Pathological findings at radical prostatectomy in patients initially managed by active surveillance: a comparative analysis.

BACKGROUND: The purpose of our analysis was to determine if delays in treatment caused by active surveillance result in significant pathological changes when patients no longer meet the criteria on repeat biopsy and to study whether or not these changes may affect treatment outcomes. METHODS: Out of 207 men who were on active surveillance, 47 (23%) no longer met the criteria after one of the repeat biopsies. Twenty-two underwent radical prostatectomy at our institution and formed the main group (Group 1) of this study. One hundred sixty-four patients met the criteria for active surveillance but underwent immediate surgery. Of these patients, we selected 38 (23%) with the lowest predicted biochemical recurrence-free survival. These patients formed the comparison group (Group 2). Pathological features as well as postoperative biochemical outcomes were compared between the groups. RESULTS: Seven patients (32%) in Group 1 and four (11%) in Group 2 have predominantly high-grade cancer (i.e., ≥4/5 + 3) at pathology. The visually estimated percent of carcinoma was also higher in patients initially managed by active surveillance (median 12.5 vs. 5.0 in Groups 1 and 2, respectively, P = 0.009). Other pathological characteristics were similar in both groups. With limited duration of follow-up, postoperative biochemical recurrence-free survival did not differ significantly between the groups. CONCLUSIONS: Our study has demonstrated that both tumor grade and volume may increase during active surveillance. However, the clinical significance of these changes with respect to the outcomes of delayed treatment remains to be established.

Tumor focality is not associated with biochemical outcome after radical prostatectomy.

BACKGROUND: The clinical and prognostic significance of unifocal prostatic carcinoma is not clearly understood. In the current study, we sought to characterize the clinical and pathologic characteristics of unifocal and multifocal prostate cancers and to investigate the effects of tumor focality on biochemical outcome after radical prostatectomy. METHODS: Our analysis included 1,444 radical prostatectomy patients with available information concerning the number and location of tumor foci in the specimen. Each patient was assigned to one of three groups depending on whether they had unifocal, multifocal, or extensive cancer. Clinical and pathological features as well as biochemical outcomes were compared between the groups. RESULTS: Two hundred and seventy-two mens in the study cohort (18.8%) had unifocal cancer. The rates of unifocal cancer did not differ significantly between the three studied time intervals (17.3% in 1992-1998, 20.5% in 1999-2004, and 17.8% in 2005-2011). The number of positive biopsy cores was slightly lower in the unifocal group, while the overall amount of biopsy tissue containing cancer was similar in both groups. The patients in the multifocal group had higher pathologic Gleason scores, increased incidence of positive surgical margin, and larger tumors. The rate of clinically significant Gleason score upgrade was significantly higher in the multifocal group compared to the unifocal group (35.7% vs. 21.7%, respectively, P < 0.001). The biochemical outcome after radical prostatectomy did not differ between patients with unifocal and multifocal cancers both on univariate and multivariate analyses. CONCLUSIONS: Tumor focality is not an independent prognostic factor of biochemical outcome in radical prostatectomy patients.

Association of hyaluronic acid family members (HAS1, HAS2, and HYAL-1) with bladder cancer diagnosis and prognosis.

BACKGROUND: Cancer biomarkers are the backbone for the implementation of individualized approaches to bladder cancer (BCa). Hyaluronic acid (HA) and all 7 members of the HA family, that is, HA synthases (HA1, HA2, HA3), HYAL-1 hyaluronidase, and HA receptors (CD44s, CD44v, and RHAMM), function in tumor growth and progression. However, the diagnostic and prognostic potential of these 7 HA family members has not been compared simultaneously in any cancer. We evaluated the diagnostic and prognostic potential of HA family members in BCa. METHODS: Using quantitative PCR and immunohistochemistry, expression of HA family members was evaluated in prospectively collected bladder tissues (n = 72); mean and median follow-up were 29.6 ± 5.3 and 24 months, respectively. Transcript levels were also measured in exfoliated urothelial cells from urine specimens (n = 148). RESULTS: Among the HA family members, transcript levels of the HA synthases, HYAL-1, CD44v, and RHAMM were 4- to 16-fold higher in BCa tissues than in normal tissues (P < .0001); however, CD44s levels were lower. In univariate and multivariate analyses, tumor stage (P = .003), lymph node invasion (P = .033), HYAL-1 (P = .019), and HAS1 (P = .027) transcript levels, and HYAL-1 staining (P = .021) were independently associated with metastasis. Tumor stage (P = .019) and HYAL-1 (P = .046) transcript levels were also associated with disease-specific mortality. Although HA synthase and HYAL-1 transcript levels were elevated in exfoliated urothelial cells from BCa patients, the combined HAS2-HYAL-1 expression detected BCa with an overall sensitivity of 85.4% and a specificity of 79.5% and predicted BCa recurrence within 6 months (P = .004; RR = 6.7). CONCLUSIONS: HYAL-1 and HAS1 expression predicted BCa metastasis, and HYAL-1 expression also predicted disease-specific survival. Furthermore, the combined HAS2-HYAL-1 biomarker detected BCa and significantly predicted its recurrence.

Anomalies of the inferior vena cava and renal veins and implications for renal surgery.

Abnormalities of the inferior vena cava (IVC) and renal veins are extremely rare. However, with the increasing use of computed tomography (CT), these anomalies are more frequently diagnosed. The majority of venous anomalies are asymptomatic and they include left sided IVC, duplicated IVC, absent IVC as well as retro-aortic and circumaortic renal veins. The embryological development of the IVC is complex and involves the development and regression of three sets of paired veins. During renal surgery, undiagnosed venous anomalies may lead to major complications. There may be significant hemorrhage or damage to vascular structures. In addition, aberrant vessels may be mistaken for lymphadenopathy and may be biopsied. In this review we discuss the embryology of the IVC and the possible anomalies of IVC and its tributaries paying particular attention to diagnosis and implications for renal surgery.

Careful selection and close monitoring of low-risk prostate cancer patients on active surveillance minimizes the need for treatment.

BACKGROUND: With the advent of prostate-specific antigen (PSA) screening and the increase in the number of transrectal ultrasound-guided biopsy cores, there has been a dramatic rise in the incidence of low-risk prostate cancer (LRPC). Because > 97% of men with LRPC are likely to die of something other than prostate cancer, it is critical that patients give thought to whether early curative treatment is the only option at diagnosis. OBJECTIVE: To identify a group of men with LRPC who may not require initial treatment and monitor them on our active surveillance (AS) protocol, to determine the percentage treated and the outcome and to analyze the quality-of-life data. DESIGN, SETTING, AND PARTICIPANTS: We defined patients eligible for AS as Gleason ≤ 6, PSA ≤ 10, and two or fewer biopsy cores with ≤ 20% tumor in each core. MEASUREMENTS: Kaplan Meier analysis was used to predict the 5-year treatment free survival. Logistic regression determined the predictors of treatment. Data on sexual function, continence, and outcome were obtained and analyzed. RESULTS AND LIMITATIONS: The AS cohort consisted of 230 patients with a mean age of 63.4 yr; 86% remained on AS for a mean follow-up of 44 mo. Thirty-two of the 230 patients (14%) were treated for a mean follow-up of 33 mo. Twelve had a total prostatectomy (TP). The pathologic stage of these patients was similar to initially treated TP patients with LRPC. Fourteen underwent radiation therapy, and six underwent androgen-deprivation therapy. Fifty percent of patients had no tumor on the first rebiopsy, and only 5% of these patients were subsequently treated. PSA doubling time and clinical stage were not predictors of treatment. No patient progressed after treatment. Among the AS patients, 30% had incontinence, yet < 15% were bothered by it. As measured by the Sexual Health Inventory for Men, 49% of patients had, at a minimum, moderate (≤ 16) erectile dysfunction. CONCLUSIONS: If guidelines for AS are narrowly defined to include only patients with Gleason 6, tumor volume ≤ 20% in one or two biopsy cores, and PSA levels ≤ 10, few patients are likely to require treatment. Progression-free survival of those treated is likely to be equivalent to patients with similar clinical findings treated at diagnosis.