distribution of tumor volume, pathologic stage, and Gleason score. An arbitrarily constructed categorization model was used to assess clinical significance. In all, 17 (33%) of the patients had clinical stage T1c disease. In our categorization mode, 88% of the T1c tumors fit the criteria for clinically significant tumors. T1c tumors, however, were significantly smaller (P < 0.01) and were more likely to be organ-confined (P = 0.01) as compared with non-T1c tumors in patients with an elevated preoperative serum PSA level. In contrast, tumors detected at preoperative PSA levels of < 4 ng/ml had comparably the lowest pathologic stages and tumor volumes in our series. In our categorization model, 42% of these tumors fit the criteria for minimal tumor. This group of radical prostatectomies was therefore most likely to harbor clinically insignificant cancer, a finding that was consistent in two other categorization models derived from earlier reports. T1c tumors comprise a large fraction of the tumors found in population-based screening. As judged by their pathologic characteristics. T1c tumors are clinically significant tumors. The overall low pathologic stage and Gleason score of these tumors make these patients excellent candidates for curative treatment by radical prostatectomy or radiotherapy. In contrast, some concern should be raised on the detection of tumors at low serum PSA levels by means of digital rectal examination and transrectal ultrasound alone, since a substantial proportion of these tumors could be considered clinically insignificant. Long-term follow-up, however, is necessary to substantiate this view.     

Selective induction of a cationic amino acid transporter by tumor necrosis factor-alpha in vascular endothelium

Preoperative parameters were assessed for their usefulness in predicting tumor volume in 26 cases of nonpalpable prostate cancer. The number of positive biopsy cores was found to be the parameter which predicted most accurately tumor volume in surgical specimens. All 14 patients with multiple positive cores had an index tumor of 0.5 cm3 or more in radical prostatectomy specimens. Only six tumors with a single positive core were substantial. Three of the patients showed a serum level of prostate specific antigen (PSA) of 4.0 ng/ml or more. The pathological stage and prostatectomy Gleason sum could not be predicted accurately by this variable (P>0.05). To predict index tumor volumes of 1.0 cm3 or greater, stepwise logistic regression analysis was conducted, and on the basis of the results it was possible to single out multiple positive biopsies as the only significant variable. The number of positive biopsies appeared reliable for predicting tumor volume of surgical specimens in cases of nonpalpable disease. The presence of significant tumors despite "normal" levels of PSA warrants further investigation of variables that can predict such prostate cancers. An adequate model for predicting significant tumors in oriental male populations should be established using samples of larger size.     

Pathologic features from prostate needle biopsy and prognosis after I-125 brachytherapy

To evaluate the role of detailed pathologic features in predicting outcome for early-stage prostate cancer treated with I-125 brachytherapy. The pretreatment biopsy slides of 103 patients with T1/T2 and Gleason scores of 4-7 prostatic carcinoma, which was treated by transperineal I-125 implantation, were reviewed retrospectively by a single pathologist (P.B.G.). Biochemical tumor control rates [prostate-specific antigen (PSA) below 1.0] were correlated with pretreatment PSA, Gleason score, the amount of tumor in the biopsy samples, and the presence of perineural invasion. In Cox proportional-hazard, multivariate analysis, the strongest predictors of failure were pretreatment PSA above 10 ng/ml (P = 0.013) and the length of the biopsy specimen replaced by tumor (P = 0.15). The percent of biopsy tissue replaced by tumor (P = 0. 74), perineural invasion (P = 0.78), and Gleason score (P = 0.66) were less predictive of prognosis. It was concluded that pretreatment PSA is the strongest predictor of biochemical failure. Detailed assessment of pathological features on needle biopsy added little prognostic information beyond that of pretreatment PSA alone. Like all other prognostic parameters for prostate cancer, there is considerable overlap in pathologic features between those patients who will or will not be controlled biochemically.     

Biodistribution studies on L-3-[fluorine-18]fluoro-alpha-methyl tyrosine: a potential tumor-detecting agent

OBJECTIVES: To prospectively evaluate a clinical algorithm that predicts nodal status in patients with prostate cancer and to assess the impact on the outcome. METHODS: Between September 1988 and December 1994, 192 patients with organ-confined prostate cancer and considered surgical candidates for radical perineal prostatectomy (RPP) were stratified using the algorithm: prostate-specific antigen (PSA) 20 ng/mL or less, Gleason score 7 or lower, and clinical Stage T2a or lower. Patients failing any of these criteria were placed in the high-risk group and underwent a pelvic lymphadenectomy. Patients who satisfied all the criteria were placed in the low-risk group and underwent RPP without evaluation of the pelvic lymph nodes. Another contemporaneous cohort of patients (n = 65) underwent pelvic lymphadenectomy and radical retropubic prostatectomy (RRP) without use of the algorithm and were used as a control group. Patients were monitored for at least 24 months. RESULTS: In the RPP group, 177 patients were considered low risk according to the algorithm and were not offered staging lymphadenectomy before surgery, whereas 15 patients were categorized as high risk for metastasis and underwent staging lymphadenectomy. In the RRP and lymphadenectomy group, 41 patients were considered at low risk and 24 at high risk of disease spread according to the algorithm. In the RPP group, low-risk patients (no lymphadenectomy) had a PSA recurrence rate (27%) similar to that of low-risk patients in the RRP group with negative lymph nodes (29%), P = 0.8. Similarly, high-risk patients with negative lymph nodes in both groups had a similar recurrence rate (53% for RPP and 50% for RRP). Univariate logistic regression analysis showed that PSA was the most significant predictor for disease recurrence (P = 0.0004) followed by preoperative Gleason scores (P = 0.02) and clinical stages (P = 0.03). Multivariate stepwise analysis demonstrated that Gleason score and clinical stage did not add to the prediction of recurrence over PSA alone. CONCLUSIONS: Staging lymphadenectomy can be omitted in low-risk patients without deleterious effects on the outcome as measured by PSA recurrence.     

Probability of seminal vesicle involvement in localized prostatic carcinoma. Significance in conformal radiotherapy

PURPOSE: The development of objective criteria for selecting patients for seminal vesicle irradiation on radical radiotherapy for prostate cancer will be important for successful planning of 3D conformal radiotherapy. MATERIALS AND METHODS: Based on morphometric studies from radical prostatectomy specimens, new imaging modalities with potential in the investigation of patients with gross seminal vesicle involvement and clinical factors with potential in the identification of patients with subclinical disease the development of objective guidelines is possible. RESULTS: Clinical tumor stage as determined by digital rectal examination, diagnostic tumor biopsy (Gleason Score), and pretherapy serum prostate-specific antigen value were significant factors for the probability of involvement of seminal vesicles. Studies show that seminal vesicle involvement is unlikely if the PSA is < 4 ng/ml or 4 to 10 ng/ml and Gleason Score < 7 and stage < or = T2b. In contrast, involvement of seminal vesicles is highly likely with levels above 20 ng/ml. In patients with PSA levels between 10 and 20 ng/ml and Gleason Score < 7 ultrasonographic findings with regard to tumor volume and localization will be useful to determine the extent of the target volume. For treatment planning a significant reduction in the volumes of irradiation to the rectum and bladder is evident when seminal vesicles were excluded. CONCLUSION: Prospective use of the objective criteria will be useful in the selection of patients for seminal vesicle involvement and should be an integral part in 3D conformal radiotherapy of prostate cancer.     

Radical prostatectomy after complete androgen blockade in stage B2 and C cancer

Despite recent advances in imaging techniques, the staging process is still unsatisfactory in cancer of the prostate. The underestimation for stage B2 and C tumours in about 50%. We present our findings in a retrospective study analyzing the clinical and biological effects of complete androgen blockade before radical prostatectomy in patients with advanced stage localized tumours. We treated 21 patients from 1989 to 1993. All received preoperative homonotherapy by complete androgen block for at least 3 months before node dissection preceding suprapubic radical prostatectomy. Only 20 prostatectomies were performed as metastasis was found in the extemporaneous examination in 1 patient. The volume of the prostate gland had diminished in all patients after the hormonotherapy (27.8%) as did PSA (95%). When evaluated, the tumour stage of the surgical specimen was always more advanced than the needle biopsy. Only 1 tumour was strictly limited to the intracapsule and all the others had either invaded the capsule, reached the margins or had invaded the seminal vessels or lymph nodes. With a mean follow up of 45 months, recurrence rate is 50%, mainly due to tumours with positive margins or seminal invasion in patients who were not given adjuvant treatment. Our results are in agreement with those in the literature showing that although the volume of the prostate is reduced and PSA declines, no improvement in pathology staging is observed.     

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.     

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.