Biomedical subjects

Horst Zincke

Publications and source records attributed to Horst Zincke.

At least 19 recordsLinked to original sources

PubMed2007

Impact of tumor size on the predictive ability of the pT3a primary tumor classification for renal cell carcinoma.

PURPOSE: The accuracy of the pT3a primary tumor classification for renal cell carcinoma has been questioned recently. We investigated the association of perinephric and renal sinus fat invasion with death from renal cell carcinoma independent of tumor size. MATERIALS AND METHODS: We identified 2,165 patients treated with open radical nephrectomy or nephron sparing surgery for clinically localized, sporadic pT1a, pT1b, pT2 or pT3a renal cell carcinoma between 1970 and 2002. Patients with pT3a disease were then subdivided into 3 groups according to tumor size to match the size definitions for the pT1a, pT1b and pT2 tumor classifications. RESULTS: There were 834 patients with pT1a RCC, 674 with pT1b, 494 with pT2 and 163 with pT3a RCC. At last followup 317 patients died of RCC at a median of 3.8 years following surgery. The median followup among the 1,087 patients still alive at last followup was 7.8 years (range 0 to 34). The risk ratios (95% CI) for the association between fat invasion and death from RCC among patients with tumors 4 cm or smaller, 4 to 7 cm and more than 7 cm were 6.15 (1.84-20.50, p = 0.003), 4.12 (2.50-6.78, p <0.001) and 2.13 (1.53-2.97, p <0.001), respectively. These associations remained statistically significant in a multivariate analysis that included nuclear grade and histological coagulative tumor necrosis. CONCLUSIONS: Peripheral perinephric and renal sinus fat invasion was associated with death from RCC independent of tumor size. Our data contradict reports suggesting that pT3a tumors should be reclassified according to tumor size only.

Aged↗

PubMed2007

The impact of ischemia time during open nephron sparing surgery on solitary kidneys: a multi-institutional study.

PURPOSE: The safe duration of ischemia during nephron sparing surgery remains controversial. We performed a multi-institutional study to evaluate the renal effects of vascular clamping in patients with solitary kidneys. MATERIALS AND METHODS: Using the Cleveland Clinic and Mayo Clinic databases, we identified 537 patients with solitary kidneys who underwent open nephron sparing surgery. Renal complications were compared among patients who did not require vascular clamping (85), and those who had warm ischemia (174) and cold ischemia (278). RESULTS: Median patient age (63, 65, 64 years) and preoperative creatinine (1.4, 1.3, 1.4 mg/dl) were similar among patients with no ischemia, warm ischemia and cold ischemia, respectively. Median tumor size was smaller in patients with no ischemia (2.5 cm), compared to patients with warm (3.5 cm) and cold (4.0 cm) ischemia (p <0.001). Warm and cold ischemia was associated with a significantly increased risk of urine leak (p = 0.006), acute (p <0.001) and chronic (p = 0.027) renal failure, and temporary dialysis (p = 0.028) compared to patients with no ischemia. Warm ischemia longer than 20 minutes and cold ischemia longer than 35 minutes were associated with a higher incidence of acute renal failure (p = 0.002 and p = 0.003, respectively). Additionally, warm ischemia more than 20 minutes was associated with an increased risk of chronic renal insufficiency (41% vs 19%, p = 0.008), increase in creatinine greater than 0.5 (42% vs 15%, p <0.001) and permanent dialysis (10% vs 4%, p = 0.145). CONCLUSIONS: Vascular clamping during open nephron sparing surgery is associated with a higher incidence of renal complications. Attempts to limit warm ischemia to 20 minutes and cold ischemia to 35 minutes should be used when vascular clamping is necessary.

Adult↗

PubMed2007

Dynamic outcome prediction in patients with clear cell renal cell carcinoma treated with radical nephrectomy: the D-SSIGN score.

PURPOSE: To date all prediction models for patients with renal cell carcinoma have estimated outcome in static fashion starting from the date of surgery only. We created a dynamic outcome prediction model for continual surveillance that accounts for the disease-free interval following surgery. MATERIALS AND METHODS: We identified 1,560 patients treated with radical nephrectomy for pM0 clear cell renal cell carcinoma between 1970 and 1999. The previously published stage, size, grade and necrosis score was used to stratify patients according to the risk of death from renal cell carcinoma. Cancer specific survival rates were calculated using the Kaplan-Meier method at surgery and at various disease-free intervals following surgery. RESULTS: At last followup 461 of the 1,560 patients had died of renal cell carcinoma at a median of 3.1 years following surgery. Median followup in patients still alive was 11.2 years. Patient outcome improved as the disease-free interval following surgery increased. For example, patients with a stage, size, grade and necrosis score of 5 had an estimated 5-year cancer specific survival rate of 69.6% at surgery. However, those who survived without disease for 1, 2 and 3 years following surgery had adjusted estimated 5-year cancer specific survival rates of 81.9%, 91.9% and 93.2%, respectively. Patients with a stage, size, grade and necrosis score of 7 had a 5-year cancer specific survival rate of 44.9% at surgery, which increased to 63.3%, 71.0% and 72.8% after 1 to 3 years of disease-free followup, respectively. CONCLUSIONS: Within each stage, size, grade and necrosis score cancer specific survival rates increase as the disease-free interval following surgery increases. We present a dynamic outcome prediction model that allows clinicians to continually adjust surveillance as the disease-free interval increases.

Adult↗

PubMed2006

Outcomes of Gleason score 10 prostate carcinoma treated by radical prostatectomy.

OBJECTIVES: To evaluate the outcome of radical prostatectomy for the rarest and most poorly differentiated prostate tumors of all: those with Gleason score 10. Controversy exists as to which form of therapy is most effective for high-grade prostate cancer (PCa). METHODS: We retrospectively reviewed the charts of all patients with pathologic Gleason score 10 PCa treated at our institution with radical prostatectomy from 1977 to 1999. All pathology specimens were reviewed by a urologic pathologist, and 13 cases with true Gleason score 10 PCa were identified. The preoperative covariables (prostate-specific antigen level, biopsy Gleason score, and clinical stage), perioperative covariables (pathologic stage, margin status, and tumor ploidy), and postoperative covariables (prostate-specific antigen level and adjuvant and salvage treatments) were assessed with respect to the oncologic outcomes. RESULTS: The median follow-up was 4.2 years. Preoperatively, only 4 of the 13 cases were correctly identified at biopsy, and the median preoperative prostate-specific antigen level was 4.5 ng/mL (interquartile range 0.3 to 12.5). Pathologic examination showed a small cell component in 7 cases, seminal vesicle invasion in 11, and positive lymph nodes in 3. Six patients developed recurrent PCa: three local, two systemic, and one biochemical recurrence. The biochemical recurrence-free and cancer-specific survival rate at 5 years was 53.8% and 76.9%, respectively. CONCLUSIONS: Gleason score 10 PCa is a highly aggressive disease that is usually lethal if managed conservatively. The results of the present study have provided some evidence that radical prostatectomy may be of benefit to patients with Gleason score 10 PCa.

Aged↗

PubMed2006

Urachal carcinoma: clinicopathologic features and long-term outcomes of an aggressive malignancy.

BACKGROUND: Urachal carcinoma (UrC) is a rare malignancy, and patients with this disease have a poor prognosis. In this article, the authors report 50 years of experience with this tumor at the Mayo Clinic. METHODS: A urachal mass was described in 130 patients, and 66 of those masses were malignant. The authors identified multivariate predictors of malignancy in clinically diagnosed urachal masses and predictors of UrC-specific survival. This report presents a novel 4-category staging system for UrC along with the treatment history of this tumor and the results of salvage therapy. RESULTS: Twenty women and 46 men were identified with UrC. The strongest predictors of malignancy in a urachal mass were hematuria and age older than 55 years. The 5-year cancer-specific survival rate was 49%. The new Mayo staging system was less complicated than the Sheldon system, although both systems predicted cancer-specific mortality equally well. Positive surgical margins (hazard ratio [HR], 4.7), high tumor grade (HR, 3.6), positive local lymph nodes (HR, 5.1), metastases at diagnosis (HR, 3.3), advanced tumor stage (HR, 4.8), failure to perform umbilectomy (HR, 3.0), and primary radiation therapy (HR, 2.9) were all univariately associated with death (P <.05). Only grade and margins were significant in the multivariate analysis. No survival benefit was noted for lymphadenectomy or adjuvant therapy. Salvage surgery resulted in a long-term cure for 50% of patients who had local recurrences. No effective treatment was identified for patients with metastatic UrC. CONCLUSIONS: Early and complete extended partial cystectomy, including umbilectomy, is critical to the survival of patients with UrC. The authors recommend using the Mayo staging system in future studies because of its simplicity. The current results indicated that the most important predictors of prognosis were tumor grade and surgical margin status.

Cohort Studies↗

PubMed2006

Obesity and survival after radical prostatectomy: A 10-year prospective cohort study.

BACKGROUND: Obesity and prostate cancer are among the most common health problems affecting American men today. The authors' goal was to assess the impact of obesity on clinical and pathologic features of prostate cancer and long-term outcomes. METHODS: The authors performed a prospective cohort study on 5313 men who underwent radical prostatectomy between 1990 and 1999. Patient height and weight were measured at the time of surgery to calculate the body mass index (BMI). The patients were separated into 3 BMI groups: BMI <25, 25-29.9, and > or =30 kg/m2. The associations between BMI and age, prostate-specific antigen (PSA) level, and Gleason score were assessed with the Spearman rank correlation test. The associations between BMI and pathologic features were assessed with the Mantel-Haenszel chi 2 test. Fifteen-year biochemical progression-free survival, systemic progression-free survival, cancer-specific survival, and overall survival were estimated using the Kaplan-Meier method and evaluated using Cox models. RESULTS.: The median length of follow-up for the entire cohort was 10.1 years. Clinical and pathologic features appear worse in patients with a higher BMI. On univariate and multivariate analyses, it was found that BMI had no impact on biochemical progression, systemic progression, prostate cancer survival, or overall survival. CONCLUSIONS: Obese patients appear to have worse pathologic features at the time of prostatectomy. Despite these features, long-term oncologic outcomes, including cancer-specific survival, remain the same regardless of BMI. BMI appears to influence prostate cancer outcomes at the time of prostatectomy, as evidenced by more aggressive pathologic features. However, after prostatectomy, BMI does not appear to be an independent predictor of recurrence or survival.

Age Factors↗

PubMed2006

Trends in distribution and prognostic significance of Gleason grades on radical retropubic prostatectomy specimens between 1989 and 2001.

BACKGROUND: The objectives of the current study were to examine time trends in the prevalence of Gleason grades of prostate cancer on radical retropubic prostatectomy (RRP) specimens and to assess the resultant impact on prognosis. METHODS: The authors examined the prevalence over time of each grade and Gleason score (GS) on RRP specimens from 8750 patients who were treated between 1989 and 2001. Biochemical recurrence-free survival (BRFS), which was estimated by using Kaplan-Meier methodology, was examined in subgroups of patients defined by tumor grade and era of surgery. RESULTS: The prevalence of Grade 3 prostate cancers increased (86% vs. 49% for primary Gleason grade and 71% vs. 47% for secondary Gleason grade; 1999-2001 vs. 1989-1990, respectively), whereas the prevalence of Grade 2 tumors decreased (0.4% vs. 38% for primary Gleason grade and 1.3% vs. 28% for secondary Gleason grade, respectively) over the study period, leading to fewer GS 4 and 5 tumors and more GS 6 and 7 tumors. BRFS improved over time for patients who had GS 5 tumors (hazards ratio [HR], 0.92 per year; P = .003) and GS 6 tumors (HR, 0.93; P < .001) but remained unchanged for GS 7 tumors (HR 0.99; P = .462) and GS 8-10 tumors (HR 1.02; P = .360). Patients who were treated in the recent era (1997-2001) had greater differentiation of BRFS based on GS or Gleason grade compared with patients who were treated earlier (1989-1991). CONCLUSIONS: The current results confirmed that there were changes in the prevalence of Gleason grades on RRP specimens between 1989 and 2001. A chronological change in pathologic grading classification is suggested by evolving prognostic implications, which must be accounted for when comparing outcomes from different eras.

Adult↗

PubMed2006

Tumor B7-H1 is associated with poor prognosis in renal cell carcinoma patients with long-term follow-up.

B7-H1 participates in T-cell costimulation functioning as a negative regulator of immunity. Recent observations suggest that B7-H1 is expressed by renal cell carcinoma (RCC) tumor cells and is associated with poor prognosis. However, outcome analyses have been restricted to patients with fresh-frozen tissue and limited follow-up. We report the clinical effect of B7-H1 in RCC patients with a median of 10 years of follow-up. Between 1990 and 1994, 306 patients underwent nephrectomy for clear cell RCC and had paraffin tissue available for review. We did immunohistochemistry with anti-B7-H1 and conducted outcome analyses. Among the 306 patients, 73 (23.9%) harbored tumors with B7-H1 expression. Patients with tumor B7-H1 were at a significantly increased risk of both death from RCC [risk ratio (RR), 3.92; P < 0.001] and overall mortality (RR, 2.37; P < 0.001). The 5-year cancer-specific survival rates were 41.9% and 82.9% for patients with and without tumor B7-H1, respectively. In a multivariate model, tumor B7-H1 remained associated with cancer-specific death even after adjusting for tumor-node-metastasis stage, grade, and performance status (RR, 2.00; P = 0.003). In the subset of 268 patients with localized RCC, tumor B7-H1 was significantly associated with metastatic cancer progression (RR, 3.46; P < 0.001) and death from RCC (RR, 4.13; P < 0.001) even after adjusting for stage, grade, and performance status (RR, 1.78, P = 0.036). RCC patients with tumor B7-H1 are at significant risk of rapid cancer progression and accelerated rates of mortality. B7-H1 may function as a key determinant in RCC, abrogating immune responses directed against this immunogenic tumor.

Antigens, CD↗

PubMed2006

The preoperative erythrocyte sedimentation rate is an independent prognostic factor in renal cell carcinoma.

BACKGROUND: Prognostic nomograms are used increasingly in clinical trials and to guide surveillance for patients with renal cell carcinoma (RCC). An elevated erythrocyte sedimentation rate (ESR) reportedly has been associated with a poor prognosis among patients with RCC, but the ESR is not incorporated into existing nomograms. Hence, the current study was conducted to expand on prior observations pertaining to the ESR as a prognostic indicator in patients with RCC. METHODS: The authors identified 3008 patients who underwent nephrectomy for RCC between 1970 and 2002. Disease-specific survival was estimated using the Kaplan-Meier method, and its association with the ESR and other clinical and pathologic features was evaluated using Cox proportional hazards regression analysis. RESULTS: A preoperative ESR was available for 1075 patients (35.7%), 501 of whom (46.6%) exhibited an elevated ESR, including 437 of 881 patients (49.2%) with clear cell RCC, 41 of 134 patients (30.6%) with papillary RCC, and 20 of 48 patients (41.7%) with chromophobe RCC. An elevated ESR was associated with adverse clinical, laboratory, and pathologic profiles for all three histologic subtypes. The risk ratios (RRs) and 95% confidence intervals (95% CIs) for death because of clear cell RCC, papillary RCC, and chromophobe RCC for patients with an elevated ESR were 3.6 (95% CI, 1.1-1.9), 3.8 (95% CI, 1.4-10.6), and 10.3 (95% CI, 1.2-89.5), respectively. The association between an elevated ESR and death from clear cell RCC persisted even after multivariate analysis (RR of 1.5; 95% CI, 1.2-2.0). CONCLUSIONS: An elevated ESR in patients with RCC suggested the presence of aggressive disease and poorer outcomes after surgical treatment. For patients with clear cell RCC, the ESR provided useful information above and beyond traditional prognostic algorithms, and it may be valuable for preoperative prognostication.

Adult↗

PubMed2006

Detectable prostate specific antigen between 60 and 120 days following radical prostatectomy for prostate cancer: natural history and prognostic significance.

PURPOSE: Following radical retropubic prostatectomy for prostate cancer, if the serum prostate specific antigen fails to become undetectable, occult micrometastatic disease is suspected. We assessed the natural history of disease progression, and predictors of recurrence and survival in this group of patients. MATERIALS AND METHODS: We identified 303 men treated with radical retropubic prostatectomy for prostate cancer between 1990 and 1999, who had a detectable prostate specific antigen between 60 and 120 days postoperatively. Systemic recurrence-free and cancer specific survival were estimated using the Kaplan-Meier method, and analyzed using Cox proportional hazards models. RESULTS: Clinical and pathological features were more adverse among men whose postoperative prostate specific antigen was detectable. These men had poorer systemic recurrence-free survival and cancer specific survival compared to men with an undetectable postoperative prostate specific antigen, and even men whose prostate specific antigen subsequently became detectable. These differences persisted after multivariate adjustment for preoperative prostate specific antigen, specimen Gleason score, seminal vesicle and margin status. With a median followup of 8.5 years, 50 systemic recurrences and 26 deaths from cancer were observed. Gleason score and the prostate specific antigen doubling time were multivariate predictors of systemic recurrence, while Gleason score, margin status and seminal vesicle invasion were predictors of death from cancer. CONCLUSIONS: A detectable prostate specific antigen immediately following radical retropubic prostatectomy confers an increased risk of progression and death, but only in a subset of patients, who may be identified on the basis of pathological features and prostate specific antigen doubling time. In future such patients may be suitable for trials of systemic therapy.

Adult↗

PubMed2006

Impact of familial and hereditary prostate cancer on cancer specific survival after radical retropubic prostatectomy.

PURPOSE: Men with a family history of prostate cancer are at higher risk for prostate cancer. There are conflicting data regarding the impact of hereditary forms of prostate cancer on long-term outcomes after radical prostatectomy. We examined the impact of familial and hereditary prostate cancer treatment in the prostate specific antigen era. MATERIALS AND METHODS: Patients who underwent radical prostatectomy for prostate cancer from 1987 to 1997 were surveyed (3,560 responders) to determine the family history of prostate cancer. Patients were categorized as having familial prostate cancer if they had at least 1 first-degree relative with prostate cancer. Hereditary prostate cancer was defined as nuclear families with 3 cases of prostate cancer, families with prostate cancer in each of 3 generations and families with 2 men diagnosed before age 55 years. Sporadic prostate cancer was defined as patients with no family history. Clinical and pathological features, and long-term outcome measures, including biochemical recurrence-free, systemic progression-free and cancer specific survival, were compared among patients with familial, hereditary and sporadic prostate cancer. RESULTS: A total of 865 and 133 patients were categorized as having familial prostate cancer and hereditary prostate cancer, respectively. Preoperatively prostate specific antigen was higher in patients with hereditary prostate cancer than in the other 2 groups (p = 0.04). Ten-year biochemical progression-free, systemic progression-free and cancer specific survival were equivalent. CONCLUSIONS: Except for preoperative prostate specific antigen, clinicopathological features and long-term oncological outcomes are equivalent after radical prostatectomy in patients with familial, hereditary and sporadic prostate cancer.

Adult↗

PubMed2006

Second primary malignancies associated with renal cell carcinoma histological subtypes.

PURPOSE: Renal cell carcinoma has been linked to numerous secondary malignancies. We evaluated the risk of secondary malignancies by renal cell carcinoma histological subtype in patients with clear cell, papillary and chromophobe renal cell carcinoma. MATERIALS AND METHODS: We studied 2,722 patients who underwent nephrectomy for sporadic renal cell carcinoma at our institution between 1970 and 2000. All specimens were reviewed by a single urological pathologist for histological subtype. Associations of second primary malignancies by histological subtype were evaluated using the chi-square and Fisher exact tests. RESULTS: Of the patients studied 2,188 (80.4%) had clear cell, 378 (13.9%) had papillary and 128 (4.7%) had chromophobe renal cell carcinoma. Patients with papillary renal cell carcinoma were significantly more likely to have colon cancer (p = 0.041), prostate cancer (p = 0.003), any second malignancy (p <0.001) and multiple malignancies (p <0.001) compared with patients with clear cell renal cell carcinoma. In addition, patients with chromophobe renal cell carcinoma were significantly more likely to have colon cancer than patients with clear cell renal cell carcinoma (p = 0.020). Although patients with papillary renal cell carcinoma were more likely to have bladder cancer, the incidence did not differ significantly compared with that in patients harboring clear cell and chromophobe renal cell carcinoma (p = 0.193). We did not find a significant difference in the incidence of breast cancer, lung cancer, rectal cancer or lymphoma among histological subtypes. CONCLUSIONS: Our data indicate that patients with papillary renal cell carcinoma are more likely to harbor secondary malignancies, including colon and prostate cancer, than patients with clear cell renal cell carcinoma. These results may have important implications for patient education and followup evaluation, and they should prompt mechanistic investigations.

Carcinoma, Renal Cell↗

PubMed2006

The role of nephron sparing surgery for metastatic (pM1) renal cell carcinoma.

PURPOSE: Studies have demonstrated increased time to progression when cytoreductive nephrectomy is performed for metastatic renal cell carcinoma. We evaluated the role of nephron sparing surgery in these patients. MATERIALS AND METHODS: We selected all patients with pM1 renal cell carcinoma treated with nephron sparing surgery or radical nephrectomy, and all patients with pM0 renal cell carcinoma undergoing nephron sparing surgery for solitary kidney from 1970 to 2002 from the Mayo Clinic Nephrectomy Registry. RESULTS: We identified 16 patients who underwent nephron sparing surgery for pM1 renal cell carcinoma. Solitary kidney was present in 12, 3 had bilateral synchronous disease and 1 had elective nephron sparing surgery. Cancer specific survival rates at 1, 3 and 5 years were 81%, 49% and 49%, respectively. We identified 404 patients who underwent radical nephrectomy for pM1 renal cell carcinoma. Cancer specific survival rates at 1, 3 and 5 years were 51%, 21% and 13%, respectively. The pM1 nephron sparing surgery for solitary kidney cases were more likely to have early (33% vs 10%, p = 0.009) or late (50% vs 19%, p = 0.018) complications compared with pM1 radical nephrectomy cases. There were no significant differences in early (p = 0.475) or late (p = 0.350) complications between pM1 nephron sparing surgery cases and 139 pM0 nephron sparing surgery cases. CONCLUSIONS: Cancer specific survival rates in pM1 nephron sparing surgery cases were comparable to pM1 radical nephrectomy cases. Although there were differences in early and late complications between the pM1 nephron sparing surgery and pM1 radical nephrectomy groups, there were no differences when compared with imperative pM0 nephron sparing surgery cases. This study demonstrates that nephron sparing surgery can achieve adequate cytoreductive therapy while preserving renal function, with postoperative complication rates similar to those of pM0 nephron sparing surgery cases.

Aged↗

PubMed2006

Conventional assessment of needle biopsy specimens is more useful than digital image analysis of proliferation and DNA ploidy in prediction of positive surgical margins at radical prostatectomy.

OBJECTIVES: The preoperative prediction of the likelihood of positive surgical margins (+SMs) at radical retropubic prostatectomy (RRP) may be useful for counseling and determining the surgical approach. The aim of this study was to assess the additional value of digital image analysis (DIA) of ploidy and proliferation on needle biopsies, in addition to the known preoperative predictors of +SMs at RRP. METHODS: We identified 454 patients treated by RRP at our institution from 1995 to 1998 for prostate cancer verified by transrectal ultrasound-guided biopsy, with a specimen adequate for DIA. Patients receiving preoperative hormonal therapy were excluded. The clinical features, transrectal ultrasound-guided biopsy findings, and DIA evaluation of MIB-I immunostaining and DNA ploidy were assessed in a multivariate logistic regression model to predict for +SMs at RRP. RESULTS: The mean +/- SD age at treatment was 64.5 +/- 6.5 years, the percentage of positive cores was 40.4% +/- 24.3%, the median prostate-specific antigen level was 6.3 ng/mL (range 0.6 to 112.0), median biopsy Gleason score was 6 (range 4 to 9), and median percentage of diploid nuclei was 67% (range 0% to 100%). Of the 454 patients, 185 (40.7%) had +SMs; this finding was time dependent (1995 to 1996, 45% and 1997 to 1998, 31%; P = 0.004). Univariately, preoperative prostate-specific antigen, biopsy Gleason score, extent of cancer on biopsy, MIB-1 expression, percentage of diploid or nondiploid nuclei, and year of surgery were predictive for +SMs. On multivariate analysis, the preoperative prostate-specific antigen level, biopsy Gleason score, percentage of positive cores, and year of surgery remained significant. CONCLUSIONS: The results of our study have shown that the likelihood of +SMs at RRP is best predicted on the basis of conventional prognostic factors. The DIA features of needle biopsies did not provide additional predictive power.

Adult↗

PubMed2006

Rare expression of KIT and absence of KIT mutations in high grade renal cell carcinoma.

PURPOSE: RCCs with sarcomatoid differentiation have been reported to frequently express KIT protein, suggesting that imatinib mesylate (STI-571 or Gleevectrade mark) may be effective treatment for these aggressive tumors. We determined the frequency of KIT expression and mutation in a large series of high grade RCCs. MATERIALS AND METHODS: We identified 194 patients who underwent nephrectomy for unilateral, sporadic nuclear grade 4 RCC between 1970 and 2002, including 123 with sarcomatoid differentiation. Sections from representative paraffin embedded tissue blocks were immunostained in an autostainer using ethylenediaminetetraacetic acid antigen retrieval, a polyclonal KIT antibody and the avidin-biotin peroxidase complex method. Mutational analysis was performed in all immunopositive and select negative cases by polymerase chain reaction amplification of KIT exons 9, 11, 13 and 17. RESULTS: Only 7 tumors (3.6%) showed KIT expression, including 5 of the 123 (4.1%) with sarcomatoid differentiation. Four of the 7 tumors showed focal staining only. No mutations were identified in the 7 positive cases or in 8 randomly selected negative samples. Death from RCC occurred in all 7 patients with KIT positive tumors at a median of 0.6 years (range 0.3 to 2.3) and in 139 of 187 with KIT negative tumors at a median of 0.8 years (range 0 to 10.2). CONCLUSIONS: KIT expression was identified in less than 5% of high grade RCCs with or without sarcomatoid differentiation but none of the tumors showed KIT mutations. These findings indicate that imatinib therapy is unlikely to be effective in patients with high grade RCC.

Carcinoma, Renal Cell↗

PubMed2006

Long-term prognostic significance of primary Gleason pattern in patients with Gleason score 7 prostate cancer: impact on prostate cancer specific survival.

PURPOSE: We determined the long-term clinical significance of primary Gleason pattern in patients with Gleason score 7 prostate cancer. MATERIALS AND METHODS: We reviewed the records of all patients who underwent bilateral pelvic lymph node dissection and radical retropubic prostatectomy for Gleason score 7 prostate cancer at our institution. All patients who underwent adjuvant hormonal or radiation therapy were excluded from analysis. Patients were monitored for biochemical failure, that is PSA progression, systemic recurrence and cancer specific survival. RESULTS: We identified 1,688 patients who met admission criteria, of whom 1,256 (74.4%) had primary Gleason pattern 3 and 432 (25.6%) had primary Gleason pattern 4. Median followup was 6.9 years. At 10 years primary Gleason pattern 3 was associated with increased biochemical recurrence-free survival (48% vs 38%, p <0.001), lower systemic recurrence (8% vs 15%, p <0.001) and higher cancer specific survival (97% vs 93%, p = 0.013) for Gleason primary grades 3 and 4, respectively. All of these end points remained significant on multivariate analysis when controlling for preoperative PSA, seminal vesicle involvement, margin status, DNA ploidy and TNM staging. PSA doubling time was shorter in patients with primary Gleason pattern 4 (1.64 vs 1.01 years). Systemic recurrence and cancer specific survival were associated with a PSA doubling time of less than 1 year. CONCLUSIONS: Gleason score 7 prostate cancer is a heterogeneous entity. We should continue to stratify patients according to primary Gleason pattern. Patients with Gleason score 4 + 3 prostate cancer have more aggressive disease and experience higher rates of biochemical failure, systemic recurrence and cancer specific death.

Adult↗

PubMed2006

Impact of patient age at treatment on outcome following radical retropubic prostatectomy for prostate cancer.

PURPOSE: Historically young patients with prostate cancer have been found to have poorer outcomes. Recent studies suggest favorable pathological findings and improved survival in younger patients undergoing RRP. We assessed age at treatment as a predictor of post-RRP survival. MATERIALS AND METHODS: We identified 5,509 patients treated with RRP for prostate cancer at our institution between 1987 and 1995. Age at treatment was classified into categories of younger than 55, 55 to 59, 60 to 64, 65 to 69 and 70 years or older. CSS, sPFS and biochemical PFS were estimated by the Kaplan-Meier method and analyzed using Cox proportional hazard models. RESULTS: Younger patients had lower preoperative prostate specific antigen, and tumor grade and stage. CSS, sPFS and biochemical PFS were similar across age groups but overall survival decreased with older age at treatment. After multivariate adjustment the risk of cancer death was lower in patients 70 years or older (RR 0.53, 95% CI 0.30 to 0.90), while the risk of progression was lower in all age groups compared to that in men younger than 55 years (RR 0.57 to 0.62). On stratified subset analysis sPFS was progressively worse with younger age in patients with high risk pathological findings. However, the addition of age to multivariate models incorporating preoperative prostate specific antigen, pathological features and adjuvant therapy failed to improve their predictive value for CSS and sPFS. CONCLUSIONS: Despite more favorable clinicopathological features younger patients undergoing RRP for prostate cancer have survival similar to that of older counterparts. Given the greater proportionate impact of prostate cancer on survival, it is particularly important to pursue aggressive treatment in younger patients.

Age Factors↗

PubMed2006

Increasing prostate specific antigen following radical prostatectomy and adjuvant hormonal therapy: doubling time predicts survival.

PURPOSE: Adjuvant hormonal therapy may be beneficial in patients who are treated with RRP and found to have adverse pathological findings. We assessed the natural history of detectable PSA in such patients with particular emphasis on the prognostic usefulness of PSADT. MATERIALS AND METHODS: We identified 903 patients treated with RRP and adjuvant hormonal therapy (started less than 90 days postoperatively) for prostate cancer at our institution between 1990 and 1999. PSADT was calculated by log linear regression in men with 2 or more PSA measurements available at least 90 days apart. CSS and sRFS were estimated by the Kaplan-Meier method and analyzed using Cox proportional hazard models. RESULTS: At a median followup of 9.1 years PSA had become detectable in 369 of 771 patients (47.9%) who achieved an undetectable nadir. PSADT evaluable in 463 patients was less than 12 months in 68 (14.6%) and more than 10 years in 283 (61.1%). N stage and Gleason score were significantly associated with sRFS and CSS. PSADT was a significant predictor of sRFS and CSS in N+ and N0 cases with a cancer death HR of 0.55 (95% CI 0.43 to 0.71) and 0.50 (95% CI 0.31 to 0.79), respectively. The association between PSADT and survival persisted after multivariate adjustment for preoperative PSA, specimen Gleason score and seminal vesicle invasion. CONCLUSIONS: This study demonstrates that many patients have slow progression despite increasing PSA following RRP and adjuvant hormonal therapy. Nodal status, cancer grade and PSADT are predictive of sRFS and CSS, and may be a useful means of selecting patients for future adjuvant therapy trials.

Androgen Antagonists↗