Tarek A. Dufan

The dosimetric quality of brachytherapy implants in patients with small prostate volume depends on the experience of the brachytherapy team

PURPOSE To investigate the dosimetric outcome of brachytherapy in patients with small prostate volume (PV). METHODS AND MATERIALS Forty-three patients with small PV (<25 cm(3)) as determined using transrectal ultrasound and 120 patients with non-small PV (>25 cm(3)) that had received (125)I seed implants were reviewed in a retrospective cohort study. Implantations were performed under transrectal ultrasound guidance, and the prescription dose was 145 Gy. A CT and MRI scan of the pelvis were performed 1 month after implantation for dosimetric study. RESULTS Compared with non-small PV patients, patients with small PV experienced larger 1-month edema (p<0.001); lower dose to 90% (the isodose enclosing 90% of PV and representing a minimum dose to that volume of the prostate [D(90)]) of the prostate (p=0.03); higher intracapsular seed density (p<0.001); and were less likely to achieve D(90)>or=140 Gy (p=0.013) in a postimplant dosimetric study. The number of patients with D(90)<140 Gy decreased steadily in both subsets of patients as the implant program matured (odds ratio=0.56 per year, p<0.001), but the small prostate group exhibited more improvement compared with the non-small prostate patients over the same time period. Multivariate analysis revealed that brachytherapy team experience rather than the size of prostate was a more important predictive factor of implant quality (p<0.001). CONCLUSIONS This single institution experience demonstrated a significant learning curve in the initial years of a prostate brachytherapy program, especially for patients with small prostates. A small prostate itself is not a contraindication of brachytherapy. The quality of implant for patients with small prostates depends more on the skill of the brachytherapy team.

Margin involvement at prostatectomy for clinically localized prostate cancer: Does a low-risk group exist?

PURPOSE To determine whether additional pathology details may provide risk stratification for patients with involved surgical margins at radical prostatectomy (RP). METHODS AND MATERIALS Eligible patients underwent RP between 2003 and 2010. Patients with preoperative prostate-specific antigen (PSA) ≥20, follow-up <12 months, lymph node or seminal vesicle involvement, or who received radiation therapy or hormone therapy prior to PSA relapse were excluded. Surgical specimens were reviewed by a study pathologist, blinded to outcomes. Survival analysis methods were employed to assess disease control and survival rates, as well as association of patient-, tumor-, and treatment-specific factors for endpoints. RESULTS Of 355 RP cases, 279 patients were eligible for the present analysis. At a median follow-up of 53 months (range, 16-127), 31/114 (27%) of patients with involved surgical margins experienced PSA relapse, as compared with 7/165 (4%) for negative margins (hazard ratio, 4.997; 95% confidence interval, 2.425-10.296; P < .0001). Detailed pathology review demonstrated associations between PSA relapse and Gleason score at RP, extent of margin involvement (width), capsule penetration, and perineural invasion. Subgroup analysis identified low risk (4%) of 5-year PSA relapse for patients with Gleason ≤6 mm and margin width ≤4 mm (single maximal or cumulative). All subgroups with higher Gleason score or wider margin were associated with >20% risk of PSA relapse at 5 years. CONCLUSIONS Within the present study, Gleason score, 6 patients with margin width ≤4 mm appear to have low rates of early PSA relapse following RP. Low-grade cases with larger extent of margin involvement or higher risk Gleason score patients with any margin involvement have high rates of early PSA relapse.

Margin details matter: The prognostic significance of pseudocapsule invasion at the site of involved margin in prostatectomy specimens.

BACKGROUND An involved surgical margin at prostatectomy has long been associated with elevated risk of prostate cancer recurrence; however, not all patients with an involved margin will relapse, and thus details of the involved margin may provide an opportunity for risk subset stratification. The present investigation seeks to determine whether a difference exists in recurrence rates when the margin involvement is at a site of prostate pseudocapsule invasion vs. within the prostate parenchyma proper. METHODS Patients were retrospectively identified for inclusion by clinically localized disease and prostate-specific antigen (PSA) level of< 30 ng/ml at diagnosis, managed with prostatectomy alone and identified to have involvement of surgical margin(s). Exclusion criteria were: pT3b or pN1 disease, immediate/nonsalvage postoperative radiation or hormone therapy, or insufficient follow-up (<12 mo). Pathology slides were reviewed by a pathologist blinded to outcome, for determination of pseudocapsule invasion at a site of margin involvement. Disease recurrence was defined as PSA level of ≥ 0.2 ng/ml and rising, per contemporary guidelines. Kaplan-Meier method was used for construction of disease control estimate confidence intervals; Cox Proportional Hazards Model was used to compare disease control across groups. RESULTS Between 2003 and 2010, 155 patients were identified for inclusion in the present study. The median age was 61 years, and all had clinical stage T1 and T2 disease (75% T1c). At diagnosis, the Gleason score was 6, 7, and 8-9 for 103 (66%), 42 (27%), and 10 (6%) patients, respectively, with median PSA level of 5.6 ng/ml (85%≤ 10). For 149 patients with reviewable margin site data, 51 (34%) demonstrated involvement within or beyond the pseudocapsule. At a median follow-up of 68 months (range: 13-137), 62 patients had experienced PSA relapse. The estimated 5-year PSA relapse rates for patients with an involved margin at the site of pseudocapsule invasion vs. prostate parenchyma were 49% vs. 34%, respectively (P = 0.017; hazard ratio = 1.853). CONCLUSIONS Early PSA relapse rates are high for patients with involved surgical margin(s) without seminal vesicle or node involvement at prostatectomy; however, for patients who are followed without immediate adjuvant therapy, presence of tumor cells at the margin in a site of pseudocapsule invasion or penetration confers a higher risk of recurrence.

Do margin details matter? The prognostic significance of capsule invasion at the site of involved margin in prostatectomy specimens.

131 Background: An involved surgical margin at prostatectomy has long been associated with elevated risk of prostate cancer recurrence; however, not all patients with an involved margin will relapse, and thus details of the involved margin may provide an opportunity for risk subset stratification. The present investigation seeks to determine whether a difference exists in recurrence rates when the margin involvement is at a site of prostate capsule invasion versus within the prostate parenchyma proper. Methods: Patients were retrospectively identified for inclusion by clinically localized disease and PSA <30 at diagnosis, managed with prostatectomy alone and identified to have involvement of surgical margin(s). Exclusion criteria were: pT3b or pN1 disease, immediate/non-salvage post-operative radiation or hormone therapy, or insufficient follow-up (<12 months). Pathology slides were reviewed by a pathologist blinded to outcome, for determination of capsule invasion at a site of margin involvement. Disease...

What is the optimal management of Gleason score 7 prostate cancer at biopsy? A comparison of disease control for prostatectomy versus radiotherapy.

OBJECTIVES To compare outcomes between radical prostatectomy (RP) or radiotherapy (RT) approaches for Gleason 7 (GS7) prostate cancer. METHODS Patients were retrospectively identified for inclusion by clinically localized disease, GS7, prostate-specific antigen (PSA) < 30 ng/mL at diagnosis, and follow-up with PSA at > 12 months. Comparison of demographic, tumor, staging, and outcome variables was performed. Disease recurrence was defined as per contemporary society guidelines. The Kaplan-Meier method was used for disease control estimates. RESULTS Between 2003 and 2010, a total of 253 patients were diagnosed with GS7 prostate cancer, of whom 207 were eligible for the current analysis (120 RP, 87 RT). Excepting older age for RT patients (median 73 vs. 62 years), the groups were well balanced. For RP patients, 82 patients (60%) had at least 1 high-risk feature, 4 (5%) of whom received adjuvant RT. For RT patients, 71 patients (82%) received hormone therapy (median duration 6 months). At a median follow-up of 62.2 months (range 13.1-136.6 months, with no difference between treatment groups), 64 patients had PSA relapse (51 RP, 13 RT), and 15 had died (5 of or with disease). PSA relapse-free survival was inferior for RP versus RT (P < .0001), with 5-year rates of 55.4% versus 82.6%, respectively. CONCLUSION For GS7 prostate cancer patients, RT is associated with superior disease-free survival at 5 years compared to RP alone, without difference in disease-specific survival. Whether this difference remains in the setting of appropriately used adjuvant RT after RP, and the effect of possible delay in testosterone recovery for older RT patients remain to be determined.