Hepatic PSMA-Avid Postradiation Inflammation.

ABSTRACT: A 62-year-old man with de novo large volume metastatic prostate cancer to the bone, liver, and nodes status post multiple lines of therapy including external beam radiation to T12-L2 approximately 13 months prior underwent 68 Ga-PSMA PET/CT to determine eligibility for 177 Lu-PSMA therapy. 68 Ga-PSMA PET/CT demonstrated tracer-avid osseous and nodal lesions consistent with metastases. In addition, regional geographic tracer avidity was seen in the midline left hepatic lobe associated with capsular retraction and demonstrated no FDG avidity on subsequent imaging, probably inflammatory related to prior radiation to T12-L2.

Correlation of 68Ga-FAPi-46 PET Biodistribution with FAP Expression by Immunohistochemistry in Patients with Solid Cancers: Interim Analysis of a Prospective Translational Exploratory Study.

Fibroblast activation protein (FAP)-expressing cancer-associated fibroblasts confer treatment resistance and promote metastasis and immunosuppression. Because FAP is overexpressed in many cancers, radiolabeled molecules targeting FAP are studied for their use as pancancer theranostic agents. This study aimed to establish the spectrum of FAP expression across various cancers by immunohistochemistry and to explore whether 68Ga FAP inhibitor (FAPi)-46 PET biodistribution faithfully reflects FAP expression from resected cancer and non-cancer specimens. Methods: We conducted a FAP expression screening using immunohistochemistry on a pancancer human tissue microarray (141 patients, 14 different types of cancer) and an interim analysis of a prospective exploratory imaging trial in cancer patients. Volunteer patients underwent 1 whole-body 68Ga-FAPi-46 PET/CT scan and, subsequently, surgical resection of their primary tumor or metastasis. 68Ga-FAPi-46 PET SUVmax and SUVmean was correlated with FAP immunohistochemistry score in cancer and tumor-adjacent non-cancer tissues for each patient. Results: FAP was expressed across all 14 cancer types on tissue microarray with variable intensity and frequency, ranging from 25% to 100% (mean, 76.6% ± 25.3%). Strong FAP expression was observed in 50%-100% of cancers of the bile duct, bladder, colon, esophagus, stomach, lung, oropharynx, ovary, and pancreas. Fifteen patients with various cancer types (colorectal [n = 4], head and neck [n = 3], pancreas [n = 2], breast [n = 2], stomach [n = 1], esophagus [n = 2], and uterus [n = 1]) underwent surgery after their 68Ga-FAPi-46 PET/CT scan within a mean interval of 16.1 ± 14.4 d. 68Ga-FAPi-46 SUVs and immunohistochemistry scores were higher in cancer than in tumor-adjacent non-cancer tissue: mean SUVmax 7.7 versus 1.6 (P < 0.001), mean SUVmean 6.2 versus 1.0 (P < 0.001), and mean FAP immunohistochemistry score 2.8 versus 0.9 (P < 0.001). FAP immunohistochemistry scores strongly correlated with 68Ga-FAPi 46 SUVmax and SUVmean: r = 0.781 (95% CI, 0.376-0.936; P < 0.001) and r = 0.783 (95% CI, 0.379-0.936; P < 0.001), respectively. Conclusion: In this interim analysis of a prospective exploratory imaging trial, 68Ga-FAPi-46 PET biodistribution across multiple cancers strongly correlated with FAP tissue expression. These findings support further exploration of FAPi PET as a pancancer imaging biomarker for FAP expression and as a stratification tool for FAP-targeted therapies.

The Future of Nuclear Medicine as an Independent Specialty.

In this article, we provide an overview of established and emerging conventional nuclear medicine and PET imaging biomarkers, as the diagnostic nuclear medicine portfolio is rapidly expanding. Next, we review briefly nuclear theranostic approaches that have already entered or are about to enter clinical routine. Using some approximations and taking into account emerging applications, we also provide some simplified business forecasts for nuclear theranostics. We argue that an optimistic outlook by the nuclear medicine community is crucial to the growth of the specialty and emphasize the urgent need for training adaptations.

Nerve Bundle Hydrodissection and Sexual Function after Robot Prostatectomy.

BACKGROUND AND OBJECTIVES: Loss of erectile function is common after prostatectomy, and surgeons have long sought techniques that reduce this adverse outcome. This study was conducted to assess erectile function after robot-assisted laparoscopic prostatectomy, with and without hydrodissection (HD) of the neurovascular bundles (NVBs). METHODS: Using a database of 335 consecutive RALP procedures conducted by 2 surgeons, we identified all nerve-sparing surgeries performed by HD or standard dissection (SD). The primary and secondary endpoints were Sexual Health Inventory for Men (SHIM) scores and surgical margin positivity, respectively. Subset analyses were performed on men with preoperative SHIM scores ≥17. Determinants of the postoperative SHIM score were evaluated by multivariate linear regression. RESULTS: Among men with preoperative SHIM scores ≥17 who underwent bilateral complete nerve sparing (n = 73), mean preoperative SHIM scores were similar in the HD and SD groups, but were significantly higher in the HD group at 6 months (16.1 ± 8.6 vs 8.3 ± 8.1; P = .024) and >1 year after surgery (16.9 ± 7.1 vs 9.1 ± 6.4; P = .004). According to multivariate linear regression analysis including all patients, HD at RALP (odds ratio [OR] 6.9; 95% confidence interval (CI) 2.8-11.0; P = .001) and preoperative SHIM score were independent predictors of erectile function at >1 year after surgery. There was no significant difference in surgical margin positivity between groups (P = .36). CONCLUSION: HD of the NVB appears to improve erectile function after RALP.

Extraprostatic Extension Is Extremely Rare for Contemporary Gleason Score 6 Prostate Cancer.

BACKGROUND: A significant proportion of men with Gleason score 6 (GS6) prostate cancer undergo treatment with radiation or surgery. OBJECTIVE: To assess pathologic stage of pure GS6 at radical prostatectomy (RP). DESIGN, SETTING, AND PARTICIPANTS: In the period 2003-2014, 7817 patients underwent RP at two institutions. Of 2502 patients with GS6 at surgery, 60 were identified as stage pT3a-b on initial pathologic review, 55 with pT3a (extraprostatic extension, EPE), and five with pT3b (seminal vesicle invasion; SVI). All cases of GS6 with pT3 disease underwent contemporary pathologic evaluation for Gleason grade, stage, and extent of EPE. At one institution, all GS≥7 pT3b cases were re-reviewed for downgrading. The 2014 International Society of Urological Pathology (ISUP) Gleason grading criteria and 2009 ISUP recommendations on pT3 staging were applied. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Calculated incidence (%) of pT3a, pT3b, pT4, and lymph node-positive disease. RESULTS AND LIMITATIONS: Of the 60 GS6 pT3a-b cases identified in the period 2003-2014, seven (0.28% of entire GS6 cohort) with GS6 and pT3a were identified after re-review, all focal EPE. Among the re-examined cohort, no cases of GS6 with pT3b were observed. None of the 132 GS≥7 pT3b cases were downgraded to GS6. Limitations include partial embedding of specimens and separate pathologic review at each institution. CONCLUSIONS: In a large prostatectomy cohort, GS6 never had seminal vesicle invasion (0%) and was very rarely (0.28%) associated with extraprostatic extension. PATIENT SUMMARY: GS6 prostate cancer rarely spreads outside the prostate. A new finding in this study was that GS6 prostate cancer never spread to the seminal vesicles.

Risk of lymph node metastases in pathological gleason score≤6 prostate adenocarcinoma: Analysis of institutional and population-based databases.

INTRODUCTION: Several institutional studies have suggested that pathological Gleason score≤6 prostate cancer has little or no capacity for metastasis. MATERIALS AND METHODS: Using the Surveillance, Epidemiology, and End Results database (SEER, 2004-2011, n = 19,594) and the National Cancer Database (NCDB, 2004-2013, n = 57,540), we identified patients with pathological Gleason score≤6 prostate cancer following radical prostatectomy and lymph node dissection. At the University of Chicago Medicine (UCM, 2003-2014), we considered men with Gleason score≤6 prostate cancer who did (n = 267) and did not receive (n = 770) a lymph node dissection at the time of radical prostatectomy. Temporal trends in lymph node dissection and lymph node metastases were determined, and multivariable logistic regressions were used to analyze factors associated with lymph node metastases. In the UCM cohort, we also evaluated secondary endpoints, including biochemical recurrence (BCR), metastatic disease on follow-up imaging, and response to salvage radiation therapy. RESULTS: The incidence of lymph node dissection at the time of radical prostatectomy decreased from 60% to 37% in SEER (2004-2011) and from 62% to 45% in NCDB (2004-2013). Positive lymph node metastases were found in 0.2% of SEER and 0.18% of NCDB patients who received a lymph node dissection. Elevated PSA, higher clinical stage, and African American race were associated with lymph node positivity in one or both of these databases (P<0.05). Among UCM patients who received a lymph node dissection, no lymph node metastases were found, though a BCR occurred in 3 cases (1%). All 3 men responded favorably to salvage therapy, suggestive of local recurrence. A total of 21 patients (3%) from UCM who did not receive a lymph node dissection had a BCR and underwent salvage radiation therapy. Of these, 4 patients had persistently detectable PSA levels without evidence of local or distant disease at median follow-up of 65 months (range: 29-79) following salvage therapy. Surgical specimens were available for contemporary pathologic review in 3 of these cases, and all were upgraded to Gleason 7 disease. CONCLUSIONS: Our population-based and institutional analyses suggest metastases in cases of Gleason score≤6 prostate cancer to be extremely rare.

Positive Surgical Margins Increase Risk of Recurrence after Partial Nephrectomy for High Risk Renal Tumors.

PURPOSE: The clinical significance of a positive surgical margin after partial nephrectomy remains controversial. The association between positive margin and risk of disease recurrence in patients with clinically localized renal neoplasms undergoing partial nephrectomy was evaluated. MATERIALS AND METHODS: A retrospective multi-institutional review of 1,240 patients undergoing partial nephrectomy for clinically localized renal cell carcinoma between 2006 and 2013 was performed. Recurrence-free survival was estimated using the Kaplan-Meier method and evaluated as a function of positive surgical margin with the log rank test and Cox models adjusting for tumor size, grade, histology, pathological stage, focality and laterality. The relationship between positive margin and risk of relapse was evaluated independently for pathological high risk (pT2-3a or Fuhrman grades III-IV) and low risk (pT1 and Fuhrman grades I-II) groups. RESULTS: A positive surgical margin was encountered in 97 (7.8%) patients. Recurrence developed in 69 (5.6%) patients during a median followup of 33 months, including 37 (10.3%) with high risk disease (eg pT2-pT3a or Fuhrman grade III-IV). A positive margin was associated with an increased risk of relapse on multivariable analysis (HR 2.08, 95% CI 1.09-3.97, p=0.03) but not with site of recurrence. In a stratified analysis based on pathological features, a positive surgical margin was significantly associated with a higher risk of recurrence in cases considered high risk (HR 7.48, 95% CI 2.75-20.34, p <0.001) but not low risk (HR 0.62, 95% CI 0.08-4.75, p=0.647). CONCLUSIONS: Positive surgical margins after partial nephrectomy increase the risk of disease recurrence, primarily in patients with adverse pathological features.

Bladder Cancer Mortality in the United States: A Geographic and Temporal Analysis of Socioeconomic and Environmental Factors.

PURPOSE: We assessed the association of temporal, socioeconomic and environmental factors with bladder cancer mortality in the United States. Our hypothesis was that bladder cancer mortality is associated with distinct environmental and socioeconomic factors with effects varying by region, race and gender. MATERIALS AND METHODS: NCI (National Cancer Institute) age adjusted, county level bladder cancer mortality data from 1950 to 2007 were analyzed to identify clusters of increased bladder cancer death using the Getis-Ord Gi* statistic. Socioeconomic, clinical and environmental data were assessed using geographically weighted spatial regression analysis adjusting for spatial autocorrelation. County level socioeconomic, clinical and environmental data were obtained from national databases, including the United States Census, CDC (Centers for Disease Control and Prevention), NCHS (National Center for Health Statistics) and County Health Rankings. RESULTS: Bladder cancer mortality hot spots and risk factors for bladder cancer death differed significantly by gender, race and geographic region. From 1996 to 2007 smoking, unemployment, physically unhealthy days, air pollution ozone days, percent of houses with well water, employment in the mining industry and urban residences were associated with increased rates of bladder cancer mortality (p <0.05). Model fit was significantly improved in hot spots compared to all American counties (R(2) = 0.20 vs 0.05). CONCLUSIONS: Environmental and socioeconomic factors affect bladder cancer mortality and effects appear to vary by gender and race. Additionally there were temporal trends of bladder cancer hot spots which, when persistent, should be the focus of individual level studies of occupational and environmental factors.

Robotic-assisted pelvic lymph node dissection for prostate cancer: frequency of nodal metastases and oncological outcomes.

PURPOSE: Limited data are available regarding the oncologic efficacy of pelvic lymph node dissection (PLND) performed during robotic-assisted laparoscopic prostatectomy (RALP) for prostate cancer. We aimed to determine the frequency of pelvic lymph node metastasis and oncological outcomes following RALP with PLND in patients who did not receive adjuvant androgen deprivation therapy (ADT). METHODS: We retrospectively reviewed the records of 1740 consecutive patients who underwent RALP and extended PLND. The primary endpoint was biochemical recurrence (BCR). The estimated BCR probability was obtained using the Kaplan-Meier method. Cox proportional hazard regression models were used to assess for predictors of BCR. RESULTS: One hundred and eight patients (6 %) with positive LNs were identified. The median number of LNs removed was 17 (IQR 11-24), and median follow-up was 26 months (IQR 14-43). Ninety-one (84 %) patients did not receive adjuvant ADT of whom 60 % had BCR with a median time to recurrence of 8 months. The 1- and 3-year BCR-free probability was 42 and 28 %, respectively. Patients with ≤2 LN+ had significantly better biochemical-free estimated probability compared to those with >2 LN+ (p = 0.002). The total number of LN+ (HR = 1.1; 95 % CI 1.01-1.2, p = 0.04) and Gleason 8-10 (HR = 1.96; 95 % CI 1.1-3.4, p = 0.02) were predictors of BCR on multivariate analysis. CONCLUSION: Among men with positive lymph nodes at time of robotic prostatectomy, those with two or fewer positive nodes and Gleason <8 exhibited favorable biochemical-free survival without adjuvant therapy.