<Superscript>99m</Superscript>Tc-HDP bone scintigraphy and <Superscript>18</Superscript>F-sodiumfluoride PET/CT in primary staging of patients with prostate cancer

Introduction/Aim

Correct staging of patients with prostate cancer is important for treatment planning and prognosis. Although bone scintigraphy with ^99mTc-phosphonates (BS) is generally advised for staging by guidelines in high risk prostate cancer, this imaging technique is hampered by a high rate of inconclusive results and moderate accuracy. Potentially better imaging techniques for detection of bone metastases such as ¹⁸F-sodiumfluoride PET/CT (NaF PET/CT) are therefore being evaluated. In this observational cohort study we evaluate the performance and clinical impact of both BS and NaF PET/CT in primary staging of patients with prostate cancer.

Methods

The first of two cohorts consisted of patients who received a BS while the second included patients who received a NaF PET/CT for primary staging of prostate cancer. For both cohorts the number of positive, negative and equivocal findings, calculated diagnostic performance of the imaging modality in terms of sensitivity and specificity, as well as the impact on clinical management were studied. The ranges of the diagnostic performance were calculated both assuming that equivocal findings were positive and assuming that they were negative for bone metastases. For the NaF PET/CT cohort the number of patients with signs of lymph node metastases on low dose CT were also recorded, including the impact of these findings on clinical management.

Results

One-hundred-and-four patients underwent NaF PET/CT, whereas 122 patients underwent BS. Sensitivities of 97–100 and 84–95% and specificities of 98–100 and 72–100% were found on a patient basis for detection of bone metastases with NaF PET/CT and BS, respectively. Equivocal findings warranted further diagnostic procedures in 2% of the patients in the NaF cohort and in 16% in the BS cohort. In addition NaF PET/CT demonstrated lymph node metastases in 50% of the included patients, of which 25% showed evidence of lymph node metastases only.

Conclusion

Our data indicate better diagnostic performance of NaF PET/CT compared to BS for detection of bone metastases in primary staging of prostate cancer patients. Less equivocal findings are encountered with NaF PET/CT. Moreover, NaF PET/CT has additional value over BS since lymph node metastases are encountered frequently.

     

A Multimodal Imaging Protocol, <Superscript>123</Superscript>I/<Superscript>99</Superscript>Tc-Sestamibi,SPECT, and SPECT/CT,in Primary Hyperparathyroidism Adds Limited Benefit for Preoperative Localization

Introduction

Focused parathyroidectomy in primary hyperparathyroidism (1°HPT) is possible with accurate preoperative localization and intraoperative PTH monitoring (IOPTH). The added benefit of multimodal imaging techniques for operative success is unknown.

Method

Patients with 1°HPT, who underwent parathyroidectomy in 2012–2014 at a single institution, were retrospectively reviewed. Only the patients who underwent the standardized multimodal imaging workup consisting of ¹²³I/⁹⁹Tc-sestamibi subtraction scintigraphy, SPECT, and SPECT/CT were assessed.

Results

Of 360 patients who were identified, a curative operation was performed in 96 %, using pre-operative imaging and IOPTH. Imaging analysis showed that ¹²³I/⁹⁹Tc-sestamibi had a sensitivity of 86 % (95 % CI 82–90 %), positive predictive value (PPV) 93 %, and accuracy 81 %, based on correct lateralization. SPECT had a sensitivity of 77 % (95 % CI 72–82 %), PPV 92 % and accuracy 72 %. SPECT/CT had a sensitivity of 75 % (95 % CI 70–80 %), PPV of 94 %, and accuracy 71 %. There were 3 of 45 (7 %) patients with negative sestamibi imaging that had an accurate SPECT and SPECT/CT. Of 312 patients (87 %) with positive uptake on sestamibi (93 % true positive, 7 % false positive), concordant findings were present in 86 % SPECT and 84 % SPECT/CT. In cases where imaging modalities were discordant, but at least one method was true-positive, ¹²³I/⁹⁹Tc-sestamibi was significantly better than both SPECT and SPECT/CT (p < 0.001). The inclusion of SPECT and SPECT/CT in 1°HPT imaging protocol increases patient cost up to 2.4-fold.

Conclusion

¹²³I/⁹⁹Tc-sestamibi subtraction imaging is highly sensitive for preoperative localization in 1°HPT. SPECT and SPECT/CT are commonly concordant with ¹²³I/⁹⁹Tc-sestamibi and rarely increase the sensitivity. Routine inclusion of multimodality imaging technique adds minimal clinical benefit but increases cost to patient in high-volume setting.

     

Ten-year outcomes of I<Superscript>125</Superscript> low-dose-rate brachytherapy for clinically localized prostate cancer: a single-institution experience in Japan

Purpose

To report 10-year outcomes of patients treated with I¹²⁵ low-dose-rate brachytherapy (BT) for clinically localized prostate cancer.

Methods

A group of 1,060 patients with clinically localized prostate cancer treated with I¹²⁵ BT between March 2004 and December 2013 at the Yokohama City University Hospital were identified. The records of 743 patients with a minimum of 2 years of follow-up were reviewed. Cohorts were categorized according to National Comprehensive Cancer Network risk classification, and biochemical outcomes plus overall survival were examined. Biochemical failure was defined as nadir prostate-specific antigen (PSA) level + 2 ng/mL. Univariate and multivariate Cox proportional hazards were used to determine predictors of biochemical failure.

Results

A total of 743 patients met the criteria with a median follow-up of 54.6 months (range 24–114 months). The median age was 70 years (range 48–83). The 5- and 7-year overall survival rates were 98.8 and 97.6 %, and the 5- and 7-year biochemical failure-free survival rates were 92.6 and 91.0 %, respectively. With regard to distant metastases and survival, the 5- and 7-year metastatic-free survival rates were 98.2 and 95.9 %, respectively. A multivariate analysis revealed that initial PSA (p = 0.005; HR 1.097, 95 % CI 1.028–1.170), age (p = 0.001; HR 0.931, 95 % CI 0.893–0.971), and T stage (T1c vs. T2a) (p = 0.002; HR2.417, 95 % CI 1.319–4.267) were independent predictors of biochemical failure.

Conclusions

I¹²⁵ low-dose-rate BT resulted in excellent survival and morbidity outcomes for localized prostate cancer at a single institution. Further studies are needed to obtain long-term outcomes.

     

The diagnostic accuracy of 18F-fluorodeoxyglucose positron emission tomography and computed tomography in staging bladder cancer: a single-institution study and a systematic review with meta-analysis

Purpose

The purpose of this study was to assess the diagnostic accuracy of 18F-fluorodeoxyglucose with positron emission tomography and computed tomography (FDG–PET–CT) to predict nodal metastases in patients with bladder cancer (BC) scheduled to undergo radical cystectomy (RC).

Methods

We retrospectively reviewed records of patients diagnosed with BC and scheduled to undergo RC at our center from January 2011 through February 2015, who also underwent FDG–PET–CT at the time of diagnosis. All patients underwent RC and an extended pelvic lymph node dissection as the reference standard. The primary endpoints were the sensitivity, specificity and overall accuracy of FDG–PET–CT in detecting lymph node metastasis. We also examined its accuracy in identifying distant metastasis. In addition, we conducted a protocol-driven systematic review and meta-analysis of accuracy of FDG–PET–CT for preoperative staging of BC, as compared to CT alone, as reported in individual studies. To assess the methodological quality of eligible studies, we used the QUADAS-2 tool (a revised tool for the Quality Assessment of Diagnostic Accuracy Studies) and pooled diagnostic accuracy measures using Meta-DiSc statistical software.

Results

For detecting nodal metastases in 78 patients, the sensitivity of FDG–PET–CT was 0.56 (95 % CI 0.29–0.80) and the specificity, 0.98 (95 % CI 0.91–1.00). Pooled sensitivity and specificity for detecting lymph node metastasis were 0.57 and 0.95, respectively. Positive likelihood ratio was 9.02. All lesions that were suspicious for distant metastasis were found to be positive on biopsy.

Conclusion

FDG–PET–CT was more accurate than CT alone in staging BC in patients undergoing surgery. Standardization of FDG–PET–CT protocol and cost-effectiveness analysis are required before widespread implementation of this technology.

     

The Added Diagnostic Value of <Superscript>18</Superscript>F-Fluorodihydroxyphenylalanine PET/CT in the Preoperative Work-Up of Small Bowel Neuroendocrine Tumors

Background

The precise localization of the primary tumor and/or the identification of multiple primary tumors improves the preoperative work-up in patients with small bowel (SB) neuroendocrine tumor (NET). The present study assesses the diagnostic value of ¹⁸F-fluorodihydroxyphenylalanine (¹⁸F-FDOPA) positron emission tomography/computed tomography (PET/CT) during the preoperative wok-up of SB NETs.

Methods

Between January 2010 and June 2017, all consecutive patients with SB NETs undergoing preoperative ¹⁸F-FDOPA PET/CT and successive resection were analyzed. Preoperative work-up included computed tomography (CT), somatostatin receptor scintigraphy (SRS), and ¹⁸F-FDOPA PET/CT. Sensitivity and accuracy ratio for primary and multiple tumor detection were compared with data from surgery and pathology.

Results

There were 17 consecutive patients with SB NETs undergoing surgery. Nine patients (53%) had multiple tumors, 15 (88%) metastatic lymph nodes, 3 (18%) peritoneal carcinomatosis, and 9 patients (53%) liver metastases. A total of 70 SB NETs were found by pathology. Surgery identified the primary in 17/17 (100%) patients and recognized seven of 9 patients (78%) with multiple synchronous SB. Preoperatively, ¹⁸F-FDOPA PET/CT displayed a statistically significant higher sensitivity for primary tumor localization (100 vs. 23.5 vs. 29.5%) and multiple tumor detection (78 vs. 22 vs. 11%) over SRS and CT. Compared with pathology, ¹⁸F-FDOPA PET/CT displayed the highest accuracy ratio for number of tumor detected over CT and SRS (2.0?±?2.2 vs. 0.4?±?0.7 vs. 0.6?±?1.5, p?=?0.0003).

Conclusion

¹⁸F-FDOPA PET/CT significantly increased the sensitivity and accuracy for primary and multiple SB NET identification. ¹⁸F-FDOPA PET/CT should be included systematically in the preoperative work-up of SB NET.

     

Relationship Between <Superscript>18</Superscript>F-fluorodeoxyglucose Accumulation and the <Emphasis Type="Italic">BRAF</Emphasis><Superscript>V600E</Superscript> Mutation in Papillary Thyroid Cancer

Background

To determine whether ¹⁸F-fluoro-2-deoxyglucose (¹⁸F-FDG)-PET/CT is useful for predicting the BRAF ^V600E mutation status of a primary papillary thyroid carcinoma (PTC).

Methods

A retrospective analysis was performed in 108 patients who underwent ¹⁸F-FDG positron emission tomography–computed tomography (PET/CT) for staging before thyroidectomy and BRAF analysis in biopsy-confirmed PTC. The maximum standardized uptake value (SUV_max) of the primary tumor was calculated according to FDG accumulation. Univariate and multivariate analyses were performed to assess the association between the SUV_max and clinicopathological variables.

Results

The BRAF ^V600E mutation was detected in 71 of 108 (65.7%) patients. In all subjects, the tumor size and BRAF ^V600E mutation were independently related to the SUV_max according to multivariate analyses (P = 0.002 and 0.007, respectively). The SUV_max was significantly higher in tumors with the BRAF ^V600E mutation than in tumors with wild-type BRAF (10.24 ± 11.89 versus 4.02 ± 3.86; P = 0.007). In the tumor size >1 cm subgroup, the BRAF ^V600E mutation was the only factor significantly associated with the SUV_max (P = 0.016). A SUV_max cutoff level of 4.9 was determined to be significant for predicting the BRAF ^V600E mutation status (sensitivity 77.4%, specificity 100.0%, area under the curve 0.929; P < 0.0001) according to ROC curve analysis.

Conclusions

The BRAF ^V600E mutation is independently associated with high ¹⁸F-FDG uptake in PTC, especially in those with a tumor size >1 cm.

     

PSA kinetics following primary focal cryotherapy (hemiablation) in organ-confined prostate cancer patients

Purpose

We aim to evaluate prostate-specific antigen (PSA) trends in post-primary focal cryotherapy (PFC) patients.

Materials and methods

This was an institutional review board-approved retrospective study of PFC patients from 2010 to 2015. Patients with at least one post-PFC PSA were included in the study. Biochemical recurrence (BCR) was determined using the Phoenix criteria. PSA bounce was also assessed. We analyzed rates of change of PSA over time of post-PFC between BCR and no BCR groups. PSA-derived variables were analyzed as potential predictors of BCR.

Results

A total of 104 PFC patients were included in our analysis. Median (range) age and follow-up time were 66 (48–82) years and 19 (6.3–38.6) months, respectively. Four (3.8%) patients experienced PSA bounce. The median percent drop in first post-PFC PSA of 80.0% was not associated with BCR (p = 0.256) and may indicate elimination of the index lesion. The rate of increase of PSA in BCR patients was significantly higher compared to patients who did not recur (median PSA velocity (PSAV): 0.15 vs 0.04 ng/ml/month, p = 0.001). Similar to PSAV (HR 9.570, 95% CI 3.725–24.592, p < 0.0001), PSA nadir ≥ 2 ng/ml [HR (hazard ratio) 1.251, 95% CI 1.100–1.422, p = 0.001] was independently associated with BCR.

Conclusion

A significant drop in post-PFC PSA may indicate elimination of the index lesion. Patients who are likely to recur biochemically have a significantly higher PSAV compared to those who do not recur. Nadir PSA of less than 2 ng/ml may be considered the new normal PSA in focal cryotherapy (hemiablation) follow-up.

     

Optimal screening interval for men with low baseline prostate-specific antigen levels (≤1.0 ng/mL) in a prostate cancer screening program

Purpose

To optimize the rescreening schedule for men with low baseline prostate-specific antigen (PSA) levels, we evaluated men with baseline PSA levels of ≤1.0 ng/mL in PSA-based population screening.

Methods

We enrolled 8086 men aged 55–69 years with baseline PSA levels of ≤1.0 ng/mL, who were screened annually. The relationships of baseline PSA and age with the cumulative risks and clinicopathological features of screening-detected cancer were investigated.

Results

Among the 8086 participants, 28 (0.35 %) and 18 (0.22 %) were diagnosed with prostate cancer and cancer with a Gleason score (GS) of ≥7 during the observation period, respectively. The cumulative probabilities of prostate cancer at 12 years were 0.42, 1.0, 3.4, and 4.3 % in men with baseline PSA levels of 0.0–0.4, 0.5–0.6, 0.7–0.8, and 0.9–1.0 ng/mL, respectively. Those with GS of ≥7 had cumulative probabilities of 0.42, 0.73, 2.8, and 1.9 %, respectively. The cumulative probabilities of prostate cancer were significantly lower when baseline PSA levels were 0.0–0.6 ng/mL compared with 0.7–1.0 ng/mL. Prostate cancer with a GS of ≥7 was not detected during the first 10 years of screening when baseline PSA levels were 0.0–0.6 ng/mL and was not detected during the first 2 years when baseline PSA levels were 0.7–1.0 ng/mL.

Conclusions

Our study demonstrated that men with baseline PSA levels of 0.0–0.6 ng/mL might benefit from longer screening intervals than those recommended in the guidelines of the Japanese Urological Association. Further investigation is needed to confirm the optimal screening interval for men with low baseline PSA levels.

     

Meta-analysis of metabolic syndrome and benign prostatic hyperplasia in Chinese patients

Purpose

To investigate the impact of metabolic syndrome (MetS) on benign prostatic hyperplasia (BPH), focusing on MetS and its relationship with prostate volume and prostate-specific antigen (PSA) in Chinese patients by performing a meta-analysis.

Methods

We systematically searched the PubMed, Embase, China National Knowledge Infrastructure, Wanfang, and VIP databases from inception to November 2014. All studies investigating the impact of MetS on prostate volume and PSA among BPH patients were included. Pooled mean difference (WMD) and 95 % confidence interval (CI) were used to analyze the difference between patients with MetS and those without MetS.

Results

Sixteen studies enrolled 1895 BPH patients, of whom 2224 had MetS. Compared with those without MetS, BHP patients with MetS had significantly higher total prostate volume (WMD 10.15 ml; 95 % CI 7.37–12.93) and serum PSA level (WMD 0.53 ng/ml; 95 % CI 0.17–0.88), respectively. In addition, annual prostate growth rate in patients with MetS was higher (WMD 0.49 ml/year; 95 % CI 0.24–0.73) than in those without MetS.

Conclusions

This meta-analysis supports that the presence of MetS increases total prostate volume and annual prostate growth rate in Chinese BPH patients. Future studies are needed to explain the detailed underlying mechanisms.

     

Comparison of remifentanil EC50 for facilitating i-gel and laryngeal mask airway insertion with propofol anesthesia

Objective

Each supraglottic airway requires different anesthetic depth because it has a specific structure and different compressive force in the oropharyngeal cavity. We designed the study to compare the effect-site concentration (Ce) of remifentanil in 50 % of patients (EC50) for successful insertion of the i-gel second-generation supraglottic airway device with that for laryngeal mask airway (LMA) insertion during target-controlled infusion (TCI) of propofol.

Methods

Forty-one female patients were randomized to the i-gel group (n = 20) or the LMA group (n = 21). Anesthesia was induced with propofol Ce of 5 μg/ml and the predetermined remifentanil Ce, and the i-gel or LMA was inserted 5 min later. The remifentanil Ce was estimated by modified Dixon’s up-and-down method (initial concentration: 3.0 ng/ml, step size: 0.5 ng/ml). The patient’s response to device insertion was classified as either “success (no movement)” or “failure (movement)”.

Results

Using the Dixon’s up-and-down method, EC50 of remifentanil Ce for the i-gel (1.58 ± 0.41 ng/ml) was significantly lower than that for LMA (2.25 ± 0.55 ng/ml) (p = 0.038). Using isotonic regression, EC50 (83 % CI) of remifentanil in the i-gel group [1.50 (1.37–1.80) ng/ml] was statistically lower than that in the LMA group [2.00 (1.82–2.34) ng/ml]. EC95 (95 % CI) of remifentanil in the i-gel group [2.38 (1.48–2.50) ng/ml] was statistically lower than that in the LMA group [3.35 (2.58–3.48) ng/ml].

Conclusions

We found that EC50 of remifentanil Ce for i-gel insertion (1.58 ng/ml) was significantly lower than that for LMA insertion (2.25 ng/ml) in female patients during propofol TCI without neuromuscular blockade.

     

Oncologic control provided by HIFU therapy as single treatment in men with clinically localized prostate cancer

Objective

To assess the long term oncologic results of high-intensity focused ultrasound therapy (HIFU) as a primary and single treatment for clinically localized prostate cancer.

Methods

A total of 119 patients with clinically localized prostate cancer underwent HIFU (Ablatherm^®, EDAP, France) as first-line treatment and were retrospectively reviewed. They were stratified according to risk groups proposed by D’Amico. No patient had undergone previous hormonal therapy. PSA level was monitored at 3, 6, 12, 18, 24 months and then yearly. According to the latest ASTRO criteria, failure was defined by a PSA rise of 2 ng/ml or more above the PSA nadir. The biochemical-free survival rate (BFSR) was calculated.

Results

Mean patient age was 68 ± 7.8 years (46–83). Mean follow-up was 3.9 years (1–6.8). Overall 52 patients (43.7%) experienced a biochemical recurrence which included 26, 23 and 3 patients in the low, intermediate and high-risk groups, respectively. In univariate and multivariate analyses, there was a statistical association between preoperative PSA value > 10, a nadir PSA value > 1 and the risk of biochemical recurrence (P < 0.05). The 5-year BFSR rate was 30% with no statistical difference between low- and intermediate-risk patients. None of the 119 patients died of prostate cancer.

Conclusion

High-intensity focused ultrasound therapy provides efficient oncologic control only in patients with low-risk prostate cancer. However, our data could be used to improve the selection of patients who are potential candidates for HIFU therapy.

     

A 12-year follow-up of ANNA/C-TRUS image-targeted biopsies in patients suspicious for prostate cancer

Purpose

PSA screening has been rehabilitated. PSA is not specific and can be elevated by benign reasons. Additionally, a subgroup of patients with prostate hyperplasia may harbor prostate cancer (PCa). During monitoring, the clinician aims to detect significant tumors in time, submitting patients to minimal psychological and physical burden, especially in men with high serum PSA and repeat biopsies. We aimed to determine long-term outcomes with respect to ANNA/C-TRUS ability to detect PCa with six targeted biopsies.

Methods

A subset of 71 patients were enrolled. During monitoring, they were subjected to primary, secondary, or even multiple prostate biopsies when needed. Protocol monitoring included PSA measurements, digital rectal examination (DRE) and imaging.

Results

The median follow-up was 12 years. Forty-one patients had a history of negative systematic random biopsies (1–3 sessions). Their age ranges 62–85 years, PSA 0.5–47.3 ng/ml, and the median prostate volume 11–255 cc. During monitoring, 15 patients were diagnosed with PCa. Only two harbored aggressive tumors. The median time to diagnosis was 6 years. All PCa patients are free from biochemical relapse. From the remaining 56 patients, 11 did not have any biopsies, 12 had one, 13 had two, and 20 had three or more biopsy sessions.

Conclusions

ANNA/C-TRUS is a useful method monitoring patients with a risk of PCa. 50–75% of the usually performed biopsy cores could be spared and, after 12 years, 97% of the patients were either without evidence of a PCa or were diagnosed with a good prognosis tumor.

     

HAROW: the first comprehensive prospective observational study comparing treatment options in localized prostate cancer

Purpose

To collect data on primary treatment decision and follow-up in patients with diagnosed, histologically confirmed localized (T1a–T2c/N0/M0) prostate cancer (PCa) for up to 5 years in a prospective observational non-interventional study.

Methods

Patients were non-randomly allocated to one of the five treatment strategies: hormone therapy, active surveillance, radiation, operation, or watchful waiting.

Results

A total of 3169 patients were included by 259 participating sites; 2957 patients had at least one follow-up visit. 54.8 % of tumors at baseline were staged as T1c, 38 % as T2a–T2c, and 7.1 % as T1a or T1b (missing: 0.2 %). 38.9, 32.6 and 26.6 % of patients were classified as low risk, intermediate risk, and high risk according to d’Amico, respectively (missing: 1.8 %). 56.6 % of patients underwent prostatectomy as primary therapy, 16.4 % received radiation, 6.9 % HT, 15.8 and 4.3 % decided for AS or WW. Mean follow-up was 28.4 months. Progression rates were between 8.6 % (RT) and 33.1 % (AS).

Conclusion

Whereas RP remains the main treatment option of localized PCa, active surveillance appears to become an accepted and selectively employed treatment option. Careful selection of patients is documented by the highest proportion of patients with low risk (82.5 %), PSA density <0.2 ng/ml/ml (77.5 %), T1 staging (83.6 %), Gleason score ≤6 (92.5 %), ≤2 positive biopsies (79.4 %), and lowest mean PSA (5.8 ng/ml) in the AS group. The relatively high progression rate in the AS group has to be considered in the context of treatment changes; 71/155 patients had a documented change of treatment and 62 of them with a follow-up period of >3 months.

     

Prediction of sentinel lymph node status using single-photon emission computed tomography (SPECT)/computed tomography (CT) imaging of breast cancer

Purpose

Single-photon emission computed tomography (SPECT)/computed tomography (CT) improves the anatomical identification of sentinel lymph nodes (SNs). We aimed to evaluate the possibility of predicting the SN status using SPECT/CT.

Methods

SN mapping using a SPECT/CT system was performed in 381 cases of clinically node-negative, operable invasive breast cancer. We evaluated and compared the values of SN mapping on SPECT/CT, the findings of other modalities and clinicopathological factors in predicting the SN status.

Results

Patients with SNs located in the Level I area were evaluated. Of the 355 lesions (94.8 %) assessed, six cases (1.6 %) were not detected using any imaging method. According to the final histological diagnosis, 298 lesions (78.2 %) were node negative and 83 lesions (21.7 %) were node positive. The univariate analysis showed that SN status was significantly correlated with the number of SNs detected on SPECT/CT in the Level I area (P = 0.0048), total number of SNs detected on SPECT/CT (P = 0.011), findings of planar lymphoscintigraphy (P = 0.011) and findings of a handheld gamma probe during surgery (P = 0.012). According to the multivariate analysis, the detection of multiple SNs on SPECT/CT imaging helped to predict SN metastasis.

Conclusions

The number of SNs located in the Level I area detected using the SPECT/CT system may be a predictive factor for SN metastasis.

     

Immunohistochemically detected IDH1<Superscript>R132H</Superscript> mutation is rare and mostly heterogeneous in prostate cancer

Background

IDH1 mutations are oncogenic through induction of DNA damage and genome instability. They are of therapeutic interest because they confer increased sensitivity to radiation and cytotoxic therapy and hold potential for vaccination therapy.

Methods

In this study, we analyzed more than 17,000 primary prostate cancer tissues with a mutation-specific antibody for the IDH1^R132H mutation.

Results

IDH1 mutation-specific staining was found in 42 of 15,531 (0.3%) interpretable cancers. IDH1 mutation was associated with higher preoperative PSA and Gleason grade (p < 0.05, each) but was unrelated to PSA recurrence. A comparison with other molecular tumor features available from earlier studies revealed that TMPRSS2-ERG fusion as well as deletion of PTEN, 5q21, 6q15, and 3p13 was less frequent in IDH1-mutated than in non-mutated cancer. Increased lethality of genetically instable, “aberration-rich” cancer cells in the presence of IDH1 mutations could possibly explain this observation. Heterogeneity analysis revealed a homogeneous mutation in only 1 of 16 IDH1-mutated cancers. This high degree of heterogeneity may profoundly limit therapeutic targeting of IDH1 mutations in prostate cancer.

Conclusions

The data show that 0.3% of prostate cancers have an IDH1^R132H mutation and that these are mostly heterogeneous. Once specific anti-IDH1 therapy becomes reality, only a very small group of prostate cancer patients may benefit from such a treatment.

     

Can MRI/TRUS fusion targeted biopsy replace saturation prostate biopsy in the re-evaluation of men in active surveillance?

Purpose

The detection rate for significant prostate cancer of mMRI/TRUS fusion targeted biopsy versus saturation prostate biopsy was prospectively evaluated in men enrolled in active surveillance (AS) protocol.

Methods

From May 2013 to January 2015, 40 men aged 66 years (median) with very low-risk PCa were enrolled in an AS protocol, and eligible criteria were: life expectancy greater than 10 years, cT1C, PSA below 10 ng/ml, PSA density <0.20, ≤2 unilateral positive biopsy cores, Gleason score (GS) equal to 6, greatest percentage of cancer (GPC) in a core ≤50 %. All patients underwent 3.0-Tesla pelvic mpMRI before confirmatory transperineal saturation biopsy (SPBx; median 30 cores) combined with mpMRI/TRUS fusion targeted biopsy (median 4 cores) of suspicious lesions (PI-RADS 4–5).

Results

Ten out of 40 (25 %) patients were reclassified by SPBx based on upgraded GS ≥ 7; mpMRI found all the lesions predictive of significant PCa showing a false-positive rate equal to 5 %; on the contrary, mpMRI/TRUS targeted biopsy missed 3/10 (30 %) significant PCa characterised by the presence of a single positive core of GS ≥ 7 and GPC ≤ 5 %, suggesting that reduced number of targeted biopsies could miss small but significant PCa. Diagnostic accuracy, sensitivity, specificity, and positive and negative predictive value of mpMRI in diagnosing significant PCa were 95.2, 100, 93.8, 83.4, 100 %, respectively.

Conclusions

Although mpMRI provided high diagnostic accuracy (about 95 %) in diagnosing clinically significant PCa, mpMRI/TRUS fusion targeted biopsy cannot replace SPBx at confirmatory biopsy of men enrolled in AS protocols.

     

Carcinoembryonic antigen testing after curative liver resection for synchronous liver metastasis of colorectal cancer: a Japanese multicenter analysis

Purpose

To identify the possible roles of carcinoembryonic antigen (CEA) testing after liver resection for synchronous colorectal liver metastasis (CLM).

Methods

The subjects of this retrospective study were patients who underwent complete resection of primary tumors and synchronous CLM between 1997 and 2007 at 20 institutions in Japan. We studied the associations between perioperative CEA levels and the characteristics of recurrence.

Results

Recurrence was detected during the median follow-up time of 52 months in 445 (73.7%) of the total 604 patients analyzed. A postoperative CEA level >5 ng/ml was an independent predictor, with the highest hazard ratio (2.25, 95% confidence interval 1.29–3.91, P = 0.004). A postoperative CEA level >5 ng/ml had a specificity of 86.2% and a positive predictive value of 84.2% for recurrence. Patients with a high postoperative CEA level had a significantly higher recurrence rate, with a shorter time until recurrence and a higher frequency of multiple metastatic sites than those with a low postoperative CEA level. Among the patients with recurrence, 173 (52.7%) had an elevated CEA level (>5 ng/ml) when recurrence was detected.

Conclusions

A postoperative CEA level >5 ng/ml was an independent predictor of recurrence; however, CEA testing was not a reliable surveillance tool to identity recurrence after liver resection.

     

Evaluation of clinical staging of the American Joint Committee on Cancer (eighth edition) for prostate cancer

Objectives

This study aimed to evaluate the eighth edition of the American Joint Committee on Cancer (AJCC) for clinical staging of prostate cancer based upon Surveillance, Epidemiology and, End Results (SEER) database.

Materials and methods

Patients diagnosed as prostate adenocarcinoma during 2004–2009 without any surgical treatment to the primary site were selected from the SEER registry. Excluded were cases with incomplete or unavailable staging, PSA and Gleason score information.

Results

A total of 144,443 cases were identified. The median follow-up time was 84 months. The median age at diagnosis was 69 years, and median PSA was 7 ng/ml. CSS at 10th years was 96.2% for cT2a and 86.2% for cT2b/2c, respectively. The survival differences between clinical stage cT2a and cT2b/2c still had statistical significance (P < 0.001). For patients with grade group 1, there was no statistically significant difference for CCS between the cT2a and cT1 (P = 0.310), and between the subgroup of cT1/cT2a with 10 ng/ml ≤ PSA < 20 ng/ml and the subgroup of cT2b/2c with PSA < 20 ng/ml (P = 0.126), respectively. The CSS of IIIA (T1/2 with PSA ≥ 20 ng/ml) was less than IIC (P < 0.001), which has worst prognosis within stage I/II. The prognosis of T1/2 stage with Gleason score grade group 5 and PSA < 20 ng/ml was not only worse than AJCC IIC (P < 0.001) but also worse than AJCC IIIB (P < 0.001).

Conclusion

It is necessary to maintain a three-tier system to subdivide T2 disease clinically. For patients with grade group 1, cT2a and cT1 could merge into one group. Organ-confined disease with PSA ≥ 20 ng/ml or grade group 5 should be separated from stage II.

     

18-Fluorodeoxyglucose Positron Emission Tomography Predicts Recurrence in Resected Pancreatic Ductal Adenocarcinoma

Background

We aimed to determine whether treatment should be stratified according to 18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) maximum standardized uptake values (SUV_max) in pancreatic ductal adenocarcinoma.

Methods

Patients who underwent preoperative 18F-FDG PET/CT between 2006 and 2014 (n = 138) were stratified into high (≥ 4.85) and low (< 4.85) PET groups. The clinicopathological characteristics and prognostic outcomes were analyzed retrospectively.

Results

The primary tumor SUV_max was positively correlated with preoperative CA19-9 levels (P < 0.001). The high PET group failed to achieve postoperative CA19-9 normalization (P = 0.014). Disease-specific (P < 0.001), recurrence-free (P < 0.001), liver recurrence-free (P < 0.001), and peritoneal recurrence-free (P = 0.020) survivals were significantly shorter in the high PET group. The primary tumor SUV_max was an independent predictive risk factor for liver metastasis (hazard ratio 3.46, 95% confidence interval 1.61–7.87; P = 0.001) and peritoneal recurrence (hazard ratio 3.36, 95% confidence interval 1.18–10.89; P = 0.023).

Conclusions

Surgical resection failed to achieve CA19-9 normalization in the high PET group and distant recurrence was frequent. This suggests the potential for residual cancer at distant sites, even after curative resection. Stronger preoperative systemic chemotherapy is preferred for the high PET group patients.