This Month in Adult Urology

Article Outline

• Response of Primary Renal Cell Carcinoma to Neoadjuvant Sunitinib
• Age, Tumor Size and Relative Survival of Patients With Localized Renal Cell Carcinoma
• Prostate Specific Membrane Antigen and Pepsinogen C Tissue Expression
• Prostate Cancer Severity and Low Income, Uninsured Men
• Phase II Study of Prostate Cancer Recurrence During Androgen Deprivation Therapy
• Obesity Related Plasma Hemodilution and Tumor Markers
• Morbidity of Laparoscopic Versus Open Cystectomy for Bladder Cancer
• Pretreatment Semen Parameters in Men With Cancer
• Perceptions and Confidence in Evidence-Based Medicine
• Copyright

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Response of Primary Renal Cell Carcinoma to Neoadjuvant Sunitinib 

Recent advances in chemotherapy for advanced renal cell carcinoma have been made possible by exploiting the molecular mechanisms that are altered in various forms of renal cell carcinoma. One promising area is using agents such as sunitinib which work through antiangiogenic pathways. Thomas et al (page 518) from Cleveland, Ohio report the results of a new adjuvant trial of sunitinib in high risk patients with renal cell carcinoma who were deemed unsuitable for initial nephrectomy due to either locally advanced disease or extensive metastatic burden. Patients were treated with 50 mg sunitinib daily for 4 weeks. In the 25 patients studied mean tumor size was 10.5 cm. Although no patient experienced complete response, partial responses were noted in 16% of patients and 37% had stabilization of disease. Unfortunately, 47% of patients had disease progression of the primary tumor. At a median followup of 6 months 4 patients had undergone nephrectomy for viable tumor. Sunitinib was associated with grade 3–4 toxicity in 37% of patients. This trial demonstrates that sunitinib can lead to a reduction in tumor burden in a select group of patients, allowing subsequent nephrectomy. It is also noteworthy that 42% of patients experienced primary tumor shrinkage. However, the authors warn that investigative biases may have affected determination of tumor resectability.

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Age, Tumor Size and Relative Survival of Patients With Localized Renal Cell Carcinoma 

Age has been suggested as an independent predictor of survival after surgery for renal cell carcinoma. Using the SEER (Surveillance, Epidemiology and End Results) database of more than 8,000 patients, Scoll et al (pages 506) from Philadelphia, Pennsylvania clarified the role of tumor size and age, and found no effect of age on survival for those with small or large tumors. Age was possibly a predictor of lower relative survival for patients with mid sized tumors (4 to 7 cm). Data analysis suggests there was a high survival rate for patients with tumors smaller than 4 cm regardless of age.

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Prostate Specific Membrane Antigen and Pepsinogen C Tissue Expression 

Persistently increased prostate specific antigen (PSA) levels after a negative initial prostate biopsy represent a challenge for urologists and pathologists, and discovery of new diagnostic markers has become an important field of research. Antunes et al (page 594) from Sao Paulo, Brazil tested 6 genes in patients with prostate cancer versus patients with benign prostatic hyperplasia (BPH). Using a quantitative reverse transcription polymerase chain reaction method, malignant tissues from 33 patients were analyzed along with benign tissue samples from 17 patients with cancer and a control group with BPH. Analysis of malignant prostate tissues showed that prostate specific membrane antigen was over expressed by roughly 9 times and pepsinogen C was under expressed by a mean of 1.3 × 10⁻⁴ in all cases compared to BPH. The decreased expression of the pepsinogen C gene offers a potential biomarker to prostate biopsy for prostate cancer diagnosis. This gene encodes for a protein precursor to pepsin in the stomach, and the relation to prostate malignancy is still unknown.

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Prostate Cancer Severity and Low Income, Uninsured Men 

The current debate on access to health care highlights the importance of identifying patient groups who may receive inadequate urological care. Miller et al (page 579) performed a retrospective cohort study of 570 disadvantaged men enrolled in a California public health program from 2001 through 2006. The results were astonishing in that PSA was greater than 10 and Gleason score was 7 or greater in more than half of the men, 43% had clinical stage T2 or greater disease and 19% had metastatic disease at diagnosis. Compared to broader contemporary studies in the United States, the proportion of disadvantaged men with organ confined, low risk prostate cancer has not increased in the last decade. Only a fifth of these men had low risk prostate cancer as defined by the D'Amico risk group classification. The authors note that for uninsured low income men under detection and under treatment of prostate cancer are significant concerns. The majority of these men (79%) self-identified as belonging to a racial or ethnic minority group, including 49% Hispanic and 18% black men. These results reflect a disparity in health care in the United States with regard to prostate cancer diagnosis. Although possible, it is unlikely that these findings can be explained entirely by a different biology in this population.

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Phase II Study of Prostate Cancer Recurrence During Androgen Deprivation Therapy 

In a phase II multi-institutional study Shah et al (page 621) used 3.5 mg dutasteride daily based on the rationale that hormone refractory prostate cancer often expresses increased type I 5α-reductase. In vitro work also suggests a potential effect of dihydrotestosterone on prostate cancer. Dutasteride was administered in addition to luteinizing hormone releasing hormone agonist therapy to 28 patients with castration recurrent prostate cancer. The 25 evaluable men had an average PSA of 62 and Gleason score of 8, and 15 had bone metastases. Disease progressed in 14 men, was stable in 9 and partially responded to therapy in 2. No patient had a complete response. The overall median time to progression was 1.9 months. The authors conclude that dutasteride rarely causes additional biochemical responses in men with castration recurrent prostate cancer.

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Obesity Related Plasma Hemodilution and Tumor Markers 

Previous studies have suggested that an increase in body mass index (BMI) causes a reduction in PSA and it is associated with an increase in plasma volume. In a study by Chang et al (page 567) from Seoul, Republic of Korea every 10 pound weight gain was associated with a 0.024 reduction in PSA. When compared to waist circumference, BMI had a more significant effect. A total of 8,776 men were screened not only for PSA, but for other tumor markers including CEA, AFP and CA19-9. Increase in BMI was associated with hemodilution resulting in an overall decrease in tumor marker concentration. Investigators should consider this phenomenon when obtaining any current or future tumor markers in obese patients.

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Morbidity of Laparoscopic Versus Open Cystectomy for Bladder Cancer 

A prospective randomized study was conducted by Guillotreau et al (page 554) from Toulouse, France comparing morbidity of open (30) vs laparoscopic (38) cystectomy for bladder cancer. Patients were comparable in regard to age, ASA score, and tumor grade and stage. Intraoperative blood loss and transfusion rate were significantly lower in the laparoscopic group. Minor complications and mortality were also significantly lower with laparoscopic surgery, as was the amount and duration of opioid consumption. The authors conclude that laparoscopic surgery for bladder cancer has a significantly lower morbidity than open cystectomy, and a more rapid resumption of oral fluid and solid intake. They did exclude laparoscopic surgery patients whose preoperative disease stage was lower than T3b.

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Pretreatment Semen Parameters in Men With Cancer 

Cryopreservation of semen is often encouraged for men before treatment for malignancies if they anticipate future issues with fertility. However, previous data have suggested an overall reduction in semen quality of specimens donated for cryopreservation. Williams et al (page 736) from Madison, Wisconsin reviewed data of 409 cases from their cryopreservation laboratory during a 5-year period. The majority of men (45%) had testicular cancer, while others had lymphoma, leukemia, gastrointestinal cancers, sarcoma or neurotumors. For men with testicular cancer sperm density and motility were in the intermediate range but for all other malignancies semen parameters were in the fertile range for density and intermediate range for motility. The authors conclude that for most types of cancer pretreatment semen parameters are in the fertile range. Only men with testicular cancer have statistically lower semen quality than donors without cancer. The authors stress the importance of pretreatment cryopreservation for men before receiving gonadotoxic therapy.

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Perceptions and Confidence in Evidence-Based Medicine 

Dahm et al (page 767) from Gainesville, Florida queried a random sample of 2,000 members of the American Urological Association in regard to their confidence in evidence-based medicine. A total of 889 members responded and agreed that every urologist should be familiar with critical appraisal techniques for evidence-based medicine. The AUA guidelines were used regularly by 35% and occasionally by 51% of members. Of the respondents 44% were unaware of the PubMed® search engine and only 14% used it regularly, and 76% were unaware of the Cochrane Database of Systematic Reviews and only 8% had ever used it. The mean evidence-based medicine competence score for all respondents was 67.2%. The authors conclude that although urologists have a favorable attitude toward evidence-based medicine, they have a limited understanding of the terminology, concepts and use of related resources. Increased efforts are needed to promote an understanding of evidence-based medicine through workshops, publications and web based resources.