Clinical Stage T2 Disease Research Articles

Analysis of Nonsurgical Treatment Options for Metastatic Rectal Cancer

IntroductionUsing a large national registry, we investigated patterns of care and overall survival (OS) for metastatic rectal cancer patients treated with chemotherapy or radiotherapy (RT), or with a multimodal approach. Patients and MethodsAdult patients with metastatic rectal cancer who did not undergo resection diagnosed from 2004 to 2014 were included. Kaplan-Meier, log-rank, and Cox regression analyses were performed. ResultsWe identified 2385 patients. Of these, 1020 patients (43%) received chemotherapy alone, 228 (10%) received RT alone, 850 (36%) received chemotherapy and RT, and 287 (12%) received no treatment. Receipt of chemotherapy alone increased over the study period, and receipt of chemoradiotherapy decreased (P < .01). The only factor predictive of receiving any RT on multivariate analysis was clinical stage T3 disease. Factors predictive of OS on multivariate analysis included receipt of chemotherapy, Hispanic race, income greater than $46,000, and presence of lung metastasis. The OS for patients treated with chemotherapy and RT was not significantly different than chemotherapy alone. Five-year OS with chemotherapy alone, RT alone, chemoradiotherapy, and no treatment were, respectively, 84%, 56%, 79%, and 46%. ConclusionMetastatic rectal cancer patients with T3 tumors were more likely to receive RT. Local RT does not improve survival for patients with metastatic rectal cancer who do not also undergo surgery. The use of chemotherapy alone for metastatic rectal cancer is increasing, and chemotherapy is associated with higher OS compared to no treatment and RT alone. This remained true even in patients older than 80 years.

Erectile Function Recovery after Radical Prostatectomy in Men with High Risk Features

We describe the efficacy of radical prostatectomy to achieve complete primary tumor excision while preserving erectile function in a cohort of patients with high risk features in whom surgical resection was tailored according to clinical staging, biopsy data, preoperative imaging and intraoperative findings. In a retrospective review we identified 584 patients with high risk features (prostate specific antigen 20 ng/ml or greater, clinical stage T3 or greater, preoperative Gleason grade 8-10) who underwent radical prostatectomy between 2006 and 2012. The probability of neurovascular bundle preservation was estimated based on preoperative characteristics. Positive surgical margin rates and erectile function recovery were determined in patients who had some degree of neurovascular bundle preservation. The neurovascular bundles were resected bilaterally in 69 (12%) and unilaterally in 91 (16%) patients. The remaining patients had some degree of bilateral neurovascular bundle preservation. Preoperative features associated with a lower probability of neurovascular bundle preservation were primary biopsy Gleason grade 5 and clinical stage T3 disease. Among the patients with some degree of neurovascular bundle preservation 125 of 515 (24%) had a positive surgical margin, and 75 of 160 (47%) men with preoperatively functional erections and available erectile function followup had recovered erectile function within 2 years. High risk features should not be considered an indication for complete bilateral neurovascular bundle resection. Some degree of neurovascular bundle preservation can be done safely by high volume surgeons in the majority of these patients with an acceptable rate of positive surgical margins. Nearly half of high risk patients with functional erections preoperatively recover erectile function after radical prostatectomy.

Population-based analysis of treatment modalities and survival for clinically localized small-cell carcinoma of the prostate.

Small-cell carcinoma of the prostate is an aggressive cancer whose rarity has prevented the development of a consensus management approach. The objective of the current study was to determine the treatment patterns and evaluate factors affecting overall survival for patients with localized small-cell carcinoma of the prostate. After querying the National Cancer Database, we identified all patients diagnosed with localized small-cell carcinoma of the prostate between 1998 and 2011 (n=287). Using Kaplan-Meier curves and Cox regression analyses, we assessed the effect of treatment and clinical stage on overall survival. Treatments included radiation therapy in 46% (n=131), chemotherapy in 38% (n=107), androgen deprivation therapy (ADT) in 22% (n=63) and radical prostatectomy in 13% (n=38). Median overall survival was 14.8 months. Upon multivariate analysis, local therapy (radical prostatectomy or radiation therapy) was associated with improved survival (hazard ratio (HR) 0.23, 95% confidence interval (CI) 0.14-0.38, P<0.001). Advanced clinical stage predicted worse survival among all men (cT3: HR 2.83, 95% CI 1.27-6.32, P=0.011; cT4: HR 3.26, 95% CI 1.50-7.07, P=0.003) and men who received local therapy (cT3: HR 4.67, 95% CI 1.41-15.44, P=0.012; cT4: HR 4.01, 95% CI 1.14-14.08, P=0.03) but not among men who received no local therapy (cT3: HR 1.64, 95% CI 0.51-5.27, P=0.4; cT4: HR 2.35, 95% CI 0.74-7.48, P=0.15). Age, receipt of chemotherapy and ADT, and clinical stage T2 disease (compared with T1) did not predict survival. Men with localized small-cell carcinoma of the prostate have a poor overall survival. Local therapy may represent a suitable and underused modality for select patients.

Five-year Nationwide Follow-up Study of Active Surveillance for Prostate Cancer

BackgroundActive surveillance (AS) is an important yet underutilized strategy to reduce prostate cancer (PCa) overtreatment. ObjectiveTo examine the 5-yr outcomes of AS in a population-based setting. Design, setting, and participantsFrom the National Prostate Cancer Register of Sweden, we identified 11 726 men ≤70 yr diagnosed with very low-risk to intermediate-risk PCa from 2003 to 2007 who completed 5 yr of follow-up. Of these men, 1729 (15%) chose AS for the primary management strategy. Outcome measurements and statistical analysisWe calculated the probability of discontinuation of AS over time, and Cox proportional hazards models were used to determine factors associated with discontinuation. Reasons for discontinuation were assessed by data extraction from medical charts. Results and limitationsBy 5 yr, 64% of the men remained on AS. Predictors of discontinuation were younger age, fewer comorbidities, more education, higher prostate-specific antigen (PSA), and clinical stage T2 disease; marital status did not predict discontinuation. In a subset with data on the reason for discontinuation (86%), 20% of men discontinued because of patient preference, 52% because of PSA progression, 24% because of biopsy progression, and 3% for other reasons. ConclusionsIn a population-based setting, the majority of men remained on AS at 5 yr. However, one-fifth of the men who discontinued AS did so for nonbiologic reasons. Thus, there is a need for support and counseling for men to continue AS in the absence of signs of progression to improve adherence to AS and decrease overtreatment. Patient summaryActive surveillance (AS) is an important option to delay or avoid treatment for men with favorable prostate cancer features. This study shows that at 5 yr, 64% of men across an entire population remained on AS. We concluded that AS is a durable option and that counseling may be useful to promote adherence for men without progression.

Performance characteristics of PSA in patients undergoing radical prostatectomy.

199 Background: The Prostate Cancer Prevention Trial demonstrated that the performance characteristics of PSA are improved for diagnosis of high grade disease. We assessed the performance of PSA for determining total and high grade cancer volume in a radical prostatectomy series. Methods: We identified 1307 patients from the Stanford Radical Prostatectomy Database with clinical stage T1c (n=658) and T2 (n=549) disease who had surgery between 1988 and 2002 and detailed morphometric mapping by a single pathologist. Patients with T1c and T2 disease were analyzed separately as the indication for biopsy was different in these two populations (elevated PSA versus abnormal DRE). We generated receiver operating characteristic (ROC) curves for PSA based on total tumor volume and volume of Gleason 4 or 5 disease and compared the areas under the curve (AUC) for different cut points of total and high grade cancer volume. Results: For patients with clinical stage T1c disease, as total and high grade cancer volumes increased, so did the AUC for PSA performance. There was a significant difference in AUC for PSA for total cancer volumes greater than 0.5 cc (AUC=0.62) compared to greater than 2 cc (AUC=0.72, p=0.02), and also between volumes greater than 2 cc (AUC=0.72) and 5 cc (AUC=0.79, p=0.0003, Fig.1). The AUC for PSA performance for volume of high grade disease increased from 0.66, to 0.68, to 0.76 for Gleason 4 or 5 volumes of 0, 0.5, and 3 cc, respectively (Fig. 2). For patients with clinical stage T2 disease, the AUCs for total or high grade cancer volume were not different across cut points, but were overall higher compared to the T1c group. Conclusions: In T1c patients, PSA performance improved in a stepwise fashion with higher total and high grade cancer volumes as evidenced by improved receiver operating characteristics. In T2 patients, no similar trend was observed, although overall PSA performance was improved compared to T1c patients. Prior studies show that PSA performs better for the detection of high grade disease; here, we show that PSA performs better in predicting volume of high grade disease in radical prostatectomy specimens.

Quality of Life After Hypofractionated Concomitant Intensity-Modulated Radiotherapy Boost for High-Risk Prostate Cancer

To evaluate the change in health-related quality of life (QOL) of patients with high-risk prostate cancer treated using hypofractionated radiotherapy combined with long-term androgen deprivation therapy. A prospective Phase I-II study enrolled patients with any of the following: clinical Stage T3 disease, prostate-specific antigen level ≥20 ng/mL, or Gleason score 8-10. Radiotherapy consisted of 45 Gy (1.8 Gy per fraction) to the pelvic lymph nodes with a concomitant 22.5 Gy intensity-modulated radiotherapy boost to the prostate, for a total of 67.5 Gy (2.7 Gy per fraction) in 25 fractions over 5 weeks. Daily image guidance was performed using three gold seed fiducials. Quality of life was measured using the Expanded Prostate Cancer Index Composite (EPIC), a validated tool that assesses four primary domains (urinary, bowel, sexual, and hormonal). From 2004 to 2007, 97 patients were treated. Median follow-up was 39 months. Compared with baseline, at 24 months there was no statistically significant change in the mean urinary domain score (p = 0.99), whereas there were decreases in the bowel (p < 0.01), sexual (p < 0.01), and hormonal (p < 0.01) domains. The proportion of patients reporting a clinically significant difference in EPIC urinary, bowel, sexual, and hormonal scores at 24 months was 27%, 31%, 55%, and 60%, respectively. However, moderate and severe distress related to these symptoms was minimal, with increases of only 3% and 5% in the urinary and bowel domains, respectively. Hypofractionated radiotherapy combined with long-term androgen deprivation therapy was well tolerated. Although there were modest rates of clinically significant patient-reported urinary and bowel toxicity, most of this caused only mild distress, and moderate and severe effects on QOL were limited. Additional follow-up is ongoing to characterize long-term QOL.

1468 INTRAFASCIAL BILATERAL NERVE SPARING RADICAL PROSTATECTOMY: DOES THE ROBOTIC-ASSISTED APPROACH PREDISPOSE TO HIGHER RISK OF POSITIVE SURGICAL MARGINS? IMPORTANCE OF PATIENT SELECTION

You have accessJournal of UrologyProstate Cancer: Localized1 Apr 20111468 INTRAFASCIAL BILATERAL NERVE SPARING RADICAL PROSTATECTOMY: DOES THE ROBOTIC-ASSISTED APPROACH PREDISPOSE TO HIGHER RISK OF POSITIVE SURGICAL MARGINS? IMPORTANCE OF PATIENT SELECTION Nazareno Suardi, Andrea Gallina, Niccolò Buffi, Emanuele Scapaticci, Matteo Zanoni, Giulio Gadda, Giovanni Lughezzani, Aldo Bocciardi, Luciano Nava, Alberto Briganti, Andrea Cestari, Patrizio Rigatti, Giorgio Guazzoni, and Francesco Montorsi Nazareno SuardiNazareno Suardi milan, Italy More articles by this author , Andrea GallinaAndrea Gallina milan, Italy More articles by this author , Niccolò BuffiNiccolò Buffi milan, Italy More articles by this author , Emanuele ScapaticciEmanuele Scapaticci milan, Italy More articles by this author , Matteo ZanoniMatteo Zanoni milan, Italy More articles by this author , Giulio GaddaGiulio Gadda milan, Italy More articles by this author , Giovanni LughezzaniGiovanni Lughezzani milan, Italy More articles by this author , Aldo BocciardiAldo Bocciardi milan, Italy More articles by this author , Luciano NavaLuciano Nava milan, Italy More articles by this author , Alberto BrigantiAlberto Briganti milan, Italy More articles by this author , Andrea CestariAndrea Cestari milan, Italy More articles by this author , Patrizio RigattiPatrizio Rigatti milan, Italy More articles by this author , Giorgio GuazzoniGiorgio Guazzoni milan, Italy More articles by this author , and Francesco MontorsiFrancesco Montorsi milan, Italy More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.1403AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The effect of the type of intrafascial approach (open vs robotic assisted) on the rate of positive surgical margins (PSM) has not been addressed yet. We hypothesized that RA intrafascial BNSRP might be associated with a higher risk of PSM due to a surgical dissection plane potentially closer to the prostatic capsule. METHODS Between 2004 and 2009, 501 consecutive patients underwent either open or RA intrafascial BNSRP for clinically localized PCa. Exclusion criteria for intrafascial approach were: clinical stage T3 disease, PSA>20 ng/ml or biopsy Gleason sum (GS) ≥8. Patients were stratified according to surgical approach (open vs RA). Uni and multivariable logistic regression models tested the association between surgical approach and the risk of positive surgical margins (PSM), after adjusting for PSA, biopsy GS, clinical stage and % of positive cores. The same analyses were repeated in patients with pre-operative very low-risk patients (PSA<10 ng/ml, clinical stage T1, biopsy GS≤ 6 and % positive cores ≤33%). RESULTS 293 (58.5%) and 208 (41.5%) patients were treated with open RP and RA BNSRP, respectively. Patients treated with RALP were younger (mean age: 60.1 vs. 63.5 yrs, p<0.001) and had lower PSA (6.1 vs. 7.1, p=0.008). Clinical stage (T2 in 34.6% vs. 16.7%;p<0.001) and Biopsy GS(7 in 28.6% vs. 7.7%) were higher in the open group (p<0.001). Patients in RALP group had significantly lower % of positive cores (35.7% vs. 28.4% respectively, p=0.02). The rate of PSM was higher in patients submitted to RA BNSRP in the overall population (22.1% vs. 12.5% respectively, p=0.005) as well as in patients with pathologically organ-confined disease (20.0 vs. 9.4%, respectively, p=0.02). At multivariable analyses, the surgical approach independently associated with PSM (p=0.01). Patients treated with RALP had a 2.8 fold increased risk of PSM as compared to open. However, when only patients with very low-risk disease were considered (n=84), patients treated with RALP had the same rate of PSM as compared to open(8.7 vs. 2.6% respectively, p=0.2). In this category, the surgical approach was not associated with a higher risk of PSM (p=0.3). CONCLUSIONS We demonstrated that patients treated with RA intrafascial BNSRP the has an higher risk of PSM. However, in patients with very low-risk disease open and RALP intrafascial BNSRP achieve the same PSM rates. Therefore, only highly selected patients (PSA<10 ng/ml, clinical stage T1, biopsy GS≤ 6 and 33% positive cores) should be candidated to intrafascial RA BNSRP. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e588 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Nazareno Suardi milan, Italy More articles by this author Andrea Gallina milan, Italy More articles by this author Niccolò Buffi milan, Italy More articles by this author Emanuele Scapaticci milan, Italy More articles by this author Matteo Zanoni milan, Italy More articles by this author Giulio Gadda milan, Italy More articles by this author Giovanni Lughezzani milan, Italy More articles by this author Aldo Bocciardi milan, Italy More articles by this author Luciano Nava milan, Italy More articles by this author Alberto Briganti milan, Italy More articles by this author Andrea Cestari milan, Italy More articles by this author Patrizio Rigatti milan, Italy More articles by this author Giorgio Guazzoni milan, Italy More articles by this author Francesco Montorsi milan, Italy More articles by this author Expand All Advertisement Advertisement PDF DownloadLoading ...

Hypofractionated Concomitant Intensity-Modulated Radiotherapy Boost for High-Risk Prostate Cancer: Late Toxicity

To report the acute and late toxicities of patients with high-risk localized prostate cancer treated using a concomitant hypofractionated, intensity-modulated radiotherapy boost combined with long-term androgen deprivation therapy. A prospective Phase I-II study of patients with any of the following: clinical Stage T3 disease, prostate-specific antigen level ≥ 20 ng/mL, or Gleason score 8-10. A dose of 45 Gy (1.8 Gy/fraction) was delivered to the pelvic lymph nodes with a concomitant 22.5 Gy prostate intensity-modulated radiotherapy boost, to a total of 67.5 Gy (2.7 Gy/fraction) in 25 fractions within 5 weeks. Image guidance was performed using three gold seed fiducials. The National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0, and Radiation Therapy Oncology Group late morbidity scores were used to assess the acute and late toxicities, respectively. Biochemical failure was determined using the Phoenix definition. A total of 97 patients were treated and followed up for a median of 39 months, with 88% having a minimum of 24 months of follow-up. The maximal toxicity scores were recorded. The grade of acute gastrointestinal toxicity was Grade 0 in 4%, 1 in 59%, and 2 in 37%. The grade of acute urinary toxicity was Grade 0 in 8%, 1 in 50%, 2 in 39%, and 3 in 4%. The grade of late gastrointestinal toxicity was Grade 0 in 54%, 1 in 40%, and 2 in 7%. No Grade 3 or greater late gastrointestinal toxicities developed. The grade of late urinary toxicity was Grade 0 in 82%, 1 in 9%, 2 in 5%, 3 in 3%, and 4 in 1% (1 patient). All severe toxicities (Grade 3 or greater) had resolved at the last follow-up visit. The 4-year biochemical disease-free survival rate was 90.5%. A hypofractionated intensity-modulated radiotherapy boost delivering 67.5 Gy in 25 fractions within 5 weeks combined with pelvic nodal radiotherapy and long-term androgen deprivation therapy was well tolerated, with low rates of severe toxicity. The biochemical control rate at early follow-up has been promising. Additional follow-up is needed to determine the long-term biochemical control and prostate biopsy results.

High-Dose-Rate Brachytherapy Boost for Prostate Cancer: Comparison of Two Different Fractionation Schemes

This is a retrospective study comparing our experience with high-dose-rate (HDR) brachytherapy boost for prostate cancer, using two different fractionation schemes, 600 cGy × 3 fractions (patient group 1) and 950 cGy × 2 fractions (patient group 2). A total of 165 patients were treated for prostate cancer using external beam radiation therapy up to a dose of 45 Gy, followed by an HDR brachytherapy prostate radiation boost. Between July 1997 and Nov 1999, 64 patients were treated with an HDR boost of 600 cGy × 3 fractions; and between June 2000 and Nov 2005, 101 patients were treated with an HDR boost of 950 cGy × 2 fractions. All but 9 patients had at least one of the following risk features: pretreatment prostate-specific antigen (PSA) level >10, a Gleason score ≥7, and/or clinical stage T3 disease. Median follow-up was 105 months for group 1 and 43 months for group 2. Patients in group 2 had a greater number of high-risk features than group 1 (p = 0.02). Adjusted for comparable follow-up, there was no difference in biochemical no-evidence-of-disease (bNED) rate between the two fractionation scheme approaches, with 5-year Kaplan-Meier estimates of 93.5% in group 1 and 87.3% in group 2 (p = 0.19). The 5-year estimates of progression-free survival were 86% for group 1 and 83% for group 2 (p = 0.53). Among high-risk patients, there were no differences in bNED or PFS rate due to fractionation. Results were excellent for both groups. Adjusted for comparable follow-up, no differences were found between groups.

A phase II trial of neoadjuvant erlotinib in patients with muscle‐invasive bladder cancer undergoing radical cystectomy: clinical and pathological results

To evaluate the clinicopathological efficacy of neoadjuvant erlotinib (an epidermal growth factor receptor, EGFR, inhibitor) for invasive bladder cancer in patients undergoing radical cystectomy (RC) as despite definitive surgical therapy, only half of patients undergoing RC will have long-term disease-free survival, and effective adjunctive therapies, especially using agents with lower toxicity, would be a significant advance in the treatment of invasive bladder cancer. The primary endpoint of this phase II trial is to determine the effect of neoadjuvant erlotinib (150 mg once daily for 4 weeks) before RC on the pathological complete response rate (pT0 rate) in RC specimens. In addition, the safety of therapy with erlotinib was also evaluated. Patients selected for study included those with histologically confirmed muscle-invasive bladder cancer who had undergone initial transurethral resection. In all, 20 patients with clinical stage T2 disease had neoadjuvant erlotinib therapy followed by RC. On surgical pathology, five patients (25%) were pT0; in addition, seven (35%) were clinically down-staged (< or = pT1) and 15 (75%) had organ-confined disease at surgical pathology. At a mean follow-up of 24.8 months, 10 patients remain alive and with no evidence of disease, four with organ-confined disease had progression and nine died, including six from disease and three from other causes. Erlotinib was tolerated in all patients, with drug rash being the most common side-effect, in 15 patients (75%). Interestingly, all pT0 and pTis/T1 patients had a rash. The EGFR inhibitor erlotinib, when administered in the neoadjuvant setting, can have beneficial effects in terms of surgical pathology and short-term clinical outcomes in patients undergoing RC for invasive bladder cancer. Analyses are underway to examine the molecular correlates of the apparent clinical effect of neoadjuvant therapy in these patients.

Dose-Escalated Radiotherapy for High-Risk Prostate Cancer: Outcomes in Modern Era With Short-Term Androgen Deprivation Therapy

Randomized data have supported the use of long-term androgen deprivation therapy (ADT) combined with radiotherapy (RT) for men with high-risk prostate cancer. The present study reviewed the outcomes of intermediate- and high-risk men treated with RT and short-term ADT. A total of 184 men with any single risk factor of prostate-specific antigen >or=10 ng/mL, clinical Stage T2b or greater, or Gleason score >or=7 were treated with primary external beam RT for nonmetastatic adenocarcinoma of the prostate. The median radiation dose was 74 Gy; 55% were treated with intensity-modulated RT. All patients received ADT for 1 to 6 months (median, 4), consisting of a gonadotropin-releasing hormone analog. Univariate and multivariable analyses were performed for risk factors, including T stage, Gleason score, radiation dose, and prostate-specific antigen level. With a median follow-up of 51 months, the 4-year freedom from biochemical failure (FFBF) using the nadir plus 2 ng/mL definition was 83% for all patients. Clinical Stage T3 disease was the only variable tested associated with FFBF on univariate (4-year FFBF rate, 46% vs. 87% for Stage T1-T2c disease; p = .0303) and multivariable analysis (hazard ratio, 3.9; p = .0016). On a subset analysis of high-risk patients (National Comprehensive Cancer Network criteria), those with clinical Stage T3 disease (4-year FFBF rate, 46% vs. 80%; p = .0303) and a radiation dose <74 Gy (4-year FFBF rate, 64% vs. 80%) had a poorer outcome on univariate analysis. However, clinical Stage T3 disease and radiation dose were not significant on multivariable analysis, although a statistical multivariable trend was seen for both (p = .0650 and p = .0597, respectively). Short-term ADT and RT might be acceptable for men with intermediate- and high-risk prostate cancer, especially for clinically localized disease treated with doses of >or=74 Gy.

725: Radical Prostatectomy for Clinical Stage T3 Disease

725: Radical Prostatectomy for Clinical Stage T3 Disease

The Effect of Age on Prostate Implantation Results

The current study was undertaken to determine the effect of young age (60 years or younger) on the 5-year biochemical disease-free survival rate following ultrasound-guided transperineal prostate implantation. The radiation therapy charts of 330 patients who underwent ultrasound-guided transperineal prostate implantation who were treated from 1992 through 2004 were retrospectively reviewed. Follow-up ranged from 12 to 120 months, with a mean of 48 months. A total of 63 patients were 60 years of age or younger, and 267 patients were over 60 years of age. Prostate-specific antigen (PSA) recurrence was defined as three successive increases following ultrasound-guided transperineal prostate implantation. Biochemical disease-free survival was determined using the life-table method. There were no statistically significant differences in the 5-year biochemical disease-free survival rates for the younger versus the older group. On univariate analysis, age was not a statistically significant factor in predicting PSA failure. Univariate analysis revealed that Gleason score, PSA at diagnosis, and clinical T stage were significant in predicting for PSA failure. Patients with Gleason score<7, PSA<10, and clinical stage T1c disease had statistically significant lower PSA failure rates than patients with Gleason score>or=7, PSA>or=10, and clinical stage T2 disease, respectively. Patients who are 60 years of age or younger who are treated with ultrasound-guided transperineal prostate implantation can expect 5-year biochemical disease-free survival rates similar to those of older patients treated with ultrasound-guided transperineal prostate implantation therapy.

Neoadjuvant Docetaxel before Radical Prostatectomy in Patients with High-Risk Localized Prostate Cancer

To determine the clinical, pathologic, and molecular effects of neoadjuvant docetaxel chemotherapy in high-risk localized prostate cancer. Patients with biopsy Gleason scores of 8 to 10, serum prostate-specific antigen levels >20 ng/mL, and/or clinical stage T3 disease received weekly docetaxel (36 mg/m2) for 6 months, followed by radical prostatectomy, and were monitored with weekly visits, serum prostate-specific antigen measurements, and endorectal magnetic resonance imaging (MRI). Frozen tumor specimens were collected for microarray analysis. The 19 patients enrolled received 82% of the planned chemotherapy. Toxicity was mild to moderate; fatigue and taste disturbance were common. Prostate-specific antigen declines of >50% were seen in 11 of 19 patients (58%; 95% confidence interval, 33-80%) and endorectal MRI showed maximum tumor volume reduction of at least 25% in 13 of 19 patients (68%; 95% confidence interval, 47-85%) and at least 50% in 4 patients (21%; 95% confidence interval, 6-46%). Sixteen patients completed chemotherapy and had radical prostatectomy; none achieved pathologic complete response. Microarray analysis identified coordinate up-regulation of genes involved in androgen metabolism associated with docetaxel therapy. Specifically, RNA expression for genes that decrease cellular levels of bioactive androgens was coordinately increased in response to chemotherapy. Neoadjuvant docetaxel administered for 6 months before radical prostatectomy is feasible, well tolerated, and often results in prostate-specific antigen declines of >50% and decreased tumor volume on endorectal MRI. No pathologic complete responses were observed. Altered androgen metabolism may partially account for the noted declines in prostate-specific antigen and be a mechanism for chemotherapy resistance.

Lymphovascular Invasion is a Pathological Feature of Biologically Aggressive Disease in Patients Treated With Radical Prostatectomy

We examined whether invasion of lymphatic and/or vascular vessels (LVI), or perineural spaces (PNI) is associated with prostate cancer features and outcome. A total of 630 consecutive men underwent radical retropubic prostatectomy for clinically localized disease. LVI and PNI examination was part of the routine specimen evaluation. Foci of LVI were identified in 32 patients (5%) and 381 (60.5%) had PNI. LVI and PNI were associated with clinical stage T2 disease, higher biopsy and final Gleason sum, extraprostatic extension, seminal vesicle involvement, positive surgical margins and a higher percent of positive biopsy cores (p <0.001). LVI was associated with metastases to regional lymph nodes and higher preoperative serum prostate specific antigen (p <0.001 and 0.004, respectively). PNI and LVI were associated with an increased risk of rapid biochemical progression after radical prostatectomy on univariate (p <0.001 and 0.001, respectively) but not on multivariate analysis. LVI was associated with shorter prostate specific antigen doubling time after biochemical progression (p = 0.012) and higher probabilities of failed local salvage radiation therapy (p = 0.0169), distant metastases (p <0.001) and death (p <0.001). Only LVI is associated with metastases to regional and distant sites, and most importantly with overall survival. LVI and PNI are associated with established markers of biologically aggressive disease and rapid biochemical progression in patients who underwent radical prostatectomy. Our findings support the routine evaluation of LVI status in radical prostatectomy specimens and its inclusion in predictive models for clinical outcomes, since it appears to be a pathological marker of the lethal phenotype of prostate cancer.

The Evolving Role of Chemotherapy and Other Systemic Therapies for Managing Localized Prostate Cancer

The recent literature is reviewed regarding the use of neoadjuvant and adjuvant chemotherapy, and promising new molecular targeted agents in patients with high risk localized prostate cancer. A MEDLINE literature review was performed of studies evaluating chemotherapy and other systemic therapies for localized prostate cancer. Patients with prostate cancer at high risk for recurrence despite local therapy include those with clinical stage T3 disease, biopsy Gleason scores of 8 to 10 or serum prostate specific antigen greater than 20 ng/ml. Although hormonal therapy has palliative benefit for the majority of patients with metastatic disease, randomized trials have not demonstrated a survival benefit from its administration before surgery for high risk localized disease. Recent trials have shown that cytotoxic chemotherapy has significant activity in hormone refractory prostate cancer, which has led to ongoing clinical trials that are investigating the use of chemotherapy in the neoadjuvant setting. Published and ongoing clinical trials in the use of systemic therapy for localized prostate cancer are reviewed. Systemic therapy for advanced prostate cancer is improving. Efforts to use such therapies for managing localized disease are ongoing.

Neoadjuvant therapy for high-risk localized prostate cancer.

Prostate cancer patients with clinical stage T3 disease, biopsy Gleason scores of 8 to 10, or serum prostate-specific antigen levels greater than 20 ng/mL are at high risk of recurrence despite local therapy. Although hormonal therapy has palliative benefit for the majority of patients with metastatic disease, randomized trials have not demonstrated a survival benefit for its administration prior to surgery for locally advanced disease. Historically, chemotherapy has been felt to have little activity in hormone-refractory prostate cancer, but new evidence may refute this belief. Ongoing clinical trials are now investigating the use of chemotherapy in the neoadjuvant setting. We review the recent literature regarding the use of neoadjuvant hormonal manipulation, chemotherapy, and promising new molecular targeted agents in patients with high-risk localized prostate cancer.

THE ROLE OF IMAGING STUDIES AND MOLECULAR MARKERS FOR SELECTING CANDIDATES FOR RADICAL PROSTATECTOMY

For the typical patient who has newly diagnosed prostate cancer, clinically organ-confined disease of moderate grade, and a PSA less than 10 ng/mL, the current role of imaging studies and molecular biomarkers is limited. Bone scans are not necessary for newly diagnosed men with a PSA less than 10 ng/mL in the absence of bone pain. Similarly, abdominal and pelvic CT scanning rarely provides any useful diagnostic or staging information when the PSA is less the 20 ng/mL and is indicated rarely. Endorectal coil MR imaging adds staging information for patients with a PSA between 10 and 20 ng/mL, a Gleason score of 7 or less, and 50% or more positive biopsies on a sextant sampling. Indium 111 capromab pendetide scanning (ProstaScint) is FDA-approved to evaluate newly diagnosed patients at high risk for metastases. These patients have a Gleason score of 7 or greater and a PSA greater than 20 ng/mL, a Gleason score of 8 to 10 regardless of the PSA value, or clinical stage T3 disease and a Gleason score of 6 or greater. RT-PCR testing of blood or bone marrow for prostate-specific or prostate cancer-specific gene expression, or "molecular staging," is a promising technique whose current use is still investigational. Much useful information may be gained by careful study of prostate needle biopsy material. Aside from current Gleason grading and the number or percentage of cores involved with cancer, no molecular biomarker is approved for clinical use. p27, p53, bcl-2, Ki-67 (MIB-1), and the assessment of neovascularity hold promise, but prospective multicenter studies are needed. In the long-term, multiple gene expression profiling of biopsy material using gene chips may revolutionize the care of patients with prostate cancer and those who elect radical prostatectomy.

Neoadjuvant docetaxel followed by radical prostatectomy in patients with high-risk localized prostate cancer: A preliminary report

Effective treatment options for high-risk localized prostate cancer are limited. Patients at high risk for recurrence include those with biopsy Gleason scores of 8 to 10, prostate specific antigen (PSA) levels > 20 ng/mL, and clinical stage T3 disease. Docetaxel chemotherapy is active in hormone-refractory prostate cancer, either combined with estramustine or used as a single agent. To determine if systemic therapy can improve the out-come of radical prostatectomy in men with high-risk localized prostate cancer, we are undertaking a pilot phase II clinical trial of weekly docetaxel at 36 mg/m 2 for up to 6 months, followed by surgery. Patients are monitored with weekly visits, monthly digital rectal examinations, PSA measurement, and testosterone tests, and endorectal magnetic resonance imaging done at baseline, after two cycles, and again after six cycles. To date, 15 patients have been enrolled, and 70 cycles of chemotherapy have been administered. Toxicity has been mostly grade 1 in intensity, and fatigue has been the most common grade 2 toxicity reported. The primary endpoint of the trial is measurement of pathologic complete response rate, for which data are not yet available. Recruitment to the trial is ongoing.

PATIENTS WITH ABNORMAL ULTRASOUND OF THE PROSTATE BUT NORMAL DIGITAL RECTAL EXAMINATION SHOULD BE CLASSIFIED AS HAVING CLINICAL STAGE T2 TUMORS

The current TNM staging system classifies prostate tumors with abnormal transrectal ultrasound but normal digital rectal examination as clinical stage T2. However, most urologists consider these tumors as clinical stage T1c due to the perceived inaccuracy of transrectal ultrasound in clinical staging. To determine the role of transrectal ultrasound in the clinical staging of prostate cancer we evaluated the pathological stage and disease-free survival of patients undergoing radical prostatectomy who had tumor detected by needle biopsy because of elevated serum prostate specific antigen with or without transrectal ultrasound abnormalities. Between 1991 and 1996, 738 patients underwent radical retropubic prostatectomy as monotherapy for clinically localized prostate cancer. Patients were classified into group 1-normal digital rectal examination and transrectal ultrasound (138), group 2-normal digital rectal examination but abnormal transrectal ultrasound (366) and group 3 -abnormal digital rectal examination (234). We compared pathological parameters and disease-free-survival among the 3 groups. Tumors were organ confined in 61%, 42% and 41% of patients in groups 1, 2 and 3, respectively (p = 0.0001). Overall disease-free survival was 80% with a mean followup of 68 months. Disease recurred in 8%, 22% and 25% of patients in groups 1, 2 and 3, respectively (p = 0.007). Group 1 had better disease-free survival compared to groups 2 and 3 (p = 0.003 and p = 0.002, respectively), and there was no difference in disease-free survival between groups 2 and 3 (p = 0.39). We provide evidence to support the use of transrectal ultrasound findings in the clinical staging system for prostate cancer. Patients with normal digital rectal examination, elevated serum prostate specific antigen and abnormal transrectal ultrasound should be considered as having clinical stage T2 disease.