Davis, Brian J.

4595 Background: For stage I-II testicular seminoma, RT is highly effective at eradicating disease in the abdominopelvic lymph nodes, but results in unnecessary exposure to normal tissues including the GI tract. The purpose of this study was to define the incidence and risk factors for late GI complications in this patient population. Methods: A retrospective review was performed of 251 patients with stage I-II testicular seminoma treated with curative intent RT at our institution from 1974-2009. All patients underwent orchiectomy and postoperative external beam RT to the involved and/or at-risk nodal basins. Potential late GI complications that were assessed included endoscopically-confirmed gastric or duodenal ulceration, small bowel obstruction (SBO), and biopsy-confirmed malignancy of the GI tract. Risks were estimated using the Kaplan-Meier (KM) technique and univariate/multivariate analyses were performed using the Cox proportional hazards model. Results: Median age at diagnosis was 36 years (range 18 – 80). Clinical stage was I (n=199) or II (n=52). Median abdominopelvic RT dose was 26 Gy (interquartile range 25 – 30). Median follow-up was 15 years (range 0.1 – 38). KM estimates for any GI complication (ulcer, SBO, or GI malignancy) at 10, 20, and 30 years were 7, 10 and 24%, respectively. Four patients died as result of a GI complication. KM estimates for ulcer at 10, 20, and 30 years were 4, 7, and 9%, respectively. Age at RT (Hazard Ratio [HR] 1.05, 95% Confidence Interval [CI] 1.00 – 1.10, p=0.03) and RT total dose (per Gy, HR 1.20, 95% CI 1.09 – 1.31, p<0.01) were associated with risk of ulcer. KM estimates for SBO at 10, 20, and 30 years were 2%, 2%, and 3%, respectively. History of inflammatory bowel disease was associated with risk of SBO (HR 43, 95% CI 7-325, p<0.01). KM estimates for GI malignancy at 10, 20, and 30 years were 0.5, 3 and 16%, respectively. Age at RT was associated with risk of GI malignancy (HR 1.07, 95% CI 1.02-1.14, p=0.01). Conclusions: In patients with stage I-II testicular seminoma treated with RT, late GI complications were a relatively uncommon, but clinically significant source of late morbidity. Use of low dose, limited field, and/or proton RT may reduce these risks.

15639 Background: Permanent prostate brachytherapy (PPB) assesses implant quality but may suffer significant variability due to: 1) Prostate edema may occur during the procedure which usually subsides within several months, and 2) interobserver variability of CT- derived prostate volumes. An analysis is described, which uses the seeds as prostate fiducials to produce an implant reference volume (IRV). The ratio of the IRV volumes at day 0 and day 33 provides a unique way to quantify prostate edema; thus reducing this factor as a source of variability. Methods: Thirteen low risk prostate cancer patients, (Stage ≤ T2, PSA<13.9, Gleason Score ≤7) were implanted with 125Iodine seeds (77% stranded; prescription dose of 145 Gy). PPB was completed for each patient on day 0 and 33 ±3 days following the implant. The IRV was defined as the volume obtained by contouring the outer most peripheral seeds, circumferentially, on each axial image, resulting in a 3D volume. Contouring was performed by three separate investigators (KJM, DCG, EKM), who were blinded with respect to patient identification. The IRV's were compared both by investigator and by time of PPB (day 0 vs. day 33). The radiation dose encompassing 90% (D90) of the IRV and Prostate (PST) was calculated and compared . Results: The IRVs contoured were reproducible between the investigators with a maximum mean difference of .56 (SD .33) cc. There was no statistical difference between any of the investigators contoured volume (minimum Spearman correlation was 0.978). The average IRV was significantly larger on day 0 (Avg. 52.7;SD 19.7 cc) compared to day 33 (Avg. 44.6; SD 19.1 cc) (p<0.001). The day 0 IRV was an average of 1.18 times larger than the Day 33 PRV. There was no difference between either the day 0 D90PST (Avg.149.1; SD18.7 cGy) vs the day 0 D90IRV (Avg.149.8, SD 27.5 cGy) (p=.442) nor between the day 33 D90PST (Avg.163.7; SD22.7 cGy) vs the day 33 D90IRV (Avg.166.6, SD 30.3 cGy) (p=.257). Both the D90IRV and D90PST were significantly different at day 0 vs 33 (p=.0003, p=<.0001 respectively). Conclusions: The IRV analysis demonstrates no significant interobserver variability, provides accurate quantification of prostate swelling after PPB, and is an accurate objective surrogate analysis for PSI quality. No significant financial relationships to disclose.

5017 Background: The majority of men with prostate cancer are diagnosed with cancers with low mortality. Such men are treated with radical prostatectomy, external beam radiotherapy, or brachytherapy and followed by serum PSA evaluations. Some men with a rising PSA therapy will have local recurrence or metastasis, but many will have no other evidence of recurrent disease other than a rising PSA. The PSA doubling time has been used to determine which of these men deserve adjuvant hormonal ablation, radiation therapy, or observation. We hypothesize that additional biomarkers will predict which men with a rising PSA post-definitive therapy would benefit from additional therapy. Methods: We designed a custom array containing 526 RNA targets whose expression has been reported to be altered in association with prostate cancer progression. We included targets from Mayo Clinic prostate cancer research. Together with a second commercial array, 530 genes implicated in prostate cancer progression and 420 other cancer-related genes were evaluated. A case-control design was used to test the association of the expression results with outcome. Cases were men post-radical prostatectomy who developed systemic progression within 5 years after PSA recurrence (N=213). Controls were matched men post-radical prostatectomy with PSA recurrence but no evidence of clinical progression within 5 years (N=213). Results: Of 426 eligible patients, paraffin blocks were available on 418 (98.1%). RNA was prepared from all 418 blocks, and both arrays were both successful on 405 (96.9%) RNAs. Upon univariate analysis, 40 genes were highly significantly over- or under-expressed in the cases versus controls (1x10-22 < p < 1x10-7). Recursive partitioning (RP) selected 4 genes (TPX2, FAM13C1, TOPO2A and TSP2) that distinguished cases from controls. Random Forest analysis selected 24 genes (including 3 of the RP 4). A multivariable ROC analysis using these 24 genes generated an AUC of 0.80 (95% CI: 0.75–0.84). Conclusions: A specific gene expression pattern was significantly associated with systemic progression after PSA recurrence. The measurement of gene expression pattern may be useful for determining which men may benefit from additional therapy after PSA recurrence. No significant financial relationships to disclose.

Prostate cancer (PCa) represents a significant source of morbidity and mortality for men in the United States, with approximately 1 in 9 being diagnosed with PCa in their lifetime. The role of imaging in the evaluation of men with PCa has evolved and currently plays a central role in diagnosis, treatment planning, and evaluation of recurrence. Appropriate use of multiparametric MRI (mpMRI) and MRI-guided transrectal ultrasound (MR-TRUS) biopsy increases the detection of clinically significant PCa while decreasing the detection of clinically insignificant PCa. This process may help patients with clinically insignificant PCa avoid the adverse effects of unnecessary therapy. In the setting of a known PCa, patients with low-grade disease can be observed using active surveillance, which often includes a combination of prostate-specific antigen (PSA) testing, serial mpMRI, and, if indicated, follow-up systematic and targeted TRUS-guided tissue sampling. mpMRI can provide important information in the posttreatment setting, but PET/CT is creating a paradigm shift in imaging standards for patients with locally recurrent and metastatic PCa. This article examines the strengths and limitations of mpMRI for initial PCa diagnosis, active surveillance, recurrent disease evaluation, and image-guided biopsies, and the use of PET/CT imaging in men with recurrent PCa. The goal of this review is to provide a rational basis for current NCCN Clinical Practice Guidelines in Oncology for PCa as they pertain to the use of these advanced imaging modalities.

The NCCN Guidelines for Prostate Cancer include recommendations regarding diagnosis, risk stratification and workup, treatment options for localized disease, and management of recurrent and advanced disease for clinicians who treat patients with prostate cancer. The portions of the guidelines included herein focus on the roles of germline and somatic genetic testing, risk stratification with nomograms and tumor multigene molecular testing, androgen deprivation therapy, secondary hormonal therapy, chemotherapy, and immunotherapy in patients with prostate cancer.

255 Background: The purpose of this study was to identify site-specific recurrence patterns for patients (pts) with biochemical recurrence (BCR) after prostatectomy (RP) using C-11 Choline PET/CT (C11Ch) and 3T pelvic MRI with endorectal coil (pMRI). Methods: Between 2008 and 2006, 2,466 men underwent C11Ch and pMRI for BCR after RP. From this cohort, we identified 261 pts who received no adjuvant or salvage therapy (androgen deprivation or radiation). Suspected radiographic relapse was confirmed by biopsy (46%) or progression/response to treatment in concordance with subsequent rise/decline in PSA (54%). Results: Of the 261 men evaluated, 202 (75%) had positive pMRI, C11Ch or both. Seventy nine (39%), 105 (52%) and 18 (9%) pts had high, intermediate, and low risk CaP, respectively at RP. Median PSA at the time of positive scan was 2.3 ng/mL, with a median time from BCR to radiographic disease identification of 15 months. Of these 202 men, 67 (33%) harbored prostate fossa recurrence only, 44 (22%) had a combination of local and metastatic disease and 91 (45%) had metastatic disease without local recurrence. Forty (20%) pts had pelvic nodal recurrence only and 18 (9%) had perirectal nodal involvement. Median PSA for pts with local only recurrence, distant metastases only, and local + distant disease was 2.3, 2.7 and 2.2 ng/mL, respectively, with a median interval from BCR to positive scan of 16.7, 7.9 and 11 months. Imaging revealed that 33% to 66% of our cohort would have all sites of disease treated by salvage RT depending on the extent of the treatment field Conclusions: C11Ch and pMRI were used to identify recurrence patterns in pts with BCR after RP only. At median PSA of 2.3 ng/ml, our study demonstrates a low rate of local-only recurrence, higher than anticipated frequency of metastatic recurrence with peak frequency within the pelvic lymph nodes, and substantial perirectal recurrences. Despite the high rates of distant recurrences, 2/3 of our cohort had their disease limited to the pelvis and could be potential candidates for local therapies, including salvage radiation.