[Indications for and results of radical prostatectomy]. / Indikationstellung und Ergebnisse der radikalen Prostatektomie.

Radical prostatectomy represents the mainstay of therapy for clinically localized prostate cancer. The combination of diagnostic parameters such as PSA or biopsy Gleason grade in nomograms allows a safe prediction of pathologic stage and prognosis of the disease. Imaging techniques are useful in a subset of patients. International studies have proven a high cancer control rate of radical prostatectomy. A nerve-sparing modification of the operative technique does not compromise radicality of the procedure if patients are carefully selected. For this purpose simple and reliable algorithms are available.

[Can nomograms derived in the U.S. applied to German patients? A study about the validation of preoperative nomograms predicting the risk of recurrence after radical prostatectomy]. / Sind statistische Vorhersagemodelle aus den USA auf deutsche Patienten übertragbar? Eine Validierungstudie präoperativer Nomogramme zur Vorhersage des Rezidivrisikos nach radikaler Prostatektomie.

In patients suffering from prostate cancer, preoperative nomograms, which predict the risk of recurrence may provide a helpful tool in regard to the counselling and planning of an appropriate therapy. The best known nomograms were published by the Baylor College of Medicine, Houston and the Harvard Medical School, Boston. We investigated these nomograms derived in the U.S. when applied to German patients. Data from 1003 patients who underwent radical prostatectomy at the University-Hospital Hamburg were used for validation. Nomogram predictions of the probability for 2-years (Harvard nomogram) and 5-years (Kattan nomogram) freedom from PSA recurrence were compared with actual follow-up recurrence data using areas under the receiver-operating-characteristic curves (AUC). The recurrence free survival after 2 and 5 years was 78% and 58%, respectively. The AUC of the Harvard nomogram predicting 2-years probability of freedom from PSA recurrence was 0.80 vs. Kattan-Nomogram 5-years prediction of 0.83. Thereby, the Kattan nomogram showed a significant higher predictive accuracy (p=0.0274). For that reason preoperative nomograms derived in the U.S. can be applied to german patients. However, we would recommend the utilization of the Kattan nomogram due to its higher predictive accuracy.

Differences in biopsy features between prostate cancers located in the transition and peripheral zone.

OBJECTIVE: To identify the zonal location of prostate cancers before surgery, by analysing the mapping of ultrasonography-guided systematic sextant biopsies for differences between cancers located in the transition zone (TZ) and peripheral zone (PZ); and to compare the correlation between Gleason scores of needle biopsies and those of radical prostatectomy (RP) specimens. PATIENTS AND METHODS: In all, 186 patients with TZ (46) and PZ cancers (140) underwent ultrasonography-guided systematic sextant biopsy and RP at the same institution. The clinical and pathological characteristics, and the anatomical location of positive biopsies, were determined and compared using t-tests and chi-square tests. Differences between Gleason scores of needle biopsies and those of RP specimens were evaluated and compared by Cohen kappa testing. RESULTS: TZ cancers had a significantly lower rate of positive biopsies in the middle (63% vs 80%) and base (50% vs 80%) of the prostate than had PZ cancers. Positive biopsies were exclusively obtained from the apex in 19.6% of TZ and 5% of PZ cancers (P = 0.002). There was exact agreement between Gleason scores of needle biopsies and those of RP specimens in 15.2% of TZ (kappa = 0.02) and 55% of PZ cancers (kappa = 0.25), respectively. CONCLUSION: Compared with PZ cancers, TZ cancers had a different anatomical pattern of positive biopsies, with lower rates in the middle and base of the prostate. The finding of positive biopsies exclusively in the apex favoured prostate cancer located in the TZ. Furthermore, the correlation between needle biopsy Gleason scores and those of the RP specimens was clearly lower in TZ cancers.

Disease recurrence after radical prostatectomy. Contemporary diagnostic and therapeutical strategies.

In this paper the authors provide an overview of contemporary diagnostic and therapeutic strategies in patients with disease recurrence after radical prostatectomy. Literature on disease progression after radical prostatectomy (RP) is reviewed and a selection of articles made. Key words used for the Medline research included: prostate cancer (PC), RP, disease recurrence, prostate-specific antigen (PSA) progression and biochemical failure (BF). Within 10 years following RP for clinically localized PC, about 1/3 of patients will present disease recurrence. This is generally diagnosed by BF. The prognosis of these men may vary considerably. Differences in PSA kinetics (PSA doubling time, PSADT, onset of PSA rise) are useful for differentiating between local recurrence and distant disease. Indications and results are provided for different treatment strategies such as local radiation therapy, hormone therapy or watchful waiting. The present paper reviews the recent international literature. Diagnostic strategies and therapeutic manoeuvres are discussed. Prognostic factors as well as treatment indications are presented with the aim of applying an individual therapy.

A validated strategy for side specific prediction of organ confined prostate cancer: a tool to select for nerve sparing radical prostatectomy.

PURPOSE: Nerve sparing radical prostatectomy for prostate cancer should be restricted to patients who harbor tumors without capsular penetration. To our knowledge the selection criteria for nerve sparing radical prostatectomy are not clearly defined. We investigated a panel of preoperative tumor characteristics with respect to their ability to predict organ confined tumor growth for each lobe of the prostate to indicate unilateral or bilateral nerve sparing radical prostatectomy. MATERIALS AND METHODS: Nine preoperative tumor characteristics in 278 patients with clinically localized prostate cancer were included in retrospective univariate and multivariate tree structured regression analysis. The association of clinical stage, serum prostate specific antigen (PSA), PSA density, and results of transrectal ultrasound and systematic sextant biopsy, including a quantitative assessment of cancer in the biopsies with organ confined tumor growth, was statistically evaluated. Except for serum PSA and PSA density preoperative characteristics were considered separately for each prostate lobe. Multivariate analysis results were validated prospectively in 353 patients. RESULTS: On univariate analysis the number of positive biopsies was the most useful single parameter with a positive predictive value of 83% in 274 lobes and a negative predictive value of 55%, followed by mm. of tumor in the biopsy. Of all characteristics included in multivariate analysis only the number of biopsies with high grade cancer, the number of positive biopsies and serum PSA were independent for predicting organ confined cancer. When PSA was less than 10 ng./ml. and not more than 1 biopsy with high grade cancer was identified in a lobe, organ confined tumor growth was present in 86.1% of cases. On prospective validation the same criteria led to an 88.5% incidence of organ confined prostate cancer. Pooling the 2 most favorable groups led to 391 prostate lobes (70.8% of those investigated) with a positive predictive value of 82.1% (95% confidence interval 77.9% to 85.8%). Using the multivariate approach more prostate lobes were assigned to a favorable risk group than on univariate analysis. Clinical stage and simple Gleason grade did not contribute independent information for predicting organ confined disease. CONCLUSIONS: Quantifying cancer and high grade cancer by systematic biopsy and serum PSA concentration are useful preoperative characteristics for predicting organ confined prostate cancer. Side specific analysis of these parameters is a flexible and reliable tool for selecting patients for nerve sparing radical prostatectomy.

Relevance of p53 gene alterations for tumor recurrence in patients with superficial transitional cell carcinoma of the bladder.

PURPOSE: The prognostic relevance of p53 protein accumulation in muscle-invasive bladder carcinoma is well documented, but the prognostic relevance of p53 alterations in superficial bladder tumors remains uncertain. Immunohistochemical data are divergent, possibly because of the use of nonstandardized techniques. We therefore investigated the relevance of p53 gene point mutations and loss of heterozygosity (LOH) for tumor recurrence. The results of this molecular analysis were compared with accumulation of the p53 protein as shown by immunohistochemistry. MATERIAL AND METHODS: Representative tumor tissue was selected and microdissected from 40 patients (pTa, 18 patients; pT1, 22 patients; grade I, 7 patients; grade II, 28 patients; grade III, 5 patients). Polymerase chain reaction (PCR) was carried out with exons 5-8. All PCR products were screened for p53 mutations with temperature-gradient gel electrophoresis (TGGE). When mobility shift was observed, direct nucleotide sequencing was performed. Detection of LOH was performed with nonradioactive microsatellite analysis using three markers (TP 53, D17S513 and D17S786) on chromosome 17p. Immunohistochemistry was performed with the DO 7 antibody. Tumor samples with p53 accumulation of 5% or more positive nuclei were classified as positive. Univariate analysis for disease-free survival was performed using Kaplan-Meier analysis and the log-rank test. RESULTS: TGGE and direct sequencing detected mutations in 10 of 40 patients (2 of 18 pTa and 8 of 22 pT1 patients). LOH was detected in 11 patients. Both a mutation and LOH were detected in 3 patients. p53 immunohistochemistry detected at least 5% positive nuclei in 28 of 40 patients (70%). After a median follow-up of 26 months 14 patients suffered disease recurrence. Whereas disease-free survival did not correlate with a mutation (p = 0.77, log-rank test), LOH (p = 0.2) or a mutation in combination with LOH (p = 0.23), a positive p 53 immunoreaction was significantly associated with short disease-free survival (p = 0.009). CONCLUSION: Despite the relatively high percentage of patients with p53 gene alteration in this population no significant correlation between the detection of molecular alteration and disease recurrence could be found. We conclude that, in contrast to immunohistochemical accumulation, gene alterations play only a minor role in tumor recurrence of p53 in patients with superficial transitional cell carcinoma of the bladder, and that immunohistochemical accumulation of the p53 protein has to be explained by mechanisms other than gene mutations.

Comparison of ultrasound imaging in patients undergoing transperineal and transrectal prostate ultrasound.

OBJECTIVES: Prostatic evaluation in men who have undergone prior abdominoperineal resection pose an unusual challenge for the urologist. Neither digital rectal examination nor transrectal ultrasound (TRUS) can be performed. Transperineal ultrasound (TPUS) has been suggested as an alternative means of imaging. This imaging modality was compared directly with the standard TRUS method. METHODS: TPUS was performed with a 4-MHz abdominal probe or biplane multiple frequency probe at a frequency of 5 to 7 MHz followed by TRUS at 7 MHz in 50 consecutive men referred for prostate ultrasound and biopsy who had not undergone prior abdominoperineal resection. Dimensions of the prostate and ultrasound findings such as hypoechoic, anechoic, or hyperechoic areas were noted for each sonographic approach. Volume calculation was performed by the prolate spheroid method. RESULTS: There was good TPUS visualization of the prostate in the transverse plane in 48 (96%) of 50 patients and in the sagittal plane in 45 (90%) of 50 patients. Prostate volume calculation by TPUS correlated well with the volume calculated by TRUS (r=0.876). Twenty-nine patients (58%) were found to have suspicious hypoechoic lesions by TRUS; none were seen by TPUS. Prostatic calcifications were present in 12 patients and were visualized by both TPUS and TRUS in all 12 patients. Six prostate glands demonstrated cystic lesions on TRUS imaging; three of these cystic lesions were also seen with TPUS imaging. CONCLUSIONS: TPUS allows visualization of the prostate with volume determination that is comparable to the volume determination by TRUS. Some intraprostatic findings such as calcifications and cysts can be identified; however, suspicious hypoechoic lesions were not identified by TPUS imaging of the prostate.

Systematic sextant biopsies improve preoperative prediction of pelvic lymph node metastases in patients with clinically localized prostatic carcinoma.

PURPOSE: An algorithm including the results of systematic sextant biopsies was statistically developed and evaluated to predict the probability of pelvic lymph node metastases in patients with clinically localized carcinoma of the prostate. MATERIALS AND METHODS: Clinical stage, serum prostate specific antigen concentration, Gleason score, number of positive biopsies, number of biopsies containing any Gleason grade 4 or 5 cancer and number of biopsies predominated by Gleason grade 4 or 5 cancer were recorded in 345 patients undergoing pelvic lymph node dissection and correlated with the incidence of lymph node metastases. Multivariate logistic regression, and classification and regression trees analyses were performed. RESULTS: In univariate analysis all variables had a statistically significant influence on lymph node status. Logistic regression showed that the amount and distribution of undifferentiated Gleason grade 4 and 5 cancer in the biopsies were the best predictors of lymphatic spread followed by serum prostate specific antigen. Classification and regression trees analysis classified 79.9% of patients who had 3 or fewer biopsies with Gleason grade 4 or 5 cancer and no biopsies predominated by undifferentiated cancer as a low risk group. In this group positive lymph nodes occurred in only 2.2% (95% confidence interval 0.8 to 4.7%). CONCLUSIONS: Including the results of systematic sextant biopsies substantially enhances the predictive accuracy of algorithms that define the probability of lymph node metastases in prostatic cancer. Patients thus defined as having no lymphatic spread could potentially be spared pelvic lymph node dissection before definitive local treatment.

Correlation between serum prostate specific antigen levels and the volume of the individual glandular zones of the human prostate.

To analyze the correlation between serum prostate specific antigen (PSA) levels and the volume of the individual glandular zones of the human prostate, we examined 31 cystoprostatectomy specimens as well as 13 radical prostatectomy specimens with a prostate cancer volume of 0.3 cc or less, no bladder cancer infiltrating the prostate, no granulomas or severe inflammation, as well as no patient history of radiation, transurethral resection of the prostate or hormonal treatment. The volumes of the peripheral zone, transition zone and central zone were separately determined by outlining the zonal boundaries during microscopic examination of all slides at each level of section. PSA was measured by the Yang polyclonal assay. In the univariant regression analysis the correlation coefficients among serum PSA and transition zone, peripheral zone and central zone volumes were 0.934, 0.546 and 0.368, respectively, strongly suggesting that most PSA leakage from the prostate into the serum comes from the transition zone. The regression of serum PSA and transition zone volumes leads to a prediction of approximately 0.261 ng./ml. PSA per gm. benign prostatic hyperplasia (BPH) plus an intercept of 0.878, a number in keeping with our 1987 estimates of 0.3 ng./ml./gm. BPH. The volumes of the 3 zones appeared to be independent variables. Transition zone volume showed the greatest variation because of BPH. The mean average ratio of peripheral zone volume to central zone volume was nearly 3:1. These data strongly support the concept of age-adjusted PSA levels, since most of the increase in size of the prostate with increasing patient age comes from the transition zone from which BPH develops.

[Sonographic diagnosis of prostatic cancer]. / Sonographische Diagnostik des Prostatakarzinoms.

In 75-80% of all clinically significant prostate cancer, the peripheral zone appears to be hypoechoic on transrectal ultrasound (TRUS). However, examination by TRUS alone in a screening program is not recommended due to its low sensitivity. The combination of prostate-specific antigen, digital rectal examination, and TRUS increases the detection rate of prostate cancer. In prostate cancer arising from the transition zone, TRUS findings are often nonspecific. Even prostate biopsies might be negative due to the location of this tumor. Anterior biopsies of the transition zone will identify these prostate cancers. Color Doppler ultrasound of the prostate has little additional value over TRUS alone in the diagnosis of prostate cancer.