Population-based study of grade progression in patients who harboured Gleason 3 + 3.

PURPOSE: This study aimed to evaluate (1) the time interval between a decision to commence on active surveillance (AS) and grade progression in community practice; (2) factors predicting grade progression in localised prostate cancer (CaP) patients apparently undergoing AS. METHODS: Data from the Prostate Cancer Outcomes Registry-Victoria were used to analyze men with Gleason 3 + 3 CaP or less who had at least one repeat biopsy. Unadjusted and adjusted 5-year Kaplan-Meier survival curves were used to assess the time to grade progression. Both univariate and multivariate analyses for grade progression were performed using Cox proportional hazards. RESULTS: The cohort included 951 men. Overall, 39% of men had Gleason grade reclassified to a higher risk disease state with median of 2.2 years [IQR 1.2-3.7 years]. Men who harboured cT2 disease were 30% more likely to have upgrading compared to men with cT1 disease (adjusted HR: 1.3, 95% CI 1.0-1.6, p = 0.048). Half of the men with cT2 in our cohort had their Gleason grade reclassified within 1.6 years from diagnosis as compared with 2.7 years for the cT1 group. The presence of percentage of core involvement >25.0% and a PSA velocity of >1.01 ng/mL/year remained significant for a higher progression rate. The adjusted HR: 1.6; 95% CI [1.2-2.3], p = 0.004; adjusted HR: 1.6, 95% CI [1.2-2.4], p = 0.021, for percent of core involvement of 25.1-37.5%, and ≥37.6%, respectively. The adjusted HRs and p value associated with PSA velocity were 1.5; 95% CI [1.1-2.1], p = 0.016 and 1.6; 95% CI [1.2-2.3], p = 0.003 for PSA velocity values of 1.01-2 ng/mL per year and >2 ng/mL per year, respectively. Men who were diagnosed in regional hospital and subsequently had biopsy in metropolitan hospital were twice at risk of having Gleason upgrade compared to those whom both diagnostic and surveillance biopsies were carried out in metropolitan hospitals (adjusted HR: 1.9; 95% CI 1.1-3.3, p = 0.029). CONCLUSIONS: When placing men on AS and considering time to histologic progression, clinicians should pay particular attention to the likely accuracy of the diagnostic specimen, their tumour stage, volume of tumour (percent of core involvement), and rising PSA. Those diagnosed with T2 disease and had >25.0% of core involvement, and a PSA velocity greater than 1 ng/mL per year is at particular risk for more rapid disease progression and, for this reason, should be counselled on the importance of following the recommended surveillance regimen. For half of these men, their disease will have 'progressed' according to biopsy results in 2 years.

High Gleason grade carcinoma at a positive surgical margin predicts biochemical failure after radical prostatectomy and may guide adjuvant radiotherapy.

UNLABELLED: Study Type - Prognosis (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Only 30-35% of patients with positive surgical margins after radical prostatectomy develop recurrent disease. Adjuvant radiotherapy reduces the rate of biochemical relapse or metastasis and improves overall survival after radical prostatectomy. Various pathological factors, such as location and extent of positive margins, have been proposed as possible prognostic factors in men with margin-positive prostate cancer, however, the recent International Society of Urological Pathology consensus meeting in Boston noted that there is limited data on the significance of Gleason grade of the carcinoma at a positive margin. The present study shows that the presence of high grade prostate cancer, i.e. Gleason pattern 4 or 5, at a positive surgical margin is an independent predictor of biochemical recurrence after radical prostatectomy. Moreover, patients with lower grade carcinoma at the margin have a similar prognosis to men with negative margins. Hence, assessment of Gleason grade at the site of positive margin may aid optimal selection of patients for adjuvant radiotherapy. OBJECTIVE: • To establish predictors of biochemical recurrence by analysing the pathological characteristics of positive surgical margins (PSMs), including Gleason grade of the carcinoma at the involved margin. PATIENTS AND METHODS: • Clinicopathological and outcome data on 940 patients who underwent radical prostatectomy (RP) between 1997 and 2003 were collected. • Of these, 285 (30.3%) patients with PSMs were identified for pathological review, including assessment of location of margin, linear extent, number of PSMs, plane of margin and Gleason grade (3 vs 4 or 5) at the margin. RESULTS: • At a median follow-up of 82 months, the biochemical recurrence rate of the PSM cohort was 29%. • On univariate analysis, the presence of Gleason grade 4 or 5 at the margin (34.4% of cases) was significantly associated with biochemical recurrence (hazard ratio [HR] 2.80, 95% confidence interval [CI]= 1.82-4.32, P < 0.001) compared with the presence of Gleason grade 3. • Linear extent of margin involvement was also associated with recurrence (P= 0.009). • Single vs multiple margin involvement, location, and plane of the involved margin were not significant predictors of recurrence. • On multivariate analysis, Gleason grade 4 or 5 at the margin remained an independent predictor of recurrence (HR 2.14, 95% CI = 1.29-4.03, P= 0.003). CONCLUSION: • The Gleason grade at the site of a PSM identifies patients at increased risk of biochemical recurrence and should aid stratification of patients for adjuvant radiation therapy.

Super selective radio embolization of the porcine kidney with 90yttrium resin microspheres: a feasibility, safety and dose ranging study.

PURPOSE: We determined whether super selective radio embolization of the porcine kidney was technically feasible and evaluated histopathological changes in the treatment target zone (upper or lower renal pole), adjacent nontargeted kidney, and adjacent and distant organs after administering (90)Y labeled vs bland resin microspheres. MATERIALS AND METHODS: We performed super selective radio embolization with (90)Y resin microspheres in 1 kidney and with an equivalent number of bland microspheres in the corresponding pole of the contralateral kidney as a control. The aim was to achieve radio embolization of a target zone equivalent to approximately a third of the kidney volume. A pathologist independently graded macroscopic and microscopic changes in the kidney, and adjacent and distant tissue resulting from incremental increases (0.15 to 0.35 GBq) in implanted activity in 6 pigs. RESULTS: We recorded grade 4 histological changes in the treatment target zone (upper or lower renal pole) in 5 of 6 pigs after injecting (90)Y resin microspheres with evidence of nephron sparing effects in the adjacent renal tissue at the lowest activity. At activity greater than 0.3 GBq increasing damage was noted to adjacent renal tissue beyond the treatment target zone. No toxicity was evident in adjacent or distant organs. CONCLUSIONS: Delivery of highly targeted intra-arterial radiotherapy to the kidney is feasible and safe in the pig model. Further evaluation is warranted as a potential treatment for advanced renal cell carcinoma or for localized disease in patients who are not candidates for surgery.