11C-choline PET/CT predicts prostate cancer-specific survival in patients with biochemical failure during androgen-deprivation therapy.

UNLABELLED: Several studies have shown that (11)C-choline PET/CT may be useful for restaging prostate cancer (PCa) patients with biochemical failure after radical prostatectomy. However, validation of (11)C-choline PET/CT findings scarcely relied on histologic findings, and prognostic implications of (11)C-choline PET/CT are currently unknown. The aim of this study was to assess whether (11)C-choline PET/CT predicts survival in PCa patients. METHODS: This retrospective study included 195 PCa patients treated with radical prostatectomy who underwent (11)C-choline PET/CT from December 1, 2004, to July 31, 2007, due to biochemical failure (prostate-specific antigen > 0.2 mg/mL) during androgen-deprivation therapy. PCa-specific survival was computed as the interval from radical prostatectomy to PCa-specific death. RESULTS: The median interval after radical prostatectomy was 8.9 y (95% confidence interval [CI], 1.7-18.9 y). The median follow-up after (11)C-choline PET/CT was 4.5 y (95% CI, 0.4-8.5 y). (11)C-choline PET/CT results were positive in 57% of patients. The median PCa-specific survival was 16.4 y (95% CI, 14.0-18.8 y) in patients with negative (11)C-choline PET/CT results and 11.2 y (95% CI, 9.8-12.6 y) in patients with positive (11)C-choline PET/CT results (log-rank: χ(2) = 19.3, P < 0001). At multivariate analysis, statistical significance was obtained for (11)C-choline PET/CT (hazard ratio, 2.53; 95% CI, 1.41-4.53; P = 0.002), prostate-specific antigen (hazard ratio, 1.03; 95% CI, 1.00-1.05; P = 0.037), and Gleason score (>7: hazard ratio, 2.49; 95% CI, 1.25-4.95; P = 0.009). Patients with pathologic (11)C-choline uptake in the prostatic bed or in pelvic or retroperitoneal lymph nodes had longer PCa-specific survival (median, 12.1 y; 95% CI, 10.5-13.7 y) in comparison to patients with pathologic tracer uptake in the skeleton (median, 9.9 y; 95% CI, 6.8-13.1 y) (log-rank: χ(2) = 6.5, P = 0.010). Two internally validated nomograms predicted 10- and 15-y PCa-specific survival probability with an accuracy of 76% and 74%, respectively. In an ancillary analysis, we also showed that (11)C-choline PET/CT predicts PCa-specific survival after PET/CT, with similar statistical power. CONCLUSION: (11)C-choline PET/CT predicts PCa-specific survival in PCa patients treated with radical prostatectomy who develop biochemical failure during androgen-deprivation therapy. If independent or multicenter confirmation of these findings is obtained, (11)C-choline PET/CT might be more widely used in the follow-up of PCa patients for tailoring salvage therapy.

[11C]choline positron emission tomography/computerized tomography for early detection of prostate cancer recurrence in patients with low increasing prostate specific antigen.

PURPOSE: The effectiveness of salvage therapy in prostate cancer is greater for low prostate specific antigen values. Therefore, early detection of tumor recurrence is warranted. [(11)C]choline positron emission tomography/computerized tomography has the potential of early restaging of prostate cancer with low prostate specific antigen, but the selection of patients at high risk for positive [(11)C]choline positron emission tomography/computerized tomography is desirable to optimize salvage therapy. MATERIALS AND METHODS: This retrospective study included 75 patients with prostate cancer with an increasing prostate specific antigen less than 1.5 ng/ml after radical prostatectomy who never received antiandrogen deprivation therapy or salvage radiotherapy who underwent [(11)C]choline positron emission tomography/computerized tomography for the restaging of disease. Binary logistic regression was used to assess predictive factors of positive [(11)C]choline positron emission tomography/computerized tomography. Included variables were trigger prostate specific antigen, prostate specific antigen doubling time, age, pathological stage and Gleason score. RESULTS: Median prostate specific antigen was 0.61 ng/ml. [(11)C]choline positron emission tomography/computerized tomography was positive in 16 of 75 patients (21%). On univariate analysis prostate specific antigen doubling time less than 6 months was the only factor significantly associated with an increased risk of positive [(11)C]choline positron emission tomography/computerized tomography (OR 7.77, 95% CI 2.34-25.80, p = 0.001). In patients with prostate specific antigen doubling time less than 6 months, the positive detection rate of [(11)C]choline positron emission tomography/computerized tomography increased to 50%. CONCLUSIONS: In patients with prostate cancer with biochemical failure after radical prostatectomy and prostate specific antigen less than 1.5 ng/ml, prostate specific antigen doubling time less than 6 months predicts positive [(11)C]choline positron emission tomography/computerized tomography. In these patients [(11)C]choline positron emission tomography/computerized tomography may reduce by 50% the number in whom salvage therapy is initiated empirically without knowing the disease location.

Investigation on tumor hypoxia in resectable primary prostate cancer as demonstrated by 18F-FAZA PET/CT utilizing multimodality fusion techniques.

PURPOSE: As hypoxia is believed to play an important role in the development and progression of prostate cancer, we evaluated whether 18F-labeled fluoroazomycin arabinoside (18F-FAZA) would be useful to identify tumor hypoxia in resectable prostate cancer. METHODS: Positron emission tomography (PET)/CT was performed on 14 patients with untreated localized primary prostate cancer 3 h post-injection of approximately 390 MBq of 18F-FAZA using forced diuresis to decrease radioactivity in the urinary bladder. Anatomical trans-pelvic coil and pre- and post-contrast 1.5 T MRI with endorectal coil were performed on the same day. Patients underwent radical prostatectomy and ex vivo 3 T MRI of the prostatectomy specimen within 14 days following in vivo imaging. Imaging results were verified by whole mount histopathology plus tissue microarray (TMA) immunohistochemical (IHC) analysis for carbonic anhydrase IX (CAIX) and hypoxia-inducible factor 1α (HIF-1α). Registration of in vivo imaging with histology was achieved using mutual information software and performing ex vivo MRI of the prostatectomy specimen and whole mount sectioning with block face photography as intermediate steps. RESULTS: Whole mount histology identified 43 tumor nodules, 19 of them larger than 1 ml as determined on coregistered volumes featuring 18F-FAZA, MRI, and histological 3-D image information. None of these lesions was found to be positive for CAIX or visualized by 18F-FAZA PET/CT while IHC for HIF-1α showed variable staining of tumor tissues. Accordingly, no correlation was found between 18F-FAZA uptake and Gleason scores. CONCLUSION: Our data based on 18F-FAZA PET/CT and CAIX IHC do not support the presence of clinically relevant hypoxia in localized primary prostate cancer including high-grade disease. Activation of HIF-1α may be independent of tissue hypoxia in primary prostate cancer.

Performance of beta- and high-energy gamma probes for the detection of cancer tissue in experimental surgical resection beds.

OBJECTIVE: While high-energy gamma and beta probes have gained considerable attention due to their ability to detect cancerous lesions using (18)F-FDG in humans intraoperatively, it is unknown whether the sensitivity of such probes would allow the detection of remaining tumor tissue in the resection bed after removal of macroscopically evident disease. METHODS: 9L tumors (13 primaries, 17 lymph node metastases) were generated at the upper thigh of Fisher 344 rats. After approximately 2 weeks, microPET was performed to verify increased (18)F-FDG tumor uptake. Tumors were surgically exposed and probe readings of tumor and background tissues were performed in triplicate. To evaluate the ability to detect tiny tumor lesions, 12 tumor fragments (range 0.001-0.032 g) were placed into the resection bed and measured to obtain a tumor-to-muscle ratio (TMR). Lesions were classified as positive if count rates were above 2.5 SD of muscle background. All tumor and muscle tissues were weighed and counted to obtain the "true" tumor-to-muscle background ratio (TMR(counter)) for reference. The presence or absence of tumor tissue was verified by histology. RESULTS: In the presence of background gamma radiation, the beta probe detected all tumor lesions with TMR greater than 2.5 SD of muscle background (TMR range 1.24-3.9 for all 41 lesions). Despite suitable shielding, lesion identification by the gamma probe was clearly limited by the presence of background radioactivity. As a result, only 11/13 primary tumors, 6/17 lymph nodes and 1/11 tumor fragments were identified above 2.5 SD of muscle background (TMR range 0.64-3.59 for all lesions). CONCLUSION: Under experimental conditions, the beta probe was capable to detect minute amounts of tumor tissue at the surface of resection beds. While clinical application of the current beta probe design may depend on the particular intraoperative circumstances including time requirements for surface scanning of resection beds, the data indicate clinical potential for novel designs of hand-held beta probes.

PSA doubling time for prediction of [(11)C]choline PET/CT findings in prostate cancer patients with biochemical failure after radical prostatectomy.

PURPOSE: Previous studies have shown that the positive detection rate of [(11)C]choline positron emission tomography/computed tomography (PET/CT) depends on prostate-specific antigen (PSA) plasma levels. This study compared PSA levels and PSA doubling time (PSADT) to predict [(11)C]choline PET/CT findings. METHODS: PSADT was retrospectively calculated in 170 prostate cancer (PCa) patients with biochemical failure after radical prostatectomy who underwent [(11)C]choline PET/CT. PSADT was calculated as PSADT = ln2/m, where m is the slope of the linear regression line of the natural log of PSA values. At least three PSA measurements were used (median: 4; range: 3-16), separated by at least 3 months, each with a minimum increase of 0.20 ng/ml. PET/CT findings were validated using criteria based on histological analysis and clinical and imaging data. Statistical analysis was performed using the t test, chi-square test, analysis of variance and binary logistic regression. Regression-based coefficients were used to develop a nomogram predicting the probability of positive [(11)C]choline PET/CT and 200 bootstrap resamples were used for internal validation. RESULTS: The median PSA was 1.25 ng/ml (range: 0.23-48.6 ng/ml), and the median PSADT was 7.0 months (range: 0.97-45.3 months). [(11)C]choline PET/CT was positive in 75 of 170 patients (44%). PET/CT findings were validated using histological criteria (11%) and clinical and imaging criteria (89%). The overall accuracy of [(11)C]choline PET/CT was 88%. Multivariate logistic regression showed that high PSA and short PSADT were significant (p < 0.05) predictors of positive [(11)C]choline PET/CT [PSA: odds ratio (OR) = 1.43; 95% confidence interval (CI): 1.15-1.78; PSADT: OR = 1.12; 95% CI: 1.04-1.21]. The percentage of patients with positive [(11)C]choline PET/CT was 27% for PSADT >6 months, 61% for PSADT between 3 and 6 months and 81% for PSADT <3 months. The percentage of patients who displayed pathological [(11)C]choline uptake in the skeleton significantly increased (p < 0.05) from 3% for PSADT >6 months to 52% for PSADT <3 months. Conversely, patients who displayed pathological [(11)C]choline uptake in the prostatectomy bed were 0% for PSADT <3 months and 17% for PSADT >6 months (p < 0.05). A nomogram based on age, PSA, PSADT, time to trigger PSA, Gleason score, pathological stage and androgen deprivation therapy demonstrated bootstrap-corrected predictive accuracy of 81%. CONCLUSION: Like PSA, PSADT is an independent predictor of [(11)C]choline PET/CT. [(11)C]choline PET/CT is very sensitive to PCa tumour growth, as reflected by PSA kinetics. PSADT should be taken into account by physicians when referring PCa patients for [(11)C]choline PET/CT.

Prevalence and viral load of oncogenic human papillomavirus types associated with cervical carcinoma in a population of North Italy.

A cross-sectional study was carried out in a population of North Italy to determine the prevalence of eight oncogenic human papillomavirus (HPV) types most commonly found in cervical carcinoma and to study the relationship between HPV DNA loads and severity of disease. A total of 597 cervical samples obtained from patients with pathological findings (n = 472) and from women with normal cytology (n = 125) were analyzed by means of normalized Real-time PCR assays to quantify HPV-16, -18, -31, -45, and -33 group (including -33, -52, -58, -67); the normalization of oncogenic HPV viral load was carried out by quantitation of a single copy gene. The two most common oncogenic HPV types found were 16 and 31 (24.3% and 22.9% of pathological samples, respectively); multiple infections were demonstrated in 22% of pathological samples. Overall, the HPV total viral load was found to increase with increasing severity of associated lesions, although a stronger association was observed only for HPV-31 and HPV-16 (gamma = 0.49 and 0.41, respectively) as compared to HPV-18 and -33 group (gamma = 0.19 and 0.02, respectively). However, we found that high levels of HPV-31 or 33 group DNA could be prognostic of minor oncogenic risk for high-grade squamous intraepithelial lesions (H-SIL) (age adjusted odds ratio [AORs] = 1.57 and 1.26, respectively) than HPV-16 and HPV-18 (AORs = 30 and 8, respectively). The AORs also increased with HPV total viral load and reached a maximum of AORs = 15.7. Thus, HPV load is a type-dependent risk marker for the development of H-SIL.

Conservative management in primary genital lymphomas: the role of chemotherapy.

BACKGROUND: The female genital lymphomas are an extremely rare disease accounting for less than 0.5% of gynecological cancers and for 1.5% of all NHL. Because of their low incidence there is no widely accepted consensus on its treatment. Literature data support a radiotherapy-based treatment in case of primary genital lymphomas stages I-II. The role of chemotherapy as neoadjuvant or exclusive treatment is still to be defined. METHODS: From 1984 to 2003, the treatments in our institution of 19 patients with genital lymphoma were reviewed. Nine women presented with cervical, 3 with vaginal, 1 with cervical-vaginal, 2 with vulvar and 4 with ovarian lymphoma. Seven were staged IE, nine IIE, one IIIE and two IVE. As a whole, chemotherapy was used in 18/19 cases: chemotherapy was proposed as first line treatment in 12 cases, while surgery in 7 (followed by chemotherapy in 6 cases). RESULTS: Primary chemotherapy alone obtained a complete response (CR) in 9/12 patients; pathological complete response (pCR) was confirmed in 3 operated patients out of 9. Partial response (PR) was observed in 3, requiring radiotherapy. Chemotherapy obtained CR after incomplete surgical debulking in 3 out of 4 cases. Two patients relapsed in the group treated with chemotherapy alone. Both have been salvaged by further chemotherapy. Only one patient deceased due to her tumor after surgery and chemotherapy. CONCLUSION: The use of exclusive chemotherapy obtained promising results not only as regards survival rates but also for reducing the need of radiotherapy. A conservative management based on exclusive chemotherapy in primary genital lymphoma stages I-II may be attempted in selected patients desiring pregnancy.