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Background Prostate radiotherapy has been associated with an increased risk of developing a second malignancy (SM). However, relative SM probabilities following treatment with contemporary radiation techniques such as stereotactic body radiotherapy (SBRT) or moderately hypofractionated intensity modulated radiotherapy (HF-IMRT) remain unknown. Methods A cohort analysis was performed of men from a nationally representative database with localized prostate cancer with at least 60 months of follow-up comparing SM probability amongst men receiving either radical prostatectomy (RP), conventionally fractionated intensity-modulated radiotherapy (CF-IMRT), HF-IMRT, brachytherapy (BT), or SBRT, using multivariable logistic models, which were used to generate predicted probabilities. Additionally, propensity score-adjusted pairwise assessments of modalities were performed. Results For 303,432 patients included in the study, median follow-up was 9.08 years (IQR 7.01–11.21). Predicted rates of SM by treatment modality and adjusted odds ratios (AOR) for development of SM (referent: RP) were: 6.0% for RP (AOR n/a), 7.1% for CF-IMRT (AOR 1.20, 95%CI 1.14–1.25, P Conclusions Conventionally fractionated intensity-modulated radiotherapy, moderately hypofractionated intensity-modulated radiotherapy, and brachytherapy but not stereotactic body radiotherapy were associated with increased probability of a second malignancy compared to radical prostatectomy. Patients treated with SBRT may be at lower risk of second malignancy due to improved conformality, radiobiological differences or patient selection. The possibility that SBRT in select patients may minimize the probability of SM underscores the need for assessment of second malignancy risk in prospective studies of SBRT.

To inform treatment decisions for patients with high-risk prostate cancer (PCa), we determined rates of adverse pathologic factors and overall survival (OS) among subgroups of high-risk men.Using the National Cancer Database, 89,450 patients with clinical N0M0 unfavorable intermediate-risk, favorable high-risk (cT1c, Gleason 6, prostate-specific antigen [PSA]20 ng/mL or cT1c, biopsy Gleason 8, PSA10 ng/mL), standard high-risk (all other cT3a, biopsy Gleason ≥ 8, or PSA20 ng/mL), or very high-risk (cT3b-T4 or biopsy primary Gleason pattern 5) PCa treated with radical prostatectomy were identified. Rates of adverse pathologic factors (positive surgical margins, T4 disease, or pathologic lymph node involvement) were compared across subgroups.Patients with unfavorable intermediate-risk (n = 31,381) and favorable high-risk (n = 10,296) disease had similar rates of adverse features (7.6% vs 8.2%, adjusted odds ratio 1.00, 95% confidence interval 0.92-1.08, P= .974). Patients with standard high-risk (n = 30,260) or very high-risk (n = 7513) disease were significantly more likely to have adverse pathologic factors (15.9% and 26.5%, P.001 for both). Patients with unfavorable intermediate-risk and favorable high-risk disease had similar 5-year OS (95.7% vs 95.1%, adjusted hazard ratio 1.06, 95% confidence interval 0.92-1.21, P = .411) but better OS compared to standard and very high-risk patients (93.4% and 88.1%, respectively; P.001).Unfavorable intermediate-risk or favorable high-risk PCa patients had low rates of adverse pathologic factors and similar OS. In contrast, standard and very high-risk PCa patients had significantly higher rates of adverse pathologic factors and worse OS. This 3-tiered subclassification of high-risk disease may allow for improved treatment selection among patients considering surgery.

BACKGROUND Certain patients with intermediate-risk prostate cancer (PCa) may be appropriate candidates for active surveillance (AS). In the current study, the authors sought to characterize AS use and early mortality outcomes for patients with intermediate-risk PCa in the United States. METHODS The novel Surveillance, Epidemiology, and End Results Active Surveillance/Watchful Waiting database identified 52,940 men diagnosed with National Comprehensive Cancer Network intermediate-risk PCa (cT2b-c, Gleason score of 7, or a prostate-specific antigen level of 10-20 ng/mL) and actively managed (AS, radiotherapy, or radical prostatectomy) from 2010 through 2015. The Cuzick test assessed AS time trends, and logistic multivariable regression characterized features associated with AS. Fine-Gray and Cox modeling determined PCa-specific mortality (PCSM) and overall survival, respectively. RESULTS The rate of AS increased from 3.7% in 2010 to 7.3% in 2015, and from 7.2% to 11.7% among men aged ≥70 years. Among men with favorable and unfavorable intermediate-risk disease, the use of AS increased from 7.2% to 14.9% and from 2.2% to 3.8%, respectively (all P value for trend

PURPOSE/OBJECTIVE(S) Stereotactic body radiotherapy (SBRT) is increasingly being utilized in the management of localized prostate cancer. MR guided adaptive radiotherapy may be a valuable tool for delivery of prostate SBRT as it allows for MR based soft tissue contouring, real time MR motion management and daily plan adaptation to account for interfraction anatomic variability. The goal of the present study is to identify dosimetric gains that can be achieved with an MR guided adaptive prostate SBRT platform and describe acute clinical outcomes. MATERIALS/METHODS We reviewed our institutional experience treating patients with prostate cancer with MR guided adaptive SBRT to a dose of 36.25 Gy in 5 fractions. The adaptive workflow involves development of an "original" plan which is re-optimized daily based on anatomical variation for each fraction. "Predicted" plan dosimetry is generated for each fraction by re-calculating the original plan on the re-contoured daily anatomy, estimating what would have been delivered without adaptive capabilities. A "re-optimized" plan is developed based on the anatomy of the day to improve target coverage and organ-at-risk (OAR) metrics. Wilcoxon rank sum testing was used to compare predicted dosimetry to re-optimized dosimetry. Acute urinary and GI toxicity rates were assessed according to CTCAE v5. RESULTS A cohort of 16 patients treated was analyzed with median follow up time of 3 months. Acute G2+ GU toxicity was observed in 19% and acute G2+ GI toxicity in 6%. No G3+ events were noted. Comparison of dosimetry metrics for PTV coverage, urethra, rectum and bladder are shown in table 1; 100% of fractions required plan adaptation due to either exceeding OAR metrics (68%) or sub-optimal PTV coverage (33%). Adaptive planning increased the proportion of fractions meeting prescription metrics for PTV coverage (V34.44 from 71% to 100%), urethra (V38.78 from 58% to 100%) and rectum (V38.06 from 80% to 100%). Urethral metrics were most frequently violated in predicted plans (42% of fractions) and re-optimized to acceptable dosimetry in 100% of fractions. Re-optimization significantly improved PTV coverage, rectal metrics and urethral metrics. CONCLUSION Online adaptive re-optimization significantly improved plan dosimetry and achieved minimal acute toxicity. The clinical benefits of MR guided adaptive prostate SBRT for optimizing target coverage with urethral protection warrant further investigation.

PURPOSE/OBJECTIVE(S) Prostate radiotherapy has been associated with an increased risk of developing a second malignancy (SM). Relative SM probabilities following stereotactic body radiotherapy (SBRT) or moderately hypofractionated radiation (HF-IMRT) remain unknown. We hypothesized that the probability of SM following SBRT or HF-IMRT would differ compared with conventionally fractionated intensity modulated radiotherapy (CF-IMRT). MATERIALS/METHODS Cohort analysis of men from a nationally representative database with localized prostate cancer with at least 60 months of follow-up compared SM probability amongst men receiving either radical prostatectomy (RP), CF-IMRT, HF-IMRT, brachytherapy (BT), or SBRT, using multivariable logistic models. Sensitivity analyses were conducted to evaluate differences in SM stratified by year of treatment and follow up length. Propensity score-adjusted pairwise assessments of modalities were also performed. RESULTS For 303,432 patients, median follow-up was 9.08 years (IQR 7.01 - 11.21), and median age was 64 years (IQR 58-69). Crude rates of SM by treatment modality were: 5.2% for RP, 8.9% for CF-IMRT, 7.7% for HF-IMRT, 7.9% for BT, and 5.3% for SBRT. Adjusted odds ratios (AOR) for development of SM (referent: RP) were: CF-IMRT vs. RP 1.20 (95% CI 1.14-1.25, P < 0.001), HF-IMRT vs. RP 1.25 (95% CI 1.01-1.55, P = 0.045), BT vs. RP 1.11 (95% CI 1.07-1.16, P < 0.001), and SBRT vs. RP 0.95 (95% CI 0.81-1.12, P = 0.567). Sensitivity analyses confirmed higher probability of SM comparing CF-IMRT to RP (P < 0.01 for all) and no statistically significant difference comparing SBRT to RP at all year and follow-up length groupings (P = NS for all). On propensity score-adjusted analysis, SBRT was associated with lower probability of SM compared to CF-IMRT (AOR 0.78, 95% CI 0.66-0.93, P = 0.005); no significant difference was found when SBRT was compared to RP (AOR 0.86, 95% CI 0.73-1.03, P = 0.102). CONCLUSION Conventionally fractionated intensity-modulated radiotherapy, moderately hypofractionated intensity-modulated radiotherapy, and brachytherapy, but not stereotactic body radiotherapy, were associated with increased probability of a second malignancy compared to radical prostatectomy. Our findings underscore the need for assessment of second malignancy risk in prospective studies of SBRT.

Purpose: Outcomes of stereotactic body radiation therapy (SBRT) with respect to androgen receptor signaling inhibitors (ARSI) have not been characterized for oligometastatic prostate cancer. We sought to characterize prostate specific antigen (PSA) response and progression-free survival (PFS) after SBRT among men who have progressed on ARSI therapy in the oligometastatic castration-resistant setting. Methods and Materials: A single-institution retrospective analysis was performed for men with ARSI-resistant, oligometastatic, castrate-resistant prostate cancer (omCRPC). Intervention consisted of SBRT. PSA reduction greater than 50% and median PFS (PSA or radiographic progression) as determined by routine care comprised outcome measurements. Cox regression analysis was used to determine factors influencing PFS. Results: Thirty-five men with ARSI-resistant omCRPC and 65 lesions treated with SBRT were followed for a median of 17.2 months. In 63% of men PSA reduction greater than 50% was achieved. Median PFS was 9.0 months. Incomplete ablation (defined as the presence of untreated lesions after SBRT or receipt of prior palliative radiation therapy doses) was associated with worse PFS (hazard ratio 4.21 [1.74-10.19]; P < .01). For a subgroup of 22 men with complete ablation of metastatic sites with SBRT, the median PFS was 13.1 months. One-year overall survival was 93.1% (95% confidence interval, 84.4-100). Conclusions: SBRT may augment the efficacy of ARSI in omCRPC, provided that all lesions receive ablative radiation doses. Future prospective study of SBRT for men receiving ARSI is warranted.

Purpose Clinical trials assessing evaluation prostate stereotactic body radiation therapy (SBRT) have used a wide range of allowed doses to the intraprostatic urethra, but the relationship between urethral dose and urinary toxicity has not been thoroughly evaluated. The goal of this study was to characterize urinary toxicity outcomes according to urethral dose administered during prostate SBRT. Methods and Materials The MEDLINE (PubMed) database was searched for published prospective studies of prostate SBRT through August 2020 that documented a maximum urethral dose metric (MUDM). Reported acute and late urinary toxicity rates were collected. Logistic regression and weighted Pearson correlation models were used to assess associations between urinary toxicity rates and MUDM. Results Twenty-three unique studies (n = 2232 patients) met the inclusion criteria and included a wide range of MUDMs (equivalent dose in 2 Gy fractions [EQD2]: 69-141.75 Gy; α/β = 3 Gy). The median follow-up ranged from 3 to 67 months (median, 32 months). On logistic regression analysis, the MUDM EQD2 was significantly associated with multiple urinary toxicity endpoints, including acute grade (G) 2+ (odds ratio [OR], 1.02; P Conclusions Radiation dose to the urethra correlates closely with urinary toxicity in patients with prostate cancer treated with SBRT. Attention should be paid to the urethral dose when delivering prostate SBRT to high doses, and approaches for urethral dose reduction warrant further investigation.

Background: This study examined sociodemographic factors, cisplatin-related adverse health outcomes (AHO), and cumulative burden of morbidity (CBMPt) scores associated with medication use for anxiety and/or depression in testicular cancer survivors (TCS). Methods: A total of 1,802 TCS who completed cisplatin-based chemotherapy ≥12 months previously completed questionnaires regarding sociodemographic features and cisplatin-related AHOs [hearing impairment, tinnitus, peripheral sensory neuropathy (PSN), and kidney disease]. A CBMPt score encompassed the number and severity of cisplatin-related AHOs. Multivariable logistic regression models assessed the relationship of individual AHOs and CBMPt with medication use for anxiety and/or depression. Results: A total of 151 TCS (8.4%) used medications for anxiety and/or depression. No cisplatin-related AHOs were reported by 511 (28.4%) participants, whereas 622 (34.5%), 334 (18.5%), 287 (15.9%), and 48 (2.7%), respectively, had very low, low, medium, and high CBMPt scores. In the multivariable model, higher CBMPt scores were significantly associated with medication use for anxiety and/or depression (P < 0.0001). In addition, tinnitus (P = 0.0009), PSN (P = 0.02), and having health insurance (P = 0.05) were significantly associated with greater use of these medications, whereas being employed (P = 0.0005) and vigorous physical activity (P = 0.01) were significantly associated with diminished use. Conclusions: TCS with higher CBMPt scores had a higher probability of using medications for anxiety and/or depression, and conversely, those who were employed and physically active tended to have reduced use of these medications. Impact: Healthcare providers should encourage TCS to increase physical activity to improve both physical and mental health. Rehabilitation programs should assess work-related skills and provide career development counseling/training.

Purpose The role of multimodality therapy (MMT) in the treatment of Gleason 8–10 prostate cancer remains controversial. We sought to evaluate factors associated with MMT utilization for primary radical prostatectomy (RP) and primary radiation therapy (RT). Methods and Materials From the National Cancer Database, we conducted a retrospective review of 81,528 men with National Cancer Center Network Gleason 8–10 prostate cancer diagnosed between 2004 and 2015, who underwent (1) primary RP with or without early postoperative external beam RT (EBRT) or (2) primary RT (androgen deprivation therapy + EBRT) with or without brachytherapy (BT) boost. Using multivariable logistic regression models, we evaluated factors associated with the utilization of MMT, defined as early postoperative EBRT for primary RP or BT boost for primary RT. Results For primary RP, the percentages of men who underwent MMT for Gleason 8 and 9–10 disease were 12.2% and 24.1%, respectively. On multivariable logistic regression, men with Gleason 9–10 were more likely to undergo MMT (odds ratio 1.03 [1.02, 1.04]), although adverse pathologic features such as T3b-4 (1.24 [1.23, 1.25]) disease demonstrated the strongest associations. For primary RT, the percentages of men who underwent BT boost for Gleason 8 and 9–10 disease were 11.8% and 9.8%, respectively. On multivariable logistic regression, men with Gleason 9–10 disease were less likely to receive BT boost (0.99 [0.98, 0.99]). Conclusions Men with more aggressive Gleason 9 disease were more likely to undergo MMT if they underwent primary RP but not primary RT. Further blood-based or imaging biomarkers may aid in identifying optimal candidates for MMT, especially for primary RT.

Background While the addition of androgen deprivation therapy (ADT) to external beam radiation therapy (EBRT) is known to improve overall survival (OS) in Gleason 8–10 (Grade Group 4–5) prostate cancer (PCa), it has been hypothesized that Gleason 9–10 disease, which is less differentiated than Gleason 8 disease, may be less sensitive to ADT. Objective To examine the association between ADT and OS for Gleason 8 versus Gleason 9–10 PCa. Design, setting, and participants A retrospective cohort study of 20 139 men from the National Cancer Database with localized or locally advanced, Gleason 8–10 PCa who received EBRT. Data were collected from 2004 to 2012. Intervention ADT. Outcome measurements and statistical analysis Cox proportional hazards regression was used to examine the association between ADT and OS. Results and limitations Overall, 9509 (78%) of the 12 160 men with Gleason 8 disease and 6908 (87%) of the 7979 men with Gleason 9–10 disease received ADT. On multivariable analysis, ADT was associated with a significant improvement in OS for Gleason 8 patients (adjusted hazard ratio 0.78, 95% confidence interval 0.70–0.87, p Conclusions In contrast to the significant survival advantage of ADT for Gleason 8 disease, our results suggest that Gleason 9–10 disease derives less survival benefit from ADT and that a higher Gleason score predicts lesser benefit. Consideration should be given to treatment intensification for Gleason 9–10 patients through enrollment in clinical trials or potentially adding novel antiandrogens or docetaxel, which have shown efficacy in both castration-resistant and castration-sensitive settings. Patient summary In this study, we examined the effect of androgen deprivation therapy (ADT) for Gleason 8 (Grade Group 4) versus Gleason 9–10 (Grade Group 5) prostate cancer. We found that Gleason 9–10 disease may derive a smaller survival benefit from ADT than Gleason 8 disease.

BackgroundFew data exist on the relationship of cisplatin-related adverse health outcomes (AHOs) with disability, unemployment, and self-reported health (SRH) among testicular cancer survivors (TCS).MethodsA total of 1815 TCS at least 1 year postchemotherapy underwent clinical examination and completed questionnaires. Treatment data were abstracted from medical records. A cumulative burden of morbidity score (CBMPt) encompassed the number and severity of platinum-related AHOs (peripheral sensory neuropathy [PSN], hearing loss, tinnitus, renal disease). Multivariable regression assessed the association of AHOs and CBMPt with employment status and SRH, adjusting for sociodemographic and clinical characteristics. Unemployment was compared with a male normative population of similar age, race, and ethnicity.ResultsAlmost 1 in 10 TCS was out of work (2.4%, disability leave; 6.8%, unemployed) at a median age of 37 years (median follow-up = 4 years). PSN (odds ratio [OR] = 2.89, 95% confidence interval [CI] = 1.01 to 8.26, grade 3 vs 0, P = .048), renal dysfunction defined by estimated glomerular filtration rate (OR = 12.1, 95% CI = 2.06 to 70.8, grade 2 vs 0, P = .01), pain (OR = 10.6, 95% CI = 4.40 to 25.40, grade 2 or 3 vs 0, P ConclusionsOur findings have important implications regarding treatment-associated productivity losses and socioeconomic costs in this young population. Survivorship care strategies should include inquiries about disability and unemployment status, with efforts made to assist affected TCS in returning to the workforce.

Clinical pathways increase compliance with treatment guidelines, improve outcomes, and reduce costs. Guidelines recommend single fraction radiation therapy (SFRT) for palliation of uncomplicated bone metastases, but implementation is variable. We examined the effects of a pathway tool on SFRT rates in an academic radiation oncology practice.Using published literature, clinical guidelines, and expert input, we designed a clinical pathway for bone metastases radiation therapy displayed on a Web-based electronic interface. In March 2016, the pathway launched on a palliative radiation service at the Dana Farber/Brigham and Women's Cancer Center main campus and at affiliated community sites. Providers were surveyed pre- and postimplementation to assess expectations and elicit feedback. Rates of pathway utilization, compliance with SFRT recommendations, and reasons for noncompliance were assessed.The final pathway includes 20 endpoints and several validated prognostic scoring systems. It was used in 38% of 723 bone metastases radiation prescriptions, with appropriate SFRT rates rising from 18% before implementation to 48% after launch (P.01). Major reasons for rejecting recommendations included disagreement with life expectancy prognostication and patient convenience. The pathway increased physicians' confidence regarding compliance with treatment guidelines and made it easier to find well-supported treatment recommendations. Workflow disruptions and the inability to handle nuanced situations emerged as limitations.Our experience demonstrates the utility of clinical pathway decision support for bone metastases radiation in complex academic settings. Next steps include increasing the pathway's ease of use, refining the pathway's prognostic abilities, and measuring cost savings related to the pathway.

Background Prior studies have only considered the association between static marital status and cancer-specific outcomes. We aim to measure the effect of recent divorce on cancer-specific outcomes. Methods There were 83,804 patients with 2 malignancies, diagnosed 12 to 60 months apart, from 1973-2006 from the Surveillance, Epidemiology, and End Results database. Patients were identified as newly divorced if married at their first diagnosis and single/divorced at their second. Multivariable logistic regression and competing-risks regression were used to analyze the association of becoming newly divorced or newly married with cancer-specific outcomes from the second malignancy, including advanced diagnosis (T4 or N1 or M1), receipt of treatment, and cancer-specific survival. Results Four percent became newly divorced and 3.4% became newly married. Compared with long-term married, newly divorced patients were most likely to be diagnosed with advanced disease (adjusted odds ratio [AOR] 1.31; 95% confidence interval [CI], 1.19-1.43), followed by long-term divorced (AOR 1.18; 95% CI, 1.11-1.25), and were least likely to receive curative treatment (AOR 0.74; 95% CI, 0.67-0.81). Newly divorced patients had the worst cancer-specific survival (adjusted hazard ratio [AHR] 1.17; 95% CI, 1.05-1.30, P = .005), followed by long-term divorced (AHR 1.08; 95% CI, 1.01-1.16, P = .032), while newly married patients had similar cancer-specific survival to long-term married (AHR 0.96; 95% CI, 0.85-1.08, P = .46). Conclusion Recent divorce, which represents an acute disruption of a patient's social support network, was associated with the worst cancer outcomes, followed by long-term divorce. Clinicians should consider recent divorce as a risk factor for worse cancer outcomes, and encourage appropriate screening, treatment, and access to social and financial supports for recently divorced patients.

Background Controversy exists regarding the optimal management strategy for clinical stage IS seminomatous (SGCT) and nonseminomatous germ cell tumors (NSGCT) of the testis. Objective To assess contemporary treatment patterns and outcomes for clinical stage IS testicular cancer. Design, setting, and participants Using the National Cancer Data Base (2004–2012), we identified 1362 patients with clinical stage IS SGCT and NSGCT of the testis, treated with either adjuvant treatment (AT) or observation. Outcome measures and statistical analysis We calculated the annual percent change (APC) to assess treatment trends. Inverse probability of treatment weighting (IPTW)-adjusted Kaplan-Meier curves and Cox regression analyses were used to compare overall survival (OS) between AT and observation groups. Analyses were stratified by histologic type. Results and limitations Overall, there were 581 (43%) and 781 (57%) men with SGCT and NSGCT, respectively. Among men with SGCT, the use of AT decreased over the study period (APC=–2.7, 95% confidence interval [CI]: –4.4, –1.1, p =0.001). The 5-yr IPTW-adjusted rates of OS were 99% and 97% in the AT and observation groups, respectively (hazard ratio=0.36, 95% CI: 0.12, 1.14, p =0.08). Among men with NSGCT, the use of AT remained stable over the study period (APC = +0.8, 95% CI: –0.7, +2.2, p =0.29). The 5-yr IPTW-adjusted rates of OS were 97% and 95% in the AT and observation groups, respectively (HR=0.66, 95% CI: 0.27, 1.61, p =0.36). Limitations include the lack of full treatment details and cancer-specific survival information. Conclusions Trends in the use of AT significantly decreased over time for SGCT, while it remained stable for NSGCT. Nonetheless, we report 5-yr OS rates of ≥95% for both histologies without any significant benefit with the use of AT. Further studies are warranted to confirm these findings. Patient summary We evaluated treatment trends and outcomes for stage IS testicular cancer. We found that treatment changed over time for seminoma and remained stable for nonseminoma; there was no significant survival benefit in the use of adjuvant treatment versus observation for both seminomatous and nonseminomatous germ cell tumors.

Purpose/objective(s) The use of ablative stereotactic body radiation therapy (SBRT) in pancreatic cancer is constrained by nearby radiation-sensitive organs. Magnetic resonance (MR)-guided adaptive radiation therapy (SMART) is an innovation that offers superior anatomical imaging during treatment allowing for daily plan adaptation based on the volumetric images prior to each treatment. We report results of a prospective phase 1 trial (NCT04115254) assessing feasibility of SMART and describe early outcomes of patients with pancreatic cancer. Secondary objectives included analysis of 90-day toxicity, local control, and patient-reported outcomes (PROMs) in patients undergoing SMART. Materials/methods In this prospective IRB approved study, patient eligibility criteria included: biopsy-proven diagnosis of pancreatic cancer, eligibility for SBRT, and ability to undergo and tolerate MRI imaging. Patients were ineligible if they had prior abdominal radiation, active ulcerative disease, or tumor invasion of the stomach, duodenum or bowel on endoscopy. Patients were monitored for acute and late grade ≥ 3 toxicity. PROMs included the FACT-HEP and PROMIS Physical and Mental Health batteries and were completed at baseline and during follow-up. Feasibility was defined as 1) enrolling patients and delivering SMART on the MR-Linac; 2) assessing tumor using MR guidance before, during and after MR-guided treatment and 3) generating adaptive plans. Results All 10 patients successfully completed SMART, receiving 40 Gy in 5 fractions with 48 of 50 fractions requiring adaptation to meet target or critical organ-at-risk metrics. The median follow up was 10.49 months (range 5.00 - 11.38). The median age was 72 (range 55 - 89), 60% were female, and 80% were white. Disease stages included 30% T1-T2, 10% T3, and 60% T4 disease, as well as 30% N0, 60% N1, 10% N2 disease, and 80% M0, 10% MX, and 10% M1. 90% of patients had other medical comorbidities. ECOG performance status was 0-1 in 90% of patients. There were no acute or late grade ≥ 3 treatment related toxicities. There were no local recurrences. The 6-month survival rate was 90% (95% CI 47.3-98.5) with two deaths due to progressive disease. The median change between baseline and follow-up within 6 months of treatment was -0.5 on FACT-HEP, -2.5 on PROMIS Physical, and -4.7 on PROMIS Mental Health (table 1). Conclusion We successfully demonstrated the feasibility and safety of SMART with daily adaptation in patients with pancreatic cancer. PROMs highlight that patients tolerated treatment well with minimal toxicity. Further investigation in dose escalation in pancreatic cancer is warranted.

PURPOSE/OBJECTIVE(S) Dose escalated stereotactic body radiotherapy (SBRT) may improve both local control and overall survival for patients with pancreatic cancer. However, escalated dose cannot be routinely offered because of the risk of injury to adjacent normal organs. Stereotactic magnetic resonance (MR)-guided adaptive radiation therapy (SMART) represents an innovation that may achieve safer delivery of ablative doses and improve outcomes. The goal of the present study is to identify specific dosimetric gains that can be achieved with MR-guided adaptive pancreatic SBRT and describe acute clinical outcomes. MATERIALS/METHODS We performed a single institution IRB approved retrospective analysis of 37 consecutive pancreatic cancer patients treated with 40 Gy in 5 fractions with SMART on a MR-linear accelerator using a light inspiration breath hold. The adaptive workflow starts with an "original" plan which is then adapted daily based on anatomical variation for each fraction. "Predicted" plan dosimetry is generated for each fraction by re-calculating the original plan on the re-contoured pre-treatment anatomy, estimating what would have been delivered without adaptive capabilities. A "re-optimized" plan is developed based on the anatomy of the day to improve target coverage and meet critical organ-at-risk (OAR) metrics, including stomach, duodenum, large bowel and small bowel V33 < 1cc. Acute GI toxicity rates were assessed according to CTCAE v5. RESULTS The median age of our cohort was 71 (range 35-87) with 23/37 (62%) patients having locally advanced disease and 14/37 (38%) having borderline resectable disease. Adaptive planning was used in all cases with a prescription goal of 40 Gy in 5 fractions prescribed to 90% of the target volume. The median CTV was 80.5 cc (range, 10-180cc) and the PTV was a 3mm expansion. Adaptive planning was required in 156/185 fractions to meet either the stomach (63.8%), duodenum (33.5%), large bowel (12.4%) or small bowel (11.4%) V33 < 1cc metric. Of the plans adapted for OAR sparing, 90 plans required adaptation for one gastrointestinal organ, 50 plans for two, 10 plans for three and 1 plan for four. For predicted plans exceeding the V33 < 1cc metric, the median V33 for duodenum was 2.475cc (range: 1.01-10.68cc), stomach was 2.67cc (range: 1.01-8.21cc), small bowel was 2.71cc (range: 1.14-9.54cc) and large bowel was 1.93cc (range: 1.05-8.36cc). All re-optimized plans met the V33 < 1cc metric. No local failure or acute grade 3 toxicities were observed with a median follow-up of 6 months (range 3-15). CONCLUSION Online adaptive re-optimization was necessary for the majority of fractions and improved plan dosimetry was achieved specifically for duodenum, stomach, large and small bowel, achieving low rates of acute toxicity. The clinical benefits of MR-guided adaptive pancreatic SBRT for dose escalation warrant further investigation.

PURPOSE/OBJECTIVE(S) To describe the development, clinical impact, financial impact, and patient satisfaction with a Virtual Prostate Cancer Clinic (VPCC) for follow up of patients treated for prostate cancer. MATERIALS/METHODS In 2015, we developed an algorithm-based, nurse-practitioner led, VPCC with a digital health platform (DHP) infrastructure to take the place of routine in-person follow-ups for men who had completed definitive treatment with prostate cancer. Virtual monitoring consisted of PSA at an affiliated lab reporting directly into our EHR or a local lab, and patient-electronically submitted AUA and EPIC-CP questionnaires. The DHP analyzed PSA levels to indicate relapse or no relapse, and provided symptom scores based on questionnaire responses. Interaction was either by telephone, secure email, SMS, or messaging through the electronic health record portal. Post-treatment symptoms were managed virtually and patients with evidence of PSA recurrence were worked up with appropriate scanning per guidelines and discussed with the referring physician. We analyzed clinical volume, financial data, and surveyed patients on their satisfaction. RESULTS From March 15, 2016, to July 31, 2020, a total of 1397 patients enrolled in the VPCC. 94.3% of patients were comfortable with this form of monitoring, with 3.4% neutral, and 2.3% uncomfortable. 92.4% saved time & 53.2% saved > 3 hours per visit. There were 702 in-person prostate cancer follow-up visits in FY15, but after the VPCC, this number was lower in each subsequent year by 13.5% (607) in FY16, 17.5% (579) in FY17, 21.0% (554) in FY18, and 24.0% (533) in FY19. Consults of all malignancy types conducted by radiation oncologists that treat GU malignancies on the main campus in FY15 were 534. Comparing pre-VPCC FY 15 to post-VPCC, we saw consult increases of 44.4% (771) in FY16, 45.5% (777) in FY17, 49.6% (799) in FY18, and 109.74% (1120) in FY19. GU new start volume in FY15 was 213, FY16 284, FY17 335, FY18 297, and FY19 382. Comparing pre-VPCC FY15 to post-VPCC, we observed increases of 33.3% in FY16, 57.3% in FY17, 39.4% in FY18, and 79.3 in FY19. There was no reimbursement for VPCC visits, but it increased physician availability for new patients and was associated with genitourinary radiation oncology revenue growth of 26.6%, 43.3%, 40.3%, and 74.4% for FY16, FY17, FY18, and FY19 compared to pre-VPCC FY15. Prior to Covid-19 (Oct-19: Feb-20), the FY20 monthly average was 26.4 referrals and 91.2 visits. During Covid-19 (Mar-20: Jul-20) dramatic increases in monthly referrals (59, +123%) and virtual visits (127, +39.3%) were observed. CONCLUSION The VPCC is a novel method of delivering follow-up care virtually with a DHP infrastructure that led to high patient satisfaction, significant patient time-savings, significant revenue growth from provider availability for new patients, and finally, we found that during the COVID-19 era, this model allowed for very rapid switching of patients from in-person follow-ups to virtual monitoring.

PURPOSE/OBJECTIVE(S) Clinical trials of prostate SBRT have utilized a wide range of allowed doses to the intraprostatic urethra but the relationship between urethral dose and urinary toxicity has not been thoroughly evaluated. We aimed to characterize urinary toxicity outcomes according to urethral dose administered during prostate SBRT. MATERIALS/METHODS We searched MEDLINE (PubMed) for published prospective studies of prostate SBRT through August 2020 that documented a maximum urethral dose metric (MUDM). Reported acute and late urinary toxicity rates were collected. Weighted correlation and weighted linear regression models were used to assess the associations between urinary toxicity rates and MUDM. RESULTS Twenty-three unique studies (n = 2232 patients) met the inclusion criteria and included a wide range of MUDMs (EQD2 69 Gy to 141.75 Gy, a/b = 3). Median follow up ranged from 3-67 months (median 32 months). MUDM was strongly associated with urinary toxicity and was more closely associated with toxicity than prescription dose, including acute G2+ (r = 0.51, P = 0.02), late G2+ (r = 0.9, P < 0.0001) and late G3+ toxicity (r = 0.7, P = 0.003). Weighted linear regression accounting for age, prostate size and baseline urinary function confirmed association between urinary outcomes and MUDM. The weighted correlation model predicted late grade 2+ urinary toxicity rates of 2.5%, 5%, 10% and 15% corresponding to MUDMs of 34.2 Gy, 37.7 Gy, 43.9 Gy and 49.4 Gy, respectively, for 5 fraction regimens. Within the studied dose range, each increase of 1 Gy to the MUDM corresponded to a 0.8% and 0.9% increase in acute G2+ and late G2+ toxicity, respectively. CONCLUSION Radiation dose to the urethra correlates closely with urinary toxicity in prostate cancer patients treated with SBRT. Attention should be paid to urethral dose when delivering prostate SBRT to high doses and approaches for urethral dose reduction warrant further investigation. These techniques may be facilitated by online adaptive planning with daily urethral delineation.

Purpose/Objective(s) Patient reported outcome measures (PROMs) are tools, usually questionnaires, that measure patient reported outcomes (PROs), directly recording a patient's health status and symptoms without interpretation by clinicians. Use of PROs can improve patient survival, quality of life, and financial toxicity. The goal of this study was to assess the collection rate of PROs in our academic radiation oncology department since implementing an electronic PROs collection system as a part of routine clinical care in 2016. Our hypothesis was that we could collect PROs from a significant proportion of our patients using digital tools without significantly changing our clinical workflows. Materials/Methods Patients were assigned cancer-specific PROMs by their clinicians, and could submit answers by using a tablet provided in clinic or by using our electronic health record (EHR)-associated patient portal on a computer or mobile device (tablet or phone). We analyzed the collection rate of PROs from adult patients who received care in our department between March 2016 and March 2020. A Chi-squared test was used to compare groups. Results In total, we requested 216,842 PROMs from 22,471 patients (43% male, 57% female) from 176,904 visits. We received 127,686 PROMs from 77,689 encounters (43.9%) where patients were assigned at least one questionnaire. Among the collected PROMs (where at least one question was answered), 72% were answered completely. The number of collected PROMs increased over time, and the completely answered rate also increased over time. Patients who were more likely to answer PROMs were female, white, married or had a civil union or life partner, lived in-state, spoke English, had completed fewer years of schooling, and had a work status of full time or not retired or disabled. Most surveys were collected using a tablet in clinic (94%) from patients with breast (33%), genitourinary (19%), or thoracic (14%) malignancies during on treatment visits (54%). All P-values for described patterns were Conclusion PROs can be collected with relatively high rates from all patients in an academic radiation oncology department, though variations exist. This suggests that more radiation oncology clinics should try to incorporate PROs into routine patient care if they have sufficient resources. Implementation strategies should be shared among institutions, especially if they share EHR vendors.

BACKGROUND Definitive stereotactic body radiotherapy (SBRT) represents an emerging and debated treatment option for patients with prostate cancer, with potential economic savings and reports of short-term efficacy since 2006. The current study sought to define national trends in definitive prostate SBRT use and determine whether patterns vary by travel distance for treatment. METHODS The National Cancer Data Base identified 181,544 men with localized prostate cancer who were treated with definitive external beam radiotherapy from 2004 through 2012. Joinpoint regression analyzed definitive prostate SBRT trends over time, whereas multivariable logistic regression defined the odds for its receipt by travel distance for treatment. RESULTS Definitive prostate SBRT use increased from 1.8% in 2004 to 5.9% in 2012 (P for trend 50 miles were associated with increasing adjusted odds of receipt of definitive prostate SBRT (1.63 [95% confidence interval, 1.51-1.76] and 2.35 [95% confidence interval, 2.14-2.57], respectively; both P

Background Decipher is a validated genomic classifier developed to determine the biological potential for metastasis after radical prostatectomy (RP). Objective To evaluate the ability of biopsy Decipher to predict metastasis and Prostate cancer-specific mortality (PCSM) in primarily intermediate- to high-risk patients treated with RP or radiation therapy (RT). Design, setting, and participants Two hundred and thirty-five patients treated with either RP ( n =105) or RT±androgen deprivation therapy ( n =130) with available genomic expression profiles generated from diagnostic biopsy specimens from seven tertiary referral centers. The highest-grade core was sampled and Decipher was calculated based on a locked random forest model. Outcome measurements and statistical analysis Metastasis and PCSM were the primary and secondary outcomes of the study, respectively. Cox analysis and c-index were used to evaluate the performance of Decipher. Results and limitations With a median follow-up of 6 yr among censored patients, 34 patients developed metastases and 11 died of prostate cancer. On multivariable analysis, biopsy Decipher remained a significant predictor of metastasis (hazard ratio: 1.37 per 10% increase in score, 95% confidence interval [CI]: 1.06–1.78, p =0.018) after adjusting for clinical variables. For predicting metastasis 5-yr post-biopsy, Cancer of the Prostate Risk Assessment score had a c-index of 0.60 (95% CI: 0.50–0.69), while Cancer of the Prostate Risk Assessment plus biopsy Decipher had a c-index of 0.71 (95% CI: 0.60–0.82). National Comprehensive Cancer Network risk group had a c-index of 0.66 (95% CI: 0.53–0.77), while National Comprehensive Cancer Network plus biopsy Decipher had a c-index of 0.74 (95% CI: 0.66–0.82). Biopsy Decipher was a significant predictor of PCSM (hazard ratio: 1.57 per 10% increase in score, 95% CI: 1.03–2.48, p =0.037), with a 5-yr PCSM rate of 0%, 0%, and 9.4% for Decipher low, intermediate, and high, respectively. Conclusions Biopsy Decipher predicted metastasis and PCSM from diagnostic biopsy specimens of primarily intermediate- and high-risk men treated with first-line RT or RP. Patient summary Biopsy Decipher predicted metastasis and prostate cancer-specific mortality risk from diagnostic biopsy specimens.

Androgen deprivation therapy (ADT) is not recommended for low-risk prostate cancer because of its lack of benefit and potential for harm. We evaluated the incidence and predictors of ADT use in low-risk disease.Using the National Cancer Database, we identified 197,957 patients with low-risk prostate cancer (Gleason score of 3 + 3 = 6, prostate-specific antigen level10 ng/mL, and cT1-T2a) diagnosed from 2004 to 2012 with complete demographic and treatment information. We used multiple logistic regression to evaluate predictors of ADT use and Cox regression to examine its association with all-cause mortality.Overall ADT use decreased from 17.6% in 2004 to 3.5% in 2012. In 2012, 11.5% of low-risk brachytherapy patients and 7.6% of external beam radiation therapy patients received ADT. Among 82,352 irradiation-managed patients, predictors of ADT use included treatment in a community versus academic cancer program (adjusted odds ratio [AOR], 1.60; 95% confidence interval [CI], 1.50-1.71; P.001; incidence, 14.0% vs 6.0% in 2012); treatment in the South (AOR, 1.51), Midwest (AOR, 1.81), or Northeast (AOR, 1.90) versus West (P.001); and brachytherapy use versus external beam radiation therapy (AOR, 1.32; 95% CI, 1.27-1.37; P.001). Among 25,196 patients who did not receive local therapy, predictors of primary ADT use included a Charlson-Deyo comorbidity score of ≥2 versus 0 (AOR, 1.42; 95% CI, 1.06-1.91; P=.018); treatment in a community versus academic cancer program (AOR, 1.61; 95% CI, 1.37-1.90; P.001); and treatment in the South (AOR, 1.26), Midwest (AOR, 1.52), or Northeast (AOR, 1.28) versus West (P≤.008). Primary ADT use was associated with increased all-cause mortality in patients who did not receive local therapy (adjusted hazard ratio, 1.28; 95% CI, 1.14-1.43; P.001) after adjustment for age and comorbidity.ADT use in low-risk prostate cancer has declined nationally but may remain an issue of concern in certain populations and regions.

In 2012, the United States Preventive Services Task Force (USPSTF) recommended against prostate-specific antigen (PSA) screening, despite evidence that Black men are at a higher risk of prostate cancer-specific mortality (PCSM). We evaluated whether Black men of potentially screening-eligible age (55-69 years) are at a disproportionally high risk of poor outcomes.The SEER database was used to study 390 259 men diagnosed with prostate cancer in the United States between 2004 and 2011. Multivariable logistic regression modeled the association between Black race and stage of presentation, while Fine-Gray competing risks regression modeled the association between Black race and PCSM, both as a function of screening eligibility (age 55-69 years versus not).Black men were more likely to present with metastatic disease (adjusted odds ratio [AOR] 1.65; 1.58-1.72; P 0.001) and were at a higher risk of PCSM (adjusted hazard ratio [AHR] 1.36; 1.27-1.46; P 0.001) compared to non-Black men. There were significant interactions between race and PSA-screening eligibility such that Black patients experienced more disproportionate rates of metastatic disease (AOR 1.76; 1.65-1.87 versus 1.55; 1.47-1.65; Pinteraction 0.001) and PCSM (AHR 1.53; 1.37-1.70 versus 1.25; 1.14-1.37; Pinteraction = 0.01) in the potentially PSA-screening eligible group than in the group not eligible for screening.Racial disparities in prostate cancer outcome among Black men are significantly worse in PSA-screening eligible populations. These results raise the possibility that Black men could be disproportionately impacted by recommendations to end PSA screening in the United States and suggest that Black race should be included in the updated USPSTF PSA screening guidelines.

Purpose: The use of large-field external beam reirradiation (re-RT) after pelvic radiation therapy (RT) for genitourinary (GU) cancers has not been reported. We report the results of such treatment in patients with either symptomatic GU second malignant neoplasms or locally recurrent pelvic tumors after initial RT for whom surgery or further systemic therapy was not an option. Methods and materials: The records of 28 consecutive patients with advanced, bulky GU malignancies treated with high-dose, large-field re-RT with palliative intent between 2008 and 2014 were retrospectively reviewed. Descriptive outcome analyses focused on toxicities and symptom control, and responses were evaluated by 2 independent observers. Results: Twenty-seven male patients (96%) were included. Median initial external beam RT dose was 64 Gy (range, 30-75.6 Gy). The median time between initial RT and re-RT was 9.5 years (range, 0.2-32 years). At the time of re-RT, there were 16 local recurrences and 12 second malignant neoplasms together comprising 16 bladder, 10 prostate, 1 ureteral, and 1 penile cancer. Indications for re-RT were pain and bleeding/hemorrhage. The median equivalent sphere diameter planning target volume for re-RT was 8.6 cm (range, 4.7-16.3 cm). Given the severity of the symptoms and the bulk of the disease at the time of re-RT, a higher dose of RT was administered. The median re-RT dose was 50 Gy (range, 27.5-66 Gy). For patients who received

Patient reported outcomes (PROs) are reports of health conditions that come directly from patients. Use of PROs has been associated with improved patient outcomes, enhanced quality of life, and reduced end-of-life spending. Yet there are still outstanding questions regarding the process of implementing PRO collection in routine practice. In this article, we describe the experience of selecting and implementing PROs in a multisite, multidisease academic medical center–based radiation oncology practice and demonstrate that such large-scale rollout is feasible. We establish that PROs can be implemented with minimal to no workflow delays, are generally seen as valuable by clinicians, and can enhance patient-doctor communication. We additionally detail the challenges involved in selecting clinically relevant PRO questionnaires and the centrality of physician buy-in, easy data access, and clear workflows to successful implementation.

Purpose The report highlights utilization of advanced practice providers (APPs) in an academic radiation oncology center and how their role benefits patient care and departmental workflow. Methods and Materials A self-reported workflow analysis of department APPs was conducted across 5 disease sites. A review of electronic medical records was performed to determine the percent of APP follow-ups completed independently versus in a shared capacity with the radiation oncologist. A review of the APP's didactic and clinical training program was performed. Results Across all disease sites, approximately 40% of the APP's time was spent on direct patient care, predominantly composed of independent follow-up visits (9%-35%) and telehealth (2%-30%). The breast malignancies group was an outlier with a higher focus on consults or shared visits (25%). Indirect patient care accounts for 30% to 50% of workflow with the focus on visit preparation or care coordination (13%-35%) and dictation (8%-13%). Administrative responsibilities including process improvement, research, education, and leadership account for the remainder (5%-26%) and are varied across disease sites. The central nervous system malignancies group and genitourinary malignancies group reported a greater percentage of their time (23%-26%) on administration compared with other groups (5%-9%). On average APPs see most of their visits independently from the physicians (86.41%) with 13.59% of visits being seen in a shared capacity. Conclusions APPs can positively affect the field of radiation oncology by augmenting clinical capacity, optimizing workflow and increasing department efficiency via both direct and indirect patient care and through involvement in administrative and leadership duties. By implementing an independent-to practice model, simultaneous APP and physician clinics run parallel to each other, limiting shared visits for complex cases. This promotes APP job satisfaction and provides greater access to patient care without compromising quality. This article highlights a model for the utilization of APPs, which can be implemented by other radiation oncology departments or practices.

Prostate tumors with TP53 gene mutations are molecularly heterogenous, and the presence of TP53 gene mutations has been linked to inferior outcomes. We developed an RNA-based gene signature that detects underlying TP53 gene mutations and identifies wild-type prostate tumors that are analogous to TP53-mutant tumors.Using genomic expression profiles from The Cancer Genome Atlas, we developed a mutation signature score to predict prostatic tumors with a molecular fingerprint similar to tumors with TP53 mutations. Area under the receiver operating characteristic curve assessed model accuracy in predicting TP53 mutations, and Cox regression models measured association between the signature and progression-free survival and metastasis-free survival (MFS).The TP53 signature score achieved an area under the receiver operating characteristic curve of 0.84 in the training and 0.82 in the validation cohorts for predicting an underlying mutation. In three retrospective cohorts, a high score was prognostic for poor 5-year MFS: 46% versus 81% (hazard ratio [HR], 3.05; P .0001; Johns Hopkins University cohort), 64% versus 83% (HR, 2.77; P .0001; Mayo Clinic cohort), and 71% versus 97% (HR, 6.8; P = .0001; Brigham and Women's Hospital cohort). The signature also identified TP53 wild-type tumors molecularly analogous to TP53 mutant tumors, wherein high signature score correlated with worse 5-year MFS (50% vs. 82%; HR, 3.05; P .0001).This novel mutational signature predicted tumors with TP53 mutations, identified TP53 wild-type tumors analogous to mutant tumors, and was independently associated with poor MFS. This signature can therefore be used to strengthen existing clinical risk-stratification tools.

12004 Background: Cisplatin is an essential component of first-line chemotherapy for many cancers, but causes neurotoxicity, including hearing loss (CisHL), tinnitus (CisTinn), and peripheral sensory neuropathy (CisPNeuro). However, few opportunities exist to identify risk factors and comorbidities for cisplatin-induced neurotoxicities among large numbers of homogenously treated patients without the confounding effect of cranial radiotherapy. Methods: Within a well-characterized clinical cohort of 1,680 cisplatin-treated testicular cancer survivors, linear and logistic regression analysis were utilized to analyze associations of CisHL (n = 1,258), CisTinn (n = 1,217), and CisPNeuro (n = 1,653) with non-genetic risk factors. Genome-wide association studies and gene-based analysis were performed on each phenotype. Results: Cisplatin-induced neurotoxicities (CisHL CisTinn, CisPNeuro), adjusting for age and cisplatin dose, were interdependent. Survivors with these neurotoxicities experienced more hypertension (CisTinn: OR = 2.62, p < 0.0001; CisHL: β = 0.25, p = 8.5 x10-4; CisPNeuro: OR = 1.86, p < 0.0001) and were more likely to report their health as poor (CisTinn: OR = 0.54, p < 0.0001; CisHL: β = -0.11, p < 0.0001; CisPNeuro: OR = 0.61, p < 0.0001). Persistent vertigo was significantly associated with both CisTinn (OR = 7.18, p < 0.0001) and CisPNeuro (OR = 4.29, p < 0.0001). In addition, CisTinn was significantly associated with hypercholesterolemia (OR = 1.78, p = 0.01). Importantly, gene-based association analyses identified significant associations between CisTinn and WNT8A (n = 1,037, p = 2.52x10-6) , encoding a signaling protein important in germ cell tumors; and marginal significance between CisHL and TXNRD1 (n = 1,071, p = 4.21x10-6) , thioredoxin reductase-1, which plays a key role in redox regulation. In silico analysis showed high expression levels of TXNRD1 were significantly correlated with cellular resistance to cisplatin in central nervous system tumor cells (Spearman Rho = 0.35, p = 0.04; R2= 0.14, p = 0.03), indicating TXNRD1 is protective for cisplatin-induced cytotoxicity. Previously, rs62283056 in WFS1 found to be significantly associated with CisHL (n = 511; subset of current population), was marginally significant in an independent replication cohort (p = 0.06; n = 606; subset of current population). Conclusions: Cisplatin-induced neurotoxicities are significantly associated with multiple clinical characteristics, including hypertension and self-reported poor health. WNT8A and TXNRD1 are notable risk factors for CisTinn and CisHL, respectively . Future studies should further investigate these genes and their potential impact on chemotherapy strategies. This study, based on the largest number of testicular cancer survivors investigated to date, highlights the clinical importance of these iatrogenic toxicities and their associated risk factors.

12063 Background: Platinum levels are measurable in the serum for decades after cisplatin therapy and higher levels may be related to chemotherapy-induced toxicities. Since cisplatin is cleared exclusively by the kidney, we hypothesized that a genetic predictor of kidney function, an estimated glomerular filtration rate polygenic risk score (eGFR PRS), would significantly associate with serum platinum levels and could improve prediction models. Methods: Within a large well-characterized, multicenter clinical cohort of cisplatin-treated testicular cancer survivors (TCS), we conducted analyses on all patients with genetic data and serum platinum levels. Genotyping was performed on the HumanOmniExpressExome chip and standard QC measures were included. Serum platinum concentrations were quantified by inductively coupled plasma mass spectrometry. For all TCS, time since therapy (TIME) and cumulative cisplatin dose were collected. The eGFR PRS was developed from the Chronic Kidney Disease Genetics (CKDGen) consortium meta-analysis summary statistics using PRS-CS. Using principal component analysis, we restricted the analysis to TCS of genetically determined European ancestry, then calculated the genome-wide PRS for all participants. We performed Cox regression analyses to evaluate prediction models of serum platinum that included cumulative dose and TIME, as well as a model including eGFR PRS. Data are presented as median(interquartile range). Results: 901 patients were included in our analysis with a median diagnosis age of 31 (26 - 38) years, cumulative cisplatin dose of 400 (300-400) mg/m2, and time since first cisplatin dose of 4.6 (2.3-9.5) years. The median serum platinum level for all TCS was 305 (121-981) ng/L. When stratified into quartiles by eGFR PRS, TCS in the lowest quartile had a median serum platinum level of 316 (139-1014) ng/L while TCS in the highest had a median of 268 (106-731) ng/L. Comparison of two Cox regression models for serum platinum prediction, one including only cumulative dose and TIME as predictors and a second including dose, TIME, eGFR PRS, and an eGFR PRS*TIME interaction term, we determined the model including eGFR PRS had a lower AIC (14350 vs 16180) suggesting a more parsimonious model. Further, eGFR PRS was a significant independent predictor of serum platinum levels (p = 0.02) and the impact of eGFR PRS varies over time (eGFR PRS*TIME, p = 0.05). Conclusions: The genetic predictor of kidney function circumvents the use of renal function measures that may have been impaired by initial cisplatin administration. It is a significant independent predictor of serum platinum levels and consistent with expectation: TCS with higher genetically predicted kidney function had lower serum platinum levels. Our results suggest kidney function inferred by genetics may improve the prediction of serum platinum levels.

5025 Background: Cancer survivors are at increased risk of anxiety and depression that can affect health-related quality of life. There is no study to date that has examined the characteristics of testicular cancer survivors (TCS) taking medications for anxiety or depression since pharmacological interventions are typically reserved for more severe cases of these disorders. In this study, we aimed to examine sociodemographic factors, cisplatin-related adverse health outcomes (AHOs), and cumulative burden of morbidity (CBMPt) scores associated with medication use for anxiety and/or depression in TCS. Methods: A total of 1,802 TCS who completed CBCT ≥12 months previously completed validated questionnaires regarding sociodemographic features and cisplatin-related AHOs (hearing impairment, tinnitus, peripheral sensory neuropathy (PSN), kidney disease). Patients were recognized as users of medications for anxiety and/or depression if they used pharmacological classes of these medications and also indicated that the reason for use was for anxiety or depression. Individual AHOs were graded 0-to-4 based on severity according to NCI Common Terminology Criteria for Adverse Events version 4.03. A CBMPt score encompassed the number and severity of cisplatin-related AHOs. Multivariable logistic regression models assessed the relationship of individual AHOs and CBMPt with medication use for anxiety and/or depression. Results: A total of 151 TCS (8.4%) used medications for anxiety and/or depression. Any grade of HL, tinnitus, PSN, and kidney disease were reported by 37.9%, 39.5%, 55.2%, and 2.4% of 1,802 participants, respectively. No cisplatin-related AHO were reported by 511 (28.4%) participants, whereas 622 (34.5%), 334 (18.5%), 287 (15.9%), and 48 (2.7%), respectively, had very low, low, medium, and high CBMPt scores. Higher CBMPt scores were significantly associated with greater medication use for anxiety and/or depression (CBMPt scores of low (OR = 2.96, 95%CI, 1.67-5.24), medium (OR = 3.47, 95%CI, 1.95-6.18), and high (OR = 3.18, 95%CI, 1.22-8.3). A multivariable model including individual AHOs indicated that tinnitus ( P= 0.0009), PSN ( P= 0.02), and having health insurance (OR = 2.15, 95%CI, 1.01-4.56) were associated with significantly greater use of these medications; whereas being employed (OR = 0.39, 95%CI, 0.23-0.66) and vigorous physical activity (OR = 0.63, 95%CI,0.44-0.89) were associated with significantly diminished use. Conclusions: We found that TCS with higher CBMPt scores had a higher probability of using medications for anxiety and/or depression and conversely, those who were employed and physically active tended to have reduced use. These findings deserve further investigation in longitudinal studies. In the interim, healthcare providers should be aware of these associations in formulating survivorship care plans.

5016 Background: Although pure-tone audiometry is the gold standard to evaluate hearing loss (HL), patient-reported outcomes are practically more time and cost effective. However, no data exist on factors associated with discrepancies between patient-reported and audiometrically-defined HL in adult-onset cancer survivors after cisplatin-based chemotherapy (CBCT); and few comprehensive assessments of factors associated with audiometrically-defined HL have been conducted. Methods: A total of 1,410 testicular cancer survivors (TCS) ≥6 months post-CBCT completed comprehensive audiometric assessments (0.25-12 kHz) and detailed questionnaires of sociodemographic, clinical, and health behaviors. Audiometrically-defined HL severity was defined using American Speech-Language-Hearing Association (ASHA) criteria. Multivariable multinomial logistic regression identified factors associated with discrepancies (overestimation and underestimation vs. concordance), between patient-reported and audiometrically-defined HL and multivariable ordinal logistic regression evaluated factors associated with the HL severity. Results: Overall, 34.8% of TCS self-reported HL, while 77.8% had audiometrically-defined HL. Among TCS without tinnitus, those with audiometrically-defined HL at only extended high frequencies (EHFs) (10-12 kHz) (17.8%) or at both EHFs and standard frequencies (0.25-8 kHz) (23.4%) were significantly more likely to self-report HL than those with no audiometrically-defined HL (8.1%) (OR = 2.48; 95%CI, 1.31-4.68 and OR = 3.49; 95%CL,1.89-6.44, respectively). Older age (OR = 1.09; P< 0.0001), absence of prior noise exposure (OR = 1.40; P= 0.02), and mixed/conductive HL (OR = 2.01; P= 0.0007) were associated with greater underestimation of audiometrically-defined HL severity. Hearing aid use (OR = 0.18; P= 0.003) and higher education ( P= 0.004) were associated with less underestimation of audiometrically-defined HL severity, while tinnitus was associated with greater overestimation ( P< 0.0001). Older age (OR = 1.13; P< 0.0001), cumulative cisplatin dose ( > 300 mg/m2, OR = 1.47; P= 0.0001), and hypertension (OR = 1.80; P= 0.0007) were associated with greater ASHA-defined HL severity, whereas post-graduate education (OR = 0.58; P= 0.005) was associated with less severe HL. Conclusions: Discrepancies between patient-reported and audiometrically-defined HL after CBCT are associated with several factors including age, education, tinnitus, prior noise exposure, use of hearing aids, and conductive HL. Understanding these factors will help clinicians to better interpret self-reported HL as a surrogate for audiometric assessments. For survivors who self-report HL, but have normal audiometric findings at standard frequencies, referral to an audiologist for additional testing and inclusion of EHFs in audiometric assessments, should be considered.

Background: We examined the ability of a biopsy-based 22-marker genomic classifier (GC) to predict for distant metastases after radiation and a median of 6 months of androgen deprivation therapy (ADT). Methods: We studied 100 patients with intermediate-risk (55%) and high-risk (45%) prostate cancer who received definitive radiation plus a median of 6 months of ADT (range 3–39 months) from 2001–2013 at a single center and had available biopsy tissue. Six to ten 4 micron sections of the needle biopsy core with the highest Gleason score and percentage of tumor involvement were macrodissected for RNA extraction. GC scores (range, 0.04–0.92) were determined. The primary end point of the study was time to distant metastasis. Median follow-up was 5.1 years. There were 18 metastases during the study period. Results: On univariable analysis (UVA), each 0.1 unit increase in GC score was significantly associated with time to distant metastasis (hazard ratio: 1.40 (1.10–1.84), P=0.006) and remained significant after adjusting for clinical variables on multivariable analysis (MVA) (adjusted hazard ratio: 1.36 (1.04–1.83), P=0.024). The c-index for 5-year distant metastasis was 0.45 (95% confidence interval: 0.27–0.64) for Cancer of the Prostate Risk Assessment score, 0.63 (0.40–0.78) for National Comprehensive Cancer Network (NCCN) risk groups, and 0.76 (0.57–0.89) for the GC score. Using pre-specified GC risk categories, the cumulative incidence of metastasis for GC>0.6 reached 20% at 5 years after radiation (P=0.02). Conclusions: We believe this is the first demonstration of the ability of the biopsy-based GC score to predict for distant metastases after definitive radiation and ADT for intermediate- and high-risk prostate cancer. Patients with the highest GC risk (GC>0.6) had high rates of metastasis despite multi-modal therapy suggesting that they could potentially be candidates for treatment intensification and/or enrollment in clinical trials of novel therapy.

BACKGROUND Most major cancer organizations seek to reduce sociodemographic disparities in high-risk cancers partly by increasing access to theoretically high-quality, academic-oriented cancer care. The objective of this study was to determine whether academic centers have less sociodemographic treatment disparities than community centers using high-risk prostate cancer as a test case. METHODS The National Cancer Data Base was used to identify 138,019 patients who were diagnosed with nonmetastatic, high-risk prostate cancer from 2004 to 2012. Multivariable logistic analysis was used to identify independent determinants of definitive therapy. The Gray test and multivariable Cox regression were used to analyze the timing of therapy. All analyses were stratified by academic versus community cancer center. RESULTS Compared with white or privately insured patients, black, Hispanic, and uninsured patients with prostate cancer were less likely to receive definitive therapy at both community centers (adjusted odds ratio: 0.60 [95% confidence interval (CI), 0.56-0.64], 0.69 [95% CI, 0.61-0.78], and 0.25 [95% CI, 0.22-0.30], respectively) and academic cancer centers (adjusted odds ratio: 0.50 [95% CI, 0.46-0.54], 0.56 [95% CI, 0.50-0.64], and 0.31 [95% CI, 0.28-0.36], respectively). Among patients who received definitive therapy, black, Hispanic, and uninsured patients were more likely to experience treatment delays at both community centers (≥15, ≥ 10, and ≥19 days, respectively; all Gray P

BACKGROUND In the current study, the authors sought to both characterize the national trends in proton therapy use for prostate cancer and determine the factors associated with receipt of this limited resource, using what to the best of their knowledge is the largest nationwide cancer registry. METHODS The National Cancer Data Base was used to identify 187,730 patients diagnosed with nonmetastatic prostate cancer from 2004 through 2012 who received external beam radiotherapy as their initial form of definitive therapy. Multivariable logistic regression analysis adjusted for sociodemographic and clinical factors was used to identify independent determinants of proton therapy use. RESULTS The rate of proton therapy use increased significantly from 2.3% in 2004 to 5.2% in 2011 and 4.8% in 2012 (P value for trend

BACKGROUND: Patient-reported outcome measures (PROMs) have become widely adopted in the care of patients with prostate cancer, but there is no validated crosswalk between two commonly used instruments, the Expanded Prostate Cancer Index Composite Short Form (EPIC-26) and the Memorial Sloan Kettering (MSK) instrument, which consists of the International Index of Erectile Function-6 (IIEF-6) questionnaire and the MSK radical prostatectomy urinary outcome scale. OBJECTIVE: To develop and validate bidirectional crosswalks between the sexual and urinary domains (single domain in MSK, separate incontinence and irritative/obstructive domains in EPIC-26) of the MSK and EPIC-26 instruments. DESIGN, SETTING, AND PARTICIPANTS: Radical prostatectomy (RP) patients completing instruments at MSK and Michigan Urological Surgery Improvement Collaborative (MUSIC) between January and May of 2017 were invited to enroll. Stratified random sampling (by institution, MSK urinary function score, and MSK erectile function score) was used to divide patient data into training and test sets. Models were developed to predict the domain score for each instrument using the other’s item responses and domain scores. Performance was evaluated using capped root-mean-squared error and accuracy at established thresholds. RESULTS AND LIMITATIONS: We received 517 instruments at MSK and 1033 within MUSIC, which were assigned to training (825), post-RP test (412), and pre-RP test (313) sets. We found the crosswalks to have low error and high accuracy. Although the crosswalks are more accurate if responses to each item are known, it is possible to convert between instruments on the basis of a total domain score. CONCLUSIONS: The crosswalks are a valid way to convert between sexual and urinary domains of the MSK and EPIC-26 instruments.

Background: Management of patients with a very high prostate-specific antigen (PSA) level (≥98.0 ng/mL) but clinically localized (N0M0) prostate cancer is challenging. This study sought to determine practice patterns and outcomes among these patients. Patients and Methods: A total of 748,825 patients with prostate cancer from 2004 through 2012 were identified using the National Cancer Database. These patients were subdivided by PSA level (0–9.9, 10.0–19.9, 20.0–39.9, 40.0–59.9, 60.0–79.9, 80.0–97.9, and ≥98.0 ng/mL), nodal status (N0 vs N1), and distant metastases (M0 vs M1). Rates of locoregional treatment and 5-year overall survival (OS) in each group were determined. Survival was compared using Cox regression after adjusting for multiple patient-specific factors. Results: The rate of locoregional treatment for patients with N0M0 disease and PSA level ≥98.0 ng/mL was significantly lower than for those with N1M0 disease (52.6% vs 60.4%; PPP=.063). The survival benefit associated with locoregional treatment was higher among those with N0M0 disease and a very high PSA level than among those with N1M0 disease (aHR, 0.28 vs 0.44; PConclusions: Patients with clinical N0M0 disease and a very high PSA level (≥98.0 ng/mL) have outcomes similar to those with N1 disease but receive locoregional treatment at a lower rate. Future work is needed to investigate the utility of locoregional treatment in this population.

To identify contemporary, clinically low-risk patients with ≥50% cores positive and compare the risk of upgrading at prostatectomy with other low- or intermediate-risk patients.We studied 14,902 patients with prostate cancer in the Surveillance, Epidemiology, and End Results database in 2010-2011 treated with prostatectomy. Patients were categorized by National Comprehensive Cancer Network clinical risk groups, separating low-risk patients by percent positive biopsy cores (PBC). We measured incidence of pathologic high-risk disease, defined as pT3a-T4 or Gleason 8-10, and multivariable logistic regression was used to determine if patients with clinical low-risk disease and ≥50% PBC were similar to other low- or intermediate-risk patients. This analysis was repeated with favorable and unfavorable intermediate risk.At prostatectomy, 9.2% of clinically low-risk patients with50% PBC, 18.6% of clinically low-risk patients with ≥50% PBC, and 27.6% of clinically intermediate-risk patients had occult, high-risk disease (P.001). On multivariable logistic regression, low-risk patients with ≥50% PBC were more likely than low-risk patients with50% PBC to have pathologic high-risk disease (adjusted odds ratio [AOR] 2.28, 95% confidence interval 1.90-2.73, P.001), had similar risk to favorable intermediate patients overall (AOR 1.09, 0.91-1.31, P = .33), and had higher risk than favorable intermediate patients aged over 60 years (AOR 1.28, 1.00-1.64, P = .04). Low-risk patients with ≥50% PBC had a mean tumor size similar to unfavorable intermediate-risk patients (21.3 vs 21.0 mm, P = .82).Nearly 1 in 5 clinically low-risk prostate cancer patients with ≥50% PBC harbor occult pT3a-T4 or Gleason 8-10, suggesting that national guidelines should not classify low-risk patients with ≥50% cores positive as "low risk," and patients should be made aware of this excess risk if considering active surveillance.

Purpose: Recent retrospective data suggest that brachytherapy (BT) boost may confer a cancer-specific survival benefit in radiation-managed high-risk prostate cancer. We sought to determine whether this survival benefit would extend to the recently defined favorable high-risk subgroup of prostate cancer patients (T1c, Gleason 4 + 4 = 8, PSA 20 ng/ml). Material and methods: We identified 45,078 patients in the Surveillance, Epidemiology, and End Results database with cT1c-T3aN0M0 intermediate- to high-risk prostate cancer diagnosed 2004-2011 treated with external beam radiation therapy (EBRT) only or EBRT plus BT. We used multivariable competing risks regression to determine differences in the rate of prostate cancer-specific mortality (PCSM) after EBRT + BT or EBRT alone in patients with intermediate-risk, favorable high-risk, or other high-risk disease after adjusting for demographic and clinical factors. Results: EBRT + BT was not associated with an improvement in 5-year PCSM compared to EBRT alone among patients with favorable high-risk disease (1.6% vs. 1.8%; adjusted hazard ratio [AHR]: 0.56; 95% confidence interval [CI]: 0.21-1.52, p = 0.258), and intermediate-risk disease (0.8% vs. 1.0%, AHR: 0.83, 95% CI: 0.59-1.16, p = 0.270). Others with high-risk disease had significantly lower 5-year PCSM when treated with EBRT + BT compared with EBRT alone (3.9% vs. 5.3%; AHR: 0.73; 95% CI: 0.55-0.95; p = 0.022). Conclusions: Brachytherapy boost is associated with a decreased rate of PCSM in some men with high-risk prostate cancer but not among patients with favorable high-risk disease. Our results suggest that the recently-defined “favorable high-risk” category may be used to personalize therapy for men with high-risk disease. J Contemp Brachytherapy 2016; 8, 1: 1–6 DOI: 10.5114/jcb.2016.58080

BACKGROUND We previously identified a protein tumor signature of PTEN, SMAD4, SPP1, and CCND1 that, together with clinical features, was associated with lethal outcomes among prostate cancer patients. In the current study, we sought to validate the molecular model using time-dependent measures of AUC and predictive values for discriminating lethal from non-lethal prostate cancer. METHODS Using data from the initial study, we fit survival models for men with prostate cancer who were participants in the Physicians' Health Study (PHS; n = 276). Based on these models, we generated prognostic risk scores in an independent population, the Health Professionals Follow-up Study (HPFS; n = 347) to evaluate external validity. In each cohort, men were followed prospectively from cancer diagnosis through 2011 for development of distant metastasis or cancer mortality. We measured protein tumor expression of PTEN, SMAD4, SPP1, and CCND1 on tissue microarrays. RESULTS During a median of 11.9 and 14.3 years follow-up in the PHS and HPFS cohorts, 24 and 32 men (9%) developed lethal disease. When used as a prognostic factor in a new population, addition of the four markers to clinical variables did not improve discriminatory accuracy through 15 years of follow-up. CONCLUSIONS Although the four markers have been identified as key biological mediators in metastatic progression, they do not provide independent, long-term prognostic information beyond clinical factors when measured at diagnosis. This finding may underscore the broad heterogeneity in aggressive prostate tumors and highlight the challenges that may result from overfitting in discovery-based research. Prostate 75:1926–1933, 2015. © 2015 Wiley Periodicals, Inc.

To determine whether very small prostate cancers present in patients who also have lymph node (LN) metastases represent a particularly aggressive disease variant compared with larger LN-positive tumours.We identified 37 501 patients diagnosed with prostate cancer between 1988 and 2001 treated with radical prostatectomy within the Surveillance, Epidemiology, and End Results database. The primary study variables were tumour size by largest dimension (stratified into: (i) microscopic focus only or 1 mm; (ii) 2-15 mm; (iii) 16-30 mm; (iv)30 mm), regional LN involvement, and the corresponding interaction term. We evaluated the risk of 10-year prostate cancer-specific mortality (PCSM) using the Fine and Gray model for competing risks after controlling for race, tumour grade, T stage, receipt of radiation, number of dissected LNs, number of positive LNs, year of diagnosis, and age at diagnosis.The median follow-up was 11.8 years. There was a significant interaction between tumour size and LN involvement (P-interaction0.001). In the absence of LN involvement (36 561 patients), the risk of 10-year PCSM increased monotonically with increasing tumour size. Among patients with LN involvement (940), those with the smallest tumours had increased 10-year PCSM compared with patients with tumours sized 2-15 mm (24.7% vs 11.8%; adjusted hazard ratio [AHR] 2.84, 95% confidence interval [CI] 1.21-6.71; P = 0.017) or 16-30 mm (24.7% vs 15.5%; AHR 3.12, 95% CI 1.51-6.49; P = 0.002), and similar 10-year PCSM as those with tumours30 mm (24.7% vs 24.9%; P = 0.156).In patients with prostate cancer with LN involvement, very small tumour size may predict for higher PCSM compared with some larger tumours, even after controlling for other prognostic variables. These tumours might be particularly aggressive, beyond what is captured by pathological assessment of tumour grade and stage.

Objectives To describe outcomes of patients with prostate cancer diagnosed after another malignancy and identify factors associated with prostate cancer death in this population, as little is known about the clinical significance of prostate cancer as a subsequent malignancy. Patients and Methods We studied 18 225 men diagnosed with prostate cancer after another malignancy from 1973 to 2006. We compared demographic and clinical variables, and the proportion of death from prostate cancer vs prior malignancy with t-test and chi-squared analyses. Fine and Gray's regression was used to consider the effect of treatment on prostate cancer death. We then studied a second cohort of 88 013 men with prostate cancer as a first or second malignancy to describe current diagnostic and treatment patterns. Results One in seven men died from prostate cancer in our first cohort. More died from prostate cancer following colorectal cancer (16.8% vs 13.7%), melanoma (13.4% vs 7.56%), and oral cancer (19.1% vs 4.04%), but fewer following bladder cancer, kidney cancer, lung cancer, leukaemia and non-Hodgkin's lymphoma (all P < 0.001). Prostate cancer treatment was associated with a nearly 50% lower risk of death when high-grade or high-stage (adjusted hazard ratio 0.55, 95% confidence interval [CI] 0.47–0.64). Patients who died from prostate cancer had higher grade and stage disease, and received less treatment than patients who died from prior malignancy. The second cohort showed subsequent prostate cancer had more high-risk disease (36.3% vs 22.2%, P < 0.001) and less prostate cancer treatment (adjusted odds ratio 0.872, 95% CI 0.818–0.930) than primary prostate cancer. Conclusions Prostate cancer remains a significant cause of mortality when diagnosed as a subsequent cancer. These results suggest prostate cancer treatment should be seriously considered in patients with prior malignancies, especially those with high-grade or locally advanced prostate cancer.

Following radical prostatectomy (RP), adjuvant radiation therapy (RT) decreases biochemical recurrence and potentially improves metastasis-free and overall survival for patients with high-risk pathologic features. Since adjuvant RT typically occurs daily over several weeks, the logistical challenges of extensive traveling may be a significant barrier to its use. We examined the association between distance to treatment facility and use of adjuvant RT.We identified 97,568 patients in the National Cancer Database diagnosed from 2004 through 2011 with cT1-4N0-xM0-x prostate cancer and found to have high-risk pathologic features (pT3-4 stage and/or positive surgical margins) at RP. Multivariable logistic regression adjusting for sociodemographic and clinicopathologic factors was used to examine the association between travel distance and receipt of adjuvant RT, defined as radiotherapy initiated within 12 months after RP.Overall, 10.6% (10,346) of the study cohort received adjuvant RT. On multivariable analysis, increasing travel distance was significantly associated with decreased use of adjuvant RT, with adjusted odds ratios of 1.0 (reference), 0.67, 0.46, 0.39, and 0.32 (all P0.001) and prevalence of use at 12.6%, 8.8%, 6.3%, 4.9%, and 3.7% for patients living ≤25.0, 25.1 to 50.0, 50.1 to 75.0, 75.1 to 100.0, and100.0 miles away, respectively.Increasing travel distance was strongly associated with decreased use of adjuvant RT in this national cohort of postprostatectomy patients with high-risk pathologic features. These results strongly suggest that the logistical challenges of extensive travel are a significant barrier to the use of adjuvant RT. Efforts aimed at improving access to radiotherapy and reducing treatment time are urgently needed.

Background The consequences of low prostate-specific antigen (PSA) in high-grade (Gleason 8–10) prostate cancer are unknown. Objective To evaluate the clinical implications and genomic features of low-PSA, high-grade disease. Design, setting, and participants This was a retrospective study of clinical data for 494 793 patients from the National Cancer Data Base and 136 113 patients from the Surveillance, Epidemiology, and End Results program with cT1–4N0M0 prostate cancer (median follow-up 48.9 and 25.0 mo, respectively), and genomic data for 4960 patients from the Decipher Genomic Resource Information Database. Data were collected for 2004–2017. Outcome measurements and statistical analysis Multivariable Fine-Gray and Cox regressions were used to analyze prostate cancer–specific mortality (PCSM) and all-cause mortality, respectively. Results and limitations For Gleason 8–10 disease, using PSA 4.1–10.0ng/ml ( n =38 719) as referent, the distribution of PCSM by PSA was U-shaped, with an adjusted hazard ratio (AHR) of 2.70 for PSA ≤2.5ng/ml ( n =3862, p n =4199), 10.1–20.0 ( n =17 372), and >20.0ng/ml ( n =16 114), respectively. By contrast, the distribution of PCSM by PSA was linear for Gleason ≤7 (using PSA 4.1–10.0ng/ml as the referent, n =359 898), with an AHR of 0.41 ( p =0.13) for PSA ≤2.5ng/ml ( n =37 812) versus 1.38, 2.28, and 4.61 for PSA of 2.6–4.0 ( n =54 152), 10.1–20.0 ( n =63 319), and >20.0ng/ml ( n =35 459), respectively ( p interaction 2.5ng/ml (AHR 2.15, p =0.002; 47-mo PCSM 14% vs 4.9%). Among Gleason 8–10 patients treated with radiotherapy, androgen deprivation therapy was associated with a survival benefit for PSA >2.5ng/ml (AHR 0.87; p p =0.084; p interaction =0.021). For Gleason 8–10 tumors, PSA ≤2.5ng/ml was associated with higher expression of neuroendocrine/small-cell markers compared to >2.5ng/ml ( p =0.046), with no such relationship for Gleason ≤7 disease. Conclusions Low-PSA, high-grade prostate cancer has very high risk for PCSM, potentially responds poorly to androgen deprivation therapy, and is associated with neuroendocrine genomic features. Patient summary In this study, we found that low–prostate-specific antigen, high-grade prostate cancer has a very high risk for prostate cancer death, may not respond well to androgen deprivation therapy, and is associated with neuroendocrine genomic features. These findings suggest that current nomograms and treatment paradigms may need modification.

The safety of active surveillance (AS) for Gleason 6 favorable intermediate-risk (FIR) prostate cancer is unknown. To provide guidance, we examined the incidence and predictors of upgrading or upstaging for Gleason 6 FIR patients treated with radical prostatectomy.We identified 2807 men in the National Cancer Database diagnosed from 2010 to 2012 with Gleason 6 FIR disease (50% positive biopsy cores [PBC] with either prostate-specific antigen [PSA] of 10-20 ng/mL or cT2b-T2c disease) treated with radical prostatectomy. Logistic regression was used to identify predictors of upgrading (Gleason 3+4 with tertiary Gleason 5 or Gleason ≥4+3) or upstaging (pT3-4/N1).Fifty-seven percent of the cohort had PSA of 10 to 20 ng/mL; 25.5% patients with PSA of 10 to 20 ng/mL and 12.4% with cT2b to T2c disease were upgraded or upstaged. In multivariable analysis, predictors of upgrading or upstaging included increasing age (P = .026), PSA (P = .001), and percent PBC (P .001), and black race versus white (P = .035) for patients with PSA of 10 to 20 ng/mL and increasing PSA (P = .001) and percent PBC (P .001) for patients with cT2b to T2c disease. Men with PSA of 15.0 to 20.0 ng/mL or 37.5% to 49.9% PBC with PSA of 10 to 20 ng/mL had30% risk of upgrading or upstaging, whereas cT2b to T2c patients with 12.5% PBC or PSA 5.0 ng/mL had 10% risk.We found that Gleason 6 FIR patients with cT2b to T2c tumors had a low risk of harboring higher grade or stage disease and would be reasonable AS candidates, whereas patients with PSA of 10 to 20 ng/mL had a high risk and might generally be poor AS candidates.

BACKGROUND Conservative management of aggressive prostate cancer in the elderly without definitive therapy has been associated with a 10-year prostate cancer-specific mortality of approximately 50%. The authors examined the prevalence of definitive therapy in elderly patients with intermediate-risk or high-risk disease. METHODS 411,343 patients who were diagnosed from 2004 through 2012 with intermediate-risk or high-risk prostate cancer were identified in the National Cancer Database. Multivariable logistic regression adjusting for sociodemographic characteristics and comorbidity was used to examine the association between age and receipt of definitive therapy, defined as radical prostatectomy or radiotherapy, and of primary androgen deprivation therapy (ADT) among patients who did not receive definitive therapy. RESULTS In total, 87.1% of high-risk patients and 91.9% of intermediate-risk patients received definitive therapy. When stratified by age, 93.7%, 92.1%, 90.8%, 87.6%, 80.9%, and 55.2% of high-risk patients and 96.1%, 94.7%, 93.4%, 89.7%, 82.7%, and 62.8% of intermediate-risk patients ages

Purpose A recent randomized controlled trial demonstrated that the addition of external beam radiation therapy (EBRT) to brachytherapy did not improve progression-free survival in select patients with intermediate-risk prostate cancer. We evaluated whether the addition of EBRT to brachytherapy improves prostate cancer–specific mortality (PCSM) for intermediate- and high-risk disease using a large national database. Methods and Materials We identified 5836 patients in the Surveillance, Epidemiology, and End Results–Medicare linked database with a diagnosis of National Comprehensive Cancer Network intermediate-risk (Gleason score 7, prostate-specific antigen 10-20 ng/mL, or stage cT2b-T2c) or high-risk (Gleason score 8-10 or prostate-specific antigen >20 ng/mL and stage ≤cT3a) prostate cancer who had undergone brachytherapy, with or without EBRT and androgen deprivation therapy (ADT). Patients were diagnosed from 2004 through 2009. Intermediate-risk patients with Gleason score ≤3+4 and 1 intermediate-risk factor were considered favorable and all others unfavorable. We used multivariable Fine-Gray competing risks regression to study PCSM while adjusting for sociodemographic and clinical factors and ADT use. Results Overall, 50.3% of intermediate- and high-risk patients who received brachytherapy and EBRT did not have significantly improved PCSM compared with that of the patients who received brachytherapy alone (adjusted hazard ratio [AHR] 1.46, 95% confidence interval [CI] 0.69-3.11; P =.322; 5-year PCSM 2.4% vs 1.0%). This lack of benefit was seen among favorable intermediate-risk (AHR 2.66, 95% CI 0.93-7.62, P =.069; 5-year PCSM 1.3% vs 0.6%), unfavorable intermediate-risk (AHR 0.68, 95% CI 0.16-2.96, P =.612; 5-year PCSM 1.0% vs 1.2%), and high-risk (AHR 1.82, 95% CI 0.67-4.98, P =.242; 5-year PCSM 5.3% vs 2.1%) subgroups. Conclusions These results suggest that certain patients with intermediate- or high-risk prostate cancer treated with brachytherapy might not benefit from the addition of EBRT. A randomized controlled trial of brachytherapy plus ADT with or without EBRT for unfavorable intermediate- and favorable high-risk organ-confined prostate cancer should be undertaken.

It is unknown whether active surveillance can be safely offered to patients with Gleason 3+4 favorable intermediate-risk (FIR) prostate cancer.To examine the incidence and predictors of upgrading and upstaging among patients with Gleason 3+4 FIR disease.The study involved 10 089 patients in the National Cancer Database diagnosed from 2010 to 2012 with Gleason 3+4 disease, prostate-specific antigen (PSA)10ng/ml, and cT1c-2a prostate cancer with50% positive biopsy cores (PBCs) who underwent radical prostatectomy.Logistic regression was used to examine predictors of upgrading (pathologic Gleason ≥4+3 or tertiary Gleason 5 in a Gleason 7 tumor) or upstaging (pT3-4/N1).Some 30.3% of Gleason 3+4 FIR patients were upgraded or upstaged. On multivariable analysis, predictors included higher PSA, percentage PBC, age, and cT2a versus cT1c (all p0.001), but not black race (p=0.895). When stratified into ordinal variables, PSA 8.1-9.9 versus ≤4.0ng/ml (adjusted odds ratio [AOR] 1.93, 38.3% vs 24.4%), PBC 37.5-49.9% versus12.5% (AOR 1.79, 37.8% vs 25.1%); highest age quartile (≥67 yr) versus lowest (≤55 yr; AOR 1.46, 35.7% vs 24.7%); and cT2a versus cT1c (AOR 1.33, 34.3% vs 29.8%) were associated with a higher risk of upgrading or upstaging (all p0.001). Men with PBC12.5% and PSA ≤4.0ng/ml had a 21.7% risk of more advanced disease. This increased to 44.3% for PBC 37.5-49.9% and PSA 8.1-9.9ng/ml. A limitation of the study is its retrospective nature.Approximately one in three patients with Gleason 3+4 FIR harbored disease of higher grade or stage. Younger patients with low percentage PBC and PSA and cT1c disease have a lower risk and may be candidates for active surveillance. However, widely available clinical information is insufficient for predicting the risk of more advanced disease, and the development and incorporation of additional tools, including magnetic resonance imaging and genomic tests, are necessary.Nearly one-third of patients with Gleason 3+4 favorable intermediate-risk prostate cancer harbor disease of higher grade or higher stage than their biopsy and clinical examination suggest. These patients would therefore be poor candidates for active surveillance.