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.

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.

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.

Irradiation of donor mononuclear cells for treatment of chemorefractory metastatic solid cancers: a community-based immune transplant pilot study.

PURPOSE: Chemotherapy has demonstrated ability to generate tumor antigens secondary to induction of apoptosis, against which human leukocyte antigen-compatible, irradiated, related donor mononuclear cells may be administered with immune stimulation to activate antigen presenting and cytotoxic T cells, while minimizing risk of graft-versus-host disease (GVHD). The present study endeavours to describe feasibility and efficacy of this treatment, specifically in the community setting. MATERIALS AND METHODS: Eligible patients had rapidly progressive, chemorefractory metastatic solid tumors. Treatment consisted of intravenous etoposide and cyclosporine for three days followed by granulocyte-macrophage colony-stimulating factor for 5 days. The following week, 5×10(7) haploidentical or more closely matched irradiated donor mononuclear cells were given weekly for 10 weeks along with interleukin-2. RESULTS: Three patients were enrolled, and the regimen was well-tolerated, with no GVHD observed. All patients had clinical response, despite advanced and heavily pretreated disease. CONCLUSION: The above-outlined protocol demonstrates favorable tolerability and efficacy, and appears to be feasible in the community setting. While the optimal chemotherapy, immunostimulation, and irradiation regimens may be further optimized, future investigation appears warranted, and may include community oncology programs.