Higher Decipher scores were associated with distant metastasis on PSMA PET in both the de novo and recurrent setting. Transcriptomic differences in pathways related to proliferation, p53 status, and PAM50 classification were seen when comparing localized, node-positive, and distant metastatic disease. Patients with de novo miN1M0 or miM1a disease may harbor more aggressive disease than those with miN1M0 or miM1a disease at recurrence.

5009 Background: Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) shows improved sensitivity and specificity for detection of locoregional and distant metastatic prostate cancer (PCa) compared to conventional imaging, especially at lower PSA levels as is often the case in the biochemically recurrent (BCR), post radical prostatectomy (RP) setting. Providers are now utilizing PSMA PET findings to guide their salvage radiotherapy (sRT) treatment fields and doses, although it is not well understood how PSMA PET guided sRT impacts patient outcomes. Methods: This was a post-hoc analysis of 5 prospective studies of PSMA PET conducted at UCLA from 2016 to 2021 that included patients with recurrent PCa following RP. Patients were included in this retrospective study if they initiated sRT within 3 months of PSMA PET, had at least 12 months of follow up after sRT completion, had available sRT treatment details, and did not have distant metastases (DM) by conventional imaging on upfront staging. Patients treated with palliative RT were excluded. BCR following sRT was defined as an increase in PSA of 0.2 ng/ml above the post sRT nadir. Metastasis directed therapy (MDT) was defined as sRT to all PSMA+ N1 and M1 lesions. Baseline patient demographics, PSMA PET findings, sRT & ADT treatment details, and patient outcome data were collected. Results: 176 patients were included in this study. Median time between RP and PSMA PET was 38 months (range 1-329). Median PSA at the time of the PSMA PET was 0.625 ng/mL (range 0.063-35). PSMA PET was positive in 128 patients (73%): 21 (12%) miT+N0M0, 55 (31%) miTxN1M0 and 52 (30%) miTxNxM1 with 19 (11%) miTxNxM1a, 31 (18%) miTxNxM1b, and 2 (1%) miTxNxM1c. Median number of lesions seen on positive PSMA scans was 1 (range 1-8). 39 (22%) patients were subsequently treated with sRT to the prostate bed (PB) only, 59 (34%) to PB + pelvic lymph nodes (PLNs), 33 (19%) to PLNs only, 7 (4%) to PB + PLNs + DM, 7 (4%) to PLNs + DM, and 31 (18%) to DM only. 59 (34%) patients were treated with concurrent ADT at a median duration of 6 months (range 1-39). At a median follow-up of 32 months (range 12-70) after sRT, 80 patients (45%) did not develop BCR or imaging relapse (IR) following sRT, 24 patients (14%) developed BCR but not IR, 1 patient (<1%) developed IR only, and 70 patients (40%) developed both BCR and IR. The median time to BCR and IR following sRT was 15 months (range 1-48) and 19 months (range 6-61), respectively. 1 year post sRT biochemical recurrence free survival was 77%. Of the 83 patients treated with MDT, 32 (39%) did not develop subsequent disease relapse. Conclusions: This post-hoc analysis assessed the outcomes of 176 patients treated with PSMA PET guided salvage RT, proving it to be an effective method for treating both pelvic and extrapelvic recurrent PCa. Further investigation is needed to assess the full extent of patient outcomes in this population.

Purpose/Objective(s)Postoperative radiotherapy (RT) to the prostate bed (PB) is a potentially curative treatment after radical prostatectomy (RP). The PB target definition follows contouring guidelines mostly based on expert consensus, and does not account for anatomical patterns of recurrence on more contemporary imaging. Herein, we analyze the patterns of recurrence in the PB of prostate cancer (PCa) patients with biochemical recurrence after RP using 68Ga-PSMA-11 PET/CT (PSMA PET). We also evaluate patterns of PSMA PET recurrence in relation to the RTOG-based clinical target volumes (CTVs) definition.Materials/MethodsPatients with biochemically recurrent PCa after RP, without previous history of PB RT, were retrospectively included if their PSMA PET showed evidence of recurrence in the PB. Two nuclear medicine physicians manually delineated the PB lesions on the CT images of the PSMA PET/CT. Four radiation oncologists, masked to the PSMA PET component of the PET/CT study and to the PSMA-based delineations, contoured the RTOG-based CTVs on the same CT. Three-dimensional heat maps of the PSMA PET-positive PB lesions were generated to visually depict patterns of PSMA PET recurrences. The coverage of the PSMA PET recurrence by the RTOG-based CTVs was categorized in consensus by a nuclear medicine physician and a radiation oncologist as follows: fully within, partly covered or fully outside.Results2,415 PSMA PET scans performed at UCLA between 11/2016 and 11/2020 were screened for inclusion criteria. 230/2,415 (10%) scans of patients with prostate bed recurrence on PSMA PET were included. 127 (55%) patients had miTrN0M0, 30 (13%) miTrN1M0, 34 (15%) miTrN0M1, and 39 (17%) miTrN1M. In the miTrN0M0 cohort, PSMA-positive recurrences were fully covered by the CTV in 68/127 (54%) of the patients, partly covered in 43/127 (34%), and fully outside in 16/127 (13%). Lesions with partial coverage or fully outside the CTV were located at posterior border in 21/127 (53%), postero-lateral in 15/127 (25%), postero-inferior in 2/127 (3%), anterior in 1/127 (2%), antero-inferior in 1/127 (2%), superior in 1/127 (2%) and inferior in 8/127 (14%) of patients. The median (IQR) PSA levels were 1.11 ng/mL (1.7), 1.10 ng/mL (2.17) and 0.84 ng/mL (0.49), and the volumes of PSMA PET recurrences were 0.57cc (0.77), 1.01cc (1.71) and 0.68cc (0.59) in patients with recurrences fully within, partially covered and fully outside the CTV, respectively.ConclusionTo our knowledge, this is the largest study with a detailed mapping of recurrences in the prostate bed using PSMA PET imaging. In patients with recurrences exclusive to the prostate bed (miTrN0M0), the RTOG contouring guidelines showed suboptimal coverage of the disease in 46% of patients. Our study suggests that PSMA PET can be an invaluable tool for postoperative radiotherapy planning and should be incorporated into a redefinition of RT contouring guidelines.

Purpose/Objective(s) A case series from China published in 2020 reported a high rate of radiation pneumonitis (RP) among 11 patients treated with concurrent thoracic radiotherapy (TRT) and osimertinib, including 9% who developed a fatal complication. We analyzed the RP rates for patients at our institution who were also treated with a similar combination for metastatic non-small cell lung cancer (NSCLC). Materials/Methods This retrospective study was performed at a single academic medical center in the US. We identified all patients who were treated with concurrent TRT and osimertinib between June 2016 and December 2021. Baseline patient characteristics, tumor size and location, and dosimetric parameters were evaluated. The highest grade of RP that developed within 6 months of treatment was scored in accordance with CTCAE v5.0. Fisher's exact test and logistic regression were performed to investigate the association of pre-treatment factors with development of grade ≥2 and grade ≥3 RP. Results Sixteen patients with metastatic NSCLC were treated with concurrent TRT and osimertinib over the study time period. The treatment site of each patient's pulmonary metastases was as follows: peripheral in 4 (25%), central in 4 (25%) (within 1-2 cm of the proximal bronchial tree [PBT]), ultra-central in 7 (44%) (within 1 cm of the PBT), and mediastinal in 1 (6%). Two of 16 patients withheld osimertinib 24-48 hours before and after TRT, both of which had tumors in an ultra-central location. Patients were treated with a median dose of 50 Gy (11-65 Gy) in a median of 7.5 fractions (1-15 fractions); the median duration of TRT was 10 days (1-22 days). The median follow-up time was 13 months (1 – 61 months). Nine patients developed grade ≥2 RP (56%) with a median time to onset of 29 days (1-84 days). The severity of RP was grade ≥3 in 6 (37.5%) and grade 4 in 1 (6.3%); no patients had grade 5 RP. Of the 6 patients who developed grade ≥3 RP, 2 (33.3%) were treated with stereotactic body radiotherapy (SBRT) while 4 (66.6%) were treated with hypofractionated TRT. All patients who developed grade ≥3 RP were female. Tumor location for patients who developed grade ≥3 RP was central in 3 (50%), ultra-central in 2 (33%) and mediastinal in 1 (17%); no patients with peripheral tumors developed grade ≥3 RP. Both patients who withheld osimertinib before and after TRT did not develop RP. The association of female sex and non-peripheral tumor location with grade ≥3 RP was not statistically significant in the context of a small case series (p=0.23). RP was not associated with the use of SBRT vs hypofractionated TRT or mean lung dose. Conclusion TRT with concurrent osimertinib was associated with a high rate of RP, particularly when the site of pulmonary metastases was in a central, ultra-central, or mediastinal location. Withholding osimertinib 24-48 hours before and after TRT may mitigate this risk. These data raise safety concerns that are not currently listed in treatment guidelines. Further research is indicated to validate these findings in larger cohorts.

Nearly 40% of patients with radiorecurrent prostate cancer have local-only recurrences on PSMA imaging, while another 40% have distant disease. PSA at the time of PSMA imaging is a significant predictor of distant recurrence. Prospective studies evaluating salvage treatment approaches that integrate PSMA imaging data are warranted, and imaging at a lower PSA threshold should be considered.

Although 24 Gy in 12 fractions is the more effective radiation schedule for indolent lymphomas and remains the standard of care in the definitive setting, 4 Gy remains a useful alternative for palliative treatment. We analyzed the cost-effectiveness of 4 Gy versus 24 Gy for the palliative treatment of patients with indolent lymphoma. We constructed a Markov model simulating 5-year outcomes for 1 million hypothetical patients with indolent lymphoma receiving palliative radiation treatment with either 24 Gy in 12 fractions or 4 Gy in 2 fractions. Patients entered the model at an initial progressive disease state requiring palliation (iPD) and transitioned to progression-free (PF), progressive disease requiring re-treatment with 4 Gy (PD1), progressive disease after re-treatment (PD2), or death states. Health utility values were obtained from published studies and transition probabilities were derived from the FORT trial. Radiation costs were calculated using 2019 National Medicare fee schedules. For the base case analysis, we assumed 3-dimensional (3-D) conformal radiation treatment. Utilities and costs were discounted at 3% annually. The primary outcome measure was the incremental cost-effectiveness ratio (ICER); we defined the willingness-to-pay (WTP) threshold at $50,000 per quality-adjusted life-year (QALY). Deterministic and probabilistic sensitivity analyses were performed to assess for uncertainty around model parameters. We found that the 4 Gy and 24 Gy treatment strategies were associated with costs of $4,666 and $6,517 and QALYs of 3.28 and 3.29, respectively. In the base case analysis, 4 Gy was the cost-effective strategy compared with 24 Gy (ICER of 24 Gy vs 4 Gy: $107,605/QALY). On sensitivity analysis, findings were robust against a WTP of $50,000 per QALY to variations in all key model parameters, including the cost of radiation treatment, the probabilities of disease progression, and utilities of the health states. The incremental cost effectiveness acceptability curve demonstrated 93.8% certainty that the 4 Gy strategy was the most cost-effective option at willingness-to-pay of $50,000/QALY. For patients with indolent lymphoma requiring palliation of local symptoms, 4 Gy in 2 fractions is the cost-effective strategy as compared with 24 Gy in 12 fractions.

Stereotactic Body Radiation Therapy (SBRT) has emerged as a convenient, effective, and safe treatment option for favorable risk prostate cancer. A benign Prostate-Specific Antigen (PSA) bounce is a temporary elevation of PSA above prior values. These PSA variations are common following ultra-hypofractionated SBRT (30-40%) and frequently lead to patient anxiety. In this report, we compare our standard PSA surveillance schedule with an alternative longer interval routine to determine its impact on the incidence of benign PSA bounces and timely detection of biochemical failures. Seven hundred thirty-three patients with low (n = 221) and intermediate (n = 512) risk prostate cancer were treated with SBRT to a total dose of 35–37.5 Gy in 5 fractions at a single academic hospital between January 2008 and December of 2017. Patients treated with androgen deprivation therapy were excluded from this study. PSA nadirs, PSA bounces, and biochemical failures were recorded during the first 3 years of follow up. Any PSA rise of ≥ 0.2 ng/ml with a subsequent return to baseline was recorded as a benign PSA bounce. Any PSA rise of ≥ 2 ng/ml from the nadir without resolution back to baseline was recorded as biochemical failure. The standard follow up schedule "A" involved PSA draws one month after the completion of SBRT, every 3 months for the first year and then every 6 months for the second and third years. The abbreviated follow up schedule "B" was derived from the same data points at 3, 12, 24, and 36 months. Schedule "A" included 4,764 PSA values drawn as compared to 1,955 in Schedule "B" – a reduction of 59%. During years 1, 2, and 3 of follow up, Schedule A identified 167, 93, and 60 benign PSA bounces, respectively. In Schedule "B" PSA bounce identification was reduced to 42, 21, and 25 during the first, second, and third years, respectively, - a reduction of 75%, 77%, and 58%, respectively, relative to Schedule "A." There were no statistically significant differences in the yearly PSA nadirs between the two schedules. Nine biochemical failures were identified during the three-year follow up period. Only one biochemical failure identification would have been delayed six months by utilization of the reduced follow-up schedule. The ideal PSA surveillance schedule after undergoing SBRT is unknown. A conservative PSA surveillance schedule following prostate SBRT reduces the rate of benign PSA bounces without a significant reduction in the early detection of biochemical failures. The proposed modified early PSA surveillance schedule may reduce patient anxiety and preserve valuable clinical resources.

Standard imaging is inadequate at identifying recurrent disease post-operatively after prostate cancer biochemical failure. Prostate cancer selectively expresses prostate specific membrane antigen (PSMA). The 18F-DCFBC is a novel radiolabeled PET agent that binds PSMA and provides new information regarding PSMA expression and localization of recurrent disease. We identified 18F-DCFBC PET avid lesions after biochemical failure and compared these to consensus Radiation Therapy Oncology Group (RTOG) volumes for prostate fossa and pelvic lymph nodes (LN). A total of 49 patients enrolled on a prospective institutional review board approved clinical trial. Each presented with biochemical recurrence post-prostatectomy, PSA of ≥0.2ng/ml, and no site of recurrence on standard imaging. All patients underwent whole body 18F-DCFBC PET/CT. RTOG consensus prostate fossa clinical target volume (PF-CTV) contours and pelvic LN volumes (LN-CTV) were drawn by 2 radiation oncologists. PF-CTV limited the superior boarder to 2cm above the pubic symphysis, while the expanded prostate fossa (EPF-CTV) limited the border to 4 cm. The 18F-DCFBC avid lesions were contoured by a radiologist on the corresponding CT while blinded to consensus contours. PET images were fused to CT, and 18F-DCFBC avid areas were compared with consensus contours. Forty-two 18F-DCFBC avid lesions were identified in 26 patients. A total of 40.5% (17/42) of lesions were encompassed within PF-CTV. No lesions were seen within the EPF-CTV. 16.7% (7/42) of lesions were encompassed by LN-CTV. A total of 4.8% (2/42) of recurrent lesions in the pelvis were not within RTOG contours. One lesion was peri-urethral at the level of the penile bulb, while another was identified adjacent to the posterior-lateral rectal wall. A total of 38.1% (16/42) of lesions were classified as distant metastatic disease. Of the 26 patients, 50% (13/26) had recurrent disease within PF-CTV only. 15.4% (4/26) patients had recurrent disease outside of PF-CTV but within LN-CTV. A total of 27.0% (7/26) patients were found to have distant metastatic disease. A total of 7.7% (2/26) patients had local recurrence in areas that were not encompassed by PF-CTV and LN-CTV. Advanced imaging may identify areas of recurrence, inform target volumes, and select appropriate patients for systemic therapy after biochemical failure in prostate cancer. Half of patients had recurrent disease encompassed by consensus radiation volumes for prostate fossa, with only a small number of patients with local disease identified outside this volume. In 15.4% of patients, inclusion of all identified disease would require regional nodal irradiation for adequate coverage. Importantly, 27% of patients had occult metastatic disease and would not have been salvaged.

Intensity modulated radiation therapy (IMRT) for prostate cancer has a favorable toxicity profile but can result in urinary symptoms. Urethra length changes have been implicated in post-prostatectomy lower urinary tract symptoms. Moreover, radiation therapy to the prostate causes changes to urethra length, prostate volume, and bladder neck enhancement as measured on MRI. We hypothesized that greater changes in bladder enhancement, prostate volume, and urethra length are associated with urinary morbidity. Patients treated with IMRT for prostate cancer who underwent MRI before treatment and six months after treatment were retrospectively reviewed. American Urological Association (AUA) symptom scores and medications for urinary symptoms were recorded at baseline, 1-month, and 6-month post-radiation therapy (post-RT). Irritative (frequency, urgency, and nocturia) and obstructive (incomplete emptying, intermittency, weak stream, and straining) AUA sub-scores were analyzed. Worsening urinary tract symptoms were defined as an increase in AUA score > 5 or an increase in medications for urinary symptoms. Urethra length (membranous plus prostatic urethra) was measured on sagittal T2W images. Bladder neck enhancement was evaluated on coronal T2W images as signal intensity (SI) normalized to bladder dome SI (outside of the irradiated volume). MRI measurements were performed by readers blinded to clinical outcomes. Changes in bladder neck enhancement, prostate volume and urethra length were evaluated by Wilcoxon signed-rank tests. Differences in MRI findings between worsened versus stable/improved urinary symptom groups were determined by Wilcoxon rank-sum tests. Thirty-nine patients that received radiation treatment to the pelvic lymph nodes (45 Gy) and prostate (mean 78.1 Gy) were included. From pre to 6 month post-treatment MRIs, median normalized bladder neck SI increased (0.89 to 1.07, p = 0.01); median urethra length decreased (60.65 mm to 57.73 mm, p = 0.03); and prostate volume decreased (39 mL to 28 mL, p <0.0001). Twenty-five of 38 patients at 1 month post-RT and 11 of 33 patients at 6 months post-RT had worsening urinary symptoms from baseline. Greater decrease in prostate volume at post-RT MRI was associated with early (1 month AUA) worsening of urinary symptoms (p = 0.05). At 6 months post-RT, patients with longer urethra length on MRI had stable or decreasing obstructive urinary symptoms (p = 0.01). Increased bladder neck enhancement was not associated with worsening overall or irritative urinary symptoms at either time point (p >0.05). Radiation therapy is associated with decrease in prostate volume, shortening of urethra length, and increase in bladder neck enhancement. Post-RT MRI at 6 months revealed an association between decrease in prostate volume and worsening urinary symptoms at early follow-up. An association between post-RT urethra length and stable or improving obstructive urinary function was observed.