Genetic ancestry and prostate cancer susceptibility SNPs in Puerto Rican and African American men.

BACKGROUND: The Puerto Rican (PR) population is a racially admixed population that has a high prostate cancer (PCa) mortality rate. We hypothesized in this pilot study that West African Ancestry (WAA) was associated with PCa in this heterogeneous (PR) population. METHODS: A case/case and case/control study was performed. Controls, 207 African American (AA) and 133 PR were defined as men with no PCa, a serum PSA < 2.5 ng/mL and a negative rectal examination. Cases were patients with pathological specimens from radical prostatectomies (RP) (291 PR and 200 AA). DNA was extracted from whole blood of controls and from paraffin embedded normal seminal vesicle from the RPs. We assessed the association of PCa and aggressiveness with genetic ancestry using an ancestry informative marker panel (AIMs) and Wilcoxon rank-sum test and the association of PCa and aggressiveness with 15 previously PCa associated SNPs using Chi square test. Gleason Score (GS) and tumor stage (TS) were used to define low risk (GS ≤ 7[3 + 4]), TS ≤ pT2) and high risk (GS≥ 7[4 + 3], TS > pT2) PCa. Statistical analyses were done using SAS. RESULTS: No difference in overall percent WAA was found between PR cases and controls. Among PR or AA cases WAA was not associated with disease severity based upon risk group, Gleason score or stage. Among AA controls WAA was significantly higher than in cases. The SNP rs7824364 (chromosome 8q24) PCa risk allele was significantly increased among cases versus controls for both AA (P < 0.0001) and PR (P = 0.0001) men. PR men with ≥1 risk allele exhibited a higher percent of WAA (39% vs 29%, P = 0.034). CONCLUSION: The SNP rs7824364, a local marker of WAA in the 8q24 region was associated with PCa among both AA and PR men and with increased WAA among PR men. This novel relationship of PCA risk loci, WAA with PCa and its phenotype among PR men deserves further study.

Outcomes of Minimally Invasive Inguinal Hernia Repair at the Time of Robotic Radical Prostatectomy.

Abdominal straining associated with voiding dysfunction or constipation has traditionally been associated with the development of abdominal wall hernias. Thus, classic general surgery dictum recommends that any coexistent bladder outlet obstruction should be addressed by the urologist before patients undergo surgical repair of a hernia. While organ-confined prostate cancer is usually not associated with the development of lower urinary tract symptoms, a modest proportion of patients treated with radical prostatectomy may have coexisting benign prostatic hyperplasia with elevated symptom scores and hernias may be incidentally detected at the time of surgery. Furthermore, dissection of the space of Retzius during retropubic or minimally invasive prostatectomy may result exposure of abdominal wall defects which may have been present, but asymptomatic if plugged with preperitoneal fat. Herein we examine the literature regarding the incidence of postoperative inguinal hernias after prostatectomy, review potential risk factors which could aid in preoperative patient identification, and discuss the published experience regarding concurrent hernia repair at the time of open or minimally invasive radical prostatectomy.

Preoperative International Prostate Symptom Score Predictive of Inguinal Hernia in Patients Undergoing Robotic Prostatectomy.

PURPOSE: Studies have shown that encountering an inguinal hernia during robotic radical prostatectomy is not uncommon. We reviewed our experience with simultaneous robotic prostatectomy and mesh hernia repair to identify variables predictive of a hernia. MATERIALS AND METHODS: Our cohort consisted of 693 consecutive men who underwent robotic radical prostatectomy as performed by 1 surgeon. Hernias were repaired with mesh composed of equal parts of absorbable polyglecaprone-25 and nonabsorbable polypropylene monofilament. Preoperative variables potentially predictive of an inguinal hernia were evaluated. RESULTS: Inguinal hernias were encountered in 55 of 639 patients (8.6%), of which 22.3% were bilateral for a total of 68 hernia sides. Only 26 of 55 hernias (47.2%) were evident preoperatively. Men with a preoperative I-PSS (International Prostate Symptom Score) of 15 or greater had a 22.4% chance (30 of 134) of requiring a hernia repair compared with 5% in those without such a score (OR 5.54, 95% CI 3.13-9.81, p <0.0001). There were no differences between the hernia and nonhernia groups in prostate size, body mass index, age, blood loss, transfusions, operative time, length of stay or any Clavien grade II-V complication. In 47 patients there was 1 recurrence at a median followup of 27.9 months. There were no cases of mesh associated pain or erosion. CONCLUSIONS: Independent of prostate size, men with preoperative lower urinary tract dysfunction were at 5 times the risk of a hernia at robotic radical prostatectomy (22.4% vs 5%). Given that half of the hernias were subclinical, patients with an I-PSS of 15 or greater should be counseled about the potential need for hernia repair at robotic radical prostatectomy.

Association of serum lipid levels and prostate cancer severity among Hispanic Puerto Rican men.

BACKGROUND: While obesity and fat intake have been associated with an increased risk of prostate cancer (PCa) aggressiveness and mortality, the association between lipid levels and PCa phenotype remains unclear. Previous reports evaluating this association are inconsistent and highly variable when considering different racial/ethnic groups. There are scarce data regarding this association among Hispanics, and specifically Puerto Rico's Hispanic men, a population with a higher burden of PCa, metabolic syndrome and overweight. This population has a different ancestry profile than other Hispanics from Central and South America. Due to the above the researchers inquired if there is a relationship between serum lipid levels and PCa phenotype in this understudied population using a cohort of patients treated with radical prostatectomy as their first treatment. METHODS: We performed an exploratory retrospective medical record review study of 199 PCa patients who underwent radical prostatectomy between 2005 and 2012. Variables analyzed included age at PCa diagnosis, Body Mass Index (BMI), preoperative serum prostate-specific antigen (PSA), lipid levels, and clinical parameters such as prostatectomy pathologic stage and Gleason Score (GS). PCa severity was defined using pathologic stage and GS. Unadjusted and adjusted logistic regression models were fitted to estimate the odds ratios (ORs) with 95 % confidence intervals (CI) to define the relationship among clinical characteristics and PCa severity. RESULTS: Mean age for the cohort was 58.8 years (range: 40-75), 78.9 % were overweight or obese, 36.7 % had hypertriglyceridemia, and 35.2 % had low HDL levels. In the unadjusted logistic regression model, hypertriglyceridemia (OR: 2.11, 95 % CI = 1.13-3.93), low HDL (OR: 1.90, 95 % CI = 1.02-3.56-), and age (OR: 2.34, 95 % CI 1.25-4.40) were significantly associated with a diagnosis of high severity of PCa. CONCLUSIONS: In Puerto Rican men with PCa, elevated hypertriglyceridemia, low HDL levels, and age were statistically associated with high grade PCa on bivariate analysis. Total cholesterol level was not associated with severity of disease. Associations lost significance upon multivariate adjustment. These data generate important hypotheses regarding the potential relationship between lipid pathways and PCa development and underscore the need to perform larger scale and longitudinal studies to sort out whether, hypertriglyceridemia is associated with PCa phenotype and development.

The ratio of matrix metalloproteinase to E-cadherin expression: a pilot study to assess mRNA and protein expression among African American prostate cancer patients.

BACKGROUND: We assessed the expression of Matrix Metalloproteinase (MMP) to E-cadherin (M/E ratio) to determine the correlation of gene expression with pathologic variables and outcome in a cohort of African American (AA) prostate cancer patients. METHODS: Tumors from formalin-fixed, paraffin embedded RP specimens were examined. Gleason scores were 6, 7, and >or=8 in 7, 16, 13 tumors, respectively. Pathologic stage was organ confined (pT2) in 18 and advanced (>pT2) in 18 tumors. A colorimetric mRNA in situ hybridization (ISH) assay was performed using biotinylated anti-sense oligonucleotide probes for MMP 2 and 9, as well as for E-cadherin gene transcripts. Immunohistochemistry (IHC) was performed utilizing specific monoclonal antibodies to detect the above genes. Image analysis was performed to determine the intensity of both mRNA and protein expression. Two reviewers analyzed ISH gene expression independently. RESULTS: The M/E expression ratio was significantly increased at the invasive edge (but not the center) of tumors of higher Gleason score (P = 0.02 and 0.0008) and pathologic stage (P = 0.0001 and <0.0001) when examined by both ISH and IHC. Significant variability in ISH staining interpretation was noted within and among the two study reviewers. An M/E ratio >2.5 was associated with biochemical recurrence after radical prostatectomy in addition to tumor pathologic stage subsequent to univariate statistical analysis. CONCLUSIONS: The M/E ratio characterizes an important aspect of the molecular phenotype associated with the histologic progression of prostate cancer among African American prostate cancer patients. A larger comparative study is required to determine potential racial variation and prognostic significance of gene expression.

Impact of FTO SNPs rs9930506 and rs9939609 in Prostate Cancer Severity in a Cohort of Puerto Rican Men.

BACKGROUND: Obesity is prevalent in PR and has been associated with prostate cancer (PCa) mortality and aggressiveness. Polymorphisms (SNPs) rs9930506 and rs9939609 in the FTO gene have been associated with both obesity and PCa. The aim of this work was to ascertain whether the presence of these SNPs is associated with PCa risk and severity in a cohort of Puerto Rican men. METHODS AND FINDINGS: The study population consisted of 513 Puerto Rican men age ranging from 40-79 years old who underwent radical prostatectomy (RP) as the first treatment for PCa and 128 healthy Puerto Rican men age ranging from 40-79 years old. Genomic DNA (gDNA) was extracted and SNPs were determined by Real-Time PCR. PCa severity was defined based on RP stage and Gleason Score. The relationship of FTO SNPs with demographic, clinical characteristics, PCa status and PCa severity were assessed. Logistic regression models with a 95% confidence interval (CI) determined SNPs interaction with PCa risk and severity odds ratio (ORs). RESULTS AND DISCUSSION: BMI, age and PSA were considered as confounders. Hardy-Weinberg equilibrium was present for both SNPs. The heterozygous forms (A/G; T/A) were the most prevalent genotypes and the frequency of alleles and genotypes for both SNPs agreed with those published in 1000 genomes. Results suggest an inverse association between the mutated rs9939609 and the risk of having PCa (OR: 0.53, 95% CI: 0.31-0.92) and a positive association with overweight (OR: 1.05, 95% CI: 0.68-1.62). Importantly, among the cases that were overweight, those with mutated rs9939609 had a greater chance of high severity PCa (OR: 1.39, 95% CI: 0.84-2.32) although these results were not statistical significant upon adjustment. Limitations of the study were the relatively small cohort and lack of access to the weight history of all our subjects. CONCLUSION: Results offer a research line to be followed with an expanded number of subjects that may provide a better statistical significance, to unravel the high mortality rate in this population.

The role of lymphadenectomy in penile cancer.

In patients with squamous carcinoma of the penis, the presence and extent of metastases involving the inguinal nodes are the most important factors predictive of survival. Favorable prognostic indicators of cure in surgically treated patients in whom metastases develop include: (1) minimal nodal disease, (2) unilateral involvement, (3) no evidence of extranodal extension of cancer, and (4) absence of pelvic nodal metastases. Prophylactic lymphadenectomy in select patients at high risk for metastasis seems reasonable in lieu of prospective randomized trials because novel procedures have significantly decreased the morbidity of surgical staging. Patients with poor prognostic indicators either before or after surgery should be considered for multimodal therapy.

Natural history, management, and surveillance of recurrent squamous cell penile carcinoma: a risk-based approach.

For men with penile carcinoma, surveillance strategies may be tailored to the risks of local and regional recurrence, which vary according to the pathologic characteristics of the primary tumor and the modalities employed for local therapy (phallus sparing or extirpative) and regional therapy (surveillance or lymphadenectomy). Men at a higher risk for local or regional recurrence who should have more rigorous follow-up include those (1) treated with phallus-sparing strategies such as laser ablation, topical therapies, or radiotherapy; (2) patients with clinically negative inguinal lymph nodes who are managed without lymphadenectomy despite high-risk primary tumors (pT2-3, grade 3, vascular invasion); and (3) those with lymph node metastases after lymphadenectomy. Good candidates for less-stringent surveillance include patients with low-risk primary tumors (pTis, pTa, pT1, grades 1-2) and those with negative inguinal nodes after lymphadenectomy whose primary tumors were managed with partial or total penectomy.

Prognostic factors for survival among Caucasian, African-American and Hispanic men with androgen-independent prostate cancer.

BACKGROUND: African-American men suffer disproportionately with respect to the incidence and mortality from prostate cancer. The objective of the current study was to define if race was an independent prognostic factor among other variables assessed for survival among men treated for androgen independent prostate cancer. METHODS: Between 1988 and 1995, 379 patients with AIPC and clinical progression were referred for novel protocol therapies. Measured variables included: 1) patient age, 2) race or ethnicity, 3) hemoglobin, 4) alkaline phosphatase, 5) serum prostate-specific antigen (PSA) level, 6) time from hormonal ablation to AIPC, 7) number of metastases on bone scan, 8) osseous stage, 9) number of organ systems with metastases and 10) type of treatment for AIPC. RESULTS: Median survival for the cohort was not significantly affected by race, on uni- or multivariate analysis. Multivariate analysis demonstrated that increasing hemoglobin (HR = 0.87 per g, 95% CI [0.81-0.94]) and time to AIPC (HR = 0.994, 95% CI [0.990-0.998]) were associated with increased survival while higher osseous stage (HR = 1.49, stage I versus II, 95% CI [1.11-1.99]), treatment group (HR = 1.68, treatment group I versus II, 95% CI [1.33-2.12]), metastases to three or more organ systems (HR = 1.31 versus less than three organs, 95% CI [1.15-1.49]), and advanced age (HR = 1.51 for age > 70 versus < or = 70, 95% CI [1.18-1.94]) were associated with a decrease in survival among patients with AIPC. CONCLUSION: Independent prognostic variables for survival among patients with AIPC included patient age, serum hemoglobin level, time to androgen-independent disease, treatment group and the extent of metastatic disease. Ethnicity did not adversely affect outcome.

Racial influence on biochemical disease-free survival in men treated with external-beam radiotherapy for localized prostate cancer.

BACKGROUND: We retrospectively analyzed the clinical characteristics and outcomes of various racial and ethnic groups who underwent radiotherapy alone for localized or locally advanced prostate cancer. METHODS: From April 1987 to January 1998, 964 patients underwent full-dose, external-beam radiotherapy alone for localized or locally advanced prostate cancer and were included in the study. The patients' medical records were reviewed for pertinent information. RESULTS: Of the 964 patients, 810 were non-Hispanic white, 86 were African-American, 54 were Hispanic, and 14 were Asian. The most significant difference between groups was in the proportion of patients who presented with initial PSA levels > 20 ng/ml. More than 20% of men in all minority groups presented with a serum PSA > 20 ng/ml, compared to only 11% of whites (p = 0.0012). Similarly, 14% of minorities presented with Gleason scores > or = 8 compared to only 11% of whites (p = 0.0265). Hispanic and Asian patients exhibited a higher incidence of Gleason score > or = 8 prostate cancer. When comparing the time intervals of 1995-1998 vs. 1987-1994, the number of men presenting for EBRT with PSA levels < 10 ng/ml increased to 74% from 57% for Caucasians (p < 0,001), 71% from 40% for African Americans (p = 0.012), 67% from 49% for Hispanics (p = 0.1 18), and no change (50%) for Asians. CONCLUSIONS: The number of African-American patients presenting with favorable characteristics (PSA < 10 ng/ml) is increasing. These findings suggest that the message of screening and early detection may be reaching the African-American community. Continued diligence in screening and early detection may improve prostate cancer outcome for other minority populations.

Renal cell carcinoma clinically involving adjacent organs: experience with aggressive surgical management.

BACKGROUND: Historically, patients with nonmetastatic renal cell carcinoma (RCC) involving adjacent organs have been considered inoperable and incurable. The oncologic efficacy of an aggressive surgical approach was evaluated in a selected subpopulation of RCC patients. Further, an attempt was made to define the clinical and pathologic characteristics predictive of surgical failure. METHODS: With Institutional Review Board approval, the institutional nephrectomy database of 3470 patients treated at MD Anderson Cancer Center from 1990 to 2006 was searched for RCC patients treated with radical nephrectomy and resection of at least 1 adjacent organ thought to be directly involved by RCC. Patients with nonmetastatic RCC and a minimum follow-up of 6 months were included in the analysis. RESULTS: In all, 30 patients with clinical T4NxM0 RCC and median follow-up of 32.3 months (range, 8.5-140.1) met the study inclusion criteria and comprise the dataset for the analysis. On pathologic evaluation 60% of patients were clinically overstaged, as only 12 (40%) of 30 patients demonstrated direct invasion into adjacent organs resected. None of the clinical tumor characteristics predicted a finding of pathologic T4 RCC. Nodal involvement and pathologic T stage were significant independent predictors of disease recurrence (hazard ratio [HR] 3.726, P = .043, and HR 2.414, P = .045, respectively) and cancer-specific survival (HR 17.145, P = .002, and HR 3.791, P = .024, respectively). Disease recurred in 11 of 18 (61.1%) of

Cytoreductive nephrectomy for T4NxM1 renal cell carcinoma: the M.D. Anderson Cancer Center experience.

OBJECTIVES: Although cytoreductive nephrectomy may provide a survival benefit in metastatic renal cell carcinoma, patients with locally advanced lesions may be denied cytoreduction because of a perceived worse outcome and increased morbidity. We reviewed our experience with cytoreductive nephrectomy in patients with contiguous organ involvement (Stage T4NxM1) to evaluate the outcome and morbidity. METHODS: From 1993 to 2004, 498 patients underwent cytoreductive nephrectomy for renal cell carcinoma. Of those, 23 patients had Stage T4NxM1 disease. The analyzed variables included surgical complications, palliation of symptoms, and survival. RESULTS: The median patient age was 55 years (range 35 to 73), with a median tumor size of 15 cm (range 7 to 30). The median overall and disease-specific survival was 6.8 months (range 1.4 to 25.7). The distribution of the histologic type was conventional in 16, papillary in 2, and unclassified in 5. Sarcomatoid features were present in 9 patients. In 2 patients, surgery was aborted because of unresectable disease. Three patients developed postoperative complications (one wound dehiscence, one pancreatic collection, and one seizure). The median length of stay was 7 days (range 5 to 19). Of the 7 patients with local symptoms, 5 experienced postoperative palliation. Most patients (79%) received postoperative systemic therapy after a median of 39 days (range 24 to 114). Five patients did not receive systemic therapy because of disease progression. The median disease-specific survival for the patients who received systemic therapy was 7.1 months (range 1.4 to 25.7), but only 2.5 months (range 0 to 5.2) for those who had not (P = 0.003). CONCLUSIONS: Cytoreductive nephrectomy in Stage T4NxM1 renal cell carcinoma is feasible and provides significant palliation in symptomatic patients; however, the survival benefit is unclear. Our retrospective series has demonstrated that the prognosis in these patients is poor.

Cytoreductive nephrectomy for metastatic renal cell carcinoma with nonclear cell histology.

PURPOSE: To our knowledge the benefit of cytoreductive surgery for patients with metastatic renal cell carcinoma with nonclear cell histology is unknown. In this retrospective study we report our experience with cytoreductive nephrectomy for nonclear cell metastatic renal cell carcinoma at M. D. Anderson Cancer Center. We compared the outcomes with those in patients with clear cell metastatic renal cell carcinoma. MATERIALS AND METHODS: From 1991 to 2006, 606 patients with metastatic renal cell carcinoma underwent cytoreductive nephrectomy and they formed the basis of this report. Of these patients 92 had nonclear cell metastatic renal cell carcinoma. The remaining 514 patients had clear cell metastatic renal cell carcinoma and they formed a comparative group. Multivariate Cox regression analysis was performed to evaluate the relationship between clinical variables and histology (clear cell vs nonclear cell) on disease specific survival. RESULTS: Compared with patients with clear cell histology those with nonclear cell metastatic renal cell carcinoma were younger (p = 0.0001), and more likely to have nodal metastases (p <0.0001) and sarcomatoid features (23% vs 13%, p = 0.026). On multivariate analysis median disease specific survival in patients with nonclear cell histology was significantly worse than that in patients with clear cell metastatic renal cell carcinoma (9.7 vs 20.3 months, p = 0.0003) even after adjusting for T stage, grade, performance status, age and sarcomatoid features. Sarcomatoid features were a predictor of poor outcome in cases of clear and nonclear cell histology, although even in the absence of sarcomatoid features nonclear cell histology was associated with worse disease specific survival (p = 0.017). Interestingly although there was a significantly higher incidence of positive nodes in patients with nonclear histology (p <0.0001), this phenotype was not associated with a worse disease specific survival, as it was in those with clear cell histology (p = 0.0001). In fact, patients with node negative disease with nonclear cell histology had the worst prognosis overall in the entire group. CONCLUSIONS: Patients with nonclear cell metastatic renal cell carcinoma were younger and had a higher incidence of nodal metastases, a higher incidence of sarcomatoid features and a worse prognosis than those with clear cell histology who underwent cytoreductive surgery.

Renal cell carcinoma with nodal metastases in the absence of distant metastatic disease (clinical stage TxN1-2M0): the impact of aggressive surgical resection on patient outcome.

PURPOSE: Nodal disease in the setting of metastatic renal cell carcinoma is associated with poor prognosis. However, to our knowledge the biology of nodal metastases in the absence of metastatic disease is unknown. We reviewed our experience with treating this subset of patients with aggressive surgical resection. MATERIALS AND METHODS: A total of 2,643 patients underwent nephrectomy at our institution between 1993 and 2003, including 40 with positive lymph nodes but no systemic metastases. All 40 patients underwent nephrectomy with extended retroperitoneal lymphadenectomy and they are the subjects of this study. Pathological characteristics and clinical outcomes were assessed. RESULTS: Median patient age was 58 years and 62% of the patients were male. Median tumor size was 11 cm. Local stage was T1 in 3% of cases, T2 in 17%, T3a in 30%, T3b in 47% and T4 in 3%. Perinephric fat invasion was present in 77% of patients and positive margins were identified in 17%. Nodal status was N1 in 30% of patients and N2 in 70%, including 10 with masses of matted nodes. Histology was conventional in 63% of cases and papillary in 17%. The remaining 20% of patients had sarcomatoid dedifferentiation. Excluding the 10 patients with matted nodes the median number of nodes harvested per patient was 7 with a median of 2 that were positive. Extranodal extension was present in 70% of cases, while in 70% disease recurred at a median of 4.9 months. Median actuarial disease specific survival was 20.3 months. At a median followup of 17.7 months 30% of patients had no evidence of disease, 8% had disease and 62% had died. On multivariate analysis more than 1 positive node was predictive of decreased recurrence-free survival (HR 2.83, 95% CI 1.06 to 7.61, p = 0.039) and overall survival (HR 9.33, 95% CI 1.85 to 47.09, p = 0.007). CONCLUSIONS: Nodal metastasis with renal cell carcinoma is an independent predictor of prognosis in patients with M0 disease. Even in the absence of distant metastatic disease patients with positive nodes should be targeted for aggressive surgical resection, followed by clinical trials of adjuvant therapy to improve the outcome.

African-American men with nonpalpable prostate cancer exhibit greater tumor volume than matched white men.

BACKGROUND: Although prostate cancer (PC) mortality disproportionately affects African-American (AA) men, limited data exist comparing the pathologic characteristics of white and AA patients with nonpalpable PC (clinical stage T1c). METHODS: The authors reviewed the radical prostatectomy (RP) specimens from 37 consecutive AA men with clinical stage T1c PC and 35 white men who were matched for age, clinical stage, serum prostate-specific antigen (PSA) level, year of surgery, prostate weight, and prostate biopsy strategy. Pathologic characteristics were compared after mapping tumor foci and calculating tumor volumes by using computer software. RESULTS: For AA men, the median age (57.7 years), mean serum PSA level (9.3 ng/mL), mean prostate weight (43 g), and biopsy strategy (73% sextant) were matched with the cohort of 35 white men (median age, 57.1 years; mean PSA, 9.3 ng/mL;, mean prostate weight, 43 g; biopsy strategy, 66% sextant). Despite similar biopsy characteristics between the 2 groups (Gleason score > or =7 in 43% of AA men vs. 37% of white men), AA men exhibited significantly higher prostatectomy Gleason scores (> or =7 in 76% of AA men vs. 34% of white men; P = .01). AA men also had a higher mean tumor volume (1.82 cm3 vs. 0.72 cm3; P = .001) and had 2.8 times more tumor per ng/mL of serum PSA (0.22 cm3 per ng/mL vs. 0.079 cm3 per ng/mL; P = .001). CONCLUSIONS: Compared with a cohort of white men with similar clinical features at the time of biopsy, AA men with nonpalpable PC had higher prostatectomy Gleason scores, greater cancer volume, and greater tumor volume per ng/mL of serum PSA. These data provide additional support for the concept of early PC detection using a serum PSA threshold of 2.5 ng/mL for biopsy among AA men.

Melanoma of the penis, scrotum and male urethra: a 40-year single institution experience.

PURPOSE: Genitourinary melanoma is rare and classically associated with a poor prognosis. We describe our experience with 10 patients with penile or urethral involvement. In addition, we present what is to our knowledge the largest reported series of melanoma of the scrotum (6 cases). MATERIALS AND METHODS: We reviewed the records of 16 men who presented consecutively to our institution with genitourinary melanoma between 1962 and 2000. Clinical and pathological characteristics were assessed, including Breslow thickness, primary surgical intervention and clinical course. RESULTS: Of 10 patients with penile or urethral melanoma 1997 American Joint Committee on Cancer melanoma pathological stage was T1 (depth less than 0.75 mm) in 4, T2 (0.75 to 1.5 mm) in 3 and T3 (1.51 to 4 mm) in 3. Only 1 of 4 patients with clinically palpable inguinal nodes had inguinal metastases at lymphadenectomy (BILND) and 3 who underwent prophylactic superficial BILND had negative findings. In 7 patients with T1-2N0M0 disease there were no local recurrences after wide local excision (WLE) or partial penectomy at a median followup of 35 months. Six of 7 men were rendered disease-free. One patient died of melanoma that developed at a second primary site. The 3 patients with T3 tumors who underwent partial (2) or radical (1) penectomy with or without BILND died of disease (2) or had progression (1). In all patients with penile melanoma the 5-year actuarial disease specific and recurrence-free survival rates were 80% and 60%, respectively, at a median followup of 39 months (range 20 to 210). Six patients with scrotal melanoma were treated with WLE without local recurrences. Three of the 6 patients had palpable inguinal nodes, of whom 2 died after chemotherapy for unresectable disease and 1 died of other causes 51 months after negative BILND. The 3 men with clinically negative groins who did not undergo prophylactic BILND had distant (1) or regional (2) metastases and died of disease. In patients with scrotal melanoma the 5-year actuarial disease specific and recurrence-free survival rates were 33.3% and 33.3%, respectively, at a median followup of 36 months. CONCLUSIONS: Partial penectomy or WLE provided effective local control for low stage penile or urethral melanomas and all scrotal lesions. Patients showing clinically positive, proven metastasis died despite appropriate surgical procedures and multi-agent chemotherapy. Prophylactic modified inguinal lymphadenectomy should be considered in select patients with penile, scrotal and anterior urethral melanoma.

Is patient age a factor in the occurrence of prostate-specific antigen bounce phenomenon after external beam radiotherapy for prostate cancer?

OBJECTIVES: To evaluate the effect of patient age on the occurrence of prostate-specific antigen (PSA) "bounce" after external beam radiotherapy (EBRT) for prostate cancer. METHODS: In this study, 964 patients received EBRT alone for prostate cancer between April 1987 and January 1998 who had been followed for at least 12 months. Prostate-specific antigen values were obtained every 3 to 6 months after radiotherapy. Median overall follow-up was 48 months. Prostate-specific antigen bounce was defined as an initial increase in serum PSA of at least 0.5 ng/mL, followed by a decrease to prebounce baseline serum PSA values, all within 60 months after EBRT. Biochemical failure was defined as three consecutive increases in posttreatment PSA concentration after achieving a nadir. Multivariate Cox regression analysis was performed to evaluate the influences of age, pretreatment PSA concentration, Gleason score (determined at biopsy), clinical T stage classification, and radiation dose on PSA bounce-free survival and biochemical disease-free survival, with P < 0.05 considered statistically significant. RESULTS: Twelve percent of the patients developed a PSA bounce. Age was not associated with the occurrence of a PSA bounce (P = 0.63), the magnitude of the PSA bounce (P = 0.90), or the duration of the PSA bounce (P = 0.39). Patients who had PSA bounce had a statistically significant higher biochemical disease-free survival than those who did not (P = 0.00004). CONCLUSIONS: In our study, age was not predictive of PSA bounce. However, younger patients with a rising PSA after radiotherapy should be followed closely for evidence of biochemical failure.

Young age is an independent prognostic factor for survival of sporadic renal cell carcinoma.

PURPOSE: Compared to older adults with renal cell carcinoma (RCC) our subjective impression has been that younger adults present with more unfavorable histological features and yet respond more favorably to aggressive therapies. We reviewed our experience to validate these observations. MATERIALS AND METHODS: We reviewed the medical records of 106 consecutive patients 40 years or younger and 145 consecutive 58 to 61-year-old patients referred for the surgical management of sporadic RCC between 1992 and 2002. Using univariate and multivariate analyses the pathological characteristics and outcome of the 2 groups were compared. RESULTS: Mean age of the young adults was 34.7 years (range 14 to 40). Of younger adults 24% had tumors with unfavorable features, such as sarcomatoid differentiation, unclassified histology, medullary carcinoma and collecting duct carcinoma, compared with 12% of older adults (p <0.02). However, older adults were more likely to have tumors of advanced local pathological stage (pT3a or greater) (46% vs 31%, p <0.04). Whereas young adults had a higher incidence rate of lymph node metastases at presentation (25% vs 15%, p <0.02), the rate of distant metastatic disease at presentation in young (34%) and older (28%) patients did not differ significantly (p = 0.33). Young age was independently associated with a higher 5-year actuarial disease specific survival rate on multivariate analysis at a median followup of 37 months (66% vs 52%, adjusted HR 2.64, 95% CI 1.45 to 4.79, p <0.002). On multivariate analysis of patients without distant metastases at presentation young adults also had improved recurrence-free survival (median time to recurrence 32.4 vs 23.5 months, HR 2.23, 95% CI 1.04 to 4.78, p <0.04). CONCLUSIONS: Young adults with RCC were more likely to have unfavorable histological features and a higher incidence of lymph node metastases than an older cohort of adults. Despite these differences on multivariate analysis young patients had improved disease-specific and recurrence-free survival following treatment. Whether age specific differences in host-tumor interaction exist in patients with RCC deserves further study.

Closed suction or penrose drainage after partial nephrectomy: does it matter?

PURPOSE: Prospective studies in the general surgery literature have shown fewer wound related complications with closed suction drainage than with open passive drainage. Nevertheless, some urologists avoid closed suction drains after partial nephrectomy mainly because of a theoretical increased risk of a prolonged urinary leak or delayed hemorrhage. MATERIALS AND METHODS: We reviewed the records of 184 patients who underwent 197 consecutive partial nephrectomies at our institution. Closed suction or open passive (Penrose) drainage was used based on surgeon preference. Drain type was compared with duration of use and the incidence of relevant complications. RESULTS: A Penrose drain was used in 37.6% (74 of 197) of partial nephrectomies and a closed suction drain was used in 62.4% (123). Clinical characteristics were equivalent between both groups, including age, body mass index, tumor size (mean 3.1 cm), number of renal tumors excised, estimated blood loss and operative time. There was no statistically significant difference in the duration of drainage between the Penrose group (mean 7.1 days) and the closed suction group (7.8 days). While we found variation in the incidence of relevant complications by drain type, none of these differences was statistically significant. Complications included prolonged urinary drainage in 7.6% of cases (8.9% closed suction, 5.4% Penrose), wound infection or perinephric abscess in 3.6% (2.4% closed suction, 5.4% Penrose) and delayed hemorrhage in 1.5% (2.4% closed suction, 0 Penrose). CONCLUSIONS: No statistically significant differences in postoperative morbidity were observed between the use of closed suction or Penrose retroperitoneal drains after partial nephrectomy.