[en] 

Purpose

Prostate-specific membrane antigen (PSMA) targeted positron emission tomography (PET) imaging significantly improved the detection of recurrent prostate cancer (PCa). However, the value of PSMA PET imaging in patients with advanced hormone-sensitive or hormone-resistant PCa is still largely unknown. The aim of this study was to analyze the detection rate and distribution of lesions using PSMA PET imaging in patients with advanced PCa and ongoing androgen deprivation therapy (ADT).

Methods

A total of 84 patients diagnosed with hormone-sensitive or hormone-resistant PCa who underwent ⁶⁸Ga-PSMA-11 PET/magnetic resonance imaging (MRI) or computer tomography (CT) under ongoing ADT were retrospectively analyzed. We assessed the detection of PSMA-positive lesions overall and for three PSA subgroups (0 to < 1 ng/mL, 1 to < 20 ng/mL and > 20 ng/mL). In addition, PSMA-positive findings were stratified by localization (prostatic fossa, pelvic, para-aortic, mediastinal/supraclavicular and axillary lymph nodes, bone lesions and visceral lesions) and hormone status (hormone-sensitive vs. hormone-resistant). Furthermore, we assessed how many patients would be classified as having oligometastatic disease (≤ 3 lesions) and theoretically qualify for metastasis-directed radiotherapy (MDRT) in a personalized patient management.

Results

We detected PSMA-positive lesions in 94.0% (79 of 84) of all patients. In the three PSA subgroups detection rates of 85.2% (0 to < 1 ng/mL, n = 27), 97.3% (1 to < 20 ng/mL, n = 37) and 100% (> 20 ng/mL, n = 20) were observed, respectively. PSMA-positive visceral metastases were observed only in patients with a PSA > 1 ng/mL. Detection of PSMA-positive lesions did not significantly differ between patients with hormone-sensitive and hormone-resistant PCa. Oligometastatic PCa was detected in 19 of 84 patients (22.6%). Almost all patients, 94.7% (n = 18) would have been eligible for MDRT.

Conclusions

In this study, we observed an overall very high detection rate of 94% using PSMA PET imaging in patients with advanced PCa and ongoing ADT. Even in a majority of patients with very low PSA values < 1 ng/ml PSMA-positive lesions were found. (author)

[en] Sensitive visualization of recurrent prostate cancer foci is a challenge in patients with early biochemical recurrence (EBR). The recently established ⁶⁸Ga-PSMA-11 PET/CT has significantly improved the detection rate with published values of up to 55% for patients with a serum PSA concentration between 0.2-0.5 ng/mL. The increased soft tissue contrast in the pelvis using simultaneous ⁶⁸Ga-PSMA-11 PET/MRI might further improve the detection rate in patients with EBR and low PSA values over PET/CT. We retrospectively analyzed a cohort of 56 consecutive patients who underwent a ⁶⁸Ga-PSMA-11 PET/MRI for biochemical recurrence in our institution between April and December 2016 with three readers. Median PSA level was 0.99 ng/mL (interquartile range: 3.1 ng/mL). Detection of PSMA-positive lesions within the prostate fossa, local and distant lymph nodes, bones, or visceral organs was recorded. Agreement among observers was evaluated with Fleiss's kappa (k). Overall, in 44 of 56 patients (78.6%) PSMA-positive lesions were detected. In four of nine patients (44.4%) with a PSA < 0.2 ng/mL, suspicious lesions were detected (two pelvic and one paraaortic lymph nodes, and two bone metastases). In eight of 11 patients (72.7%) with a PSA between 0.2 and < 0.5 ng/mL, suspicious lesions were detected (two local recurrences, six lymph nodes, and one bone metastasis). Five out of 20 patients with a PSA < 0.5 ng/mL had extrapelvic disease. In 12 of 15 patients (80.0%) with a PSA between 0.5 and < 2.0 ng/mL, suspicious lesions were detected (four local recurrences, nine lymph nodes, and four bone metastases). In 20 of 21 patients (95.2%) with a PSA >2.0 ng/mL, suspicious lesions were detected. The overall interreader agreement for cancer detection was excellent (κ = 0.796, CI 0.645-0.947). Our data show that ⁶⁸Ga-PSMA-11 PET/MRI has a high detection rate for recurrent prostate cancer even at very low PSA levels <0.5 ng/mL. Furthermore, even at those low levels extrapelvic disease can be localized in 25% of the cases and local recurrence alone is seen only in 10%. (orig.)

[en] 

Purpose

To investigate whether the use of pre-orchiectomy instead of pre-chemotherapy tumor marker (TM) levels has an impact on the International Germ Cell Consensus Classification (IGCCCG) risk group assignment in patients with metastatic germ cell tumors (GCT).

Methods

Demographic and clinical information of all patients treated for primary metastatic testicular non-seminomatous GCT in our tertiary care academic center were extracted from medical charts. IGCCCG risk group assignment was correctly performed with pre-chemotherapy marker levels and additionally with pre-orchiectomy marker levels. Agreement between pre-chemotherapy and pre-orchiectomy risk group assignments was assessed using Cohen’s kappa.

Results

Our cohort consisted of 83 patients. The use of pre-orchiectomy TMs resulted in an IGCCCG risk group upstaging in 12 patients (16%, 8 patients from good to intermediate risk and 4 patients from intermediate to poor risk) and a downstaging in 1 patient (1.2%, from intermediate- to good-risk). The agreement between pre-orchiectomy and pre-chemotherapy IGCCCG risk groups resulted in a Cohen’s kappa of 0.888 (p < 0.001).

Conclusions

Using pre-orchiectomy TMs can result in incorrect IGCCCG risk group assignment, which in turn can impact on the clinical management and follow-up of patients with metastatic GCT. Thus, adherence to the IGCCCG standard using pre-chemotherapy TMs levels is recommended.

[en] Given the good correlation between PSMA expression and intraglandular tumour aggressiveness based on immunohistochemistry, there is increasing interest in ⁶⁸Ga-PSMA-11 PET/MRI for staging prostate cancer (PCA). Therefore, accurate knowledge of prostate anatomy as well as normal distribution of PSMA within the prostate gland is becoming essential. The aim of this study was to investigate the physiological intraprostatic distribution of ⁶⁸Ga-PSMA-11. We retrospectively analysed all patients who underwent a staging ⁶⁸Ga-PSMA-11 PET/MRI scan between June 2016 and January 2018 for high-risk PCA, underwent radical prostatectomy in our institution, and gave written consent for further data analysis. In each patient, standardized volumes of interest (VOIs) were placed bilaterally in the central, transition and peripheral zones within the zonal anatomy according to T2 weighted sequences in the axial and coronal planes. VOIs were only placed if they were safely within healthy tissue without spillover from the PCA. SUV_max and SUV_mean were determined and their differences among the regions were assessed using the Wilcoxon signed-ranks test. Of 283 consecutive patients scanned with ⁶⁸Ga-PSMA-11 PET/MR, 31 were analysed. A total of 133 VOIs were placed, 46 in the central zone, 41 in the transition zone and 46 in the peripheral zone. Differences in SUV_max between the central zone (mean 3.9 ± 0.58) and transition zone (mean 3.2 ± 0.59) and between the central zone and peripheral zone (mean 2.7 ± 0.54) were statistically significant (both p < 0.001). Our results suggest that higher ⁶⁸Ga-PSMA-11 accumulation in the central zone than in the transition and peripheral zones is normal, and leads to a pattern resembling ''Mickey Mouse ears'' on ⁶⁸Ga-PSMA-11 PET. This pattern could be helpful in avoiding false-positive interpretations of PET scans. (orig.)

[en] 

Purpose

: Testicular granulosa cell tumors (tGrCT) are rare sex cord-stromal tumors. This review aims to synthesize the available evidence regarding the clinical presentation and clinicopathological characteristics, treatment and outcomes.

Methods

: We conducted a systematic literature search using the most important research databases. Whenever feasible, we extracted the data on individual patient level.

Results

: From 7863 identified records, we included 88 publications describing 239 patients with tGrCT. The majority of the cases were diagnosed with juvenile tGrCT (166/239, 69%), while 73/239 (31%) patients were diagnosed with adult tGrCT. Mean age at diagnosis was 1.5 years (± 5 SD) for juvenile tGrCT, and 42 years (± 19 SD) for adult tGrCT. Information on primary treatment was available in 231/239 (97%), of which 202/231 (87%) were treated with a radical orchiectomy and 20/231 (9%) received testis sparing surgery (TSS). Local recurrence after TSS was observed in 1/20 (5%) cases. Metastatic disease was never observed in men with juvenile tGrCT but in 7/73 (10%) men with adult tGrCT. In 5/7 men with metastatic tGrCT, metastases were diagnosed at initial staging, while 2/7 patients developed metastases after 72 and 121 months of follow-up, respectively. Primary site of metastasis is represented by the retroperitoneal lymph nodes, but other sites including lungs, liver, bone and inguinal lymph nodes can also be affected. In comparison with non-metastatic adult tGrCT, men with metastatic adult tGrCT had significantly larger primary tumors (70 vs 24 mm, p 0.001), and were more likely to present with angiolymphatic invasion (57% vs 4%, p 0.002) or gynecomastia (29% vs 3%, p 0.019). In five out of seven men with metastatic disease, resection of metastases or platinum-based chemotherapy led to complete remission.

Conclusion

: Juvenile tGrCT represent a benign entity whereas adult tGCTs have metastatic potential. Tumor size, presence of angiolymphatic invasion or gynecomastia represent risk factors for metastatic disease. The published literature supports the use of testis sparing surgery but there is only limited experience with adjuvant therapies. In the metastatic setting, the reviewed literature suggests that aggressive surgical and systemic treatment might cure patients.

[en] 

Introduction

Because spermatocytic tumors of the testis are rare, only limited evidence exists regarding the malignant potential and the optimal management of localized and metastatic disease.

Materials and methods

We performed a systematic review through MEDLINE, EMBASE, Scopus, Cochrane Database of Systematic Reviews and Web of Science to identify reports including patients with testicular spermatocytic tumors.

Results

From originally 7863 studies, we extracted data of 146 patients of which 99% were treated with radical orchiectomy. Metastases in patients with initially localised disease were diagnosed in 7% of patients and detected after a median follow-up of 5.5 months (range 2–21 months). Patients with aggressive histology (sarcoma or anaplastic subtype) were more likely to have metastatic disease (6/124 (5%) vs 9/22 (41%), p < 0.001). Patients with metastatic disease had larger primary tumors (92.5 vs 67.5 mm, p = 0.05). Life expectancy in patients with metastatic disease ranged from 1 to 25 months.

Conclusion

The published literature does neither support the use of testis sparing surgery nor adjuvant therapy. Patients with aggressive variants or larger tumors were more likely to have metastases and develop recurrences within the first few years. Patients with metastatic disease have a limited life expectancy and metastatic spermatocytic tumors are not as responsive to chemotherapy as germ cell cancers.

[en] Positron emission tomography (PET) targeting the prostate-specific membrane antigen (PSMA) has superior sensitivity over conventional imaging (CI) to stage prostate cancer (PCa) and therefore is increasingly used in staging to stratify patients before radical therapy. Whether this improved diagnostic accuracy translates into improved outcome after radical prostatectomy (RPE) has not yet been shown. Therefore, the aim of this study was to compare the oncological outcome after RPE between patients that underwent preoperative staging with CI or PSMA-PET for intermediate and high-risk PCa. We retrospectively selected all patients that underwent RPE for intermediate- or high-risk PCa at our institution before PSMA-PET introduction (between March 2014 and September 2016) and compared the oncologic outcome of patients staged with PSMA-PET (between October 2016 and October 2018). Oncological pre-surgical risk parameters (age, PSA, D’Amico score, biopsy-ISUP, and cT stage) were compared between the groups. Oncological outcome was determined as PSA persistence, nerve-sparing rate, and surgical margin status. Wilcoxon rank-sum, Fisher’s, and chi-square tests where used for statistical testing. One hundred five patients were included, 53 in the CI group and 52 in the PSMA-group. Patients in the PSMA group had higher ISUP grade (p < 0.001) and D’Amico score (p < 0.05). The rate of free surgical margins and PSA persistence after RPE was 64% and 17% for the CI and 77% and 6% for the PSMA group (p = 0.15 and 0.13, respectively). Subgroup analysis with high-risk patients revealed PSA persistence in 7% (3/44) in the PSMA group and 25% (7/28) in the CI group (p = 0.04). Limitations include the retrospective design and choline-PET for some patients in the CI group. Immediate outcome after RPE was not worse in the PSMA group compared with the CI group, despite a higher-risk cohort. In a comparison of only high-risk patients, PSMA-PET staging was associated with a significantly lower rate of postsurgical PSA persistence.

[en] Ultrasound-guided biopsy (US biopsy) with 10-12 cores has a suboptimal sensitivity for clinically significant prostate cancer (sigPCa). If US biopsy is negative, magnetic resonance imaging (MRI)-guided biopsy is recommended, despite a low specificity for lesions with score 3-5 on Prostate Imaging Reporting and Data System (PIRADS). Screening and biopsy guidance using an imaging modality with high accuracy could reduce the number of unnecessary biopsies, reducing side effects. The aim of this study was to assess the performance of positron emission tomography/MRI with ${}^{68}$Ga-labeled prostate-specific membrane antigen (PSMA-PET/MRI) to detect and localize primary sigPCa (ISUP grade group 3 and/or cancer core length ≥ 6 mm) and guide biopsy. Prospective, open-label, single-center, non-randomized, diagnostic accuracy study including patients with suspected PCa by elevation of prostate-specific antigen (PSA) level and a suspicious lesion (PIRADS ≥ 3) on multiparametric MRI (mpMRI). Forty-two patients underwent PSMA-PET/MRI followed by both PSMA-PET/MRI-guided and section-based saturation template biopsy between May 2017 and February 2019. Primary outcome was the accuracy of PSMA-PET/MRI for biopsy guidance using section-based saturation template biopsy as the reference standard. SigPCa was found in 62% of the patients. Patient-based sensitivity, specificity, negative and positive predictive value, and accuracy for sigPCa were 96%, 81%, 93%, 89%, and 90%, respectively. One patient had PSMA-negative sigPCa. Eight of nine false-positive lesions corresponded to cancer on prostatectomy and one in six false-negative lesions was negative on prostatectomy. PSMA-PET/MRI has a high accuracy for detecting sigPCa and is a promising tool to select patients with suspicion of PCa for biopsy.