A population-based analysis of the effect of marital status on overall and cancer-specific mortality in patients with squamous cell carcinoma of the penis.

PURPOSE: The association between marital status and tumor stage and grade, as well as overall mortality (OM) and cancer-specific mortality (CSM) received little attention in patients with squamous cell carcinoma of the penis (SCCP). METHODS: We relied on the surveillance, epidemiology, and end results (SEER) 17 database to identify patients diagnosed with primary SCCP. Logistic and Cox regression models, respectively, addressed the effect of marital status on the rate of locally advanced disease and its effect on OM and CSM. Covariates consisted of age, race, socioeconomic status, year of surgery, and SEER registries. RESULTS: Between 1988 and 2006, 1,884 patients with SCCP were identified. At surgery, 1,192 (63.3 %) were married and 966 (51.3 %) had locally advanced disease. In multivariable logistic regression models predicting locally advanced disease at surgery, unmarried men had a 1.5-fold higher (p < 0.001) risk than others. In multivariable Cox models predicting CSM, marital status had no effect [hazard ratio (HR) = 1.3, p = 0.1]. Finally, in multivariable Cox models predicting OM, unmarried men had a 1.3-fold higher (p = 0.001) risk than others. CONCLUSION: Unmarried men tend to present with less favorable disease stage at SCCP. Moreover, unmarried men tend to live less long than their married counterparts. However, marital status has no effect on CSM.

Competing-risks analysis in patients with T1 squamous cell carcinoma of the penis.

OBJECTIVE: To quantify and compare cancer-specific mortality (CSM) and other-cause mortality (OCM) in individuals with stage T1G1-3 clinically node-negative (cN0) squamous cell carcinoma of the penis (SCCP) since there is no consensus regarding the need for an inguinal lymph node dissection (ILND) in patients with T1G2-3 cN0 SCCP. METHODS: Relying on the Surveillance, Epidemiology and End Results database, we identified 655 patients diagnosed with primary SCCP between 1988 and 2006. Cumulative incidence plots were used to graphically depict the effect of CSM relative to OCM. Competing-risks regression analyses were used to quantify the risk of CSM or OCM after adjusting for age, race, tumour grade and surgery type. RESULTS: The 5-year CSM rates after a primary tumour excision without ILND were 2.6%, 10.0% and 15.9% in patients with respectively T1G1, T1G2 and T1G3 cN0 SCCP. The 5-year OCM rates were 29.5%, 27.3% and 29.3% in patients with respectively T1G1, T1G2 and T1G3. Age failed to provide additional stratification. CONCLUSIONS: The CSM rate was highest in T1G3 patients and appears to justify ILND. Conversely, the CSM rate was lowest in T1G1 patients, which justifies active surveillance in this patient subset. A moderate CSM rate at 5 years was recorded for T1G2 patients, which brings into question the benefits of ILND.

Conditional survival predictions after surgery for patients with penile carcinoma.

BACKGROUND: Conditional survival (CS) implies that, on average, long-term cancer survivors have a better prognosis than newly diagnosed individuals. The objective of the current study was to devise an accurate predictive tool that accounts for CS in men diagnosed with penile cancer. METHODS: Overall, 1245 patients treated with primary tumor excision (PTE) for pT(1-3)M0 squamous cell carcinoma of the penis (SCCP) between 1998 and 2006 were identified. Cox regression models were fitted for prediction of cancer-specific mortality (CSM). Nomogram development for prediction of CSM using CS methodology at 2 and 5 years was performed on 670 patients. External validation and calibration of the conditional nomogram was performed in 575 patients. RESULTS: The 5-year CSM-free survival of patients at surgery was 84.3% and increased to 95.0% and 97.8% after 2 and 5 years of disease-free survival (DFS), respectively. The predicted probabilities varied by as much as 49% (57% vs 85%) when, for example, predictions of CSM-free survival at 5 years were made after PTE versus after 2 years of DFS. Within the external validation cohort, the accuracy of the conditional nomogram was 75.3% and 78.1% at 2 and 5 years after PTE. CONCLUSIONS: The authors developed and externally validated the first conditional nomogram for predicting SCCP CSM-free survival that allows consideration of the length of survivorship.

A contemporary population-based assessment of the rate of lymph node dissection for penile carcinoma.

BACKGROUND: The adherence rate to National Cancer Institute (NCI) recommendations regarding inguinal lymph nodes dissection (ILND) in high grade T1 (G3T1) and T2-4 squamous cell carcinoma of the penis (SCCP) is not known. We assessed ILND rates in a North American cohort. MATERIALS AND METHODS: The 17 registries of the Surveillance, Epidemiology, and End Results (SEER) database included 868 patients with SCCP, diagnosed between 1988 and 2006. Analyses consisted of univariable and multivariable logistic regression models. RESULTS: Overall, 27.6% of patients underwent an ILND. ILND rates were directly proportional with T stage: 19.0%, 30.5%, 30.6%, and 32.6% for, respectively, G3T1, T2, T3, and T4 SCCP (chi-square trend, P = 0.01). ILND rates also increased over time and were 19.3, 27.3, 30.7, and 30.8% for respectively, 1988-1995, 1996-2000, 2001-2003, and 2004-2006 periods (chi-square trend, P = 0.03). Finally, ILND rates decreased with patient age and were 42.6, 33.2, 24.7, and 7.3% for, respectively, patients aged ≤ 57, 58-68, 69-78 and ≥ 79 years of age (chi-square trend, P < 0.001). All 3 variables (T-stage, year of primary tumor excision and patient age) achieved independent predictor status in multivariable analyses. CONCLUSIONS: The overall rate of ILND is low. Nonetheless, there is an upward trend over time. Our data indicate that the adherence to the NCI ILND guidelines is suboptimal. In consequence, ILNDs should be more strongly encouraged.

Tumor grade improves the prognostic ability of American Joint Committee on Cancer stage in patients with penile carcinoma.

PURPOSE: Penile cancer is rare. Thus, predicting cancer specific mortality may be difficult. We devised an accurate and yet easily applicable predictive rule that compares favorably with 2 previous models (73.8% and 74.7% accuracy, respectively). MATERIALS AND METHODS: We identified patients treated with primary tumor excision for all stages of penile squamous cell carcinoma between 1998 and 2006. Disease stage definitions using Surveillance, Epidemiology and End Results stage, American Joint Committee on Cancer stage and TNM classification, and tumor grade were used to predict cancer specific mortality. Predictive accuracy estimates were compared using the DeLong method for related AUCs. RESULTS: Surveillance, Epidemiology and End Results stage alone (1 predictor variable) was least accurate (74.5%). American Joint Committee on Cancer stage with tumor grade (2 predictor variables) was the most simple and most accurate (80.9%, p <0.001). A benefit similar to that of American Joint Committee on Cancer stage with tumor grade was seen for TNM classification and TG (80.7%, p = 0.8). However, this rule (4 predictor variables) was more complex than American Joint Committee on Cancer stage and tumor grade. CONCLUSIONS: American Joint Committee on Cancer stage combined with tumor grade is the simplest, most accurate cancer specific mortality prediction rule after primary tumor excision for penile squamous cell carcinoma. This method is also more accurate than 2 previous cancer specific mortality prediction rules.

[Long-term morbidity of living donor kidney harvesting]. / Prélèvement rénal chez le donneur vivant: morbidité et suivi à long terme.

OBJECTIVE: To evaluate the morbidity of living donor kidney harvesting and the long-term medical consequences and impact on quality of life (QoL). MATERIAL AND METHODS: Retrospective analysis of medical and surgical data for 114 living kidney donors in a single teaching hospital between 1977 and 2005. Complications were evaluated in relation to the surgical approach and body mass index (BMI) using a Chi-square test or Fisher's exact test. Changes in renal function (serum creatinine, creatinine clearance), proteinuria and blood pressure (BP) were studied by Student's t test or a Mann-Whitney U or Wilcoxon nonparametric test. Long-term QoL was evaluated by the MOS SF-36 questionnaire and a local questionnaire and was then compared to that of the French general population. RESULTS: The median follow-up was 63 months. The morbidity of kidney harvesting was significantly correlated with the surgical approach (p = 0.018) and a BMI > or = 25 kg/m2 (p = 0.014). No mortality was observed in this series. A moderate elevation of serum creatinine was observed during follow-up (mean serum creatinine increased from 82.2 micromol/l [+/- 16.3] to 104.5 micromol/l [+/- 19.9]), and mean creatinine clearance decreased from 113.4 ml/min [+/- 27.6] to 76 ml/min [+/- 29.9]. Little impact was observed on proteinuria and BP and QoL was not altered by kidney harvesting. CONCLUSION: The perioperative complication rate is correlated with BMI and a flank incision. Kidney harvesting lowers glomerular filtration, but clearance remained stable during follow-up. Macroalbuminuria or hypertension may be observed, but their frequency is not higher than in the general population. The QoL of living donors is not altered. Clear information for the general public would allow promotion of living donor transplantation.

Activating mutations of Gsalpha in kidney cancer.

PURPOSE: Heterotrimeric G proteins are signal transduction proteins coupled to hormone receptors that activate intracellular second messenger systems, mainly cyclic adenosine monophosphate mediated protein kinase. Recent studies indicate that G proteins may have a major role in oncogenesis as well as in tumor invasiveness and cell proliferation. The involvement of G proteins was formerly thought to be limited to hormonal signal transduction. Activating Gsalpha mutations have been reported in tumors arising only from highly specialized endocrine tissue, such as pituitary adenomas, toxic thyroid adenomas and differentiated thyroid carcinomas, but never in other nonendocrine tumors. We hypothesized that a constitutive activation of this pathway, that is activated Gsalpha and inhibited Gialpha, could be implicated in kidney cancers. We searched for alterations on the Gsalpha gene GNAS and the Gialpha gene in renal cell carcinoma. MATERIALS AND METHODS: Using nested polymerase chain reaction, enzyme digestions, laser microdissection and direct sequencing we looked for activating mutations on GNAS codons 201 and 227, and inhibiting mutations on the Gialpha gene in 30 consecutive patients with clear cell renal cell carcinoma between January 2003 and January 2004. RESULTS: Somatic (tumor specific) activating mutations of Gsalpha were present in a significant proportion of human clear cell renal cell carcinomas. Activating mutations were identified in 5 of the 30 patient DNA preparations (16.6%) with a substitution of arginine 201 by cysteine in 3 and histidine in 2. CONCLUSIONS: These findings suggest the implication of this pathway in human oncogenesis. It may provide a potential therapeutic approach to these frequent and aggressive tumors.