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Biochemical recurrence (BCR) occurs in 20-50% of patients with prostate cancer (PCa) undergoing primary definitive treatment. Patients with high-risk BCR have an increased risk of metastatic progression and subsequent PCa-specific mortality, and thus could benefit from treatment intensification. Given the increasing complexity of diagnostic and therapeutic modalities, multidisciplinary care (MDC) can play a crucial role in the individualized management of this patient population. This review explores the role for MDC when evaluating the clinical evidence for the evolving definition of high-risk BCR and the emerging therapeutic strategies, especially with novel hormone therapies (NHTs), for patients with either high-risk BCR or oligometastatic PCa. Clinical studies have used different characteristics to define high-risk BCR and there is no consensus regarding the definition of high-risk BCR nor for management strategies. Next-generation imaging and multigene panels offer potential enhanced patient identification and precision-based decision-making, respectively. Treatment intensification with NHTs, either alone or combined with radiotherapy or metastasis-directed therapy, has been promising in clinical trials in patients with high-risk BCR or oligometastases. As novel risk-stratification and treatment options as well as evidence-based literature evolve, it is important to involve a multidisciplinary team to identify patients with high-risk features at an earlier stage, and make informed decisions on the treatments that could optimize their care and long-term outcomes. Nevertheless, MDC data are scarce in the BCR or oligometastatic setting. Efforts to integrate MDC into the standard management of this patient population are needed, and will likely improve outcomes across this heterogeneous PCa patient population., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jason A. Efstathiou reports consulting roles for Blue Earth Diagnostics, Boston Scientific, AstraZeneca, and Genentech; honoraria from IBA; advisory boards for Merck, Roviant Pharma, Myovant Sciences, Janssen, Bayer Healthcare, Progenics Pharmaceuticals, Pfizer, Inc., Genentech, Gilead, Blue Earth Diagnostics, and Lantheus Medical Imaging. Alicia K. Morgans reports grant support from Bayer, Sanofi, Myovant Sciences, Pfizer, Inc., Astellas Scientific and Medical Affairs Inc., and Dendreon Pharmaceuticals; honoraria from AstraZeneca, Advanced Accelerator Applications, Novartis, and Pfizer, Inc.; consulting or advisory roles for AstraZeneca, Sanofi, Bayer, Astellas Pharma, Janssen, Advanced Accelerator Applications, Myovant Sciences, Blue Earth Diagnostics, Exelixis, Novartis, Myriad Genetics, Lantheus Medical Imaging, Merck, and Gilead. Christopher S. Bland reports being an employee and shareholder of Pfizer, Inc. Neal D. Shore reports grant support from AbbVie, Amgen, Astellas Pharma, Bayer, Dendreon Pharmaceuticals, Ferring Pharmaceuticals, Janssen Oncology, Pfizer, Inc., Sanofi–Genzyme, and Tolmar Pharmaceuticals; consulting or advocacy roles for AbbVie, Akido, Alessa Therapeutics, Amgen, Arquer, Asieris, Astellas Pharma, Inc., Astra Zeneca, Bayer, BMS, Boston Scientific, Clarity, Clovis, Cold Genesys, Dendreon Pharmaceuticals, Exact Images, Exact Sciences, FerGene, Ferring Pharmaceuticals, Foundation Medicine, FIZE Medical, GConcology, GenesisCare, Genetech, Guardant, ImmunityBio, Incyte, Invitae, Janssen, Lantheus, Lilly, MDX, Merck, Minomic, Myovant, Myriad, NGM, Nonagen, Novartis, NYMOX, Pacific Edge, Pfizer, Inc., Photocure, PlatformQ, Profound, Promaxo, Propella, Protara, Sanofi, SesenBio, Speciality Networks, Telix, Tolmar Pharmaceuticals, Urogen, Vaxiion, and Vessi., (Copyright © 2023. Published by Elsevier Ltd.)

Background: Non-muscle invasive bladder cancer (non-MIBC) that is high-grade and confined to the lamina propria (HGT1) often has an aggressive clinical course. Currently, there is limited data on the comparative effectiveness of RT vs. CRT for HGT1 non-MIBC. We hypothesized that CRT would be associated with improved overall survival (OS) vs. RT in HGT1 bladder cancer., Methods: Patients diagnosed with HGT1 non-MIBC, and treated with transurethral resection of bladder tumor followed by either treatment with RT alone or CRT, were identified in the National Cancer Database. Inverse probability of treatment weighting (IPTW) was employed and weight-adjusted multivariable analysis (MVA) using Cox regression modeling was used to compare overall survival (OS) hazard ratios. OS was the primary endpoint, and was estimated using the Kaplan-Meier method and log-rank tests., Results: A total of 259 patients with HGT1 UC were treated with: (i) RT alone (n = 123) or (ii) CRT (n = 136). Propensity-weighted MVA showed that combined modality treatment with CRT was associated with improved OS relative to radiation alone (Hazard Ratio [HR]: 0.62, 95% Confidence Interval (95% CI): 0.44-0.88, P = .007). Four-year OS for the CRT vs. RT alone was 36% and 19%, respectively (log-rank P <.008)., Conclusion: For patients with HGT1 bladder cancer, concurrent CRT was associated with improved OS compared with radiation alone in a retrospective cohort. These results are hypothesis-generating. The NRG is currently developing a phase II randomized clinical trial comparing CRT to other novel, bladder preservation strategies., Competing Interests: Declaration of interests The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: BCB declares consulting work for Varian Medical Systems and Boston Scientific, outside of the scope of thesubmitted work. The others have no conflicts of interest that are relevant to the submitted work., (Copyright © 2023. Published by Elsevier Inc.)

Objective: Most prostate cancer active surveillance (AS) protocols suggest a confirmatory biopsy within 12 to 18 months of diagnosis to mitigate the risk of unsampled high-grade disease. We investigate whether the results of confirmatory biopsy impact AS outcomes and could be used to tailor surveillance intensity., Methods: We retrospectively reviewed our institutional database of prostate cancer patients managed by AS from 1997 to 2019 who underwent confirmatory biopsy and ≥3 biopsies overall. Biopsy progression was defined as either an increase in grade group or an increase in the proportion of positive biopsy cores to >34% and was compared between patients with a negative vs positive confirmatory biopsy using the Kaplan-Meier method and Cox proportional hazards regression., Results: We identified 452 patients meeting inclusion criteria for this analysis, of whom 169 (37%) had a negative confirmatory biopsy. With a median follow-up of 6.8 years, 37% of patients progressed to treatment, most commonly due to biopsy progression. A negative confirmatory biopsy was significantly associated with biopsy progression-free survival in multivariable analysis (HR 0.54, 95% CI 0.34-0.88, P = 0.013), adjusting for known clinical and pathologic factors, including use of mpMRI prior to confirmatory biopsy. Negative confirmatory biopsy was also associated with an increased risk of adverse pathologic features at prostatectomy but not with biochemical recurrence among men who ultimately underwent definitive treatment., Conclusions: A negative confirmatory biopsy is associated with a lower risk of biopsy progression. While the increased risk of adverse pathology at time of definitive treatment sounds a small cautionary note regarding decreasing surveillance intensity, the majority of such patients have a favorable outcome on AS., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Bladder-sparing chemoradiation therapy (CRT) is a definitive first-line treatment for muscle-invasive bladder cancer. The optimal radiotherapy target volume, either bladder-only (BO) or bladder plus pelvic lymph nodes (BPN), remains unclear., Methods: We identified 2,104 patients in the National Cancer Database with cT2-4N0M0 urothelial cell carcinoma of the bladder treated with CRT following maximal transurethral resection of bladder tumor from 2004 to 2016. The exposure of interest was BO vs. BPN treatment volume. The primary outcome was overall survival (OS), compared between groups using Kaplan-Meier and multivariable Cox proportional hazards. Sensitivity analysis tested an interaction term for clinical T stage (T2 vs. T3-4) and radiation modality (3-dimensional conformal radiotherapy vs. intensity modulated radiotherapy or proton therapy). Annual use of BO vs. BPN from 2004 to 2016 was compared using Cochran-Armitage test., Results: A total of 578 patients were treated with BO and 1,526 patients treated with BPN CRT. There was a significant increase in BPN use from 2004 to 2016 (66.9%-76.8%, P < 0.0001). With a median follow-up of 6.2 years, there was no survival difference between groups: 5- and 10-year OS 27.4% (95% CI 23.4%-31.4%) in the BO group vs. 31.9% (95% CI 29.3%-34.6%) in the BPN group, and 13.1% (95% CI 9.7%-17.1%) in the BO group vs. 13.2% (95% CI 10.6%-16.0%) in the BPN group, respectively (log-rank P = 0.10). On multivariable analysis, there was no significant association between BPN and OS (adjusted HR 0.90, 95% CI 0.81-1.02, P = 0.09). On sensitivity analysis, we found no differential effect by T stage or radiation modality., Conclusion: Use of pelvic lymph node radiation has risen in the US but may not impact long-term survival outcomes for patients with node-negative muscle-invasive bladder cancer (MIBC). Optimizing radiation treatment volumes for CRT for MIBC will be important to study under prospective trials, such as the SWOG/NRG 1806., Competing Interests: Conflict of interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: The use of prostate fiducial markers and perirectal hydrogel spacers can reduce the acute and late toxic effects associated with prostate radiation therapy. These procedures are usually performed days to weeks before simulation during a separate clinic visit to ensure resolution of procedure-related inflammation. The purpose of this study was to assess whether same-day intraprostatic fiducial marker placement, perirectal hydrogel injection, and computed tomography (CT) and magnetic resonance imaging (MRI) simulation were feasible without adversely affecting hydrogel volume, perirectal spacing, or rectal dose. If feasible, performing these procedures on the same day as simulation would expedite the start of radiation therapy, improve patient convenience, and reduce costs., Methods and Materials: Twenty-one patients with clinically localized prostate cancer who were enrolled on a prospective clinical trial (NCT01617161) underwent same-day marker placement, hydrogel injection, and CT and MRI simulation, then underwent T2 MRI verification scans 3 to 4 weeks later. The MRI scans were fused to the CT planning scans by clinical target volumes (CTVs) to generate comparison treatment plans (70 Gy in 28 fractions). Hydrogel volume and symmetry, perirectal spacing, CTV dose, and organ-at-risk dose were evaluated., Results: Verification scans occurred a mean of 24.9 ± 4.6 days after simulation and 9.3 ± 4.9 days after treatment start. Prostate volume did not change between scans (median, 67.3 ± 22.1 cm 3 vs 64.1 ± 21.8 cm 3 ; P = .64). The median hydrogel change between simulation and verification was - 1.8% ± 4.5% (P = .27). No significant differences in perirectal spacing (midgland: 1.33 ± 0.45 cm vs 1.3 ± 0.7 cm; 1 cm superior: 1.25 ± 0.95 cm vs 1.43 ± 0.91 cm; 1 cm inferior: 1.16 ± 0.28 cm vs 1.41 ± 0.49 cm) were identified. No significant differences in rectal V66 (median 2.3 ± 2.18% vs 2.3 ± 2.28%; P = .99), V35 (median 14.79 ± 7.61 vs 14.67 ± 8.4; P = .73), or D1cc (65.7 ± 9.2 Gy vs 68.2 ± 9.0 Gy; P = .80) were found. All plans met CTV and organ-at-risk constraints., Conclusion: Same-day placement of intraprostatic fiducial markers, perirectal hydrogel, and simulation scans was feasible and did not significantly affect hydrogel volume, position, CTV coverage, or rectal dose., (Copyright © 2021. Published by Elsevier Inc.)

Purpose: Conventional rectal spacers (nonI-SPs) are low-contrast on computed tomography (CT), often necessitating magnetic resonance imaging for accurate delineation. A new formulation of spacers (I-SPs) incorporates iodine to improve radiopacity and CT visualization. We characterized placement, stability, and plan quality of I-SPs compared to nonI-SPs., Methods and Materials: Patients with intact prostate cancer (n = 50) treated with I-SPs and photons were compared to randomly selected patients (n = 50) with nonI-SPs (photon or proton therapy). The I-SP was contoured on the planning CT and cone beam CTs at 3 timepoints: first, middle, and final treatment (n = 200 scans). I-SPs Hounsfield units (HU), volume, surface area (SA), centroid position relative to prostate centroid, and distance between prostate/rectum centroids were compared on the planning CTs between each cohort. I-SP changes were evaluated on cone beam CTs over courses of treatment. Dosimetric evaluations of plan quality and robustness were performed. I-SP was tested in a phantom to characterize its relative linear stopping power for protons., Results: I-SPs yielded a distinct visible contrast on planning CTs compared to nonI-SPs (HU 138 vs 12, P < .001), allowing delineation on CT alone. The delineated volume and SA of I-SPs were smaller than nonI-SPs (volume 8.9 vs 10.6 mL, P < .001; SA 28 vs 35 cm 2 , P < .001), yet relative spacer position and prostate-rectal separation were similar (P = .79). No significant change in HU, volume, SA, or relative position of the I-SPs hydrogel occurred over courses of treatment (all P > .1). Dosimetric analysis concluded there were no significant changes in plan quality or robustness for I-SPs compared to nonI-SPs. The I-SP relative linear stopping power was 1.018, necessitating HU override for proton planning., Conclusions: I-SPs provide a manifest CT contrast, allowing for delineation on planning CT alone with no magnetic resonance imaging necessary. I-SPs radiopacity, size, and relative position remained stable over courses of treatment from 28 to 44 fractions. No changes in plan quality or robustness were seen comparing I-SPs and nonI-SPs., (Copyright © 2021 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Background: Bladder-sparing chemoradiation therapy is a definitive first-line treatment option for muscle-invasive bladder cancer. Randomized trials have demonstrated that the addition of neoadjuvant chemotherapy to radical cystectomy or radiation monotherapy results in a survival benefit. Whether neoadjuvant chemotherapy improves outcomes when used with definitive chemoradiation is unknown., Patients and Methods: We identified 2566 patients in the National Cancer Data Base with cT2-4N0M0 urothelial cell carcinoma of the bladder treated with definitive intent concurrent chemoradiation from 2004 to 2015. The exposure of interest was receipt of neoadjuvant chemotherapy versus those without neoadjuvant chemotherapy. The primary outcome was overall survival defined from the time of diagnosis. Kaplan-Meier and multivariable Cox proportional hazard analyses were used to compare survival between groups. Sensitivity analyses tested (1) an interaction term for clinical T stage and (2) defining survival from start of radiation (as opposed to time of diagnosis) to address potential leading time bias., Results: We identified 462 patients treated with neoadjuvant chemotherapy followed by chemoradiation and 2104 patients treated with chemoradiation alone. With a median follow-up of 6.2 years, we found no difference in survival between groups: 5-year or 10-year overall survival of 30.6% (95% confidence interval [CI], 28.4%-32.9%) in the neoadjuvant group versus 31.8% (95% CI, 27.0%-36.8%) in the standard chemoradiation therapy group and 13.3% (95% CI, 11.2%-15.5%) in the neoadjuvant group versus 13.0% (95% CI, 8.4%-18.7%) in the standard chemoradiation therapy group, respectively (log-rank P = .19). On multivariable analysis we found no association between receipt of neoadjuvant chemotherapy and overall survival (hazard ratio, 1.01; 95% CI, 0.88-1.15; P = .921). The sensitivity analyses did not identify any differential effect by clinical T stage nor by defining survival from start of radiation., Conclusion: These results do not support the routine addition of neoadjuvant chemotherapy to definitive chemoradiation for bladder cancer, and optimizing the chemotherapy sequencing and regimens for bladder-preserving approaches to muscle invasive bladder cancer should continue to be studied under prospective clinical trials., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: During the coronavirus disease 2019 (COVID-19) pandemic, providers and patients must engage in shared decision making to ensure that the benefit of early intervention for muscle-invasive bladder cancer exceeds the risk of contracting COVID-19 in the clinical setting. It is unknown whether treatment delays for patients eligible for curative chemoradiation (CRT) compromise long-term outcomes., Patients and Methods: We used the National Cancer Data Base to investigate whether there is an association between a ≥ 90-day delay from transurethral resection of bladder tumor (TURBT) in initiating CRT and overall survival. We included patients with cT2-4N0M0 muscle-invasive bladder cancer from 2004 to 2015 who underwent TURBT and curative-intent concurrent CRT. Patients were grouped on the basis of timing of CRT: ≤ 89 days after TURBT (earlier) vs. ≥ 90 and < 180 days after TURBT (delayed)., Results: A total of 1387 (87.5%) received earlier CRT (median, 45 days after TURBT; interquartile range, 34-59 days), and 197 (12.5%) received delayed CRT (median, 111 days after TURBT; interquartile range, 98-130 days). Median overall survival was 29.0 months (95% CI, 26.0-32.0) versus 27.0 months (95% CI, 19.75-34.24) for earlier and delayed CRT (P = .94). On multivariable analysis, delayed CRT was not associated with an overall survival difference (hazard ratio, 1.05; 95% CI, 0.87-1.27; P = .60)., Conclusion: Although these results are limited and require validation, short, strategic treatment delays during a pandemic can be considered on the basis of clinician judgment., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Men diagnosed with localized prostate cancer have many curative treatment options including several different radiotherapeutic approaches. Proton radiation is one such radiation treatment modality and, due to its unique physical properties, offers the appealing potential of reduced side effects without sacrificing cancer control. In this review, we examine the intriguing dosimetric rationale and theoretical benefit of proton radiation for prostate cancer and highlight the results of preclinical modeling studies. We then discuss the current state of the clinical evidence for proton efficacy and toxicity, derived from both large claim-based datasets and prospective patient-reported data. The result is that the data are mixed, and clinical equipoise persists in this area. We place these studies into context by summarizing the economics of proton therapy and the changing practice patterns of prostate proton irradiation. Finally, we await the results of a large prospective randomized clinical trial currently accruing and also a large prospective pragmatic comparative study which will provide more rigorous evidence regarding the clinical and comparative effectiveness of proton therapy for prostate cancer., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Interstitial brachytherapy is one of several curative therapeutic options for the treatment of localized prostate cancer. In this review, we summarize all available randomized data to support the optimal use of prostate brachytherapy. Evidence from completed randomized controlled trials is the focus of this review with a presentation also of important ongoing trials. Gaps in knowledge are identified where future investigation may be fruitful with intent to inspire well-designed prospective studies with standardized treatment that focuses on improving oncological outcomes, reducing morbidity, or maintaining quality of life., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: There are limited randomized data comparing radical cystectomy (RC) with bladder-sparing tri-modality therapy (TMT) in the treatment of muscle-invasive bladder cancer (MIBC). Both strategies are thought to have similar survival outcomes with different morbidity profiles. We compare the effectiveness of TMT and RC using decision-analytic modeling and the endpoint of quality-adjusted life years (QALYs)., Patients and Methods: Using a Markov model, we simulated the lifetime outcomes after TMT versus RC ± neoadjuvant chemotherapy for 67-year-old patients with clinical stage T2-T4aN0M0 MIBC. Model probabilities and utilities were extracted from the literature. The incremental effectiveness was reported in QALYs and sensitivity analyses were performed., Results: For all patients with MIBC, although the model showed identical survival, TMT was the most effective strategy with an incremental gain of 0.59 QALYs over RC (7.83 vs. 7.24 QALYs, respectively). When limiting the model to favorable, contemporary cohorts in both the TMT and RC strategies, TMT remained more effective with an incremental gain of 1.61 QALYs (9.37 vs. 7.76 QALYs, respectively). One-way sensitivity analyses demonstrated the model was sensitive to the quality of life parameters (ie, the utilities) for RC and TMT. When testing the 95% confidence interval of the RC utility parameter the model demonstrated an incremental gain with TMT from -0.54 to 4.23 QALYs. Probabilistic sensitivity analysis demonstrated that TMT was more effective than RC for 63% of model iterations., Conclusions: This modeling study found that treatment of MIBC with organ-sparing TMT in appropriately-selected patients may result in a gain of QALYs relative to RC., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Multidisciplinary clinics integrate the expertise of several specialties to provide effective treatment to patients. This exposure is especially relevant in the management of muscle-invasive bladder cancer (MIBC), which requires critical input from urology, radiation oncology, and medical oncology, among other supportive specialties., Materials and Methods: In the present study, we sought to catalog the different styles of multidisciplinary care models used in the management of MIBC and to identify barriers to their implementation. We surveyed providers from academic and community practices regarding their currently implemented multidisciplinary care models, available resources, and perceived barriers using the Bladder Cancer Advocacy Network and the Genitourinary Medical Oncologists of Canada e-mail databases., Results: Of the 101 responding providers, most practiced at academic institutions in the United States (61%) or Canada (29%), and only 7% were from community practices. The most frequently used model was sequential visits on different days (57%), followed by sequential same-day (39%) and concurrent (1 visit with all providers; 22%) models. However, most practitioners preferred a multidisciplinary clinic involving sequential same-day (41%) or concurrent (26%) visits. The lack of clinic space (58%), funding (41%), staff (40%), and time (32%) were the most common barriers to implementing a multidisciplinary clinic., Conclusion: Most surveyed practitioners at academic centers use some form of a multidisciplinary care model for patients with MIBC. The major barriers to more integrated multidisciplinary clinics were limited time and resources rather than a lack of provider enthusiasm. Future studies should incorporate patient preferences, further evaluate practice patterns in community settings, and assess their effects on patient outcomes., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Cancer patients treated with pelvic radiation therapy (RT) often experience sexual health-related side effects during and following treatment. A clinical needs assessment was used to evaluate sexual health needs and to determine how needs differed between patients receiving and who had completed RT., Methods and Materials: A questionnaire was used to evaluate sexual health needs among patients treated with pelvic RT. All answers were rated using a 4-point Likert scale. Convenience sampling was used, and patients were stratified by whether they were on-treatment or in follow-up. Charts were reviewed for demographic, diagnostic, and treatment information. Pearson's χ 2 test and logistic regression analysis were used to analyze the associations between sexual health-related topics and clinical variables., Results: A total of 107 of 109 (98%) invited patients completed the questionnaire (46 females, 61 males; 52 undergoing RT, 54 completed RT). Most (75%) reported some degree of change in sexual health from the effects of cancer and/or treatment; 22% and 28% reported "quite a bit" or "very much" change, respectively. Sixty-nine percent reported that they experienced some degree of distress from sexual health changes (28% reported "very much" or "quite a bit" of distress). Seventy-six percent "agreed" or "strongly agreed" that they were interested in access to a multidisciplinary sexual health clinic (MSHC). Compared with patients currently receiving RT, patients in follow-up were significantly more likely to report worsening degrees of "change" (P = .008) and "distress" (P = .04) and to express interest in having access to an MSHC (P = .03)., Conclusion: The majority of patients receiving pelvic RT reported a change in sexual health with associated distress, with more reports among those in follow-up. Patients undergoing pelvic RT expressed a high interest in attending a radiation oncology MSHC. Our findings emphasize the important role radiation oncologists can play in the quality of life of our patients., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objectives: To determine the clinical characteristics, treatment patterns, and outcomes of patients with nonurothelial cell bladder cancer (NUBC) in the United States., Methods: A total of 163,683 patients with bladder cancer from 1998 to 2014 in the National Cancer Data Base were identified. Of all, 153,262 had urothelial cell (UC) carcinoma (93.6%) and 10,421 had NUBC (6.4%) further classified as: squamous cell carcinoma (SC, 2.4%), adenocarcinoma (AC, 1.7%), neuroendocrine (NE, 1.3%), micropapillary (MP, a UC variant histology, 0.3%), lymphoid/haematopoietic (LH, 0.3%), and sarcoma/mesenchymal (SM, 0.3%). Analyses were run on the entire cohort, those with non-muscle-invasive disease (T0-1, N0, M0), muscle-invasive disease (MIBC, T2-4A, N0, M0), and metastatic disease (T4B or N+ or M+). Clinical characteristics and treatment received (surgery, chemotherapy, and radiation) were reported by histologic subtype. Survival analysis was performed via Kaplan-Meier estimates and Cox proportional hazards models., Results: Patients with NE, SC, MP, and AC were more likely to be diagnosed with metastatic disease (11.5% for UC vs. 40%, 31.3%, 17.8%, and 30.6%, respectively, P<0.001). Patients with NUBC were also more likely to have MIBC compared to UC (43% vs. 32.5%, respectively). For all patients, those with UC may be less likely to undergo cystectomy, chemotherapy, and radiation therapy (P<0.001). For all patients, NUBC, with the exception of LH, SM, and MP, was associated with inferior survival compared to UC (P<0.001)., Conclusions: This encompassing clinical characterization and prognosis of NUBC patients in the United States shows NUBC patients have significantly different disease characteristics compared to those with UC, and present with more advanced disease, receive more treatment, and overall have inferior outcomes. Further work is needed to help improve outcomes for these patients., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: To evaluate the impact of salvage therapy (ST) on overall survival (OS) in recurrent primary urethral cancer (PUC)., Patients: A series of 139 patients (96 men, 43 women; median age = 66, interquartile range: 57-77) were diagnosed with PUC at 10 referral centers between 1993 and 2012. The modality of ST of recurrence (salvage surgery vs. radiotherapy) was recorded. Kaplan-Meier analysis with log-rank was used to estimate the impact of ST on OS (median follow-up = 21, interquartile range: 5-48)., Results: The 3-year OS for patients free of any recurrence (I), with solitary or concomitant urethral recurrence (II), and nonurethral recurrence (III) was 86.5%, 74.5%, and 48.2%, respectively (P = 0.002 for I vs. III and II vs. III; P = 0.55 for I vs. II). In the 80 patients with recurrences, the modality of primary treatment of recurrence was salvage surgery in 30 (37.5%), salvage radiotherapy (RT) in 8 (10.0%), and salvage surgery plus RT in 5 (6.3%) whereas 37 patients did not receive ST for recurrence (46.3%). In patients with recurrences, those who underwent salvage surgery or RT-based ST had similar 3-year OS (84.9%, 71.6%) compared to patients without recurrence (86.7%, P = 0.65), and exhibited superior 3-year OS compared to patients who did not undergo ST (38.0%, P<0.001 compared to surgery, P = 0.045 to RT-based ST, P = 0.29 for surgery vs. RT-based ST)., Conclusions: In this study, patients who underwent ST for recurrent PUC demonstrated improved OS compared to those who did not receive ST and exhibited similar survival to those who never developed recurrence after primary treatment., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Introduction: We sought to determine whether any sociodemographic disparities are present in the receipt of local treatment for node-positive prostate cancer., Patients and Methods: We identified 9771 patients with clinical N1M0 prostate cancer diagnosed from 1998 to 2012 using the National Cancer Database. We used multivariable logistic regression modeling to identify patient-specific factors that were associated with a reduced likelihood of receiving prostate or pelvic radiation or radical prostatectomy. We also used Cox regression modeling to estimate the differences in overall survival (OS) using these factors., Results: The factors associated with a reduced likelihood of receiving local therapy included black race versus white race (43.6% vs. 49.4%; adjusted odds ratio [AOR], 0.76; P = .001), bottom income quartile versus top quartile (44.7% vs. 52.7%; AOR, 0.69; P = .001), age > 66 years versus ≤ 66 years (40.8% vs. 55.1%; AOR, 0.48; P < .001), diagnosis before 2005 versus after 2005 (30.5% vs. 61.7%; AOR, 0.66; P < .001), and Medicaid or no insurance versus private insurance (41.0% vs. 49.4%; AOR, 0.41; P < .001). Although patients had reduced 5-year OS if they were from lower income quartiles (adjusted hazard ratios [AHRs], 1.18-1.22; P < .05), were older (AHR, 1.82; P < .001), or had Medicaid or no insurance (AHR, 1.24; P = .032), these disparities were no longer present or were smaller in magnitude after adjustment for receipt of local treatment., Conclusion: Significant treatment disparities exist in the receipt of local therapy for node-positive prostate cancer. Given the accumulating evidence supporting this practice, the factors underlying these disparities should be studied and addressed., (Copyright © 2016. Published by Elsevier Inc.)

Background: Salvage radiotherapy (SRT) has been successfully used for recurrent prostate cancer after radical prostatectomy; however, the optimal timing of SRT remains controversial. Our objective was to identify the risk factors for disease progression after SRT, with a focus on the pre-SRT prostate-specific antigen (PSA) levels in the modern era of PSA testing., Patients and Methods: We performed a retrospective review of 551 consecutive patients who had undergone postradical prostatectomy SRT for recurrent prostate cancer from 2000 to 2013. The exclusion criteria were hormonal therapy before or concurrent with SRT, adjuvant RT, distant metastases, and missing data. Disease progression was defined as a repeat PSA level of ≥ 0.2 ng/mL greater than the post-SRT nadir, a continued increase in the PSA level despite SRT, initiation of systemic therapy, local recurrence, nodal failure, and/or distant metastases. Univariate and multivariable Cox regression analysis were performed to identify the predictors of disease progression. Secondarily, PSA kinetics were evaluated in the model and compared using the Akaike information criterion., Results: Of the 551 patients, 307 underwent SRT, of whom 134 experienced subsequent disease progression. The median interval to recurrence was 6.03 years (95% confidence interval, 3.74-8.36 years). On multivariable analysis, Gleason score, T stage, positive surgical margins, and pre-SRT PSA level were associated with progression; PSA kinetics did not independently predict for progression. When the pre-SRT PSA level was stratified (≤ 0.30, 0.31-0.50, 0.51-1.00, and > 1 ng/mL), incremental elevations were associated with an increased risk of disease progression., Conclusion: Multiple factors predict for progression after SRT. These risk factors could help identify those who would derive the greatest benefit from additional systemic treatment. The findings of the present study also support initiation of early SRT, irrespective of the PSA kinetics., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Purpose: The purpose of this study was to evaluate freedom from biochemical failure (FFBF), freedom from androgen deprivation therapy (FFADT), freedom from distant metastases (FFDM), and overall survival (OS) after adjuvant radiation therapy (ART) versus early salvage radiation therapy (ESRT) in men with prostate cancer and adverse pathologic features (pT3 and/or positive surgical margins)., Methods and Materials: Of 718 patients consecutively treated with postoperative radiation therapy (RT) for prostate cancer between 1992 and 2013, we retrospectively identified 171 men receiving ART and 230 receiving ESRT (RT delivered at a prostate-specific antigen level ≤0.5 ng/mL) who had adverse pathologic features. Postirradiation FFBF (BF was defined as prostate-specific antigen level rise to ≥0.2 ng/mL), FFADT, FFDM, and OS were compared using Kaplan-Meier and Cox regression methods. Propensity score (PS)-matching was performed to estimate treatment effects while accounting for covariates predicting treatment allocation., Results: Median follow-up was 7.4 and 8.0 years for patients treated with ART and ESRT, respectively. Ten-year FFBF (69% vs 56%, P = .003) and 10-year FFADT (88% vs 81%, P = .046) rates were higher after ART; however, FFDM and OS did not significantly differ. After PS-matching, ART was associated with improved FFBF (P < .0001), FFADT (P = .0001), and FFDM (P = .02). Findings were confirmed in multivariable analyses in unmatched and PS-matched cohorts. Sensitivity analyses showed that FFBF benefit associated with ART lost statistical significance only after 38% of ART patients were assumed to have been cured by surgery and excluded from the model. This corresponds to the upper bound of patients with adverse pathologic features who did not recur after observation in prior randomized trials., Conclusions: Postoperative RT confers excellent long-term cancer control. These results suggest ART may be associated with improved FFBF, FFADT, and FFDM, but comparable OS. Given the retrospective study design, these findings should be interpreted with caution. Optimal timing of postoperative RT further awaits results of ongoing trials., (Copyright © 2016 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Prostate cancer treatment with definitive radiation therapy (RT) has evolved dramatically in the past 2 decades. From the initial 2-dimensional planning using X-rays, advances in technology led to 3-dimensional conformal RT, which used computerized tomography-based planning. This has allowed delivery of higher doses of radiation to the prostate while reducing dose to the surrounding organs, resulting in improved cancer control. Today, intensity-modulated RT (IMRT) is considered standard, where radiation beams of different shapes and intensities can be delivered from a wide range of angles, thus further decreasing doses to normal organs and likely reducing treatment-related toxicity. In addition, image guidance ascertains the location of the prostate before daily treatment delivery. Brachytherapy is the placement of radioactive seeds directly in the prostate, and has a long track record as a monotherapy for low-risk prostate cancer patients with excellent long-term cancer control and quality of life outcomes. Recent studies including several randomized trials support the use of brachytherapy in combination with external beam RT for higher-risk patients. RT for prostate cancer continues to evolve. Proton therapy has a theoretical advantage over photons as it deposits most of the dose at a prescribed depth with a rapid dose fall-off thereafter; therefore it reduces some doses delivered to the bladder and rectum. Prospective studies have shown the safety and efficacy of proton therapy for prostate cancer, but whether it leads to improved patient outcomes compared to IMRT is unknown. Hypofractionated RT delivers a larger dose of daily radiation compared to conventional IMRT, and thus reduces the overall treatment time and possibly cost. An extreme form of hypofractionation is stereotactic body radiation therapy where highly precise radiation is used and treatment is completed in a total of 4 to 5 sessions. These techniques take advantage of the biological characteristic of prostate cancer, which is more sensitive to larger radiation doses per fraction, and therefore could be more effective than conventional IMRT. Multiple randomized trials have demonstrated noninferiority of moderately hypofractionated RT compared to conventional fractionation. There is also a growing body of data demonstrating the safety and efficacy of stereotactic body radiation therapy for low- and intermediate-risk prostate cancer., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Bladder cancer is a complex disease associated with high morbidity and mortality rates if not treated optimally. Awareness of haematuria as the major presenting symptom is paramount, and early diagnosis with individualised treatment and follow-up is the key to a successful outcome. For non-muscle-invasive bladder cancer, the mainstay of treatment is complete resection of the tumour followed by induction and maintenance immunotherapy with intravesical BCG vaccine or intravesical chemotherapy. For muscle-invasive bladder cancer, multimodal treatment involving radical cystectomy with neoadjuvant chemotherapy offers the best chance for cure. Selected patients with muscle-invasive tumours can be offered bladder-sparing trimodality treatment consisting of transurethral resection with chemoradiation. Advanced disease is best treated with systemic cisplatin-based chemotherapy; immunotherapy is emerging as a viable salvage treatment for patients in whom first-line chemotherapy cannot control the disease. Developments in the past 2 years have shed light on genetic subtypes of bladder cancer that might differ from one another in response to various treatments., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Purpose/objective: Disease-specific survival for testicular seminoma approaches 100%, even for those with node-positive disease. We sought to describe modern practice patterns, survival outcomes, and factors associated with postoperative therapy for patients with clinical stage (CS) IIA/B disease., Methods and Materials: Data on patients diagnosed with CS IIA/B seminoma from 1998 to 2012 were extracted from the National Cancer Data Base. Demographic, clinical, treatment, and payer characteristics were evaluated using multivariate regression to identify factors associated with receipt of chemotherapy or radiation therapy (RT) within 6 months of orchiectomy. Five-year Kaplan-Meier overall survival (OS) by CS and treatment was calculated. A Cox proportional hazards regression for 5-year OS was performed., Results: A total of 1885 patients were included; 38.5% received chemotherapy and 61.5% received RT. On multivariate analysis, factors associated with receipt of postorchiectomy RT rather than chemotherapy included CS IIA (odds ratio [OR], 3.04; P < .01) and community treatment setting (OR, 1.81-2.76; P < .01). Reduced likelihood of receiving RT was associated with Medicaid insurance (OR, 0.50; P < .01), more recent year of diagnosis (continuous OR, 0.93; P < .01), and primary pathologic tumor 3/4 stage (OR, 0.47; P < .01). On multivariate Cox regression, decreased 5-year OS was associated with receipt of chemotherapy in CS IIA patients (hazard ratio, 13.33; P < .01) but not in CS IIB patients (hazard ratio, 1.39; P = .45). For CS IIA, 5-year OS was 99.4% for orchiectomy and RT versus 91.2% for orchiectomy and chemotherapy (log-rank P < .01). For CS IIB, 5-year OS was 96.1% for orchiectomy and RT versus 92.8% for orchiectomy and chemotherapy (log-rank P = .08)., Conclusions: Consistent with national guideline recommendations, our analysis supports preferred status for RT in CS IIA. In addition, these data also support use of RT for CS IIB. CS, treatment year, primary pathologic tumor stage, insurance, and facility type were associated with type of postoperative therapy. Longer follow-up to account for potential late effects of treatment is needed., (Copyright © 2016 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Introduction: To estimate the contribution of the prostate gland and prostatic urethral inflammation to urinary symptoms after radiation therapy for prostate cancer, we performed a secondary analysis of urinary toxicity after primary radiation to an intact prostate vs. postprostatectomy radiation to the prostatic fossa in protocols RTOG 94-08 and 96-01, respectively., Materials and Methods: Patients randomized to the radiation-alone arms (without hormone therapy) of the 2 trials were evaluated, including 104 men receiving primary prostate radiation to 68.4Gy on RTOG 94-08 and 371 men receiving 64.8Gy to the prostatic fossa on RTOG 96-01. Acute and late urinary toxicity were scored prospectively by RTOG scales. Chi-square test/logistic regression and cumulative incidence approach/Fine-Gray regression model were used for analyses of acute and late toxicity, respectively., Results: Grade≥2 acute urinary toxicity was significantly higher after primary prostatic radiation compared with postprostatectomy radiation (30.8% vs. 14.0%; P<0.001), but acute grade≥3 toxicity did not differ (3.8% vs. 2.7%; P = 0.54). After adjusting for age, primary radiation resulted in significantly higher grade≥2 acute urinary toxicity (odds ratio = 3.72; 95% CI: 1.65-8.37; P = 0.02). With median follow-up of 7.1 years, late urinary toxicity was not significantly different with primary vs. postprostatectomy radiation (5-year grade≥2: 16.7% vs. 18.3%; P = 0.65; grade≥3: 6.0% vs. 3.3%; P = 0.24)., Conclusions: Primary radiation to an intact prostate resulted in higher grade≥2 acute urinary toxicity than radiation to the prostatic fossa, with no difference in late urinary toxicity. Thus, a proportion of acute urinary toxicity in men with an intact prostate may be attributable to inflammation of the prostatic gland or urethra., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Three randomized trials demonstrated that postprostatectomy adjuvant radiotherapy improves biochemical disease-free survival for patients with adverse pathologic features, and 1 trial found adjuvant radiotherapy improves overall survival. We sought to determine whether postprostatectomy radiotherapy (PPRT) utilization changed after publication of the survival benefit in March 2009., Patients and Methods: The Surveillance, Epidemiology, and End Results database was used to identify men diagnosed with prostate cancer from 2004 to 2011 who met criteria for enrollment in the randomized trials (positive margins and/or pT3-4 disease at radical prostatectomy). Joinpoint regression identified inflection points in PPRT utilization. Logistic regression was used to evaluate factors associated with PPRT recommendation., Results: Of 35,361 men, 5104 (14.4%) received a recommendation for PPRT. In joinpoint regression, 2009 was the inflection point in PPRT utilization. In multivariable analysis, PPRT recommendations were more likely after March 2009 than before 15.8% vs. 13.5%, adjusted odds ratio (AOR; 1.09; 95% confidence interval [CI], 1.02-1.16; P = .008), in men with pT3 (vs. pT2, AOR, 2.81; 95% CI, 2.53-3.11; P < .001), pT4 (vs. pT2 AOR, 4.62; 95% CI, 3.85-5.54; P < .001), or margin positive (AOR, 1.46; 95% CI, 1.34-1.58; P < .001) disease and in men who were younger (per year decrease, AOR, 1.02; 95% CI, 1.02-1.03; P < .001), married (AOR, 1.10; 95% CI, 1.02-1.19; P = .01), or lived in metropolitan areas (AOR, 1.30; 95% CI, 1.16-1.47; P < .001)., Conclusion: PPRT recommendations increased after the reporting of a survival benefit in March 2009, but absolute utilization rates remain low, suggesting that the oncologic community remains unconvinced that PPRT is needed for most patients with adverse features. Further work is needed to identify patients who might benefit most from PPRT., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objectives: The 8th Annual Bladder Cancer Think Tank (BCAN-TT) brought together a multidisciplinary group of clinicians, researchers, and patient advocates in an effort to advance bladder cancer research., Methods and Materials: With the theme of "Collaborating to Move Research Forward," the meeting included three panel presentations and seven small working groups., Results: The panel presentations and interactive discussions focused on three main areas: gender disparities, sexual dysfunction, and targeting novel pathways in bladder cancer. Small working groups also met to identify projects for the upcoming year, including: (1) improving enrollment and quality of clinical trials; (2) collecting data from multiple institutions for future research; (3) evaluating patterns of care for non-muscle-invasive bladder cancer; (4) improving delivery of care for muscle-invasive disease; (5) improving quality of life for survivors; (6) addressing upper tract disease; and (7) examining the impact of health policy changes on research and treatment of bladder cancer., Conclusions: The goal of the BCAN-TT is to advance the care of patients with bladder cancer and to promote collaborative research throughout the year. The meeting provided ample opportunities for collaboration among clinicians from multiple disciplines, patients and patient advocates, and industry representatives., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Purpose: The National Radiation Oncology Registry (NROR) is a collaborative initiative of the Radiation Oncology Institute and the American Society of Radiation Oncology, with input and guidance from other major stakeholders in oncology. The overarching mission of the NROR is to improve the care of cancer patients by capturing reliable information on treatment delivery and health outcomes., Methods: The NROR will collect patient-specific radiotherapy data electronically to allow for rapid comparison of the many competing treatment modalities and account for effectiveness, outcome, utilization, quality, safety, and cost. It will provide benchmark data and quality improvement tools for individual practitioners. The NROR steering committee has determined that prostate cancer provides an appropriate model to test the concept and the data capturing software in a limited number of sites. The NROR pilot project will begin with this disease-gathering treatment and outcomes data from a limited number of treatment sites across the range of practice; once feasibility is proven, it will scale up to more sites and diseases., Results: When the NROR is fully implemented, all radiotherapy facilities, along with their radiation oncologists, will be solicited to participate in it. With the broader participation of the radiation oncology community, NROR has the potential to serve as a resource for determining national patterns of care, gaps in treatment quality, comparative effectiveness, and hypothesis generation to identify new linkages between therapeutic processes and outcomes., Conclusions: The NROR will benefit radiation oncologists and other care providers, payors, vendors, policy-makers, and, most importantly, cancer patients by capturing reliable information on population-based radiation treatment delivery., (Copyright © 2012 (c) 2010 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved. Published by Elsevier Inc. All rights reserved.)