Extrapelvic Disease Research Articles

The Added-value of Staging 18F-FDG PET/CT in the Prediction of Overall Survival in the Patients with Bladder Cancer.

This retrospective study aimed to evaluate the prognostic importance of 18F-fluorodeoxyglucose (18F-FDG)-positive pelvic lymph nodes (LNs) and extra-pelvic disease on staging 18F-FDG positron emission tomography/computed tomography (PET/CT) in patients with bladder cancer. Bladder cancer patients who underwent staging 18F-FDG PET/CT were included in the study. Histopathologic features of tumors, therapy histories, presence of distinguishable tumors on CT and PET images, sizes and maximum standardized uptake value (SUVmax) of primary tumors, total numbers, sizes, and SUVmax of 18F-FDG-positive pelvic and extra-pelvic LNs, and total numbers and SUVmax of distant metastases (M1a/1b) were recorded. Patients were followed up until death or the last medical visit. Factors predicting overall survival were determined using Cox regression analysis. Fifty-five patients [median age: 70 (53-84), 48 (87.3%) male, 7 (12.7%) female] with bladder cancer were included in this study. Twenty-nine (52.7%) patients had 18F-FDG positive pelvic LNs, while 24 (43.7%) patients had 18F-FDG positive extra-pelvic disease. Patients with 18F-FDGpositive pelvic LNs had a higher rate of extra-pelvic disease (p=0.003). The median follow-up duration was 13.5 months. The median overall survival was 16.3 months [95% confidence interval (CI) 8.9-23.7]. The primary tumor distinguishability on PET (p=0.011) and CT (p=0.009) images, the presence of 18F-FDG-positive pelvic LNs (p<0.001) and 18F-FDG-positive extra-pelvic disease/distant metastases (M1a/M1b) (p<0.001), and the number of distant metastases (p=0.034) were associated with mortality. The 18F-FDG-positive extra-pelvic disease/distant metastases [p=0.029, odds ratio: 4.15 (95% CI 1.16-14.86)] was found to be an independent predictor of mortality in patients with bladder cancer. The presence of 18F-FDG-positive extra-pelvic disease in pretreatment 18F-FDG PET/CT is an important prognostic factor in bladder cancer patients.

PSMA PET imaging for evaluation of recurrent or persistent prostate cancer after primary prostate radiation.

35 Background: PSMA PET is increasingly utilized for the evaluation of disease stage at biochemical recurrence. Here we evaluate the association of clinico-pathologic features with PSMA findings in biochemically recurrent patients after primary prostate radiation therapy (RT). Methods: We queried the Northwestern Medical System Electronic Data Warehouse between July 2021 and March 2023 to identify 122 men treated with primary RT for presumptive localized prostate cancer who subsequently underwent Gallium-68 or F-18 piflufolastat (DCFPyL) PSMA PET/CT for staging. Patient characteristics, including demographic, clinical, pathological, and imaging variables were obtained. PSMA positivity for suspicious nodal or metastatic disease was determined based on radiology interpretation, with equivocal or likely benign lesions considered as negative findings. Patients with incomplete clinical history (n=3) were excluded. Clinical variables were compared using a Wilcoxon rank-sum and Fisher’s exact tests. Regression analysis was performed to determine variables associated with PSMA positivity in biochemically recurrent patients. Statistical significance was determined if the p-value was less than 0.05. Results: Among the 119 men staged with PET PSMA after RT, median PSA was 3.18 (IQR 1.35, 5.55 ng/mL). 78% (93/119) were found to have suspicious PSMA positive disease. 39% had PSMA positivity in the prostate only (46/119), 6.7% had pelvic nodal disease (8/119), and 33% had extrapelvic disease (39/119). On univariable regression analysis, PSA at the time of PSMA was the only factor associated with PSMA positivity (OR 1.32 per 1 point increase, 95% CI 1.10, 1.67, p=0.01; Table). Higher PSAs at the time of scan were additionally associated with distant recurrence (73.3% of men with distant recurrence if scanned at PSA &gt;10ng/mL versus 31.9% if scanned at PSA &lt;4ng/mL p=0.029). 20% (9/46) of men with PSMA positivity within the prostate were biopsied identifying 78% (7/9) positivity, of which 67% (4/6) receiving treatment selected management with salvage treatments. Conclusions: Patients with prostate cancer initially treated with RT showed significant rates of PSMA positive disease even when scanned at low PSAs (including many below the nadir+2ng/mL definition). Evaluation at low PSAs favors the identification of localized disease only which can be cured by salvage therapy if confirmed by biopsy (i.e. prostatectomy, cryoablation, HIFU). [Table: see text]

Concurrent Radiation and Deep Hyperthermia Therapy for the Treatment of Recurrent Prostate Cancer

Robustpreclinical and clinical data have established hyperthermia as an effective radiosensitizer which can be used in the setting of recurrent disease to enhance the therapeutic window. We present a single institution experience examining outcomes in recurrent prostate cancer (RPCA) patients treated with concurrent deep hyperthermia (DHT) and radiation (RT). We hypothesized that concurrent DHT and RT would be well tolerated and would provide durable local control without unexpected toxicity. Consecutive RPCA patients treated with concurrent DHT and pelvic RT were retrospectively analyzed. Patients received twice weekly DHT treatments in addition to daily or twice daily (BID) RT. DHT was delivered using a concentric ring radiofrequency phased array system to a target temperature of 40-43°C. Acute and late treatment associated toxicities, graded per Common Terminology Criteria for Adverse Events (CTCAE) v5.0, were evaluated. Survival and control outcomes were evaluated using the Kaplan-Meier method. Eighteen patients were included for analysis. Median patient age was 69 yrs (64-82 yrs). Fifteen (83%) patients had received prior RT and 12 (67%) patients had undergone radical prostatectomy. At time of treatment, two patients had RPCA which had dedifferentiated to a small cell phenotype. Eight (44%) patients had extra-pelvic disease at time of treatment. Seventeen (94%) patients received proton RT, while 1 (6%) received photon RT. Median RT dose was 49 Gy (range 30-73.8 Gy). Five (28%) patients received BID RT. Fifteen (83%) patients also received sequential or concurrent systemic therapy including androgen deprivation therapy or chemotherapy. A total of 142 DHT treatments were administered (median of 7.5 treatments). Fourteen (78%) patients completed ≥ 75% of planned DHT treatments. Reasons for inability to complete treatment included discomfort and abnormal vital signs during DHT. Only one patient reported Grade 2 pain and pruritus attributed to concurrent RT and DHT. One acute Grade 3 RT toxicity (diarrhea) was reported. No late Grade 3+ toxicities occurred. Of ten patients (56%) treated with curative intent, 8 (44%) had no reported failures at 2-year follow up while two had distant failure and biochemical failure respectively. Three (17%) patients were treated with palliative intent for disease related pain; two reported partial relief and one reported complete pain relief. With a median follow-up of 27 months (1-46 months), 2-year failure free survival was 41.4% (95% CI: 27.8-55%), local control was 76.5% (95% CI 66.2-86.8%) and overall survival was 70.9% (95% CI 58.4-83.3%). Our results suggest that concurrent RT and DHT is well tolerated and allows for safe escalation of local therapy for RPCA, providing patients with durable local control and palliation with an acceptable toxicity profile. Prospective validation is warranted.

Predicting 18F-DCFPyL-PET/CT Scan Positivity in Prostate Cancer Patients with Biochemical Recurrence

To analyze variables that can predict the positivity of 18F-DCFPyL- positron emission tomography/computed tomography (PET/CT) and extent of disease in patients with biochemically recurrent (BCR) prostate cancer after primary local therapy with either radical prostatectomy or radiation therapy. This is a retrospective analysis of a prospective single institutional review board-approved study. We included 199 patients with biochemical recurrence and negative conventional imaging after primary local therapies (radical prostatectomy n=127, radiation therapy n=72). All patients underwent 18F-DCFPyL-PET/CT. Univariate and multivariate logistic regression analyses were used to determine predictors of a positive scan for both cohort of patients. Regression-based coefficients were used to develop nomograms predicting scan positivity and extra-pelvic disease. Decision curve analysis (DCA) was implemented to quantify nomogram's clinical benefit. Of the 127 (63%) post-radical prostatectomy patients, 91 patients had positive scans - 61 of those with intrapelvic lesions and 30 with extra-pelvic lesions (i.e., retroperitoneal or distant nodes and/or bone/organ lesions). Of the 72 post-radiation therapy patients, 65 patients had positive scans - 39 of them had intrapelvic lesions and 26 extra-pelvic lesions. In the radical prostatectomy cohort, multivariate regression analysis revealed original International Society of Urological Pathology category, prostate-specific antigen (PSA), prostate-specific antigen doubling time (PSAdt), and time from BCR (mo) to scan were predictors for scan positivity and presence of extra-pelvic disease, with an area under the curve of 80% and 78%, respectively. Positive versus negative tumor margin after radical prostatectomy was not related to scan positivity or to the presence of positive extra-pelvic foci. In the radiation therapy cohort, multivariate regression analysis revealed that PSA, PSAdt, and time to BCR (mo) were predictors of extra-pelvic disease, with area under the curve of 82%. Because only seven patients in the radiation therapy cohort had negative scans, a prediction model for scan positivity could not be analyzed and only the presence of extra-pelvic disease was evaluated. PSA and PSAdt are consistently significant predictors of 18F-DCFPyL PET/CT positivity and extra-pelvic disease in BCR prostate cancer patients. Stratifying the patient population into primary local treatment group enables the use of other variables as predictors, such as time since BCR. This nomogram may guide selection of the most suitable candidates for 18F-DCFPyL-PET/CT imaging.

Castration-resistant prostate cancer (CRPC) on PSMA-PET: Imaging features, disease distribution, and a comparison to castration-sensitive prostate cancer (CSPC).

e17062 Background: 18F-DCFPyL PET/CT is increasingly used in the staging and response assessment of patients (pts) with prostate cancer. Recent studies suggest that short-term ADT increases prostate-specific membrane antigen (PSMA) expression, whereas long-term ADT suppresses PSMA. Changes in PSMA expression after the development of CRPC are uncertain. We described 18F-DCFPyL PET findings in pts with CRPC and compared them to findings in CSPC. Methods: We analyzed 538 18F-DCFPyL scans performed at our large academic center. CRPC was defined as rising PSA w/ testosterone &lt; 50 ng/dL on ADT. M0 CRPC was defined as absence of extra-pelvic disease (dz) and oligometastatic CRPC (oCRPC) was defined as ≤ 5 LN + osseous lesions and absence of visceral dz. Highest SUV max (hSUVmax) was abstracted from radiologist impression. Means between groups were compared using two-tailed t-tests; undetectable PSA levels were scored as “0”. Logistic regression was used to compare dz distribution between castrate states. Significance was defined as p &lt; 0.05. Results: There were 81 pts with CRPC, 72 pts with metastatic CRPC (mCRPC) and 123 pts with mCSPC. The median ages of pts with mCRPC (74.5 years) and mCSPC (71) were similar. The mean PSAs of mCSPC (20.2 ng/mL) and mCRPC (69.4) were significantly different. hSUVmax was higher in mCRPC (mean 40.3, 95% CI 32.7 – 47.8) than in mHSPC (22.6, 18.4 – 26.9), p &lt; 0.001. Distribution of mCRPC lesions was as follows: prostate bed (26.4%), local pelvic LN (25%), distant LN (M1a, 41.7%), osseous (M1b, 16.7%), and visceral (M1c, 16.7%). In a multivariate analysis mCRPC pts had lower rates of pelvic LN dz and higher rates of M1c, with a trend toward increased M1b (p &lt; 0.10), compared to mCSPC pts. ADT and androgen pathway inhibition did not affect hSUVmax in CRPC. Within CRPC, there were 9 pts with M0 dz, 24 pts with oCRPC, and 48 pts with polymetastatic dz (pmCRPC). The ages (Table) of pmCRPC and oCRPC pts were similar. The mean PSA of pmCRPC (100.9) was higher than that of oCRPC (8.8) and M0 CRPC (5.7). hSUVmax between oCRPC (40.3) and pmCRPC (40.3) was similar. Conclusions: The greater hSUVmax in mCRPC may implicate the effect of ADT on PSMA expression or may describe differing tumor biology. mCRPC pts had less local dz and more frequent distant metastases, likely reflecting more advanced disease. These findings will help inform detection of developing castrate resistance on PSMA-PET. More data are needed on the classification of oligometastatic dz on PSMA-PET and the impact of hormone therapy on PSMA in CRPC. [Table: see text]

68Ga-PSMA PET/CT-Based Atlas for Prostate Bed Recurrence After Radical Prostatectomy: Clinical Implications for Salvage Radiation Therapy Contouring Guidelines.

The aim of this study was to analyze the patterns of prostate bed (PB) recurrence in prostate cancer patients experiencing prostate-specific antigen (PSA) persistence (BCP) or biochemical recurrence (BCR) after radical prostatectomy using 68Ga-PSMA-11 PET/CT (68Ga-PSMA PET) in relation to the Radiation Therapy Oncology Group (RTOG) clinical target volumes (CTVs). Methods: This single-center, retrospective analysis included patients with BCP or BCR after radical prostatectomy and PB recurrence on 68Ga-PSMA PET. The PB recurrences were delineated by nuclear medicine physicians, the CTVs by radiation oncologists contouring guidelines on the 68Ga-PSMA PET, respectively, masked from each other. The coverage of the 68Ga-PSMA PET recurrence was categorized as PSMA recurrence completely covered, partially covered, or not covered by the RTOG-based CTV. Further, we evaluated the differences in PSMA recurrence patterns among patients with different 68Ga-PSMA PET staging (miTNM). Mann-Whitney U tests, the chi-square test, and Spearman (ρ) correlation analysis were used to investigate associations between CTV coverage and 68Ga-PSMA PET-based tumor volume, serum PSA levels, miTNM, and rectal/bladder involvement. Results: A total of 226 patients were included in the analysis; 127 patients had PSMA recurrence limited to the PB (miTrN0M0), 30 had pelvic nodal disease (miTrN1M0), 32 had extrapelvic disease (miTrN0M1), and 37 had both pelvic nodal disease and extrapelvic disease (miTrN1M1). In the miTrN0M0 cohort, the recurrence involved the rectal and bladder walls in 12 of 127 (9%) and 4 of 127 (3%), respectively. The PSMA-positive PB recurrences were completely covered by the CTV in 68 of 127 patients (53%), partially covered in 43 of 127 (34%), and not covered in 16 of 127 (13%). Full coverage was associated with a smaller tumor volume (P = 0.043), a lack of rectal/bladder wall involvement (P = 0.03), and lower miTNM staging (P = 0.035) but not with lower serum PSA levels (P = 0.979). Conclusion: Our study suggests that 68Ga-PSMA PET can be a valuable tool for guiding salvage radiation therapy (SRT) planning directed to the PB in the setting of postoperative BCR or BCP. These data should be incorporated into the redefinition of PB contouring guidelines.

Impact of 18 F-Fluciclovine PET/CT Findings on Failure-Free Survival in Biochemical Recurrence of Prostate Cancer Following Salvage Radiation Therapy.

We aimed to evaluate the impact of 18 F-fluciclovine PET/CT imaging on failure-free survival (FFS) post-salvage radiotherapy (SRT) for prostate cancer (PCa) recurrence. Seventy-nine patients were recruited in a phase 2/3 clinical trial to undergo 18 F-fluciclovine PET/CT before SRT for PCa. Four patients with extrapelvic disease were excluded. All patients were followed up at regular intervals up to 48 months. Treatment failure was defined as a serum prostate-specific antigen level of ≥0.2 ng/mL above the nadir after SRT, confirmed with an additional measurement, requiring systemic treatment or clinical progression. Failure-free survival was computed and compared between patients grouped according to 18 F-fluciclovine PET/CT imaging findings. Eighty percent (60/75) of patients had a positive finding on 18 F-fluciclovine PET/CT, of which 56.7% (34/60) had prostate bed-only uptake, whereas 43.3% (26/60) had pelvic nodal ± bed uptake. Following SRT, disease failure was detected in 36% (27/75) of patients. There was a significant difference in FFS between patients who had a positive versus negative scan (62.3% vs 92.9% [ P < 0.001] at 36 months and 59.4% vs 92.9% [ P < 0.001] at 48 months). Similarly, there was a significant difference in FFS between patients with uptake in pelvic nodes ± bed versus prostate bed only at 36 months (49.8% vs 70.7%; P = 0.003) and at 48 months (49.8% vs 65.6%; P = 0.040). Failure-free survival was also significantly higher in patients with either negative PET/CT or prostate bed-only disease versus those with pelvic nodal ± prostate bed disease at 36 (78% vs 49.8%, P < 0.001) and 48 months (74.4% vs 49.8%, P < 0.001). Findings on pre-SRT 18 F-fluciclovine PET/CT imaging, even when acted upon to optimize the treatment decisions and treatment planning, are predictive of post-SRT FFS in men who experience PCa recurrence after radical prostatectomy. A negative 18 F-fluciclovine PET/CT is most predictive of a lower risk of failure, whereas the presence of pelvic nodal recurrence portends a higher risk of SRT failure.

Enhancing PSMA-PET/CT with intravenous contrast: Improved tracer clearance in the prostate bed.

We observed hitherto unreported layering of radioactivity in the bladder on PET/CT in prostate cancer (PC) when combined with contrast-enhanced CT (CECT). This effect facilitates assessment of the prostate bed in PC. Among 128 patients imaged with [18F]PSMA-1007, we selected all 8 studies without and 28 studies with CECT. 20 patients also underwent PET/MR. As controls, we chose 20 and 16 males studied with [18F]FDG for extrapelvic disease with and without CECT. Posterior anterior (PA) ratio was calculated as SUVpost/SUVant * 100 % based on maximal standard uptake values (SUV) in 20 mm spheres in the anterior and posterior bladder. Four nuclear physicians scored assessibility of the bladder base on a 3-point Likert scale (3 = optimal, 1 = poor). We acquired serial PET/CT over 4 hours of a flask with layering of 100 ml intravenous contrast agent and 100 ml physiological saline with 40 MBq of [18F]PSMA-1007, while a control flask was shaken at the start of the experiment. Layering of tracer was observed in all PET/CT studies with CE-CT, but not in studies without contrast. Median PA ratios were 44 % (interquartile range 33-62) for [18F]PSMA-1007 and 73 % (52-67) for [18F]FDG, respectively. Intravenous contrast improved assessibility scores in PET of the bladder base, but the effect only reached significance in the PET/MR data. In the in vitro data, radioactivity was retained in the aqueous supernatant over the entire experiment whereas there was no separation of phases in the control flask over time. When performing PET combined with CECT, sedimentation of contrast agent in the bladder leads to upward displacement of radioactivity, enhancing clarity of PET images in the posterior bladder and the prostate bed on both PET/CT and PET/MR.

ESHRE guideline: endometriosis.

ESHRE guideline: endometriosis.

Predictors of 18F-DCFPyL PET/CT Positivity in Patients with Biochemical Recurrence of Prostate Cancer After Local Therapy.

Our objective was to investigate the factors predicting scan positivity and disease location in patients with biochemical recurrence (BCR) of prostate cancer (PCa) after primary local therapy using prostate-specific membrane antigen-targeted 18F-DCFPyL PET/CT. Methods: This was a 2-institution study including 245 BCR PCa patients after primary local therapy and negative results on conventional imaging. The patients underwent 18F-DCFPyL PET/CT. We tested for correlations of lesion detection rate and disease location with tumor characteristics, time from initial therapy, prostate-specific antigen (PSA) level, and PSA doubling time (PSAdt). Multivariate logistic regression analyses were used to determine predictors of a positive scan. Regression-based coefficients were used to develop nomograms predicting scan positivity and extrapelvic disease. Results: Overall, 79.2% (194/245) of patients had a positive 18F-DCFPyL PET/CT result, with detection rates of 48.2% (27/56), 74.3% (26/35), 84% (37/44), 96.7% (59/61), and 91.8% (45/49) for PSAs of <0.5, 0.5 to <1.0, 1.0 to <2.0, 2.0 to <5.0, and ≥5.0 ng/mL, respectively. Patients with lesions confined to the pelvis had lower PSAs than those with distant sites (1.6 ± 3.5 vs. 3.0 ± 6.3 ng/mL, P < 0.001). In patients treated with prostatectomy (n = 195), 24.1% (47/195) had a negative scan result, 46.1% (90/195) showed intrapelvic disease, and 29.7% (58/195) showed extrapelvic disease. In the postradiation subgroup (n = 50), 18F-DCFPyL PET/CT was always negative at a PSA lower than 1.0 ng/mL and extrapelvic disease was seen only when PSA was greater than 2.0 ng/mL. At multivariate analysis, PSA and PSAdt were independent predictive factors of scan positivity and the presence of extrapelvic disease in postsurgical patients, with area under the curve of 78% and 76%, respectively. PSA and PSAdt were independent predictors of the presence of extrapelvic disease in the postradiation cohort, with area under the curve of 85%. Time from treatment to scan was significantly longer for prostatectomy-bed-only recurrences than for those with bone or visceral disease (6.2 ± 6.4 vs. 2.4 ± 1.3 y, P < 0.001). Conclusion:18F-DCFPyL PET/CT offers high detection rates in BCR PCa patients. PSA and PSAdt are able to predict scan positivity and disease location. Furthermore, the presence of bone or visceral lesions is associated with shorter intervals from treatment than are prostate-bed-only recurrences. These tools might guide clinicians to select the most suitable candidates for 18F-DCFPyL PET/CT imaging.

Non-exenterative surgical management of recurrent endometrial carcinoma: patient characteristics and outcomes

<h3>Objectives:</h3> To determine what clinicopathologic variables are associated with survival outcomes for patients with recurrent endometrial cancer selected for non-exenterative surgery. <h3>Methods:</h3> All patients with recurrent endometrial cancer who underwent primary surgery between 1/1/2009 and 12/31/2017 at our center were retrospectively identified. We included patients with disease of endometrioid, serous, clear cell, and mixed histologies. Appropriate statistical tests were used. <h3>Results:</h3> We identified 350 patients with recurrent endometrial cancer; 57 (16%) were selected for secondary cytoreductive surgery (SUR) and 240 (69%) were medically managed (MM) with chemotherapy and/or radiation therapy (RT). The remaining patients were treated with hormonal therapy or did not undergo further treatment at recurrence. Median age was 62 years (range, 39-83) for the SUR and 66 years (range, 28-90) for the MM group (p<0.001). Thirty-four patients (60%) in the SUR group and 110 (46%) in the MM group had disease of endometroid histology (p=0.04). Thirty-three (58%) and 101 (42%), respectively, had stage I disease at primary diagnosis (p=0.01). Thirty-eight (67%) and 122 (51%), respectively, had undergone RT as adjuvant treatment at primary diagnosis (p=0.04). Forty-two (74%) and 116 (48%), respectively, had single-site recurrent disease (p<0.001). The most common sites of recurrence for those selected for surgery involved extra-pelvic disease in 42 patients (74%), of which an upper abdominal mass was the most frequent site of disease in 14 patients (33%), followed by lung disease in 8 patients (19%). Among SUR patients, median OR time was 145 min (11-405), estimated blood loss was 100 mL (5-1800), length of stay was 1.5 days (0-13), and 2 patients (4%) experienced a grade 3 complication. Forty-two (74%) achieved a complete gross resection and 43 (75%) underwent postoperative chemotherapy and/or RT. Patients in the SUR group had a median OS of 58 months (95% CI, 33.1-not reached) compared to 24 months (95% CI, 23-30) for those in the MM group (p<0.001). On multivariate analysis,surgery was an independent predictor of improved survival. The MM group had an HR of death of 2.0 (95% CI, 1.2-3.3; p<0.001). Among the 57 patients selected for surgery, tumor size, multisite disease, site of recurrence, and residual disease were not associated with improved post-relapse survival (p=0.259, 0.688, 0.999, 0.929, respectively). <h3>Conclusions:</h3> Medical management with chemotherapy and/or RT is the most common treatment approach for first recurrence of endometrial cancer; however, surgery was associated with acceptable perioperative outcomes and may contribute to improved long-term survival in highly selected patients. Location and multi-site recurrence should not preclude non-exenterative surgical resection if deemed safe and feasible.

Salvage Radiotherapy Management Decisions in Postprostatectomy Patients with Recurrent Prostate Cancer Based on 18F-Fluciclovine PET/CT Guidance.

Imaging with novel PET radiotracers has significantly influenced radiotherapy decision making and radiation planning in patients with recurrent prostate cancer (PCa). The purpose of this analysis was to report the final results for management decision changes based on 18F-fluciclovine PET/CT findings and determine whether the decision change trend remained after completion of accrual. Methods: Patients with detectable prostate-specific antigen (PSA) after prostatectomy were randomized to undergo either conventional imaging (CI) only (arm A) or CI plus 18F-fluciclovine PET/CT (arm B) before radiotherapy. In arm B, positivity rates on CI and 18F-fluciclovine PET/CT for detection of recurrent PCa were determined. Final decisions on whether to offer radiotherapy and whether to include only the prostate bed or also the pelvis in the radiotherapy field were based on 18F-fluciclovine PET/CT findings. Radiotherapy decisions before and after 18F-fluciclovine PET/CT were compared. The statistical significance of decision changes was determined using the Clopper-Pearson (exact) binomial method. Prognostic factors were compared between patients with and without decision changes. Results: All 165 patients enrolled in the study had standard-of-care CI and were initially planned to receive radiotherapy. Sixty-three of 79 (79.7%) patients (median PSA, 0.33 ng/mL) who underwent 18F-fluciclovine PET/CT (arm B) had positive findings. 18F-Fluciclovine PET/CT had a significantly higher positivity rate than CI did for the whole body (79.7% vs. 13.9%; P < 0.001), prostate bed (69.6% vs. 5.1%; P < 0.001), and pelvic lymph nodes (38.0% vs. 10.1%; P < 0.001). Twenty-eight of 79 (35.4%) patients had the overall radiotherapy decision changed after 18F-fluciclovine PET/CT; in 4 of 79 (5.1%), the decision to use radiotherapy was withdrawn because of extrapelvic disease detected on 18F-fluciclovine PET/CT. In 24 of 75 (32.0%) patients with a final decision to undergo radiotherapy, the radiotherapy field was changed. Changes in overall radiotherapy decisions and radiotherapy fields were statistically significant (P < 0.001). Overall, the mean PSA at PET was significantly different between patients with and without radiotherapy decision changes (P = 0.033). Conclusion:18F-Fluciclovine PET/CT significantly altered salvage radiotherapy decisions in patients with recurrent PCa after prostatectomy. Further analysis to determine the impact of 18F-fluciclovine PET/CT guidance on clinical outcomes after radiotherapy is in progress.

18F]DCFPyL PET/CT in detection and localization of recurrent prostate cancer following prostatectomy including low PSA < 0.5ng/mL.

The primary aim of this retrospective multicenter analysis was to assess the performance of PSMA PET/CT using [18F]DCFPyL in the detection and localization of recurrent prostate cancer post radical prostatectomy (RP). Particular reference is given to low PSA groups < 0.5ng/mL to aid discussion around the inclusion of this group in PSMA guidelines and funding pathways. Retrospective analysis of combined PSMA database patients from centers in Australia and New Zealand. Two hundred twenty-two patients presenting with recurrence post RP were stratified into five PSA groups (ng/mL): 0-0.19, 0.2-0.49, 0.5-0.99, 1-1.99, and ≥ 2. Lesions detected by [18F]DCFPyL PET/CT were recorded as local recurrence, locoregional nodes, and metastases. Of 222 patients, 155 (69.8%) had evidence of abnormal uptake suggestive of recurrent prostate cancer. The detection efficacies for [18F]DCFPyL PET/CT were 91.7% (44/48) for PSA levels ≥ 2ng/mL, 82.1% (23/28) for PSA levels 1-1.99ng/mL, 62.8% (27/43) for PSA levels 0.5-0.99ng/mL, 58.7% (54/92) for PSA levels 0.2-0.49ng/mL, and 63.6% (7/11) for PSA levels ≤ 0.2ng/mL. In those with PSA < 0.5ng/mL, 47.6% (49/103) had detectable lesions, 71.4% (35/49) had disease confined to the pelvis, 22.4% (11/49) had prostate bedrecurrence, 49.0% (24/49) had pelvic lymph nodes, and 28.6% (14/49) had extra pelvic disease. [18F]DCFPyL PET/CT has a high detection rate in recurrence following RP even at low PSA levels with similar detection levels in the PSA subgroups < 0.5ng/mL. Employing rigid PSA thresholds when constructing guidelines for PSMA PET/CT funding eligibility may result in a significant number of patients below such thresholds having delayed or inappropriate treatment.

Feasibility of palliating recurrent gynecological tumors with MRGHIFU: comparison of symptom, quality-of-life, and imaging response in intra and extra-pelvic disease

Objective To document longitudinal symptom, quality-of-life and imaging response in patients with recurrent gynecological tumors treated with magnetic resonance guided high intensity focused ultrasound (MRgHIFU), and compare changes in patients with intra- versus extra-pelvic lesions. Methods Eleven symptomatic patients with painful recurrent gynecological tumors were treated with MRgHIFU (Profound Sonalleve) in a prospective single center study (NCT02714621). Pain scores, analgesic intake and quality-of-life metrics, whole tumor volume, and perfused tumor volume from Gadolinium-enhanced T1W imaging documented before and up to 90 days after treatment were compared between patients with intra- and extra-pelvic tumors. Results Two of five patients with intra-pelvic and three of six patients with extra-pelvic tumors were classified as responders (>2 point reduction in NRS pain score without analgesia increase or a > 25% reduction in analgesic use). Cohort reductions in worst pain scores were not significant for either group. Emotional functioning for the whole cohort improved, although physical functioning did not. Ablative thermal temperatures were achieved in three patients with extra-pelvic tumors, but in none whose tumors were intra-pelvic. Pain response did not correlate with thermal dose. Tumor volume increased by 18% immediately post-treatment in the extra-pelvic but not in the intra-pelvic group. Ratio of perfused to whole lesion volume decreased by >20% by day 30 in extra-pelvic, but not intra-pelvic tumors although at day 30 both extra-pelvic and intra-pelvic tumors increased in volume. Conclusion MRgHIFU treatments can be delivered safely to patients with recurrent gynecological tumors. Extra-pelvic tumors responded better than intra-pelvic tumors and showed immediate swelling and reduction in perfused volume by day 30.

A Prospective Provincial PSMA-PET Registry for Recurrent Prostate Cancer: Preliminary results

To compare detection of disease with 18F-DCFPyL PET/CT (PET) versus conventional imaging (CI; CT and bone scan) for patients with undetectable or oligometastatic prostate cancer recurrence on CI, and to assess subsequent change in management. PREP was organized as a Registry Study with six participating sites and a target accrual of 1500 men. Eligibility included biochemical failure with no or limited (≤4 sites) disease on CI and 1 of 6 predefined clinical scenarios (Table). From December 1, 2018 to October 31, 2019, 410 men were enrolled. Overall, 261/410 men (64%) had PET-detected lesions. PET detected disease sites in 174/310 men (56%) with negative conventional imaging. Among men with disease sites detected on conventional imaging, new lesions were seen on PET in 63/100 (63%). PSA at enrolment was available for 408/410 patients, and the detection rate of disease by PSA at enrollment was: 54/139 (39%) for PSA <0.5; 49/78 (63%) for PSA 0.5-1.0 and 157/191 (82%) for PSA >1.0. 149/410 men (36%) had no disease detected, 144/410 men (35%) had recurrent disease localized to the pelvis and 117/410 men (29%) had extra-pelvic disease (with or without pelvic disease). 232/410 men (57%) had potentially “actionable” disease: loco-regional or oligometastatic disease (≤4 distant metastases). Post-PET questionnaires were completed in 341/410 men and 66% (226/341) had a PET-directed change in management. After PET, management intent changed from palliative to radical in 84/341 (25%) and from radical to palliative in 32/341 (9%). After PET, lesion-directed therapy for locoregional or oligometastatic recurrence was added in 135/341 (40%). For patients with local only disease, pelvic nodal disease, and distant metastatic disease on PET, 69%, 79%, and 79% had a change in planned management. 18F-DCFPyL PET/CT access, facilitated through the PREP Registry Study, has resulted in detection of more sites of disease and has impacted both local salvage planning and treatment intent (radical versus palliative).Abstract 4043; TableCohortNumber in cohortMedian PSA% CI positive% PET positive% Management changeOverall4100.9024%64%66% (226/341)N+ or detectable PSA post RP260.9112%27%61% (14/23)BF post RP1550.4417%47%62% (85/137)BF post RP + RT1390.9523%68%66% (79/119)BF post RP or RT + ADT182.7972%89%54% (7/13)BF post Rx for oligometastases82.8663%100%71% (5/7)BF post RT464.7922%87%88% (23/26)CI: conventional imaging; PSA: Prostate Specific Antigen; N+: node positive; RP: Radical Prostatectomy; BF: Biochemical failure; Rx: Treatment; RT: Radiotherapy; ADT: Androgen Deprivation Therapy; PET: Positron Emission Tomography Open table in a new tab

Umbilical endometriosis: a\xa0case series

BackgroundEndometriosis is the presence of endometrial tissue outside the uterine cavity. The lesions are typically found in the pelvic cavity but can occur in other extrapelvic areas. Umbilical endometriosis, also known as Villar’s node, is a rare disease comprising 0.5–1% of all extrapelvic disease. It commonly presents with cyclical pain and bleeding from an umbilical nodule.Case seriesWe present a retrospective case series of five African patients with umbilical endometriosis diagnosed and treated between July 2015 and February 2019 at a tertiary health facility. The patients were aged between 31 and 47 years, and all presented with an umbilical swelling and pain. They had lesions with diameters ranging from 1.6 cm to 4 cm. The duration of symptoms ranged between 3 and 60 months. Their diagnoses were made on the basis of clinical presentation followed by surgical excision. In all the cases, diagnosis was confirmed by histopathology with no malignancy detected.ConclusionUmbilical endometriosis is a rare condition that should be considered as a differential diagnosis in women with umbilical lesions. Diagnosis is mostly clinical; most patients present with umbilical swelling, cyclical pain, and bleeding or discharge. Imaging has a limited role. Surgical excision is the treatment of choice with low risk of malignancy or recurrence.

Juvenile granulosa cell tumor: An interim report from the international ovarian and testicular stromal tumor (OTST) registry.

6064 Background: Juvenile granulosa cell tumors (JGCT) are rare sex cord-stromal tumors which occur primarily in children and adolescents. Methods: All individuals or proxy caregivers provided informed consent/assent for participation in the International OTST Registry. Clinical data was collected. When available, pathology was centrally reviewed. Staging was evaluated using the International Federation of Gynecology and Obstetrics (FIGO) classification. Kaplan-Meier survival analyses and exact permutation tests were performed. Results: Forty-two individuals with ovarian JGCT were enrolled. Median age at diagnosis was 9 years (range 0-27). Most individuals had Stage I disease (Stage Ia=16; Stage Ib=1; Stage Ic=16). Seven individuals presented with higher stage (Stage II=2; Stage III=5). Stage was unknown for 2 individuals. Three-year overall survival (OS) was 88% (CI 77%, 100%) and event-free survival (EFS) was 69% (CI 54%, 88%). At median follow-up time of 25 months (range 0-416), 9 patients (Stage Ia=1, Stage Ic=5, Stage III=3) had recurrent disease. Use of post-operative adjuvant chemotherapy varied by stage and timing of rupture. Of those with Stage Ic JGCT, 2/7 with preoperative rupture and 3/9 with intraoperative rupture recurred. Among individuals with recurrence, median time to recurrence was 11.5 months (range 3-19). Four of 9 individuals with recurrence survived (no evidence of disease n=2; alive with disease n=2). All individuals who died presented with extrapelvic recurrence. Median time from recurrence to death was 10 months (range 2-53). In individuals with recurrence, advanced stage at diagnosis (HR 5.1; p-value 0.087) and recurrence outside the tumor bed (HR Infinity; p-value 0.048) were associated with inferior OS. Three-year OS for individuals with recurrence was 57% (CI 30%, 100%). Conclusions: Low stage JGCT is associated with a favorable prognosis, however, recurrence is associated with lower survival rate. Within this series, recurrences presented within 2 years of diagnosis. Novel strategies are needed to address recurrent and extrapelvic disease.

Efficacy of repeated PSMA PET-directed radiotherapy for oligorecurrent prostate cancer after initial curative therapy

PurposeTo assess the outcome of prostate cancer (PCa) patients diagnosed with oligorecurrent disease and treated with a first and a second PSMA (prostate-specific membrane antigen ligand) PET(positron-emission tomography)-directed radiotherapy (RT).Patients and methodsThirty-two patients with oligorecurrent relapse after curative therapy received a first PSMA PET-directed RT of all metastases. After biochemical progression, all patients received a second PSMA PET-directed RT of all metastases. The main outcome parameters were biochemical progression-free survival (bPFS) and androgen deprivation therapy-free survival (ADT-FS). The intervals of BPFS were analyzed separately as follows: the interval from the last day of PSMA PET-directed RT to the first biochemical progression was defined as bPFS_1 and the interval from second PSMA PET-directed RT to further biochemical progression was defined as bPFS_2.ResultsThe median follow-up duration was 39.5 months (18–60). One out of 32 (3.1%) patients died after 47 months of progressive metastatic prostate cancer (mPCa). All patients showed biochemical responses after the first PSMA PET-directed RT and the median prostate-specific antigen (PSA) level before RT was 1.70 ng/mL (0.2–3.8), which decreased significantly to a median PSA nadir level of 0.39 ng/mL (range <0.07–3.8; p = 0.004). The median PSA level at biochemical progression after the first PSMA PET-directed RT was 2.9 ng/mL (range 0.12–12.80; p = 0.24). Furthermore, the PSA level after the second PSMA PET-directed RT at the last follow-up (0.52 ng/mL, range <0.07–154.0) was not significantly different (p = 0.36) from the median PSA level (1.70 ng/mL, range 0.2–3.8) before the first PSMA PET-directed RT. The median bPFS_1 was 16.0 months after the first PSMA PET-directed RT (95% CI 11.9–19.2) and the median bPFS_2 was significantly shorter at 8.0 months (95% CI 6.3–17.7) after the second PSMA PET-directed RT (p = 0.03; 95% CI 1.9–8.3). Multivariate analysis revealed no significant parameter for bPFS_1, whereas extrapelvic disease was the only significant parameter (p = 0.02, OR 2.3; 95% CI 0.81-4.19) in multivariate analysis for bPFS_2. The median ADT-FS was 31.0 months (95% CI 20.1–41.8) and multivariate analysis showed that patients with bone metastases, compared to patients with only lymph node metastases at first PSMA PET-directed RT, had a significantly higher chance (p = 0.007, OR 4.51; 95% CI 1.8–13.47) of needing ADT at the last follow-up visit.ConclusionIf patients are followed up closely, including PSMA PET scans, a second PSMA PET-directed RT represents a viable treatment option for well-informed and well-selected patients.

PD54-09 BIOCHEMICAL RECURRENCE OF PROSTATE CANCER

INTRODUCTION AND OBJECTIVE: Clinical approach of prostate cancer (PCa) biochemical recurrence (BCR) is nowadays being questioned. Prostate-specific membrane antigen positron scan (PSMA PET) has shown good potential in this field. The aim is to evaluate PSMA PET accuracy in BCR and its utility on clinical outcome. METHODS: Of 319 patients with PCa who underwent 68-Ga PSMA PET between October 2015 and June 2019, 70 had BCR after treatment with curative intent. Two groups were created: Group submitted to surgery (GS) (N:48; 68.6%) and Group submitted to radiotherapy (GR) (N:22; 31.4%). Clinical, analytical, pathological and PSMA PET results were evaluated. RESULTS: Initial age was different (GS – 66±6.5 vs GR – 69±6.2 years, p=0.008). Initial PSA was similar (8.7±5.7 vs 7.5±5.8 ng/mL, p=0.4). GS patients were mainly at intermediate risk (85.1% vs 42.9%, p=0.001) while GR patients were at low risk of recurrence (8.5% vs 47.6%, p=0.001). In GS and GR, PSMA PET detected, respectively, pelvic relapse in 31.3% and 63.6%, and extrapelvic relapse in 18.8% and 31.8%. PSMA PET was negative in 50% (n=24) of GS and 4.5% (n=1) of GR. In positive PSMA PET, PSA was similar in pelvic and extrapelvic disease in both groups (p=0.6; p=0.2). Salvage treatment was performed in 61.9% (n=26) of GS (local radiotherapy in 54.7%, radiotherapy to a single bone metastasis in 2.4% and lymphadenectomy in 4.8%) and in 15% (n=3) of GR (radical prostatectomy with bilateral pelvic lymphadenectomy in 10% and high-dose brachytherapy in 5%), p<0.001. From GS patients submitted to salvage treatment, 59.1% returned to complete remission. Concerning these patients, local radiotherapy led to complete remission in 68.4% (N=13). Neither extended lymphadenectomy nor radiotherapy to the single bone metastasis led to complete remission. The removed ganglia did not harbour tumour. From GR patients submitted to salvage treatment, two had complete remission and one had partial remission (case of high-dose brachytherapy). Concerning diagnostic accuracy, PSMA PET was positive for pelvic relapse when pre-PET PSA≥0.8ng/mL (GS) or ≥2.3ng/mL (GR) and for extrapelvic relapse when PSA≥ 0.4ng/mL (GS) or ≥3.5ng/mL (GR), p> 0.05. CONCLUSIONS: When PSMA PET was positive, PSA was similar between patients with pelvic and extrapelvic relapse. Biochemical persistence rate after salvage therapy was similar (30-40%). The cut-off PSA values for pelvic relapse detected on PSMA PET were ≥0.8 ng/mL (GS) and ≥2.3ng/mL (GR). Source of Funding: None

Potentiation of the Abscopal Effect by Modulated Electro-Hyperthermia in Locally Advanced Cervical Cancer Patients.

Background: A Phase III randomized controlled trial investigating the addition of modulated electro-hyperthermia (mEHT) to chemoradiotherapy for locally advanced cervical cancer patients is being conducted in South Africa (Human Research Ethics Committee approval: M1704133; ClincialTrials.gov ID: NCT03332069). Two hundred and ten participants were randomized and 202 participants were eligible for six month local disease control evaluation. Screening 18F-FDG PET/CT scans were conducted and repeated at six months post-treatment. Significant improvement in local control was reported in the mEHT group and complete metabolic resolution (CMR) of extra-pelvic disease was noted in some participants. We report on an analysis of the participants with CMR of disease inside and outside the radiation field.Method: Participants were included in this analysis if nodes outside the treatment field (FDG-uptake SUV>2.5) were visualized on pre-treatment scans and if participants were evaluated by 18F-FDG PET/CT scans at six months post-treatment.Results: One hundred and eight participants (mEHT: HIV-positive n = 25, HIV-negative n = 29; Control Group: HIV-positive n = 26, HIV-negative n = 28) were eligible for analysis. There was a higher CMR of all disease inside and outside the radiation field in the mEHT Group: n = 13 [24.1%] than the control group: n = 3 [5.6%] (Chi squared, Fisher's exact: p = 0.013) with no significant difference in the extra-pelvic response to treatment between the HIV-positive and -negative participants of each group.Conclusion: The CMR of disease outside the radiation field at six months post-treatment provides evidence of an abscopal effect which was significantly associated with the addition of mEHT to treatment protocols. This finding is important as the combined synergistic use of radiotherapy with mEHT could broaden the scope of radiotherapy to include systemic disease.