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ImportanceRadiotherapy combined with androgen deprivation therapy (ADT) is a standard of care for high-risk prostate cancer. However, the interplay between radiotherapy dose and the required minimum duration of ADT is uncertain.ObjectiveTo determine the specific ADT duration threshold that provides a distant metastasis-free survival (DMFS) benefit in patients with high-risk prostate cancer receiving external beam radiotherapy (EBRT) or EBRT with a brachytherapy boost (EBRT+BT).Design, settings, and participantsThis was a cohort study of 3 cohorts assembled from a multicenter retrospective study (2000-2013); a post hoc analysis of the Randomized Androgen Deprivation and Radiotherapy 03/04 (RADAR; 2003-2007) randomized clinical trial (RCT); and a cross-trial comparison of the RADAR vs the Deprivación Androgénica y Radio Terapía (Androgen Deprivation and Radiation Therapy; DART) 01/05 RCT (2005-2010). In all, the study analyzed 1827 patients treated with EBRT and 1108 patients treated with EBRT+BT from the retrospective cohort; 181 treated with EBRT and 203 with EBRT+BT from RADAR; and 91 patients treated with EBRT from DART. The study was conducted from October 15, 2020, to July 1, 2021, and the data analyses, from January 5 to June 15, 2021.ExposuresHigh-dose EBRT or EBRT+BT for an ADT duration determined by patient-physician choice (retrospective) or by randomization (RCTs).Main outcomes and measuresThe primary outcome was DMFS; secondary outcome was overall survival (OS). Natural cubic spline analysis identified minimum thresholds (months).ResultsThis cohort study of 3 studies totaling 3410 men (mean age [SD], 68 [62-74] years; race and ethnicity not collected) with high-risk prostate cancer found a significant interaction between the treatment type (EBRT vs EBRT+BT) and ADT duration (binned to

ImportanceProstate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) can detect low-volume, nonlocalized (ie, regional or metastatic) prostate cancer that was occult on conventional imaging. However, the long-term clinical implications of PSMA PET/CT upstaging remain unclear.ObjectivesTo evaluate the prognostic significance of a nomogram that models an individual's risk of nonlocalized upstaging on PSMA PET/CT and to compare its performance with existing risk-stratification tools.Design, setting, and participantsThis cohort study included patients diagnosed with high-risk or very high-risk prostate cancer (ie, prostate-specific antigen [PSA] level >20 ng/mL, Gleason score 8-10, and/or clinical stage T3-T4, without evidence of nodal or metastatic disease by conventional workup) from April 1995 to August 2018. This multinational study was conducted at 15 centers. Data were analyzed from December 2020 to March 2021.ExposuresCurative-intent radical prostatectomy (RP), external beam radiotherapy (EBRT), or EBRT plus brachytherapy (BT), with or without androgen deprivation therapy.Main outcomes and measuresPSMA upstage probability was calculated from a nomogram using the biopsy Gleason score, percentage positive systematic biopsy cores, clinical T category, and PSA level. Biochemical recurrence (BCR), distant metastasis (DM), prostate cancer-specific mortality (PCSM), and overall survival (OS) were analyzed using Fine-Gray and Cox regressions. Model performance was quantified with the concordance (C) index.ResultsOf 5275 patients, the median (IQR) age was 66 (60-72) years; 2883 (55%) were treated with RP, 1669 (32%) with EBRT, and 723 (14%) with EBRT plus BT; median (IQR) PSA level was 10.5 (5.9-23.2) ng/mL; 3987 (76%) had Gleason grade 8 to 10 disease; and 750 (14%) had stage T3 to T4 disease. Median (IQR) follow-up was 5.1 (3.1-7.9) years; 1221 (23%) were followed up for at least 8 years. Overall, 1895 (36%) had BCR, 851 (16%) developed DM, and 242 (5%) died of prostate cancer. PSMA upstage probability was significantly prognostic of all clinical end points, with 8-year C indices of 0.63 (95% CI, 0.61-0.65) for BCR, 0.69 (95% CI, 0.66-0.71) for DM, 0.71 (95% CI, 0.67-0.75) for PCSM, and 0.60 (95% CI, 0.57-0.62) for PCSM (P

The natural history of radiorecurrent high-risk prostate cancer (HRPCa) is not well-described. To better understand its clinical course, we evaluated rates of distant metastases (DM) and prostate cancer-specific mortality (PCSM) in a cohort of 978 men with radiorecurrent HRPCa who previously received either external beam radiation therapy (EBRT, n = 654, 67%) or EBRT + brachytherapy (EBRT + BT, n = 324, 33%) across 15 institutions from 1997 to 2015. In men who did not die, median follow-up after treatment was 8.9 yr and median follow-up after biochemical recurrence (BCR) was 3.7 yr. Local and systemic therapy salvage, respectively, were delivered to 21 and 390 men after EBRT, and eight and 103 men after EBRT + BT. Overall, 435 men developed DM, and 248 were detected within 1 yr of BCR. Measured from time of recurrence, 5-yr DM rates were 50% and 34% after EBRT and EBRT + BT, respectively. Measured from BCR, 5-yr PCSM rates were 27% and 29%, respectively. Interval to BCR was independently associated with DM (p

PurposeWe evaluated the short and long-term surgical outcomes of urinary diversion done for urinary adverse events arising from prostate radiation therapy. We hypothesized that patient characteristics are associated with complications after urinary diversion.Materials and methodsWe performed a retrospective cohort study of 100 men who underwent urinary diversion (urinary conduit or continent catheterizable pouch) due to urinary adverse events after prostate radiotherapy from 2007 to 2016 from 9 academic centers in the United States. Outcome measurements included predictors of short and long-term complications, and readmission after urinary diversion of patients who had prostate cancer treated with radiotherapy. The data were summarized using descriptive statistics and univariate associations with complications were identified with logistic regression controlling for center.ResultsMean patient age was 71 years and median time from radiotherapy to urinary diversion was 8 years. Overall 81 (81%) patients had combined modality therapy (radical prostatectomy plus radiotherapy or various combinations of radiotherapy). Grade 3a or greater Clavien-Dindo complications occurred in 31 (35%) men, including 4 deaths (4.5%). Normal weight men had more short-term complications compared to overweight (OR 4.9, 95% CI 1.3-23.1, p=0.02) and obese men (OR 6.3, 95% CI 1.6-31.1, p=0.009). Hospital readmission within 6 weeks of surgery occurred for 35 (38%) men. Surgery was needed to treat long-term complications after urinary diversion in 19 (22%) patients with a median followup of 16.3 months.ConclusionsUrinary diversion after prostate radiotherapy has a considerable short and long-term surgical complication rate. Urinary diversion most often cannot be avoided in these patients but appreciation of the risks allows for informed shared decision making between surgeons and patients.

PURPOSE: We aim to independently validate the prognostic utility of the combined cell-cycle risk (CCR) multimodality threshold to estimate risk of early metastasis after definitive treatment of prostate cancer and compare this prognostic ability with other validated biomarkers. METHODS: Patients diagnosed with localized prostate cancer were enrolled into a single-institutional registry for the prospective observational cohort study. The primary end point was risk of metastasis within 3 years of diagnostic biopsy. Secondary end points included time to definitive treatment, time to subsequent therapy, and metastasis after completion of initial definitive treatment. Multivariable cause-specific Cox proportional hazards regression models were produced accounting for competing risk of death and stratified on the basis of the CCR active surveillance and multimodality (MM) thresholds. Time-dependent areas under the receiver operating characteristic curve were calculated. RESULTS: The cohort consisted of 554 men with prostate cancer and available CCR score from biopsy. The CCR score was prognostic for metastasis (hazard ratio [HR], 2.32 [95% CI, 1.17 to 4.59]; P =.02), with scores above the MM threshold having a higher risk than those below the threshold (HR, 5.44 [95% CI, 2.72 to 10.91]; P <.001). The AUC for 3-year risk of metastasis on the basis of CCR was 0.736. When men with CCR above the MM threshold received MM therapy, their 3-year risk of metastasis was significantly lower than those receiving single-modality therapy (3% v 14%). Similarly, a CCR score above the active surveillance threshold portended a faster time to first definitive treatment. CONCLUSION: CCR outperforms other commonly used biomarkers for prediction of early metastasis. We illustrate the clinical utility of the CCR active surveillance and multimodality thresholds. Molecular genomic tests can inform patient selection and personalization of treatment for localized prostate cancer. [ABSTRACT FROM AUTHOR]

Background: Survivors of non‐Hodgkin lymphoma (NHL) have increased secondary malignancy (SM) risk. We quantified this risk by patient and treatment factors. Methods: Standardized incidence ratios (SIR, observed‐to‐expected [O/E] ratio) were assessed in 142,637 NHL patients diagnosed from 1975 to 2016 in the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. Comparisons were made between subgroups in terms of their SIRs relative to respective endemic populations. Results: In total, 15,979 patients developed SM, more than the endemic rate (O/E 1.29; p < 0.05). Compared with white patients, relative to respective endemic populations, ethnic minorities had a higher risk of SM (white O/E 1.27, 95% CI 1.25–1.29; black O/E 1.40, 95% CI 1.31–1.48; other O/E 1.59, 95% CI 1.49–1.70). Relative to respective endemic populations, patients who received radiotherapy had similar SM rates to those who did not (O/E 1.29 each), but irradiated patients had increased breast cancer (p < 0.05). Patients who received chemotherapy had higher SM rates than those who did not (O/E 1.33 vs. 1.24, p < 0.05) including more leukemia, Kaposi sarcoma, kidney, pancreas, rectal, head and neck, and colon cancers (p < 0.05). Conclusions: This is the largest study to examine SM risk in NHL patients with the longest follow‐up. Treatment with radiotherapy did not increase overall SM risk, while chemotherapy was associated with a higher overall risk. However, certain subsites were associated with a higher risk of SM, and they varied by treatment, age group, race and time since treatment. These findings are helpful for informing screening and long‐term follow‐up in NHL survivors. [ABSTRACT FROM AUTHOR]