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.     

Exceptionally high seizure threshold: ECT device limitations

Numerous studies have confirmed the distinct biological behavior of two subsets of prostate cancer diagnosed incidentally after either transurethral resection (TURP) or open prostatectomy for presumed benign prostatic hyperplasia (BPH). Focal, low-grade lesions are associated with a low risk for clinical progression and are designated as stage T1a or A1. These cases have traditionally been managed conservatively with close clinical observation. In contrast, multifocal, high-volume, or high-grade tumors are associated with a more aggressive clinical course and are designated as stage T1b or A2. Early definitive intervention is usually advocated for these latter patients. Therefore, accurate pathological assignment to either stage T1a or T1b is crucial for selection of appropriate management options. A variety of methods for staging patients with incidentally detected prostate cancer have been proposed, including detailed histological analysis, repeat TURP or transurethral biopsy, serial prostate-specific antigen (PSA) analysis, and imaging with either transrectal ultrasound (TRUS) or magnetic resonance (MRI) techniques. This article critically examines the clinical utility of these staging modalities for patients with incidentally detected prostate cancer.     

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.     

Comparison of digital rectal examination and biopsy results with the radical prostatectomy specimen

PURPOSE: Digital rectal examination is integral to staging prostate cancer. Ultrasound guided biopsy establishes the diagnosis, and it may provide useful information regarding disease grade and extent. Treatment decisions are largely based on information gained from digital rectal examination and biopsy but this information is only useful if it correlates with the radical prostatectomy specimen and prognosis. We correlated digital rectal examination and transrectal ultrasound guided biopsy results with a detailed analysis of the radical prostatectomy specimen. MATERIALS AND METHODS: The accuracy of an abnormal digital rectal examination for predicting the location and extent of cancer was assessed in 89 patients thought to have clinical stage T2 disease. We evaluated 155 patients with clinical stages T1c and T2 disease to correlate the location of positive biopsies with the tumor site in the prostate. Radical prostatectomy specimens were completely sectioned at 2 mm. intervals, and tumor extent and location were recorded. RESULTS: In 85 patients a unilateral lesion was suspicious on digital rectal examination, that is stage cT2. The final pathological review revealed cancer on the suspicious side in 82 cases (96%) with tumor confined to the same lobe in only 23 (27%), bilateral disease in 59 (69%) and tumor confined to the contralateral lobe in 3 (4%). In 4 patients with a palpable bilateral abnormality a bilateral lesion was confirmed on final pathological evaluation. Digital rectal examination demonstrated a 36 and 31% incidence of extracapsular tumor extension and positive surgical margins, respectively, on the clinically benign side. In 100 patients only unilateral biopsy was positive. The final pathological evaluation revealed cancer in the biopsy positive side in 95 cases (95%) with tumor confined to the ipsilateral lobe in only 26 (26%), bilateral disease in 69 (69%) and tumor confined to the contralateral lobe in 5 (5%). In 46 of the 55 patients (84%) with bilateral positive biopsies tumor involved both sides but the pathologist did not identify cancer in both lobes in 9 (16%). While 100 patients had a unilateral negative biopsy, analysis of the prostatectomy specimen revealed carcinoma in the benign lobe in 74 (74%). Moreover, extracapsular tumor extension and a positive surgical margin were observed on the biopsy negative side in 31% of the patients. The degree to which digital rectal examination and biopsy results confirmed the final pathological evaluation was assessed using the kappa statistic, which revealed only slight agreement with each factor. The correlation of digital rectal examination and biopsy results with the location of extracapsular extension and positive margins was evaluated by the Spearman coefficient of correlation, which indicated poor agreement. When patients with unilateral versus bilateral positive biopsy were compared with respect to prognostic parameters, the difference was statistically significant for initial serum prostate specific antigen, the percentage of surface involved by tumor, biopsy and final Gleason scores, and the incidence of extracapsular extension of tumor. CONCLUSIONS: Digital rectal examination and the interpretation of prostate biopsy are not accurate clinical tools for defining the location and extent of prostatic carcinoma. Bilateral positive biopsy may be useful as an adjunct to the current clinical staging system.     

Analyzing outcome-based staging for clinically localized adenocarcinoma of the prostate

BACKGROUND: A clinical staging system based on the prostate-specific antigen (PSA) and the calculated prostate carcinoma volume (cVCa) construct previously has been proposed. This study was performed to assess whether this proposed clinical staging system was valid in an independent surgical and radiation data set in patients with clinically localized disease. METHODS: Cox regression multivariable analyses were used to assess the significance of staging systems (1992 American Joint Commission on Cancer Staging [AJCC] clinical and pathologic stage, versus cVCa-PSA clinical stage) to predict time to posttherapy PSA failure in 441 and 465 patients managed by surgery and radiation, respectively. Significant staging systems identified using Cox regression were tested further using established comparative measures to define the most clinically useful system. RESULTS: Both the 1992 AJCC pathologic stage and the cVCa-PSA clinical stage were significant predictors of time to postoperative PSA failure (P = 0.0001), whereas only the cVCa-PSA clinical stage was a significant predictor of time to postradiation PSA failure (P = 0.0001) using a Cox regression multivariable analysis. Further analyses using a pairwise comparison of the 1992 AJCC pathologic stage and cVCa-PSA clinical stage found the cVCa-PSA staging system provided a more clinically useful prediction of time to postoperative PSA failure. Specifically, the cVCa-PSA staging system was able to identify surgically managed patients with pathologic AJCC T2 disease who did poorly (3-year bNED = 22%) while also selecting patients with clinical AJCC T2b,c disease that was managed by radiation who did well (3-year bNED = 100%). CONCLUSIONS: A clinical staging system based on parameters obtained during the routine evaluation for AJCC clinical T1,2 prostate carcinoma provided a clinically useful stratification of both postoperative and postradiation PSA failure free survival.     

Combined orchiectomy and external radiotherapy versus radiotherapy alone for nonmetastatic prostate cancer with or without pelvic lymph node involvement: a prospective randomized study

PURPOSE: We compare the combination of orchiectomy and radiotherapy to radiotherapy alone as treatment for pelvic confined prostate cancer, that is T1-4, pN0-3, M0 (TNM classification). MATERIALS AND METHODS: In this prospective study 91 patients with clinically localized prostate cancer were, after surgical lymph node staging, randomized to receive definitive external beam radiotherapy (46) or combined orchiectomy and radiotherapy (45). Patients treated with radiotherapy alone had androgen ablation at clinical disease progression. The effects on progression-free, disease specific and overall survival rates were calculated. RESULTS: After a median followup of 9.3 years (range 6.0 to 11.4) clinical progression was seen in 61% of the radiotherapy only patients (group 1) and in 31% of the combined treatment patients (group 2) (p = 0.005). The mortality was 61 and 38% (p = 0.02), and cause specific mortality was 44 and 27%, respectively (p = 0.06), in groups 1 and 2. The differences in favor of combined treatment were mainly caused by lymph node positive tumors. For node negative tumors there was no significant difference in survival rates. CONCLUSIONS: The progression-free, disease specific and overall survival rates for patients with prostate cancer and pelvic lymph node involvement are significantly better after combined androgen ablation and radiotherapy than after radiotherapy alone. These results strongly suggest that early androgen deprivation is better than deferred endocrine treatment for these patients.     

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.     

Calculated prostate cancer volume greater than 4.0 cm3 identifies patients with localized prostate cancer who have a poor prognosis following radical prostatectomy or external-beam radiation therapy

PURPOSE: Patients with palpable extraprostatic disease (T3) have a poor prostate-specific antigen (PSA) failure-free (bNED) survival rate after radical prostatectomy (RP) or external-beam radiation therapy (RT). This study was performed to validate or refute the prognostic value of the previously defined calculated prostate cancer volume (cV(Ca)). PATIENTS AND METHODS: For patients with clinically localized disease (T1c,2), a Cox regression multivariable analysis was used to assess the ability of the cV(Ca) value to predict time to posttherapy PSA failure following RP or RT. RESULTS: The cV(Ca) value was a significant predictor (P < or = .0005) of time to posttherapy PSA failure in both an RP and RT data set independent of the one used to derive the cV(Ca)-based clinical staging system. In both RP- and RT-managed patients, estimates of 3-year bNED survival were not statistically different for patients with either T1c,2 disease and a cV(Ca) greater than 4.0 cm3 (RP, 27%; RT, 18%) or T3 disease (RP, 37%; RT, 34%). Despite pathologic T2 disease, the 3-year estimate of bNED survival was at most 51% in RP-managed patients with T1c,2 disease and cV(Ca) greater than 4.0 cm3. CONCLUSION: A cV(Ca) greater than 4.0 cm3 identified patients with T1c.2 disease whose bNED survival was poor after RT or RP despite pathologic T2 disease that suggests the presence of occult micrometastatic disease in many of these patients. Prospective randomized trials to evaluate the impact on survival of adjuvant systemic therapy in these high-risk patients are justified.     

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.     

Effects of immobilization and subsequent low- and high-intensity exercise on morphology of rat calf muscles

The patient presented is a 58-year-old man with newly diagnosed prostate cancer who likely has at least a 10- to 15-year life expectancy. In staging this man's extent of disease, several preoperative clinical variables are provided to assess whether the patient has local disease before offering definitive surgical therapy. It has been demonstrated that the combination of several of these variables in a multivariate analysis has greater predictive power than any of these variables do alone. Multivariate analysis using clinical stage, prostate-specific antigen (PSA), and Gleason score will provide both the physician and patient with 95% confidence intervals for determining the probability of having organ-confined disease, extracapsular penetration, seminal vesicle involvement, and lymphatic metastases. Several of the clinical variables given indicate that this patient has advanced disease, such as a PSA of 12 ng/mL, a stage T2b lesion, Gleason sum 7 disease in 2 of 3 cores from the right side associated with perineural invasion, and an additional Gleason sum 7 biopsy from the contralateral apex. For a man with these preoperative variables, there is a 13% chance of organ-confined disease, an 18% probability of seminal vesicle invasion, and a 17% chance of positive pelvic lymph nodes based on a nomogram constructed from multivariate analysis. Using this information, this man should be counseled that he has a high probability (87%) of extracapsular disease and a significant risk (15% to 20%) of having either seminal vesicle or lymph node involvement. Recognizing the risks and benefits of various forms of definitive therapy for prostate cancer, the patient has additional information to make an informed decision.     

Results of transrectal ultrasound-guided biopsies and clinical significance of Japanese prostate cancer

BACKGROUND: We review the outcomes of ultrasound-guided biopsy in consecutive patients and assess clinical significance of Japanese prostate cancer. METHODS: Examination was made of 1469 patients subsequent to transrectal ultrasound-guided biopsy of the prostate gland. For 84 patients, two or more sets of ultrasound-guided biopsies were conducted following the initial negative results during this period. Two hundred and thirty-two patients with benign histology at the initial biopsy underwent transurethral resection of the prostate (TURP). The clinical significance of the cancers was assessed based on patient age and calculated tumor volume at diagnosis, assumed cancer volume doubling time and life-expectancy in the Japanese male population. RESULTS: Overall, 327 of the 1469 patients (22.3%) had prostate carcinoma. Positive biopsy rates in patients with PSA 2.0 ng/ml or lower, 2.1-4.0 ng/ml, 4.1-10.0 ng/ml and 10.1 ng/ml or greater were 4.6%, 8.6%, 15.8% and 59.5%, respectively. Of the 232 patients who underwent TURP, 15 (6.5%) had cancer. Of the 84 patients subjected to the multiple sets of biopsies, 19 (22.6%) cancers were detected. Of the 203 cancers without distant metastasis at initial biopsy, 13.3%, 25.1%, 32.5% and 40.4% of tumors for 2-, 3-, 4- and 6-year tumor doubling times gave no indication of clinical significance. Nearly half these patients (43-52%) had clinical stage T1c disease. The estimated proportion of clinically insignificant tumors in repeat biopsy was virtually the same as first set biopsies. CONCLUSIONS: Low PSA was not necessarily an indication of indolent cancer and repeat biopsy did not often demonstrate clinically unimportant cancers. Many patients with stage T1c disease may eventually prove to require no treatment.     

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.     

Progression in and survival of patients with locally advanced prostate cancer (T3) treated with radical prostatectomy as monotherapy

PURPOSE: We determine the progression and survival rates in patients with locally advanced prostate cancer treated with radical prostatectomy without adjuvant treatment, and investigate subgroups of patients who may not benefit from this treatment. MATERIALS AND METHODS: Radical prostatectomy was performed in 83 patients with T3 prostate cancer. The patients were divided in subgroups with T3G1 to 2 and T3G3 tumors, which were evaluated for clinical progression, local recurrence, distant metastases, biochemical progression, and overall and cancer specific survival at 5 and 10 years by Kaplan-Meier curves. The results were compared to those of 190 patients with locally confined tumors. RESULTS: At 5 and 10 years overall survival was 75 and 60%, and cancer specific survival was 85 and 72%, respectively. At 5 and 10 years clinical progression was 41 and 69%, local recurrence 18 and 44%, and distant metastases 31 and 50%, respectively. Biochemical progression at 5 years was 71%. Patients with poorly differentiated tumors showed significantly lower survival and higher progression rates compared to those with well or moderately differentiated tumors. Progression and survival in patients with T3G1-2 tumor were not significantly different from those for patients with locally confined tumors. CONCLUSIONS: Radical prostatectomy as monotherapy in patients with locally advanced nonmetastatic prostate cancer (T3) produces acceptable results in those with well or moderately differentiated tumors. The results of progression and survival are not significantly different from those in patients with locally confined prostate cancer. However, patients with poorly differentiated tumors (T3G3) have early progression and need adjuvant treatment following surgery.     

Pelvic lymphadenectomy can be omitted in selected patients with carcinoma of the prostate: development of a system of patient selection

OBJECTIVES: The prevalence of pelvic lymph node metastases in men with clinically localized prostate cancer has decreased dramatically over the past decade, possibly due to efforts at early detection. With a significantly lower incidence of pelvic node involvement, it may be possible to identify a segment of patients for whom pelvic lymph node dissection (PLND) may be omitted. This study was conducted to develop a method to select patients for whom PLND could be omitted. METHODS: We analyzed serum prostate-specific antigen (PSA), clinical stage, biopsy Gleason score, and final pathologic stage in 481 men with clinically localized prostate cancer. These variables were compared to the risk of positive pelvic lymph nodes. RESULTS: Logistic regression analysis determined that combining all three variables provided the best determination of final pathologic stage. A series of probability curves have been created to estimate the risk of positive lymph nodes in a given patient. Based on the distribution of patients in this study and using these probability functions, PLND could be avoided in up to 50% of patients with localized prostate cancer diagnosed by contemporary methods. CONCLUSIONS: In properly selected patients, pelvic lymphadenectomy can be omitted in the staging and treatment of localized prostate cancer.     

Identification of a novel nuclear speckle-type protein, SPOP

A careful evaluation of local tumoral extension is mandatory in patient selected for radical surgery for prostate cancer. Nevertheless, prostatic imaging, achieved with transrectal ultrasonography (TRUS) and CT scan, is often unable to stage accurately the disease. The Authors report a retrospective analysis of 43 patients treated with radical retropublic prostatectomy: their findings support the idea that both TRUS and CT scan are unable to define the extent of the tumor, reaching respectively accuracies of 38 and 46%. From these data they conclude that CT can be excluded from the preoperatory workup of prostate cancer, except in selected patients, at high risk of nodal metastasis on the basis of PSA. TRUS is the mainstay of prostate cancer diagnosis and staging because it guides transrectal biopsies, but any conclusion made exclusively on the base of its imaging seems not reliable.     

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.