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Background: The relapse rate in patients with clinical stage I (CSI) seminomatous germ cell tumor of the testis (SGCTT) who were undergoing surveillance after radical orchidectomy is 4-30%, depending on tumor size and rete testis invasion (RTI). However, the level of evidence supporting the use of both risk factors in clinical decision-making is low., Objective: We aimed to identify the most important prognostic factors for relapse in CSI SGCTT patients., Design, Setting, and Participants: Individual patient data for 1016 CSI SGCTT patients diagnosed between 1994 and 2019 with normal postorchidectomy serum tumor marker levels and undergoing surveillance were collected from nine institutions., Outcome Measurements and Statistical Analysis: Multivariable Cox proportional hazard regression models were fit to identify the most important prognostic factors. The primary endpoint was the time to first relapse by imaging and/or markers. Relapse probabilities were estimated by the Kaplan-Meier method., Results and Limitations: After a median follow-up of 7.7 yr, 149 (14.7%) patients had relapsed. Categorical tumor size (≤2, >2-5, and >5 cm), presence of RTI, and lymphovascular invasion were used to form three risk groups: low (56.4%), intermediate (41.3%), and high (2.3%) risks with 5-yr cumulative relapse probabilities of 8%, 20%, and 44%, respectively. The model outperformed the currently used model with tumor size ≤4 versus >4 cm and presence of RTI (Harrell's C index 0.65 vs 0.61). The low- and intermediate-risk groups were validated successfully in an independent cohort of 285 patients., Conclusions: The risk of relapse after radical orchidectomy in CSI SGCTT patients under surveillance is low. We propose a new risk stratification model that outperformed the current model and identified a small subgroup with a high risk of relapse., Patient Summary: The risk of relapse after radical orchidectomy in patients with clinical stage I seminomatous germ cell tumor of the testis is low. We propose a new risk stratification model that outperformed the current model and identified a small subgroup with a high risk of relapse., (Copyright © 2023. Published by Elsevier B.V.)

Purpose: An integrated magnetic resonance scanner and linear accelerator (MR-linac) was implemented with daily online adaptive radiation therapy (ART). This study evaluated patient-reported experiences with their overall hospital care as well as treatment in the MR-linac environment., Methods: Patients pre-screened for MR eligibility and claustrophobia were referred to simulation on a 1.5 T MR-linac. Patient-reported experience measures were captured using two validated surveys. The 15-item MR-anxiety questionnaire (MR-AQ) was administered immediately after the first treatment to rate MR-related anxiety and relaxation. The 40-item satisfaction with cancer care questionnaire rating doctors, radiation therapists, the services and care organization and their outpatient experience was administered immediately after the last treatment using five-point Likert responses. Results were analyzed using descriptive statistics., Results: 205 patients were included in this analysis. Multiple sites were treated across the pelvis and abdomen with a median treatment time per fraction of 46 and 66 min respectively. Patients rated MR-related anxiety as "not at all" (87%), "somewhat" (11%), "moderately" (1%) and "very much so" (1%). Positive satisfaction responses ranged from 78 to 100% (median 93%) across all items. All radiation therapist-specific items were rated positively as 96-100%. The five lowest rated items (range 78-85%) were related to general provision of information, coordination, and communication. Overall hospital care was rated positively at 99%., Conclusion: In this large, single-institution prospective cohort, all patients had low MR-related anxiety and completed treatment as planned despite lengthy ART treatments with the MR-linac. Patients overall were highly satisfied with their cancer care involving ART using an MR-linac., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Purpose: To develop a practice-based training strategy to transition from radiation oncologist to therapist-driven prostate MR-Linac adaptive radiotherapy., Methods and Materials: In phase 1, 7 therapists independently contoured the prostate and organs-at-risk on T2-weighted MR images from 11 previously treated MR-Linac prostate patients. Contours were evaluated quantitatively (i.e. Dice similarity coefficient [DSC] calculated against oncologist generated online contours) and qualitatively (i.e. oncologist using a 5-point Likert scale; a score ≥ 4 was deemed a pass, a 90% pass rate was required to proceed to the next phase). Phase 2 consisted of supervised online workflow with therapists required no intervention from the oncologist on 10 total cases to advance. Phase 3 involved unsupervised therapist-driven workflow, with offline support from oncologists prior to the next fraction., Results: In phase 1, the mean DSC was 0.92 (range 0.85-0.97), and mean Likert score was 3.7 for the prostate. Five therapists did not attain a pass rate (3-5 cases with prostate contour score < 4), underwent follow-up one-on-one review, and performed contours on a further training set (n = 5). Each participant completed a median of 12 (range 10-13) cases in phase 2; of 82 cases, minor direction were required from the oncologist on 5 regarding target contouring. Radiation oncologists reviewed 179 treatment fractions in phase 3, and deemed 5 cases acceptable but with suggestions for next fraction; all other cases were accepted without suggestions., Conclusion: A training stepwise program was developed and successfully implemented to enable a therapist-driven workflow for online prostate MR-Linac adaptive radiotherapy., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

We conducted and previously published a phase 2 trial of metastasis-directed therapy (MDT) in men with recurrence of prostate cancer at a low prostate-specific antigen level following radical prostatectomy and postoperative radiotherapy. All patients had negative conventional imaging and underwent prostate-specific membrane antigen (PSMA) positron emission tomography (PET). Patients without visible disease ( n  = 16) or with metastatic disease not amenable to MDT ( n  = 19) were excluded from the interventional study. The remaining patients with disease visible on PSMA-PET received MDT ( n  = 37). We analyzed all three groups to identify distinct phenotypes in the era of molecular imaging-based characterization of recurrent disease. Median follow up was 37 mo (interquartile range 27.5-43.0). There was no significant difference in time to the development of metastasis on conventional imaging among the groups; however, castrate-resistant prostate cancer-free survival was significantly shorter for patients with PSMA-avid disease not amenable to MDT ( p  = 0.047). Our findings suggest that PSMA-PET findings can help in discriminating diverging clinical phenotypes among men with disease recurrence and negative conventional imaging after local therapies with curative intent. There is a pressing need for better characterization of this rapidly growing population of patients with recurrent disease defined by PSMA-PET to derive robust selection criteria and outcome definitions for ongoing and future studies., Patient Summary: In men with prostate cancer with rising PSA levels following surgery and radiation, a newer type of scan called PSMA-PET (prostate-specific membrane antigen positron emission tomography) can be used to characterize and differentiate the patterns of recurrence, and inform future cancer outcomes., (© 2023 The Author(s).)

Radiotherapy is a mainstay treatment option for localized prostate cancer (PCa), with oncological outcomes similar to those with surgery. Standard-of-care radiotherapy approaches include brachytherapy, hypofractionated external beam radiotherapy (EBRT), and EBRT with brachytherapy boost. Given the long survival associated with PCa and these curative-intent radiotherapy approaches, late toxicity is a paramount consideration. In this narrative mini-review, we summarize late toxicities associated with standard-of-care radiotherapy approaches including stereotactic body radiotherapy, an advanced radiotherapy technique supported by accumulating evidence. We also discuss stereotactic magnetic resonance imaging-guided adaptive radiotherapy (SMART), an emerging paradigm that may further improve the therapeutic index of radiotherapy and reduce late toxicities. PATIENT SUMMARY: This mini-review summarizes late side effects associated with standard and advanced radiotherapy techniques for localized prostate cancer. We also discuss a new radiotherapy approach called SMART that may reduce late side effects and increase treatment effectiveness., (Copyright © 2023 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: We have recommended active surveillance as the preferred management option for clinical stage I (CSI) testicular germ cell tumors (GCTs) since 1980. Over time, the recommended intensity of surveillance has decreased; however, the impact on relapse detection has not been investigated., Objective: To examine relapse rate, time to relapse, extent of disease, and burden of treatment at relapse across decreasing surveillance intensity over time., Design Setting and Participants: CSI GCT patients under active surveillance from 1981 to 2021 were included in this study., Outcome Measurements and Statistical Analysis: Through four major iterations in both nonseminomatous (NSGCT) and seminoma surveillance schedules, visit frequency, blood testing, and imaging have been decreased successively. Low-dose, noncontrast computed tomography (CT) scans were adopted in 2011. Categorical variables and time to relapse were compared using chi-square and Fisher's exact or Kruskal-Wallis test, respectively., Results and Limitations: A total of 1583 consecutive patients (942 with seminoma and 641 with NSGCT) were included. In seminoma, chest x-rays were reduced from 13 to one and CT scans were reduced from 20 to ten. Relapse rate, time to relapse, N or M category, and International Germ Cell Cancer Collaborative Group (IGCCCG) classification did not change. In NSGCT, chest x-rays were reduced from 27 to zero and CT scans were reduced from 11 to five. Relapse rate (from 46.2% to 21.2%, p  = 0.002) and the median time to relapse (from 6.54 to 4.47 mo, p  = 0.025) decreased. No difference in relapsed disease burden was identified by N, M, and S category or IGCCCG classification. Treatment burden at relapse and GCT cancer deaths remained similar for seminoma and NSGCT. Limitations include the retrospective design and large time period covered., Conclusions: Despite considerable reductions in surveillance intensity, we did not observe an increase in disease extent, treatment burden, or GCT cancer deaths upon relapse. These results support that our current lower-intensity active surveillance schedules are safe for managing CSI GCT., Patient Summary: Our current reduced-intensity surveillance schedules for clinical stage I germ cell tumors appear to be safe., (© 2022 The Author(s).)

Background: The risk of gastrointestinal (GI) toxicity may limit the use of curative-intent radical radiotherapy (RT) for prostate cancer (PCa) in circumstances where morbidity of treatment may exceed an acceptable threshold. Rectal spacers are used to expand the distance between the anterior rectal wall and the prostate, consequently sparing the rectum from the high-dose region., Case Presentations: We report three clinical scenarios of PCa patients treated at our institution, where risk of RT-associated rectal toxicity may be increased: inflammatory bowel disease (IBD), salvage brachytherapy (BT) after previous external beam RT (EBRT), and tailored dose-escalation with focal BT to the gross tumor volume followed by stereotactic body RT. Prior to RT, a polyethylene glycol (PEG) hydrogel spacer was successfully placed in all cases. Treatment comprised magnetic resonance (MR) guided high dose-rate BT ± EBRT. All patients completed treatment uneventfully, without any significant GI toxicity at last follow-up., Conclusions: These cases illustrate the utility of PEG hydrogel spacer, where concerns of radiation induced toxicity may have previously limited the application of radiotherapy. The synergistic use of these novel devices together with MR-guided BT may expand the indications and therapeutic index of curative-intent RT-based treatments, while minimizing the risks of GI toxicity., (© 2019 The Authors.)

Background: Extraprostatic extension (EPE) is defined as local spread of prostate cancer (PC) beyond prostate boundaries. Although extensively evaluated in radical prostatectomy (RP) specimens, its significance in prostate biopsy (PB) specimens is understudied., Objective: To analyze the clinicopathologic characteristics and treatment outcomes for patients with nonmetastatic PC with EPE on diagnostic PB., Design, Setting, and Participants: We identified all patients at Princess Margaret Cancer Center with EPE on their diagnostic PB between 2005 and 2016. All patients underwent definitive curative-intent treatment with either RP or radiotherapy (RT) with or without androgen deprivation therapy (ADT)., Outcome Measurements and Statistical Analyses: Clinicopathologic variables were compared using a χ 2 or Kruskal-Wallis test; log-rank analyses were applied for outcomes comparison. Primary and secondary endpoints were 5-yr biochemical recurrence (BCR) and the occurrence of metastasis or cancer-specific death, respectively., Results and Limitations: A total of 127 patients with reported EPE in their PB were identified. One-third of patients underwent RP (n=43) and two-thirds received RT (n=84). Baseline prognostic variables (prostate-specific antigen, clinical T stage, biopsy pathologic grade group, and proportion of cores involved with PC) were similar between the treatment groups. More than two-thirds of RT patients received concomitant ADT (median duration 36 mo, interquartile range 24-36), while 39.5% of RP patients received postoperative radiotherapy±ADT. Of the RP patients, 95.3% had ≥pT3a disease and 27.9% had pN1 disease. Median follow-up after RP and RT was similar (43.7 vs 45.8 mo; p=0.516). The 5-yr BCR and metastasis rates in the RP versus RT groups were 25.6% versus 11.9% (p=0.09) and 7% versus 11.9% (p=0.386), respectively. Only one patient died from metastatic PC (RT group). Limitations include the single-center and retrospective design with a moderate sample size and relatively short follow-up., Conclusions: EPE on PB is an infrequent finding that is strongly associated with high-risk clinicopathologic prognostic features that accurately predict EPE in RP specimens. Despite entailing aggressive disease characteristics, EPE on PB should not preclude patients from receiving definitive radical local therapy., Patient Summary: Extraprostatic extension on prostate biopsies is an uncommon finding, but is strongly correlated to additional aggressive disease features. This finding accurately predicts the presence of extraprostatic extension on the final prostate specimen after surgery. Despite the associated high-risk features, finding extraprostatic extension in prostate biopsies should not preclude patients from undergoing curative-intent radical local therapy., (Copyright © 2018. Published by Elsevier B.V.)