Long-term outcome comparison for standard fractionation (>59 Gy) versus hyperfractionated (>45 Gy) radiotherapy plus concurrent chemotherapy for limited-stage small-cell lung cancer.

BACKGROUND: Concurrent chemoradiotherapy (CCRT) is commonly employed in limited-stage small-cell lung cancer (LS-SCLC); however, the optimal radiotherapy regimen is still unknown. This 3-institution analysis compares long-term disease control and survival outcomes for once- (QD) versus twice-daily (BID) radiotherapy at contemporary doses. METHODS AND MATERIALS: Data were collected for LS-SCLC patients treated with platinum-based CCRT and planned RT doses of >5940 cGy at >180 cGy QD or >4500 cGy at 150 cGy BID. Comparative outcome analyses were performed for treatment groups. RESULTS: From 2005 through 2014, 132 patients met inclusion criteria for analysis (80 QD, 52 BID). Treatment groups were well-balanced, excepting higher rate of advanced mediastinal staging, longer interval from biopsy to treatment initiation, and lower rate of prophylactic cranial irradiation for the QD group, as well as institutional practice variation. At median survivor follow-up of 33.5 months (range, 4.6-105.8), 80 patients experienced disease failure (44 QD, 36 BID), and 106 died (62 QD, 44 BID). No differences in disease control or survival were demonstrated between treatment groups. CONCLUSION: The present analysis did not detect a difference in disease control or survival outcomes for contemporary dose QD versus BID CCRT in LS-SCLC.

An exploratory study of the relation of population density and agricultural activity to hematologic malignancies in North Dakota.

INTRODUCTION: Established risk factors for hematologic cancers include exposure to ionizing radiation, organic solvents, and genetic mutation; however, the potential roles of environmental and sociological factors are not well explored. As North Dakota engages in significant agricultural activity, the present investigation seeks to determine whether an association exists between the incidence of hematologic cancers and either population density or agricultural occupation for residents of south central North Dakota. METHODS: The present study is a retrospective analysis. Cases of hematologic malignancies and associated pre-malignant conditions were collected from the regional Central North Dakota Cancer Registry, and analysis of study-specific demographic factors was performed. RESULTS: Significantly higher incidence of hematologic cancers and pre-malignant disorders was associated with residence in an "urban" county and rural city/town. Within the latter designation, there was a higher rate of self-reported agricultural occupation (40% vs 10%, P < 0.0001). CONCLUSIONS: The increased incidence of hematologic cancer in low population density areas of south central North Dakota supports the need for more detailed prospective research centered on agricultural exposures.

Toxicity, response rates and survival outcomes of induction cisplatin and irinotecan followed by concurrent cisplatin, irinotecan and radiotherapy for locally advanced esophageal cancer.

OBJECTIVE: Cisplatin-based chemoradiotherapy is standard treatment for locally advanced esophageal and gastroesophageal cancers; however, the optimal chemotherapy regimen remains to be defined. METHODS: Retrospective single institution analysis of toxicities, response rates and survival outcomes in patients with cT3-4 or N1/M1a esophageal squamous cell or adenocarcinoma treated with induction cisplatin and irinotecan followed by concurrent cisplatin, irinotecan and radiotherapy. Secondary analysis for association of disease control and outcomes with demographic, tumor and treatment factors (including histology). RESULTS: Fifty-three patients were eligible for the present analysis. All patients underwent endoscopic ultrasonography and were either cT3-4 and/or cN1 disease. Fifty patients completed radiotherapy as planned (median dose 50.4 Gy, range 0-61.2), and 35 patients completed four cycles of chemotherapy as planned (range 1-4). Severe acute toxicities included Grade ≥ 3 neutropenia and esophagitis in 13 and 12 patients, respectively. There were no Grade 5 (fatal) toxicities noted. At mean survivor follow-up of 24.5 months (range 2.7-63), 17 patients were alive (8 without disease) and 36 deceased. Forty patients experienced disease recurrence, with initial loco-regional, distant or both failures in 28, 9 and 3 patients, respectively. Estimated 2-year overall survival and freedom from failure were 42 and 9%, respectively, without significant difference by histology. CONCLUSIONS: Cisplatin/irinotecan chemoradiotherapy is tolerable, demonstrating similar efficacy for squamous cell and adenocarcinoma esophageal cancers.

A Recursive Partitioning Analysis Demonstrating Risk Subsets for 8-Year Biochemical Relapse After Margin-Positive Radical Prostatectomy Without Adjuvant Hormone or Radiation Therapy.

PURPOSE: The cohort of patients with locally advanced prostate cancer (PC) and positive surgical margin(s) at radical prostatectomy (RP) who would benefit from salvage or adjuvant treatment is unclear. This study examines the risk of prostate-specific antigen (PSA) relapse in a large population of men with PC after margin-positive RP. METHODS AND MATERIALS: Using a multi-institutional database, patients with clinically localized PC who underwent RP between 2002 and 2010 with recorded follow-up PSA were retrospectively selected. Patients were excluded for pathologic seminal vesicle or lymph node involvement, metastatic disease, pre-RP PSA ≥ 30, or adjuvant (nonsalvage) radiation therapy or hormone therapy. The primary endpoint was biochemical relapse free survival (bRFS), where PSA failure was defined as PSA > 0.10 ng/mL and rising, or at salvage intervention. The Kaplan-Meier method was employed for bRFS estimates; recursive partitioning analysis using cumulative or single maximal margin extent (ME) and Gleason grade (GG) at RP was applied to identify variables associated with bRFS. RESULTS: At median follow-up of 105 months, 210 patients with positive margins at RP were eligible for analysis, and 89 had experienced PSA relapse. Median age was 61 years (range, 43-76), and median pre-RP PSA 5.8 ng/mL (1.6-26.0). Recursive partitioning analysis yielded 5 discrete risk groups, with the lowest risk group (GG1, ≤ 2 mm ME) demonstrating a bRFS of 92% at 8 years compared with the highest risk group (GG3-5, ≥ 3 mm ME) of 11%. CONCLUSIONS: This retrospective study suggests that it may be possible to risk-stratify patients undergoing margin-positive RP using commonly acquired clinical and pathologic variables. Patients with low-grade tumors and minimally involved margins have a very low recurrence risk and may be able to forego postprostatectomy radiation. Meanwhile, those with higher grade and greater involvement could benefit from adjuvant or early salvage radiation therapy.

High-dose radiotherapy to 78 Gy with or without temozolomide for high grade gliomas.

OBJECTIVES: To describe outcomes associated with high-dose radiotherapy with and without temozolomide for high grade central nervous system (CNS) neoplasms. METHODS: Retrospective chart review of 60 patients diagnosed with malignant glioma treated with > or =70 Gy radiotherapy. RESULTS: Median age at diagnosis was 52 years, and 52 patients had astrocytomas (38 glioblastomas). Median prescribed radiotherapy dose was 78 Gy (range 70-80), and 29 patients received concurrent temozolomide. Eighty-six percent completed the planned course treatment. Three patients experienced RTOG grade 3 acute CNS toxicity; late brain necrosis was suspected in four patients. Overall median survival was 13 months (range 2-83). Within glioblastoma patients, temozolomide provided a statistically significant survival improvement over no chemotherapy (median survival 12.7 vs. 7.5 months; P = 0.0058). CONCLUSIONS: High dose conformal radiotherapy to > or =70 Gy with chemotherapy for high-grade CNS neoplasms appears safe but survival remains suboptimal. Within glioblastoma patients, temozolomide provided statistically significant survival improvement over no chemotherapy.

Is More Always Better? An Assessment of the Impact of Lymph Node Yield on Outcome for Clinically Localized Prostate Cancer with Low/Intermediate Risk Pathology (pT2-3a/pN0) Managed with Prostatectomy Alone.

The clinical impact of lymph node dissection extent remains undetermined in the contemporary setting, as reflected in care pattern variations. Despite some series demonstrating a direct relationship between number of lymph nodes identified and detection of nodal involvement, the correlation between lymph node yield and disease control or survival outcomes remains unclear. Patients with clinically localized prostate cancer, pre-RP PSA <30, and pT2-3a/N0 disease at RP were retrospectively identified from two databases for inclusion. Those who received pre- or post-RP radiotherapy or hormone therapy were excluded. Kaplan-Meier method was employed for survival probability estimation. Cox regression models were used to assess bRFS differences between subsets. From 2002 to 2010, 667 eligible patients were identified. The median age was 61 yrs. (range, 43-76), with median PSA 5.6 ng/dL (0.9-28.0). At RP, most patients had pT2c (64%) disease with Gleason Score (GS) ≤6 (43%) or 7 (48%); 218 (33%) patients had positive margins (M+). At median clinical and PSA follow-up of 96 and 87 months, respectively, 146 patients (22%) experienced PSA failure with an estimated bRFS of 81%/76% at 5/8 years. For patients who underwent LND, univariable analysis identified PSA (at diagnosis), higher GS (≥7, at biopsy or RP), intermediate/high risk stratification, M+ as adversely associated with bRFS (all p < 0.01). A higher number of LNs excised was not associated with improved bRFS for the entire cohort (HR = 0.97, p = 0.27), nor for any clinical risk stratum, biopsy GS, or RP GS subgroup. This study did not demonstrate an association between LN yield and bRFS in patients with clinically localized pT2-3a/pN0 prostate cancer managed with RP alone, either in the entire population or with substratification by clinical risk stratum or GS.

Comparing high-dose cisplatin with cisplatin-based combination chemotherapy in definitive concurrent chemoradiation setting for locally advanced head and neck squamous cell carcinoma (LAHNSCC).

BACKGROUND: High-dose cisplatin (Cis) is a preferred systemic agent for concurrent chemoradiation (CRT) in locally advanced head and neck squamous cell cancer (LAHNSCC) patients. As some patients are unable to tolerate Cis, this study compares the toxicity and efficacy of weekly cisplatin-paclitaxel (CP) regimen with Cis. METHODS: Patients with LAHNSCC receiving definitive chemoradiation either with Cis (Cisplatin-100 mg/m2 q3w x 3) or CP (Cisplatin-20 mg/m2 ; Paclitaxel-30 mg/m2 qw x7) were included. RESULTS: Cis and CP groups were comprised of 114 and 111 subjects, respectively. Complete response for Cis versus CP groups was 88% versus 88%, respectively. Median follow-up for the study was 58.5 months. After adjusting for potential treatment selection bias, no significant differences were evident between Cis and CP groups for overall survival (hazard ratios [HR] 0.85, 95% CI 0.59-1.21, P = 0.36), progression free survival (HR 0.88, 95% CI 0.62-1.24, P = 0.46), locoregional control (HR 0.77, 95% CI 0.52-1.15, P = 0.21), and distant control (HR 0.87, 95% CI 0.61-1.23, P = 0.42). Patients in the CP group had less acute and chronic toxicities. CONCLUSIONS: Weekly CP regimen can serve as an alternative systemic therapy with radiation in patients with LAHNSCC who are not fit for Cis.

A case of orbital Rosai-Dorfman disease responding to radiotherapy.

Rosai-Dorfman disease (RDD) is a rare histiocytic disorder most often characterized by painless cervical lymphadenopathy, but it may also present with orbital disease. The clinical course of RDD is variable; it can be either relapsing-remitting or progressive, and the outcome relates to clinical location and treatment response. Orbital RDD can have an insidious onset and similar presentation to other ophthalmic conditions; this can result in a delayed diagnosis. Nearly all cases of orbital RDD cause visual disturbances and require treatment. Because orbital RDD is an uncommon presentation, a variety of interventions have been employed, including surgery, immunotherapy, chemotherapy, and radiotherapy. We present a case of salvage radiotherapy for progressive orbital RDD refractory to surgery and chemotherapy in a pediatric patient.

Incidence and prognostic factors for seroma development after MammoSite breast brachytherapy.

PURPOSE: Describe the incidence and identify risk factors for seroma development after MammoSite breast brachytherapy (MBT). METHODS AND MATERIALS: MBT patient data were prospectively recorded into a quality assurance database. Departmental and electronic records were reviewed to extract patient-, treatment-, and outcome-specific data. Stepwise logistic regression analysis was performed to identify factors associated with development of any seroma including the subset of clinically significant seroma (CSS). CSS was defined as a symptomatic seroma requiring multiple aspirations, biopsy, and/or excision. Variables analyzed included age, weight, number of excisions, time from resection to catheter placement, placement technique, balloon volume, dosimetric factors, and postbrachytherapy infection. RESULTS: MBT was performed in 109 patients, of whom 97 had minimum 6 months (median, 36) post-MBT follow-up or earlier development of seroma. All patients received 34 Gy to 1cm depth from balloon surface, delivered twice daily in 10 fractions. Seroma developed in 41% of patients at a median of 3 months (range, 0.1-25) post-MBT. One-third of seromas (13% of all patients) were CSS. The only factor identified as statistically significant for development of any seroma was catheter placement on day of resection vs. > or =1 day later (59% vs. 33%; p = 0.0066). Post-MBT infection was highly statistically significant for development of CSS (64% vs. 7%; p<0.0001). Prophylactic antibiotics reduced the risk of post-MBT infection from 37.5% to 6% (p = 0.011). CONCLUSIONS: The incidence of CSS after MBT is low. Post-MBT infection is statistically significantly associated with CSS development, the incidence of which is reduced with prophylactic antibiotics.

Radiation therapy for palliation of Eisenmenger's syndrome-associated painful splenomegaly.

Painful splenomegaly has a clinical presentation that is often associated with myeloproliferative disorders, such as acute or chronic lymphoblastic or myelogenous leukemia. In these situations low-dose radiotherapy is effective in reducing the splenomegaly and relieving pain. The potential benefit of radiotherapy for cardiogenic splenomegaly is less well established. The present report discusses a case in which radiotherapy was employed to benefit a patient with Eisenmenger's-associated painful splenomegaly. Because of the patient's high anesthesia risk, palliative surgical splenectomy was not feasible. The patient underwent three-dimensional conformal treatment planning, and a total of 42.5 Gy at 2.5 Gy per fraction was prescribed to the spleen. At 4 months following radiotherapy completion, the patient reported durable pain relief and no untoward small bowel effects; moreover, there was a 43% reduction in splenic volume on follow-up CT. Although there have been previous reports of hematological and myeloproliferative-associated splenomegaly that have been treated with a lower dose per fraction and lower total dose radiotherapy, we advocate the use of 2.0-2.5 Gy per fraction to a total dose approaching 40 Gy for adequate duration of response when treating cardiogenic-associated painful splenomegaly in patients for whom surgical splenectomy cannot be performed.

Helical tomotherapy for total lymphoid irradiation.

Total lymphoid irradiation is employed in the preparative regimens for allogeneic bone marrow and solid organ transplantation, solid organ transplant rejection, and chronic graft-versus-host disease. Linear accelerator-based radiotherapy, typically involving opposed anteroposterior and posteroanterior beams, has been commonly used; however, extended source-to-skin patient setup and/or field matching are required, and all organs within the beam coverage receive the entire prescribed dose. Megavoltage helical tomotherapy represents a technological advance in terms of both treatment delivery and patient positioning. The continuously rotating multileaf collimated fan beam allows highly conformal coverage of complex target geometries, in turn allowing avoidance of radiosensitive adjacent organs. In addition, the megavoltage computed tomographic scans allow potentially more accurate, targetbased setup verification. The present case report describes tomotherapy-based total lymphoid irradiation in an adult patient with late-onset cardiac transplant rejection. Treatment planning allowed dose minimization to the spinal cord, kidneys, intestinal compartment, and lungs. The patient tolerated treatment well without acute adverse effects, and he is now in early follow-up.

Definitive radiotherapy for medically inoperable early-stage serous and clear cell uterine carcinoma.

High-risk, early-stage endometrial cancer is optimally treated by hysterectomy followed by adjuvant radiotherapy. In 1%-9% of cases, the patient is medically unfit or personally unwilling to undergo primary surgery, and definitive radiotherapy may be offered as an alternative definitive therapy. Although several series have reported excellent intrauterine control and disease-specific survival for endometrioid histology, few outcome data are available for patients with serous or clear cell histology treated with radiotherapy alone. We herein describe one case each of early-stage, medically inoperable serous/clear cell histology endometrial cancer treated with definitive radiotherapy. Treatment was well tolerated by both patients, and neither patient required a treatment break. Acute toxicity consisted of self-limited cystitis in one patient. One patient was without evidence of disease progression at 54 months after radiotherapy.

Radioiodine Ablation following Thyroidectomy for Differentiated Thyroid Cancer: Literature Review of Utility, Dose, and Toxicity.

Management recommendations for differentiated thyroid cancer are evolving. Total thyroidectomy is the backbone of curative-intent therapy, with radioiodine ablation (RAI) of the thyroid remnant routinely performed, in order to facilitate serologic surveillance and reduce recurrence risk. Several single-institution series have identified patient subsets for whom recurrence risk is sufficiently low that RAI may not be indicated. Further, the appropriate dose of RAI specific to variable clinicopathologic presentations remains poorly defined. While recent randomized trials demonstrated equivalent thyroid remnant ablation rates between low- and high-dose RAI, long-term oncologic endpoints remain unreported. While RAI may be employed to facilitate surveillance following total thyroidectomy, cancer recurrence risk reduction is not demonstrated in favorable-risk patients with tumor size ≤1 cm without high-risk pathologic features. When RAI is indicated, in patients without macroscopic residual disease or metastasis, the evidence suggests that the rate of successful remnant ablation following total thyroidectomy is equivalent between doses of 30-50 mCi and doses ≥100 mCi, with fewer acute side effects; however, in the setting of subtotal thyroidectomy or when preablation diagnostic scan uptake is >2%, higher doses are associated with improved ablation rates. Historical series demonstrate conflicting findings of long-term cancer control rates between dose levels; long-term results from modern series have yet to be reported. For high-risk patients, including those with positive surgical margins, gross extrathyroidal extension, lymph node involvement, subtotal thyroidectomy, or >5% uptake, higher-dose RAI therapy appears to provide superior rates of ablation and cancer control.

Gleason Score ≤ 6 Prostate Cancer at Radical Prostatectomy: Does a High-Risk Setting Truly Exist? A Recursive Partitioning Analysis.

BACKGROUND: The purpose of this study was to determine whether a "high-risk" subpopulation of low-grade (Gleason score ≤6) prostate cancer defined by lower prostate-specific antigen (PSA) relapse-free survival (bRFS) might be identified within a large population of men who underwent radical prostatectomy (RP) alone, with mature follow-up. PATIENTS AND METHODS: Patients were retrospectively identified for inclusion by cT1-2 prostate cancer managed with RP alone. Exclusion criteria were: Gleason score ≥7 at RP, any pre- or post-RP radiotherapy or hormone therapy, or PSA follow-up <12 months. The Kaplan-Meier method was used for survival estimates; recursive partitioning by conditional inference analysis was applied to identify variables associated with bRFS. RESULTS: From 2002 through 2010, 284 eligible patients were identified. Median age was 60 years (range, 44-76 years), 233 (82%) were cT1c, and median PSA was 5.3 ng/dL (92% ≤10). The median biopsy to RP interval was 50 days (range, 11-410, with 97% <180 days). Eighty patients (28%) had positive margin (M+). At a median follow-up of 92.6 months (range, 16.9-160.9, with 45% followed ≥ 8 years), 32 patients (11%) had PSA failure, with an estimated 8-year bRFS rate of 89%. In univariate analysis, M+, extraprostatic extension, detectable initial post-RP PSA, and longer biopsy to RP interval were significantly associated with lower bRFS. M+ and longer biopsy to RP interval remained significant in multivariable analysis. Recursive partitioning analysis identified M+ as the only stratification factor, with 8-year bRFS estimates of 74% versus 95% for M+ versus margin-negative. CONCLUSION: Gleason score ≤6 prostate cancer managed using RP alone is associated with high rates of bRFS; however, margin positivity predicts early PSA failure rates in >20% of patients.

Incidental prostate cancer diagnosed at radical cystoprostatectomy for bladder cancer: disease-specific outcomes and survival.

BACKGROUND: The current standard of care for men with muscle-invasive bladder cancer is radical cystoprostatectomy (RCP). One-third of RCP specimens demonstrate incidental prostate cancer, primarily reported in small series with limited follow-up. The aim of this study is to report mature outcomes, including patterns of failure and disease-specific recurrence rates, and survival, for a large cohort of men with incidental prostate cancer at RCP performed at a tertiary referral center. METHODS: This retrospective study describes cancer control and survival rates for men who underwent RCP for bladder cancer and were found incidentally to have prostate cancer. Analysis of patient-, tumor-, and treatment-specific factors were analyzed for association with disease control and survival endpoints. RESULTS: Between 2002 and 2010, 94 patients with incidental discovery of prostate cancer postRCP were identified for inclusion in this study. Forty-five patients (45%) underwent RCP for recurrent (rather than initial presentation of) bladder carcinoma. At a median follow-up of 40.3 months (71.2 months for survivors; range, 8.9-155.5 months), 42 patients were alive without recurrence and 52 patients had died (25 associated with disease). The estimated 5-year bladder cancer disease-free, urinary tract malignancy disease-free, and prostate specific antigen (PSA) relapse-free survivals were 76% [95% confidence interval (CI), 65-84%], 64% (52-74%), and 97% (79-100%), respectively. The estimated 5-year urinary tract malignancy-specific and overall survivals were 61% (49-71%) and 52% (41-62%), respectively. Univariate analysis demonstrated associations between pathologic T/N-stage and nodal ratio with bladder cancer disease-free, urinary tract malignancy disease-specific, and overall survivals, with patient age at diagnosis as an additional adverse factor associated with overall survival. Multivariate analysis confirmed pN-stage and age as independently associated with worse survival. CONCLUSION: For men undergoing RCP for bladder cancer, the present study suggests that incidentally discovered prostate cancers, irrespective of pathologic stage, Gleason score, or clinical significance, do not impact 5-year disease control or survival outcomes.

Individualization of Adjuvant Therapy After Radical Prostatectomy for Clinically Localized Prostate Cancer: Current Status and Future Directions.

Radiation therapy indications in the postprostatectomy setting are evolving. Several retrospective series have identified a number of "high-risk" pathologic features associated with an elevated risk of disease recurrence after radical prostatectomy. More recently, several randomized phase III trials demonstrated superior biochemical relapse-free survival for adjuvant radiation therapy after prostatectomy for patients with these high-risk pathologic features, including positive margin status, extraprostatic extension, and/or seminal vesicle invasion. These series further suggested improvement in distant metastasis control and overall survival after 15 years. However, not all patients with high-risk features experience disease recurrence after surgery alone, and some subsets of patients experience suboptimal disease control and survival despite immediate postoperative radiotherapy. Furthermore, some patients without high-risk features will develop recurrence. The present review discusses the current data and potential future directions to improve individualization of therapy after prostatectomy.

Once Daily High-dose Radiation (≥60 Gy) Treatment in Limited Stage Small Cell Lung Cancer.

BACKGROUND: To investigate outcomes and prognostic factors in patients treated with once daily high-dose (≥60 Gy) radiation therapy (HDRT) and concurrent platinum-based chemotherapy in limited stage small cell lung cancer (LS-SCLC). While we await current phase III trials to determine optimal radiation dose fractionation schemes in LS-SCLC, we report our experience in LS-SCLC with once daily HDRT. We hypothesized that HDRT would achieve similar efficacy and tolerability as twice daily therapy. METHODS: We conducted a single institution retrospective review of all patients with LS-SCLC who underwent curative intent treatment from 2005-2013. Patients treated with HDRT (≥60 Gy) and concurrent chemotherapy (cisplatin or carboplatin and etoposide) were included in our analysis. Clinicopathologic variables assessed include gender, performance status, time to treatment, response to treatment, toxicity, volumetric tumor response at 3 months, and use of prophylactic cranial irradiation (PCI). RESULTS: 42 patients with LS-SCLC who initiated concurrent chemoradiation from 2005 to 2013 were included in the analysis. 38 patients (90%) completed definitive treatment to the lung; 16 (38%) also completed PCI. Median failure free survival (FFS) and overall survival (OS) were 11.9 and 23.1 months, respectively. Two-year and 5-year OS rates were 47% (CI=30-62%) and 21% (CI=7-38%), respectively. On univariate analysis, PCI was associated with improved FFS but this was not significant (p=0.18). Gender was the only co-variate significantly associated with statistical differences in FFS (p=0.03) and OS (p=0.02). Grade 3 and 4 esophagitis were 10.5% and 2.6%, respectively. Pre-HDRT tumor volume and 3-month post-treatment tumor volume were both associated with FFS (p<0.01) but not OS. CONCLUSIONS: In this single institution series, daily HDRT demonstrated a 2-year OS of 47% in LS-SCLC. This compares well to the historical survival of daily fractionation (47%) from INT 0096 reported by Turrisi et. al. Male gender was predictive of significantly worse FFS and OS. Once daily HDRT has similar OS to twice-daily radiation schemes; however, further studies assessing once daily HDRT for LS-SCLC are warranted.

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.

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.