Octreotide scintigraphy in the head and neck.

OBJECTIVES/HYPOTHESIS: Octreotide is a somatostatin analogue that, when coupled to a radioisotope, produces a scintigraphic image of neuroendocrine tumors (NET) expressing somatostatin type 2 receptors (SSR 2). Octreotide scintigraphy (OS) may be useful in confirming the preoperative diagnosis of certain head and neck NET. Paragangliomas (PG), like many NET, have been found to have a high density of SSR 2 on the cell surfaces. Other NET of the head and neck include merkel cell carcinomas (MCC), medullary thyroid carcinomas (MTC), and esthesioneuroblastomas. STUDY DESIGN: A retrospective study that compared the results of OS with the histopathologic diagnosis in 74 patients with head and neck NET. RESULTS: Of the 60 patients undergoing evaluation for suspected paraganglioma, OS was correctly positive in 36 of the 37 patients with PG. OS was correctly negative in 19 of the 23 patients that did not exhibit PG. For PG, this yielded a sensitivity of 97% and a specificity of 82%. There were 14 patients in the nonparaganglioma group. OS detected or diagnosed all metastases in three patients with MTC, locoregional recurrences in two patients with esthesioneuroblastoma, an extrapituitary adenoma in one patient, and metastasis in two patients with MCC. It failed to detect a paraspinal metastasis in the third patient with MCC. CONCLUSION: On the basis of this series of patients, OS appears to be a reliable test to detect PG and may be helpful in detecting primary and metastatic disease for NET.

Outcome after radical prostatectomy with a pretreatment prostate biopsy Gleason score of >/=8.

OBJECTIVE: To determine the outcome and predictors of recurrence in patients with a pretreatment prostate biopsy Gleason score (GS) of >/= 8 and treated with radical prostatectomy (RP). PATIENTS AND METHODS: We retrospectively reviewed 1048 consecutive patients who underwent RP by one surgeon (M.S.S.); patients who had a pretreatment biopsy GS of >/= 8 were identified. Information was recorded on patient age, initial prostate specific antigen (PSA) level, clinical stage, biopsy GS, pathology GS, extraprostatic extension (EPE), tumour volume, surgical margin status, seminal vesicle invasion (SVI), and lymph node involvement. The results were assessed statistically using the Kaplan-Meier method, univariate log-rank tests and multivariate analysis using Cox's proportional hazards regression. RESULTS: In all, 123 patients met the initial selection criteria; 44 were excluded from further analyses (five salvage RP, 23 < 1 year follow-up and 16 adjuvant treatment). Thus 79 patients were included in the uni- and multivariate analyses; 25 (31%) patients had a GS of /= 8. The mean follow-up was 55 months, the age of the patients 63 years and the mean (sd) initial PSA level 13 (12) ng/mL. The overall biochemical failure rate was 38% (41% if the final GS was >/= 8 and 32% if it was /= 8 in the RP specimen, 20% (11/54) were organ-confined; two patients (2.5%) in this group developed local recurrence. If the final GS was /= 20 ng/mL, EPE, SVI, a positive surgical margin and tumour volume. Cox's proportional regression indicated that a PSA of >/= 20 ng/mL (hazard ratio 7.9, 95% confidence interval 2.6-24.2, P < 0.001), the presence of EPE (4.2, 1.6-10.9, P = 0.004) and a positive surgical margin (3.8, 1.5-9.7, P = 0.005) were significant independent predictors in a multivariate analysis. CONCLUSION: RP is a reasonable treatment option for patients with a prostate biopsy GS of >/=8 and clinical stage T1-2. These patients have a high chance of remaining disease-free if their PSA level is /= 8 should be counselled about the potential differences between the biopsy and the RP specimen GS.

Intraoperative T staging in radical retropubic prostatectomy: is it reliable?

OBJECTIVES: During radical prostatectomy, wide local excision of the lateral prostatic fascia and neurovascular bundle on the ipsilateral side of the tumor is advocated if nerve sparing is likely to result in a positive surgical margin. Our intent was to validate whether intraoperative T staging can predict the presence of positive surgical margins and aid in the decision of whether to perform nerve-sparing prostatectomy. METHODS: One surgeon performed 100 consecutive radical prostatectomies, and one pathologist interpreted the pathologic findings. Topographic distribution of tumor within the specimen was assessed intraoperatively by palpation. The margin status was similarly assessed. This tactile clinical impression was compared with the final pathologic findings. RESULTS: The surgical margins were positive in 39 (39%) of 100 cases. The intraoperative assessment of the margin status had a high false-negative rate and a sensitivity of only 7%. However, the specificity was 96%, because few margins were falsely positive. The overall accuracy was 62%, with a negative predictive value of 62%. The sensitivity of the intraoperative assessment of tumor location was 73%, and the positive predictive value was 65%. CONCLUSIONS: The results of our study indicate that the intraoperative assessment of the margin status is not accurate and thus cannot help determine which patients require excision of the neurovascular bundle. We believe the decision to preserve the neurovascular bundle should be based on the preoperative prognostic factors and the presence of an intact capsule covering the region of the gland adjacent to this structure.

Elevated tissue expression of hyaluronic acid and hyaluronidase validates the HA-HAase urine test for bladder cancer.

PURPOSE: We examined the expression of 2 bladder tumor markers, hyaluronic acid (HA) and hyaluronidase (HAase), in bladder tissues and correlated tissue staining with the inferences of the HA-HAase urine test, which detects bladder cancer. MATERIALS AND METHODS: A biotinylated HA binding protein and an antiHYAL1 antibody were used to localize HA and HYAL1 type HAase, respectively, in 83 bladder tissues. Immunoblot analysis was performed using an antiHYAL1 antibody to detect HYAL1. RESULTS: A total of 12 normal bladder tissues showed no (66%) to 1+ (34%) HA staining and 0 (83%) to 1+ (17%) HYAL1 staining. The staining intensity of HA and HYAL1 increased in 71 bladder tumor specimens on chi-square analysis (p <0.001). Grade 1 tumors demonstrated 1+ (50%) to 2+ (50%) staining for HA and 1+ to 3+ staining for HYAL1 (37%, 37% and 26%, respectively). Grades 2 and 3 tumors showed 2+ to 3+ HA (94%) and HYAL1 (79%) staining. HA was expressed in tumor associated stroma and in tumor cells, whereas only tumor cells expressed HYAL1. In bladder tumor tissues HYAL1 expression was confirmed by immunoblot analysis. In 33 of the 34 patients (97%) with bladder cancer from whom urine and tumor tissue specimens were obtained at the same time 2+ to 3+ staining of HA and/or HYAL1 in 12 and 21, respectively, constituted a positive HA-HAase urine test (kappa = 0.945). CONCLUSIONS: To our knowledge this is the first report of HA localization in bladder tissues and of HYAL1 in any normal or tumor tissue. A close correlation of elevated HA and HYAL1 levels in tumor tissues with a positive HA-HAase urine test indicates that in patients with bladder cancer tumor associated HA and HYAL1 are secreted in urine, causing the HA-HAase test to be positive.

[Hyaluronic acid and hyaluronidase. 2 new bladder carcinoma markers]. / Hyaluronsäure und Hyaluronidase. Zwei neue Blasenkarzinommarker.

The heterogeneity of bladder cancer concerning progress of recurrence is an essential characteristic of this disease. Hyaluronic acid (HA) and its degrading enzyme hyaluronidase (HAase) are intricately associated with bladder cancer angiogenesis and metastasis. Tumor-associated HA and HAase are secreted in urine. In 513 urine specimens (261 bladder cancer patients, 252 patients without bladder cancer) and 83 bladder tissue specimens (71 bladder tumors, 12 normal bladder tissues), the accuracy of HA and HAase as tumor markers was studied. Elevated urinary HA levels (> or = 500 ng/ml), indicating a positive HA test, suggest the presence of bladder cancer regardless of tumor grade. Elevated urinary HAase levels (> or = 10 mU/mg) indicate high-grade (G2/G3) bladder cancer. The combined HA-HAase urine test showed 91% sensitivity and 84% specificity to detect bladder cancer. The HA-HAase test is equally sensitive for monitoring tumor recurrence. Immunohistochemistry (IHC) staining of HA and HAase in the G1 and G2/G3 bladder cancer specimens was significantly (p < 0.001) higher than in normal bladder tissue. HA and HAase appear to be useful markers in the diagnosis of bladder cancer. When compared with other noninvasive tests, the HA-HAase urine test may be less expensive and more accurate.

A novel CD44 v3 isoform is involved in head and neck squamous cell carcinoma progression.

OBJECTIVES: CD44 comprises a family of isoforms involved in tumorigenesis. Here we investigate the role of CD44 isoforms in head and neck squamous cell carcinoma (HNSCC) progression. MATERIALS AND METHODS: HNSCC specimens underwent reverse transcriptase-polymerase chain reaction (RT-PCR) followed by Southern blot analysis. After surface biotinylation, FaDu (hypopharyngeal HNSCC) and CD44v3-transfected COS-7 cells were CD44 antibody-precipitated and compared by Western blot analysis. FaDu cells underwent double immunofluorescence staining and growth assays. RESULTS: Southern blot analysis suggested differential CD44v3 isoform expression in tumor and normal tissue. Cloning and sequencing revealed 2 novel CD44v isoforms. Western blot analysis suggested CD44v3 expression in COS-7 transfectants and FaDu. Double immunofluorescence staining revealed co-localization of CD44v3 and actin in FaDu projections. Anti-CD44v3 antibody decreased FaDu growth. CONCLUSION: HNSCC tissue and FaDu appear to express CD44v3 isoforms. These isoforms may promote tumorigenesis. CLINICAL SIGNIFICANCE: CD44v3 isoforms may be effective tumor markers and targets for HNSCC therapy.

Endoscopic sinus surgery in previously irradiated patients.

PURPOSE: Our purpose was to evaluate the safety and efficacy of endoscopic sinus surgery in irradiated patients with absolute indications for sinus surgery. PATIENTS AND METHODS: During 5 years at a tertiary referral center, more than 200 patients received irradiation to a field that included the paranasal sinuses. Complaints related to the sinuses are common in such patients and often include crusting and increased mucus drainage. Six patients presented with significant sinus infections in the absence of tumor recurrence and failed medical management. Additional problems included epiphora and nasal obstruction caused by cicatricial choanal stricture. Surgical interventions included ethmoidectomy, multiple osteotomies, debridement of scarred or devitalized tissue, and dacryocystorhinostomy. Outcome measures included intraoperative findings and complications, length of hospital stays, endoscopic assessments of the healing over 6 months post-operatively, and improvement or persistence of symptoms over 2 to 3 years of follow-up. RESULTS: Surgery can be technically difficult because of derangements of normal anatomy and dehiscence of important structures. Although bleeding problems, prolonged admission, and delayed healing were noted in certain cases, they did not result in long-term morbidity. CONCLUSIONS: Endoscopic sinus surgery has become an invaluable tool in the treatment of refractory sinusitis. Our literature review has revealed no information, however, regarding endoscopic sinus surgery in previously irradiated patients. Theoretically, such patients are at risk for healing problems and anatomic derangements, which could lead to complications. There is, nevertheless, a theoretical benefit to avoiding external approaches in patients who might heal poorly.

De novo muscle invasive bladder cancer: is there a change in trend?

PURPOSE: We reviewed our radical cystectomy series to determine whether the majority of patients present with muscle invasive bladder cancer. MATERIALS AND METHODS: The records of 184 radical cystectomies performed by 1 surgeon from 1992 to 1999 were reviewed, and all slides of presenting pathology were reviewed by 1 pathologist. The pathological stage of the tumor at presentation was noted in each case, and the number of muscle invasive tumors at presentation was compared to 2 earlier series. RESULTS: Radical cystectomy was performed for muscle invasive transitional cell carcinoma of the bladder in 176 cases and for other histology in 8. There were 101 (57.3%) patients with muscle invasive cancer at presentation compared to 84% and 91% in the 2 earlier series, respectively, which was a statistically significant decrease (p <0. 0001) in the number of de novo muscle invasive bladder cancers. Women were more likely to be diagnosed with muscle invasion primarily than men (85.2% and 50.7%, respectively), and younger patients (younger than 50 years) were more likely to present with superficial bladder cancer compared to those older than 50 years who were more likely to present with de novo muscle invasive bladder cancer. CONCLUSIONS: Analysis of our data supports the findings of the earlier series that the majority of patients present with muscle invasive bladder cancer. However, there is a significant decrease in the percentage of tumors invading the muscularis propria at presentation. Although this observation is encouraging, we emphasize that it is not as dramatic as the stage migration associated with prostate cancer, which may be largely attributed to the widespread use of prostate specific antigen for early detection. Therefore, we support the suggestion that therapeutic gains might follow from improved education regarding the signs and symptoms associated with bladder cancer, with enhanced focus on women and consideration of screening methods for those at high risk for bladder cancer.

Difficulties in interpreting specimens after neoadjuvant hormonal therapy and radiation with illustration of neuroendocrine differentiation.

Pattern and cellular changes attributable to neoadjuvant hormonal therapy (NHT) might cause the unwary pathologist to overgrade or fail to recognize a treated prostatic cancer. Overdiagnosis and overgrading of surgical resections and biopsies can be avoided if an appropriate history of therapy is conveyed with the surgical specimen and if the pathologist is aware of the altered morphology of prostatic cancer treated by NHT alone or NHT plus radiation. Study of three prostatectomy specimens with post-NHT predominance of neuroendocrine cells showed positive staining for prostate specific antigen (PSA) and prostatic acid phosphatase (PAP), as well as staining for chromogranin and synaptophysin in Paneth-like and small neuroendocrine cells. Difficult-to-interpret needle biopsies and transurethral resection (TUR) biopsies of prostate, where the urologic pathologist's suspicion of a radiation effect was confirmed by additional history, showed absence of the basal cell layer with 34 beta E12 keratin immunostaining in prostatic cancer glands, while basal cells were present in the nonneoplastic glands with radiation-induced atypia. Postradiation salvage prostatectomy specimens showed greater apoptosis after combined NHT and radiation than after radiation without NHT. Changes attributable to radiation and radiation plus NHT are illustrated.

Signet ring cell carcinoma of a pulled-through sigmoid colon mimicking a primary invasive bladder tumor: case report and review of the literature.

Primary signet ring cell carcinoma of the urinary bladder and colon are rare disease entities that are aggressive, difficult to manage, and portend a poor prognosis. We present a case report of a 25-year-old man born with an imperforate anus who developed signet ring cell carcinoma of the pulled-through sigmoid colon that mimicked a primary invasive bladder tumor. Despite radical surgery and adjuvant radiation, the patient died of his disease 7 months after surgery.

Sensory recovery in melolabial flaps used for oral cavity reconstruction.

Current literature advocates the use of complex reinnervated free flaps to re-establish oral sensation after resection of oral cavity cancers. It has been demonstrated that noninnervated flaps can also re-establish sensation. We assessed the return of sensation in local melolabial flaps used in oral reconstruction. Seven patients underwent sensory testing at intervals from 12 to 18 months after surgery. The ability to distinguish differences in temperature was present in all patients. Spontaneous return of sensitivity to touch was documented by clinical testing in 71% of the patients. Less return of sensation was seen in flaps used for defects of the buccal mucosa relative to the floor of mouth. We conclude that spontaneous return of flap sensation does occur with local melolabial flaps. Given the simplicity of these procedures, melolabial flaps represent a reasonable alternative in floor-of-mouth reconstruction for selected patients.

Octreotide scintigraphy for the detection of paragangliomas.

Paragangliomas are neuroendocrine tumors located primarily in the head and neck region, but they can also occur at other sites. Confirming the preoperative diagnosis and detecting synchronous tumors may be difficult in some patients. Octreotide is a somatostatin analog that, when coupled to a radioisotope, produces a scintigraphic image of tumors expressing somatostatin type 2 receptors. Paragangliomas, like many neuroendocrine tumors, have been found to have a high density of somatostatin type 2 receptors on the cell surface. This study compared the results of preoperative octreotide scintigraphy with the histopathology in 21 patients who underwent surgery for presumed head and neck paragangliomas. Octreotide scan findings were positive in 16 patients with paragangliomas and negative in 3 patients with other pathology. One false-positive and 1 false-negative result were obtained. Thus, this test had an accuracy of 90%, a sensitivity of 94%, and a specificity of 75%. Previously unidentified synchronous tumors were identified in 5 patients. On the basis of this series of patients, octreotide scintigraphy appears to be a reliable test to detect paragangliomas and may be quite helpful in preoperative planning.

Positive surgical margins with radical retropubic prostatectomy: anatomic site-specific pathologic analysis and impact on prognosis.

OBJECTIVES: To correlate the extent and location of positive surgical margins after radical prostatectomy with disease progression. METHODS: Data on 495 patients who underwent radical prostatectomy by one surgeon were analyzed. All radical prostatectomy specimens were sectioned entirely using 2 to 3-mm step sections by one pathologist. One hundred fifty-one patients (30.5%) had one or more positive surgical margins and were subjected to further detailed analysis. Recurrence was defined as a serum prostate-specific antigen (PSA) level of 0.2 ng/mL and rising on at least two postoperative measurements. RESULTS: The mean follow-up was 25.3 months (range 3 to 73). The overall recurrence rate was 13.3%. Neoadjuvant hormonal treatment was given to 37 (25%) of those with a positive margin. Patients with positive surgical margins had a significantly higher incidence of recurrence compared with those with negative margins (27.8% versus 6.9%, P = 0.001). The recurrence rate for various locations was 29% apex/urethra, 30% posterior, 33% anterior, 36% lateral, 48% posterolateral, and 57% bladder neck. Time to recurrence was shorter in patients older than 70 years (P<0.055); with a preoperative PSA greater than 10 ng/mL (P<0.0001); with a biopsy Gleason score greater than 7 (P = 0.02); with a prostatectomy Gleason score greater than 7 (P<0.001); with seminal vesicle invasion (P = 0.0001); having more than 1 location of a positive margin (P = 0.002); or having a positive margin at the bladder neck (P = 0.0003) or the posterolateral surface of the prostate (P = 0.02) compared with other locations. Multivariate proportional hazards analyses indicated that age older than 70 (P = 0.005), a prostatectomy Gleason score of 7 (P = 0.015) or 8 to 10 (P = 0.003), and positive margin(s) at the bladder neck (P = 0.003) were independently associated with a shorter time to recurrence among patients with a positive margin. CONCLUSIONS: In our study, among patients with positive surgical margins, those with multiple positive margins, or a margin involving the bladder neck or the posterolateral surface of the specimen carried a higher risk of progression. A positive margin at the bladder neck appears to be the most significant adverse prognostic indicator. This information may help in decisions regarding additional therapy.

Age as a prognostic factor for disease recurrence after radical prostatectomy.

OBJECTIVES: To assess whether age has an impact on biochemical recurrence after radical prostatectomy for localized adenocarcinoma of the prostate. METHODS: Four hundred eighty-nine consecutive patients who underwent radical retropubic prostatectomy and did not have metastases to the lymph nodes were retrospectively analyzed. Disease recurrence was defined as a serum prostate-specific antigen greater than 0.2 ng/mL and rising on at least two postoperative measurements. Biochemical progression was compared in patients 70 years old or younger and older than age 70. The Kaplan-Meier estimator and Cox's proportional hazards model were employed to investigate the impact of age on time to recurrence. Neoadjuvant androgen deprivation was treated as a stratification variable in the Cox models. RESULTS: The mean follow-up was 25.4 +/- 20.8 months. The Gleason score and extent of cancer in the pathologic analyses of the prostatectomy specimen was not significantly different between the two groups. Biochemical recurrence was detected in 12% of patients 70 years old or younger and in 25% of those older than 70 (P = 0.01). In multivariate analyses, after adjusting for all prognostic factors, younger age (70 years or younger) was independently associated with a longer time to recurrence (P <0.02). CONCLUSIONS: Our results suggest that age per se may be an independent prognostic factor for disease recurrence after radical prostatectomy. This implies that patients 70 years old or younger are more likely to benefit from surgery. This information may be useful when counseling patients with clinically localized carcinoma of the prostate.

The value of upper tract cytology after transurethral resection of bladder tumor in patients with bladder transitional cell cancer.

PURPOSE: Patients with transitional cell carcinoma of the bladder are at risk for concurrent or subsequent cancer of the upper tract. Traditionally disease is monitored by radiography (excretory or retrograde urography). Some elect to sample the upper tract by obtaining urine for cytology. Are the results meaningful when performed in a patient with bladder cancer? MATERIALS AND METHODS: We evaluated 27 consecutive patients with transitional cell cancer of the bladder (grade 1 to 3, Ta to T2) with bladder wash for cytology and cystoscopy as well as resection of visible tumor. A 5F ureteral catheter was positioned at each ureteral orifice, flushed with saline and passed into each renal pelvis. Urine was collected for cytology. RESULTS: Of 19 patients (68%) with high grade (grade 3) bladder cancer 13 had a positive bladder wash, including 6 (32%) with tumor cells detected in the urine from the upper tract. Of 8 patients (38%) with low grade (grade 1 to 2) transitional cell cancer 3 had a positive bladder wash and 2 (25%) had a positive upper tract cytology. All patients had a normal upper tract by excretory or retrograde urography. Ureteroscopy was not performed. CONCLUSIONS: Given the normal appearance of the upper urinary tract, it is highly unlikely that most, if any, of these patients with bladder cancer have tumor in the upper tract despite tumor cells in urine obtained by retrograde catheterization. Thus, upper tract sampling by a retrograde technique lacks specificity for localizing transitional cell cancer to the upper tract when performed in a patient with bladder cancer.

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.

Pathologic Handling and Reporting of Prostate Tissue Specimens in Patients Receiving Neoadjuvant Hormonal Therapy: Report of the Pathology Committee.

Prior meetings of the International Conference on Neoadjuvant Hormonal Therapy in Prostate Cancer identified areas of concern in the pathologic analysis of post-treatment specimens. In response, a pathology subcommittee was formed to address the questions that had been raised. Recommendations are made here concerning pretreatment biopsy review and reporting, handling and reporting of radical prostatectomy specimens, Gleason scoring of treated cancer, grading of therapy effect, role of immunohistochemistry procedures, and the significance of high-grade prostatic intraepithelial neoplasia. Neoadjuvant trials with both surgery and radiation therapy were considered in drawing up these recommendations.

Neoadjuvant Hormonal Therapy Prior to Radical Prostatectomy.

The US T(2b) study of 3 months of neoadjuvant hormonal therapy (NHT) showed a reduction in the likelihood of positive margins from 48% (control group) to 18% in the treated patients. Follow-up at 42 months shows that the cumulative relapse rate (prostate specific antigen) for 129 patients having NHT was not statistically different from that of the 126 control patients. Because the T(2b) study has been criticized for lacking central pathology review, we present a review of a series involving only one surgeon (MS) and one pathologist (FC) of NHT plus prostatectomy (109 patients) v prostatectomy alone (145 patients) with 24 months' follow-up. Positive margins were decreased from 38% in the untreated to 28% in the treated group, the only statistically significant difference in the results. Biochemical recurrence (PSA >0.2 ng/mL) was higher in the treated group, reflecting selection of more aggressive tumors for NHT, but the difference was not statistically significantly. The incidence of extracapsular extension, seminal vesicle invasion, and lymph node metastasis was similar in the two groups. The largest nonrandomized experience with NHT shows a decrease in the incidence of positive surgical margins when used in high-risk patients with clinically localized carcinoma of the prostate. However, it does not have an impact on disease-free survival at a mean 24-month follow-up.