Francisco Civantos

Sentinel lymph node biopsy accurately stages the regional lymph nodes for T1-T2 oral squamous cell carcinomas: results of a prospective multi-institutional trial.

PURPOSE The validity of sentinel lymph node biopsy (SLNB) for T1 or T2, clinically N0, oral cancer was tested by correlation of sentinel node pathologic status with that of nodes within the completion neck dissection. METHODS This prospective, cooperative group trial involved 25 institutions over a 3-year period. One hundred forty patients with invasive oral cancers, stage T1 and T2, N0 including 95 cancers of the tongue, 26 of the floor of mouth, and 19 other oral cancers were studied. The study excluded lesions with diameter smaller than 6 mm or minimal invasion. Imaging was used to exclude nonpalpable gross nodal disease. Patients underwent injection of the lesion with (99m)Tc-sulfur colloid, nuclear imaging, narrow-exposure SLNB, and completion selective neck dissection. The major end point was the negative-predictive value (NPV) of SLNB. RESULTS In the 106 SLNBs, which were found to be pathologically and clinically node-negative by routine hematoxylin and eosin stain, 100 patients were found to have no other pathologically positive nodes, corresponding to a NPV of 94%. With additional sectioning and immunohistochemistry, NPV was improved to 96%. In the forty patients with proven cervical metastases, the true-positive rate was 90.2% and was superior for tongue tumors relative to floor of mouth. For T1 lesions, metastases were correctly identified in 100%. CONCLUSION For T1 or T2 N0 oral squamous cell carcinoma, SLNB with step sectioning and immunohistochemistry, performed by surgeons of mixed experience levels, correctly predicted a pathologically negative neck in 96% of patients (NPV, 96%).

Positive surgical margins with radical prostatectomy: detailed pathological analysis and prognosis

OBJECTIVES To examine the extent and location of positive surgical margins and their influence on progression. METHODS Two hundred fifteen consecutive radical prostatectomy specimens, using 2 to 3-mm step-sections, were reviewed. Particular attention was paid to the location and extent of positive margins. Seventy-three patients (34%) with one or more positive margins were subjected to further detailed analysis. Progression was defined as a serum prostate-specific antigen level greater than 0.1 ng/mL and rising. The mean follow-up period was 23.2 months; median 24 months (range 3 to 40). RESULTS Margin-positive patients had a significantly higher biopsy tumor grape (P = 0.05) than did margin-negative patients. Capsular preforation was present in 75%, seminal vesicle invasion in 33%, and nodal metastases in 10% of margin-positive patients; in contrast, these tumor characteristics were present in 47%, 8%, and 1% of margin-negative patients, respectively. The extent of involvement of linked margins was focal in 22% and extensive in 66%. An equivocal margin identified as surgical incision into the specimen (due to hemostatic staples, surgical dissection, or retraction) was present in 12%. Seventy-one percent of patients had a positive margin at only one location. Of all 99 positive-margin locations, 40% were apical, 10% anterior, 8% bladder neck, 16% posterolateral, and 25% posterior. Thirty-four percent of margin-positive and 7% of the margin-negative patients demonstrated biochemical progression. Of the 36 patients with a positive margin as their only major risk factor for progression (seminal vesicle and lymph node negative, Gleason score less than 8), 25% have progressed. Progression occurred in 2 of 9 patients with an equivocal positive margin, and 5 of 16 with a single focal-positive margin. A multivariate analysis of margin-positive patients identified tumor volume and grade as the most significant predictors, with the location and extent of the positive margin not significant. CONCLUSIONS Although more frequent at the prostatic apex, tumor at the inked margin at any location is a risk factor for postoperative biochemical progression.

Small cell carcinoma of the bladder and prostate

S mall cell carcinoma (SCC), also referred to in the lungs as oat cell carcinoma or a neuroendocrine tumor, is a distinct histologic and biologic disease entity characterized by an aggressive clinical course and a high disease-related mortality. In 1926, Barnard’ described the first case of SCC, originating in the lungs. This histology now accounts for approximately 90,000 of the 150,000 cases of lung cancer that are diagnosed yearly in the United States.2 Nonpulmonary SCC was first described by Duguid and Kennedy in 1930.3 Since that time, extrapulmonary SCCs have been described in numerous organs including pharynx,4 larynx,5 trachea,(j esophagus7 stomach,8 small intestine,9 colon,1° nasal sinuses,ll salivary glands,12 thymus, l3 skin,14 breast,l* cervix,16 as well as prostate, l7 urinary bladder,18 kidney,19 and ureter.20 These neoplasms appear to have the same aggressive biologic behavior and share similar microscopic, immunohistochemical, and often ultrastructural characteristics as SCC of the lung. SCC originating in the urinary tract is rare; it is most often reported arising in the urinary bladder or prostate. In view of its rarity, there is a relative scarcity of information on the clinicopathologic behavior and optimum treatment strategies for this tumor. In recent years, however, genitourinary SCCs have been diagnosed with increasing frequency This appears to be due to an increased use of immunohistochemical studies in the evaluation of anaplastic tumors. The present review was undertaken to discuss the current concepts of histogenesis and to analyze the existing data on the pathologic characteristics, clinical behavior, and treatment response of SCC of the bladder and prostate.

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.

Sentinel node biopsy in oral cavity cancer: Correlation with pet scan and immunohistochemistry

Lymphoscintigraphy and sentinel node biopsy (LS/SNB) is a minimally invasive technique that samples first‐echelon lymph nodes to predict the need for more extensive neck dissection.

Positive surgical margins after radical retropubic prostatectomy: The influence of site and number on progression

PURPOSE We assessed the effect of location and number of positive margins on biochemical progression in patients after radical retropubic prostatectomy for prostate cancer. MATERIALS AND METHODS The incidence, location and number of positive surgical margins as well as recurrence and time to recurrence were evaluated in a consecutive series of 734 men who underwent radical retropubic prostatectomy for localized prostate cancer from 1992 through February 1999. RESULTS Surgical margins were positive in 210 patients (29%), of whom 157 (75%) and 53 (25%) had 1 and more than 1 positive margin, respectively. Of the patients 53 (25%) with tumor at any inked margin had biochemical recurrence. We identified no significant association of a particular location with biochemical recurrence. Bladder neck location did not carry an increased risk of recurrence (hazard ratio 1.23, 95% confidence interval 0.54 to 2.80). However, these findings were made in a limited number of cases with positive bladder neck margins. Patients with more than 1 positive surgical margin were at increased risk for recurrence compared with those with a single positive surgical margin (hazard ratio 2.19, 95% confidence interval 1.11 to 4.32). In addition, prostate specific antigen greater than 20 ng./ml. and seminal vesicle invasion were significant predictors of progression. CONCLUSIONS In patients with localized prostate cancer and positive surgical margins biochemical progression is not dictated by the specific location of a positive margin. However, multiple positive margins are associated with a significantly increased risk of biochemical recurrence. Longer followup and larger sample size are necessary to confirm these findings.

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.

Incidental prostatic adenocarcinoma in patients undergoing radical cystoprostatectomy for bladder cancer.

To determine if patients with bladder cancer have a higher incidence of unsuspected prostate cancer, 40 cases were studied. All except one case had no evidence of prostate cancer on preoperative clinical assessment. Detailed pathological evaluation of cystoprostatectomy specimens with sections at 2- to 3-mm intervals was done. Adenocarcinoma of the prostate was identified in 18 of 40 patients (45%). Multifocal prostatic intraepithelial neoplasia (PIN) was present in 19 cases (47.5%); 4 (10%) without an associated prostate cancer and 15 (37.5%) in conjunction with adenocarcinoma of the prostate. Twelve cases of unsuspected prostate cancer were stage pT1a, 4 were pT1b, and 2 were pT3. No patients exhibited nodal or distance metastases by the prostate cancer. At a mean follow-up of 15.2 months (range 3-34 months), 37 of the 40 patients are alive. Among prostate cancer patients, no clinical or biochemical evidence of disease recurrence or prostate cancer related mortality has been observed. Our findings support the previously reported high incidence rate of prostate cancer in patients undergoing cystoprostatectomy for bladder cancer. This, though, may not be higher than the observed incidence in an age-matched general population. We recommend DRE and PSA as part of the bladder cancer workup in males, and complete removal of the prostate at cystoprostatectomy to prevent the dilemma of residual prostate cancer.

Comparison of the prognostic potential of hyaluronic acid, hyaluronidase (HYAL‐1), CD44v6 and microvessel density for prostate cancer

Despite the development of nomograms designed to evaluate a prostate cancer (PCa) patients prognosis, the information has been limited to PSA, clinical stage, Gleason score and tumor volume estimates. We compared the prognostic potential of 4 histologic markers, hyaluronic acid (HA), HYAL‐1‐type hyaluronidase (HAase), CD44v6 and microvessel density (MVD) using immunohistochemistry. HA is a glycosaminoglycan that promotes tumor metastasis. CD44 glycoproteins serve as cell surface receptors for HA, and the CD44v6 isoform is associated with tumor metastasis. HYAL‐1‐type HAase is expressed in tumor cells and, like other HAases, degrades HA into angiogenic fragments. Archival PCa specimens (n = 66) were obtained from patients who underwent radical prostatectomy for clinically localized PCa and had a minimum follow‐up of 72 months (range 72–131 months, mean 103 months). For HA, HYAL‐1 and CD44v6 staining and MVD determination, a biotinylated HA‐binding protein, an anti‐HYAL‐1 IgG, an anti‐CD44v6 IgG and an anti‐CD34 IgG were used, respectively. HA and HYAL‐1 staining was classified as either low‐ or high‐grade. CD44v6 staining and MVD were evaluated quantitatively and then grouped as either low‐ or high‐grade. Using 72 months as the cut‐off limit for evaluating biochemical recurrence, HA, HYAL‐1, combined HA–HYAL‐1, CD44v6 and MVD staining predicted progression with 96%, 84%, 84%, 68% and 76% sensitivity, respectively. Specificity was, 61% (HA), 80.5% (HYAL‐1), 87.8% (HA–HYAL‐1), 56.1% (CD44v6) and 61% (MVD). Sensitivity and specificity values for each marker did not change significantly in a subset of 45 patients for whom follow‐up of longer than 112 months was available. In univariate analysis using the Cox proportional hazards model, preoperative PSA, Gleason sum, margin status, seminal vesicle, extraprostatic extension (EPE), HA, HYAL‐1, HA–HYAL‐1 and MVD, but not CD44v6, age and clinical stage, were significant in predicting biochemical recurrence (p < 0.05). In multivariate analysis using stepwise selection, only preoperative PSA (hazard ratio/unit PSA change = 1.086, p < 0.0001), EPE (hazard ratio = 6.22, p = 0.0016) and HYAL‐1 (hazard ratio = 8.196, p = 0.0009)/HA–HYAL‐1 (hazard ratio = 5.191, p = 0.0021) were independent predictors of biochemical recurrence. HA was an independent predictor of prognosis if HYAL‐1 staining inference was not included in the multivariate model. In our retrospective study with 72‐ to 131‐month follow‐up, EPE, preoperative PSA and HYAL‐1 either alone or together with HA (i.e., combined HA–HYAL‐1) were independent prognostic indicators for PCa.

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.