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Castration-resistant prostate cancer and multiple lymph node and ventral bladder metastases in an 87 year-old man progressed despite various systemic therapies, including chemotherapy. Because his prostate surgical specimen displayed a microsatellite instability (MSI) -high status, pembrolizumab 200 mg/body treatment was started. After six courses of treatment, his prostate-specific antigen (PSA) level decreased by 83% versus that at treatment initiation (from 408.78 ng/ml to 69.54 ng/ml), and the para-aortic lymph node metastasis was reduced in size on imaging. After 13 courses, his PSA level (462.59 ng/ml) exceeded that at the start of treatment, and progressive disease was detected on imaging. Although case reports of pembrolizumab for MSI-high prostate cancer remain few because of its rarity, it is an important therapeutic option and further clinical research is required.

Bone is the most common metastatic site in prostate cancer (PCa). Although the extent of disease (EOD) grade is used for evaluating burden of bone metastasis, the accuracy of bone metastasis classification needs improvement. Bone scan index (BSI) was developed as a quantitative tool to enhance the interpretability and clinical relevance of the bone scan. This study aimed to explore the role of BSI using BONENAVI® software in determining the prognosis and treatment efficacy in castration-sensitive PCa (mCSPC) patients with bone metastasis. We retrospectively reviewed 61 mCSPC patients with bone metastasis who had received primary androgen deprivation therapy (PADT) at our institution. All patients received PADT with luteinizing hormone-releasing hormone agonist or surgical castration accompanied by first-generation antiandrogen, bicalutamide. Bone scans were performed with ⁹⁹[m]Tc-MDP. BSI (%) was divided into two groups (＜1.0 and ≧1.0), and BSI response rates(change at 0 months to after 6 months) were determined using thresholds of 45% decline. Castration-resistant prostate cancer (CRPC) -free survival (CRPC-FS) and Overall survival (OS) rates were analyzed using the Kaplan-Meier method. The median follow-up was 41. 9 months. Overall, 16 patients (26. 2%) died. Multivariate analysis on pretreatment factors revealed that hemoglobin (P＝0.03) and BSI (P＝0.04) were independent prognostic factors for OS. The 5-year OS rates in patients with low BSI and high BSI were 84.6% and 39.2%, respectively (P＝0.02). In 40 patients who had a bone scan before and after PADT, OS rates in patients with a good response (≧45%) were significantly higher than those with a poor response (＜45%) (P＝0.001). Nadir PSA titers within 6 months after the start of treatment (P＝0.005), Hb (P＝0.003), and BSI change (P＝0.014) were independent prognostic factors for OS. In mCSPC patients with bone metastases, BSI at diagnosis was an important predictor of CRPC progression and OS as a pre-treatment factor, and BSI change rate and PSA nadir as post-treatment factors.

The next treatment strategy after drug holidays following docetaxel (DTX) therapy for patients with castration-resistant prostate cancer (CRPC) is unclear. This study investigated the relationship between the duration of drug holidays and prognosis after DTX therapy. This study retrospectively assessed 26 patients treated with DTX in our hospital. Overall survival duration was significantly longer in the long-term withdrawal group (duration of drug holidays ≥6 months) than in the short-term withdrawal group (duration of drug holidays ＜6 months) (P＝0.015). Similarly, progression-free survival duration was significantly longer in the long-term withdrawal group than in the short-term withdrawal group (P＝0.008). The short-term withdrawal group had a significantly lower body mass index (P＝0.009) and higher prostate-specific antigen (PSA) (P＝0.017) at the initiation of DTX therapy, higher PSA nadir during DTX therapy (P＝0.009), and higher PSA at the end of DTX therapy (P＝0.022), compared to the long-term withdrawal group. This study suggests that the optimal opportunity to introduce DXT therapy is when the patients with CRPC are physically able to tolerate chemotherapy and their tumor volume remains a lower burden. This may provide a clinical benefit, longer drug holidays, and a better prognosis.

Prostate cancer is basically hormone sensitive tumor. However, once it turns to metastatic castration-resistant prostate cancer(mCRPC), it is hard to suppress tumor growth and metastasis. Despite chemotherapy and novel androgen-receptor signalling inhibitors, mCRPC remains a lethal disease with poor clinical outcomes. Immunotherapy with chimeric antigen receptor T(CAR-T)cells redirects a patient's immune cells against the tumor antigen. CAR-T cell therapy has demonstrated promise in treating patients with several haematological malignancies. On the other hand, solid tumors impose immunologic and physical barriers to the efficacy of CAR-T cell therapy. As a new strategy to mCRPC, CAR-T cells with targeting prostate-specific membrane antigen(PSMA)has been developed. Several clinical trials using anti PSMA-CAR-T cells against mCRPC are going on overseas. A few of the trials showed promising results on the safety and efficacy of this therapy in mCRPC. Herein, we review strategies of constructing CAR-T cells to mCRPC, and the latest reports of international clinical trials of anti PSMA-CAR-T therapy.

A 75-year-old man presented with macroscopic hematuria and a high serum prostate-specific antigen (PSA) level. Macroscopic hematuria had subsided by the time of consultation. The PSA level was 38.590 ng/ml, which, along with rectal examination and magnetic resonance imaging findings, led to the suspicion of prostate cancer. Transrectal needle biopsy of the prostate revealed intraductal carcinoma of the prostate (IDC-P). Computed tomography and bone scintigraphy were performed, and the prostate cancer was classified as cT2cN0M0. After 6 months of combined androgen blockade therapy, a radical prostatectomy was performed; however, PSA levels continued to increase, and the patient was diagnosed with castration resistant prostate cancer. Multiple bone metastases appeared 5 months after the initiation of abiraterone therapy. Three courses of docetaxel and two courses of cabazitaxel were administered, but the disease progression continued. The IDC-P was found to be positive for the BRCA2 mutation by BRACAnalysis® performed at the start of cabazitaxel therapy. To our knowledge, no other cases of BRCA2 mutation positive IDC-P have been reported in Japan. After we started administration of Olaparib, the patient's PSA level was lowered and the disease progression stopped.

A 73-year-old man was referred to our hospital because of a high prostate specific antigen (PSA) level. The PSA level at our hospital was 63.5 ng/ml. Pelvic magnetic resonance imaging (MRI) showed findings strongly suggestive of multiple pelvic bone metastases, but no obvious malignant findings in the prostate. A 12-core prostate biopsy was performed and no cancer was detected. Computed tomography and bone scintigraphy showed findings suspicious of bone metastases in the sternum, thoracolumbar spine, pelvic bone, and sacrum. Spine MRI revealed a mass in the vertebral body from the eighth thoracic vertebra to the first lumbar vertebra. A biopsy of the right iliac crest showed adenocarcinoma and was positive for PSA staining, leading to the diagnosis of multiple bone metastases of prostate cancer. Abiraterone acetate in combination with androgen deprivation was started. He received medication and radiation therapy to his sternum for pain relief. Spine MRI after 4 months showed decreased vertebral body weights and serum PSA levels were ＜0.003 ng/ml after 5 months. Seventeen months after treatment, PSA remains below 0.003 ng/ml, and the patient is currently pain-free.

The patient was a 63-year-old man with biopsy Gleason score of 4＋5 prostate cancer with an initial prostate specific antigen level of (PSA) 51.2ng/ml. On imaging examination, extracapsular invasion, rectal invasion, and pararectal lymph node metastasis were found (cT4N1M0). After 4 years of androgen deprivation therapy, PSA decreased to 0.631ng/ml, and then increased gradually to1.2ng/ml. Computed tomographic scan showed that the primary tumor had shrunk and lymph node metastasis had disappeared; so salvage robot-assisted resection of the prostate (RARP) was performed for non-metastatic castration-resistant prostate cancer (m0CRPC). Since PSA decreased to an undetactable level, hormone therapy was terminated at 1 year. The patient remained recurrence-free for 3 years after surgery. RARP may be effective for m0CRPC, enabling discontinuation of androgen deprivation therapy.

In our hospital, 553 patients with clinically localized prostate cancer underwent low-dose-rate (LDR) brachytherapy between March 2007 and December 2019. The patients were stratified based on the following prognosis according to the D'Amico risk classification criteria: low-risk and intermediate-risk groups (PSA ＜10, ≦T2a, GS : 3＋4 (≦30%)) were treated with LDR brachytherapy without supplemental extra beam radiotherapy (EBRT), while some patients in the high- and intermediate-risk groups were treated with LDR and supplemental EBRT. The 5- and 10-year overall survival rates were 94.8 and 85.5%, disease-specific survival rates were 99.8 and 97.7%, and biochemical recurrence-free survival rates were 95.7 and 90.7%. By risk stratification, the 5- and 10-year biochemical recurrence-free survival rates were 98.0 and 98.0% (low risk), 96.1 and 89.6% (intermediate risk), and 90.6 and 77.3% (high risk). The LDR outcome was generally good, but, 32 recurrence cases were observed. In the recurrent group, 9 patients did not undergo the recommended therapeutic strategy and 26 patients did not undergo preoperative magnetic resonance imaging.

A 70-year-old-man was referred with urination pain and pyuria. Prostate specific antigen was 10.6 ng/ml, and urine culture was Escherichia coli. The abdominal ultrasonography showed irregular low echo at the right lobe of prostate. Prostate magnetic resonance imaging (MRI) showed an extracapsular infiltrated prostate tumor in the right lobe. Levofloxacin was administered and prostate biopsy was performed. The pathological examination revealed that the prostate tissue was filled with inflammatory cells and had lost its glandular duct structure. The patient was diagnosed with malacoplakia of the prostate. Four months after prostate biopsy, prostate MRI imaging showed disappearance of the extracapsular infiltration in right peripheral zone.

We evaluated the clinical course of patients with localized prostate cancer in whom long-term successful androgen deprivation therapy (ADT) was ceased. Study subjects were 24 patients with stage B prostate cancer who were initially treated with ADT for a median duration of 93 months. The median age at the cessation of ADT was 84 years. The median nadir serum prostate specific antigen (PSA) level was 0.022 ng/ml. The median duration of follow-up from the cessation of ADT was 31 months. During follow-up, five patients showed PSA elevation of ≥2 ng/ml from the nadir. Serum testosterone level was tested in 20 patients, and five showed testosterone recovery ≥0.5 ng/ml. Seven patients died from diseases other than prostate cancer, but there were no deaths caused by prostate cancer. This study demonstrated that long-term successful ADT for localized prostate cancer could be ceased with adequate follow-up evaluation.

A total of 100 patients were retrospectively analyzed with magnetic resonance imaging-ultrasonography (MRI-US) fusion biopsy(KOELIS, TRINITY®) at our institution between October 2019 and May 2020. The median patient age was 71 years, median prostate specific antigen (PSA) level was 7.4 ng/ml, and median PSA-density was 0.183 mg/ml. Sixty-one of the patients were positive for cancer ; 14 of them were positive by targeted biopsy only, 9 were positive by systematic biopsy only, and 38 were positive by both. Clinically significant prostate cancer (CPSC ; Gleason Score ≥3＋4 and % core ≥50%) was detected by target biopsies in 46 patients and by systematic biopsies in 33 patients. The positive core detection rate for CSPC was 32.5% for targeted biopsies and 7.0% for systematic biopsies(P＜0.0001), with a significantly higher rate for targeted biopsies. These results indicate that in MRI-US fusion biopsy, targeted biopsy has a higher detection rate for cancer and a significantly higher detection rate for clinically significant prostate cancer compared with systematic biopsy.

We analyzed the perioperative parameters, postoperative urinary status, and complications of 200 patients who underwent photoselective vaporization of the prostate (PVP) with the 180W-X-ray photoelectron spectroscopy (XPS) for benign prostatic hyperplasia at our hospital. In addition, we compared perioperative parameters and complications, as well as the rate of decrease in prostate-specific antigen (PSA) and prostate volume at 3 and 12 months after surgery, with those of the last 200 patients who underwent PVP with the 120W-high-performance system (HPS). The results showed significant differences between methods in operative time (XPS: 67.9±29.0 minutes, HPS: 95.2±32.1 minutes, p＜0.05), laser exposure time (XPS: 41.4±17.8 minutes, HPS: 60.1±19.7 minutes, p＜0.05), and laser dose (XPS: 385,937±180,872, HPS: 300,316±105,528, p＜0.05). In addition, there were significant differences in the rates of decrease in PSA and prostate volume in the 180W-XPS group compared with the 120W-HPS group. The transpiration efficiency of the 180W-XPS was higher than that of the 120W-HPS.

(Background) The effects of fluctuant patterns of serum alkaline phosphatase (ALP) and lactic acid dehydrogenase (LDH) levels on overall survival of patients with prostate cancer (PC) treated with androgen deprivation therapy (ADT) remain unclear. (Methods) We enrolled 236 patients with PC and divided into 3 cohorts by fluctuant patterns of serum levels of ALP and LDH between at baseline and at 1 year later, or at diagnosis of castration-resistant prostate cancer (CRPC): intermediate, within interquartile range (IQR) [I]; lower than IQR [L]; higher than IQR [H]. (Results) In the 1 year later ALP cohort, all parameters except age were significantly different. In the L cohort, 75% of patients had bone metastasis and > 50% developed CRPC or died. In the 1 year later LDH cohort, Eastern Cooperative Oncology Group-performance status (ECOG-PS) and clinical metastasis classification were significantly different among the cohorts. In the CRPC/ALP cohorts, baseline prostate-specific antigen values and clinical metastasis classification were significantly different among the cohorts, and all cases had metastasis in the L cohort. In the CRPC/LDH cohort, the L cohort had higher ECOG-PS and shorter time to CRPC. In the 1 year later ALP cohort, the hazard ratio (HR) for death of the L and H cohort to the I cohort was 3.77 and 2.27, respectively and both were significant. In the CRPC/LDH cohort, the HR for death of L cohort to I cohort was 1.99. (Conclusions) Larger fluctuations in serum ALP and LDH levels were a sign of poorer prognosis, especially for patients in the L cohort.

Objective: [ 177 Lu]Lu-PSMA-617 is a radioisotope used in nuclear medicine. It is necessary to take appropriate measures to limit its exposure and ensures its airborne concentrations do not exceed legally permitted levels. Therefore, the purpose of this study was to measure the airborne radioactivity concentration in the inpatient room after administering [ 177 Lu]Lu-PSMA-617 to humans., Methods: Three males with advanced prostate-specific membrane antigen (PSMA)-positive metastatic castration resistant prostate cancer were intravenously administered [ 177 Lu]Lu-PSMA-617 (7.4 GBq ± 10%) in an inpatient room, and the airborne radioactivity concentrations were measured at two locations in the room (in the center of the room and at the bedside) using a filter collection method., Results: After administration of [ 177 Lu]Lu-PSMA-617, the airborne radioactivity concentrations measured were below the limit of detection (1.1 × 10 -6  Bq/cm 3 or 9.5 × 10 -7  Bq/cm 3 ) in all three humans, and all concentrations were consistently below the standard value of 1/10,000 of 2 × 10 -2  Bq/cm 3 , the legal airborne concentration limit of 177 Lu., Conclusion: The results of this study confirmed that the airborne concentration of [ 177 Lu]Lu-PSMA-617 after administration to humans was below the legally permitted level.

(Objectives)Factors related to prostate-specific antigen (PSA) recurrence, including PSA at 6 months after radical prostatectomy, were evaluated to determine if the postoperative follow-up period in the cancer regional alliances critical path could be individualized using a coordinated path. (Patients and methods)Among 352 patients who underwent laparoscopic radical prostatectomy at our hospital from May 2009 to June 2015, 331 who did not undergo preoperative hormone therapy were examined retrospectively. Cases with PSA < 0.01 ng/mL at 6 months after surgery (group A, n=209) were compared with those with PSA > 0.01 ng/mL at the same time point (group B, n=122). (Results)PSA recurrence was significantly higher in group B (n=21 (10.0%) vs. n=70 (57.4%), p< 0.001) and the time to recurrence was significantly shorter (44 vs.12.5 months, p< 0.001). In multivariate analysis within group A, the Gleason Grade Group (GGG) and extraprostatic extension in surgical specimens were predictors of PSA recurrence. In group A, all cases (n=30) of GGG1 in surgical specimens had no extraprostatic extension and no PSA recurrence. There were 90 cases of surgical specimens with GGG2 and no extracapsular infiltration, and only 4 of these cases had recurrence (4.4%). (Conclusion)The results of the study indicate that follow-up interval stratification is possible using the PSA level at 6 months after radical prostatectomy, GGG and extraprostatic extension in the surgical specimen.

The patient is a 72-year-old man who was referred to our hospital with an elevated prostate specific antigen (PSA) level. He was diagnosed with prostate cancer (cT2aN0M0) at the age of 62 years. He had undergone radical proton beam radiotherapy. The PSA level decreased to a nadir of 0.217 ng/ml after 5 years, gradually increasing thereafter to 1.595 ng/ml during the next 5 years. Although magnetic resonance imaging of the prostate showed an abnormal signal area in the prostate, repeated biopsies of the prostate revealed no malignant findings. Contrast-enhanced abdominal computed tomography (CT), bone scintigraphy and fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET)/CT did not detect any abnormalities in the prostate or metastatic lesions. ¹⁸F-prostate specific membrane antigen (PSMA)-PET/CT showed no accumulation in the prostate, but some accumulation in a left obturator lymph node. Open pelvic lymph node dissection was performed, and pathological examination confirmed lymph node metastasis from the prostate cancer. The PSA level decreased from 2.482 ng/ml preoperatively to 0.391 ng/ml at 3 months postoperatively. PSMA-PET/CT might be useful for early localization of recurrent lesions in biochemical recurrence after radical treatment for prostate cancer.

A 79-year-old man underwent a transrectal prostate needle biopsy with a prostate-specific antigen (PSA) level of 12.0 ng/ml. He was diagnosed with adenocarcinoma (Gleason score 4＋3, cT3aN0M0) and underwent radiation therapy. Eight months later, he was administered hormone therapy because of a rise in PSA level to 8.4 ng/ml. One year and 5 months later, he experienced back pain, and computed tomography revealed multiple lymphadenopathies and irregular prostate enlargement. The PSA level was 0.097 ng/ml. Re-biopsy of the prostate and biopsy of the lymph node were performed. Pathological examination revealed neuroendocrine differentiation of the prostate. The disease progressed rapidly, and the patient died 4 months after the biopsy. Neuroendocrine differentiation of prostate cancer is rare, and its development may not be consistent with PSA levels. Therefore, periodic imaging examinations should be conducted, even when PSA levels are low.

Ureteral metastasis from prostate cancer is rare. The present case report describes an 83-year-old patient with distant metastasis of prostate cancer to the right ureter that caused hydronephrosis. Upon initial examination at our hospital, he presented with a high prostate-specific antigen (PSA) level of 10.0 ng/ml. He was diagnosed with prostate adenocarcinoma, with Gleason score of 10 (5＋5) and clinical staging of cT2aN0M0. Intensity-modulated radiation therapy (IMRT) was performed after 1 year and 7 months of androgen depriation therapy. At 1 year and 4 months after IMRT, PSA increased to 3.068 ng/ml. Computed tomography scan revealed right hydronephrosis and thickening of the right ureter. We could not identify obvious malignant cells on ureteroscopic biopsy, and right nephroureterectomy was performed. Pathological examination revealed ureteral metastasis of prostate cancer. Six months after nephroureterectomy, PSA increased to 3.037 ng/ml. He was diagnosed with castration-resistant prostate cancer and has been treated with enzalutamide.

From April 2007 to April 2018, we performed lymph node dissection in 305 cases of laparoscopic radical prostatectomy and 202 cases of robot-assisted radical prostatectomy at our hospital, and there were 68 cases with positive lymph node metastasis (pN1). Of these 68 cases, we examined retrospectively 62 cases in which extended lymph node dissection (ELND) was performed. The median number of removed lymph nodes was 25 (interquartile range [IQR] ; 18-34) and the median number of metastatic lymph nodes was 1 (IQR ; 1-3). Postoperative prostate-specific antigen (PSA) recurrence was observed in 40 of the 62 patients. The median time to PSA recurrence was 24 months. After univariate analysis, PSA at initial diagnosis (iPSA) of 10 ng/ml or more, pathological Gleason score (pGS) of 8 or more, total number of lymph node metastases of 2 or more, and positive surgical margin (RM＋) were found to be riskfactors of PSA recurrence. In multivariate analysis, iPSA of 10 ng/ml or more, pGS of 8 or more and RM＋ were independent riskfactors of PSA recurrence (p＜0.05). In the cases without riskfactors such as iPSA≥10, pGS≥8, and RM＋, immediate postoperative adjuvant therapy may be avoided even with pN1.

A 56-year-old man visited our hospital with a chief complaint of worsening urinary pain after a treatment by another doctor. Prostate specific antigen (PSA) was 429.66 ng/ml, and computed tomography (CT) revealed multiple lymph node enlargement and multiple bone metastases. Prostatic adenocarcinoma (Gleason score 4＋5) was detected on the first prostate biopsy. Based on these results, the clinical stage was determined to be cT4N1M1b Androgen deprivation therapy (ADT) was started, and PSA decreased to 0.03 ng/ml at 3 months, but micturition and perineal pain tended to worsen, and multiple liver metastases were confirmed on CT. The second biopsy examination was performed and a diagnosis of neuroendocrine prostate cancer (NEPC) was made. Chemotherapy for small cell lung cancer was immediately performed, but no response was seen, and he died 8 months after the first visit. Immunostaining of prostate tissue of the first biopsy revealed that de novo NEPC expressed both PSA and synaptophysin in tumor cells.

The patient was a 78-year-old man who, at 67 years of age, had been diagnosed with prostate cancer cT3bN1M0 (Gleason score 5+5) and started on androgen ablation therapy. Thereafter, the cancer had developed into castration-resistant prostate cancer; thus, after surgical castration, the patient was treated with 27 courses of docetaxel, as well as enzalutamide and abiraterone. However, new metastases appeared in the paraaortic lymph nodes, post which, the patient was treated with 25 courses of cabazitaxel. However, the paraaortic and intrapelvic lymph nodes became enlarged, the patient developed rectal occlusion and urinary retention due to growth of the primary tumor, and his general condition deteriorated. Hence, the patient decided to abandon treatment approximately 10 years after initial diagnosis, underwent cystostomy, and transitioned to best supportive care. After stopping treatment, his general condition started to improve, and approximately 6 months later, his PSA levels had fallen from 55.5 ng/mL to 19.3 ng/mL and the lymph nodes had also reduced in size. When the cancer was treated with local radiation, the enlarged tumor disappeared, and the patient was able to urinate again. It has now been 2.5 years since treatment was stopped, and both, the paraaortic and intrapelvic lymph nodes have reduced in size to < 1 cm, and the PSA value continues to remain less than 0.008 ng/ml.

A 67-year-old male came to our department with complaints of urinary retention and gross hematuria. The prostate specific antigen (PSA) level in the serum was elevated to 69.5 ng/ml. Thus a transperineal prostate biopsy was performed. The patient was diagnosed with prostate cancer, and lung and bone metastases were also revealed. Treatment for metastatic prostate cancer was performed for approximately 5 years with combined androgen blockade therapy followed by enzalutamide, docetaxel, estramustine, Ra-223 dichloride, estradiol, and then enzalutamide reintroduction. Thereafter, the patient presented with bilateral breast nodules and we referred him to our breast surgery department. Breast needle biopsy findings revealed breast metastasis from prostate cancer, that was not primary breast cancer. The patient underwent a bilateral mastectomy.

A 72-year-old man underwent a bilateral nerve-sparing radical retropubic prostatectomy (RRP) with pelvic lymph node dissection 11 years earlier. His prostate specific antigen (PSA) value at diagnosis was 61.024 ng/ml. Bone scans and computed tomographic (CT) scans showed no metastasis. Pathological findings and stage were adenocarcinoma, Gleason score 4+3, positive surgical margin, pT3b, and no lymph node metastasis. The postoperative PSA nadir was 0.218 ng/ml, and salvage radiotherapy (SRT, total 66 Gy) was performed six months after RRP. However, the PSA value continued to rise after SRT. Therefore, androgen deprivation therapy (ADT) was started 11 months after SRT. Nine years postoperatively, the PSA value showed a continuous rise despite ADT, and prostate cancer was considered to be castration-resistant. Although he was taking enzalutamide, his PSA value rose to 18. 271 ng/ml. Repeated bone scans and CT scans were negative. Eleven years after RRP, the fluoro-2-deoxy-D-glucosepositronemissiontomography (FDG-PET) revealed a nodule lesiondorsal to the left pubic bone. The patient underwent a resection of the lesion. Three months after the resection, his PSA level declined to 0.038 ng/ml, thus ADT was discontinued. Thirteen months after the resection, PSA re-elevation was absent, and follow-up without ADT is ongoing.

Radical prostatectomy is one of the major treatment options for patients with localized prostate cancer, and biochemical recurrence (BCR) after surgery is regarded as one of the representative indicators of the oncological outcome. The positive surgical margin (PSM) of the surgical specimen is considered to be one of the risk factors for BCR and its length (LPSM) was reported to be positively correlated with the risk for BCR. We retrospectively investigated the relationship between BCR and LPSM in 115 patients who underwent radical retropubic prostatectomy or laparoscopic radical prostatectomy without neoadjuvant hormone therapy at Shimada Municipal Hospital between 2008 and 2016. We found that the patients with a LPSM of 3 mm or longer had a higher risk for BCR than those with a LPSM shorter than 3 mm (HR 10.98, 95% confidence interval : 3.09-39.06, p <0.001), and patients with pT3 disease with a LPSM of 3 mm or longer had a higher risk for early BCR. Therefore, the LPSM may be a useful parameter to predict BCR after radical prostatectomy.

This case report documents seminal vesicle cystadenoma with concurrent prostate cancer in a 49-yearold man evaluated at follow-up for a high prostate-specific antigen level (12 ng/ml). Transrectal ultrasound-guided prostate biopsy was performed for adenocarcinoma of the prostate (Gleason score 3+4= 7). Staging computed tomography showed a 6.6×5.5×5.0 cm cystic tumorof the seminal vesicle. A possible diagnosis of primary malignant tumor of the seminal vesicle with concurrent organ-confined prostate cancer was considered. However, seminal vesicle tumor biopsy was not performed because the patient underwent open radical prostatectomy with the resection of the seminal vesicle tumor. Histopathologic examination of the seminal vesicle and the prostate revealed cystadenoma (Gleason score 4+3=7) and adenocarcinoma (stage pT2cN0). Neither recurrence of the cystadenoma nor biochemical recurrence of the prostate cancer was observed 5 years and 6 months after the surgery.

A 71-year-old man with gross hematuria and urinary retention showed a 7×8 cm polycystic mass compressing the prostate on the right ventral side on pelvic magnetic resonance imaging (MRI). The prostate specific antigen (PSA) level was 6.47 ng/ml. Prostate biopsy histopathology was consistent with prostate ductal carcinoma. Considering the difficulty of surgical therapy, endocrine therapy was undertaken prior to surgery for seven months. Almost all of the cyst disappeared ; robot-assisted laparoscopic radical prostatectomy was then successfully performed. Prostate ductal carcinoma is a relatively rare pathology for which radical prostatectomy plays an important role if the disease is localized. However, when ductal carcinoma involves large cysts, surgical treatment may be difficult. This report discusses the usefulness of neoadjuvant endocrine therapy to reduce the size of the cystic lesions.

A 68-year-old man was diagnosed with prostate cancer (initial serum prostate specific antigen [PSA] 389 ng/ml, stage cT4N1M1c, Gleason score 5+4), and androgen deprivation therapy was initiated. Despite the low serum PSA level, he developed postrenal acute kidney failure 4 years later, with progression of prostate cancer and liver and lung metastases. Serum levels of neuron-specific enolase and pro-gastrinreleasing peptide (tumor markers) were elevated. He underwent re-biopsy of the prostate, and histopathological examination revealed small cell carcinoma. He was initially treated with carboplatin and etoposide therapy. Liver metastases showed partial remission, and serum tumor marker levels were temporarily reduced. However, disease progression was observed after 4 chemotherapy cycles, and he was then treated with an 8-cycle course of amrubicin. Metastases showed shrinkage, and serum tumor marker levels were reduced after 2 chemotherapy cycles. Tumor enlargement recurred after 8 cycles, and the patient is being treated with palliative therapy. Amrubicin therapy may be effective in the treatment of small cell carcinoma of the prostate.

A 73-year-old Japanese man visited the urology clinic with the chief complaint of gross hematuria in June 2015. His prostate specific antigen (PSA) level was 146.7 ng/ml and he was diagnosed with prostate adenocarcinoma with a Gleason Score of 5+4. With bone metastasis in the right femur (cT3aN0M1), he was treated by orchiectomy and bicalutamide. He had gross hematuria in October 2017 and a prostate tumor was detected by computed tomography (CT) and magnetic resonance imaging without increasing PSA levels. Prostate re-biopsy showed prostate neuroendocrine carcinoma and local radiation therapy (74 Gy) was performed. Follow-up CT revealed a left adrenal tumor with a positive positron emission tomographic scan in October 2018. Under the diagnosis of metastatic neuroendocrine carcinoma, chemotherapy using cisplatinum and etoposide was performed. The tumor shrunk after five courses of treatment, followed by regrowth in April 2019. Radiation therapy (50 Gy) was added to the left adrenal tumor and it shrunk again. However, a left retroperitoneal tumor was detected in July 2019 and it was resected under laparoscopic surgery and diagnosed as metastatic neuroendocrine carcinoma. Since then, no recurrence has been observed.

Although postoperative recurrence or prostate cancer metastasis is usually accompanied by high prostate-specific antigen (PSA)levels, it may occur even if PSA level is within the normal range. Neuroendocrine differentiation(NED), which is one of such cases, causes rapid disease progression. A man in his 70s underwent total prostatectomy for prostate cancer with high PSA levels. Twenty-two months later, liver, lung, and bone metastases appeared even though the PSA levels were normal. The levels of both neuron-specific enolase and pro-gastrin-releasing peptide were elevated and the patient was clinically diagnosed with NED. Although systemic chemotherapy was administered, the outcome was progressive disease. Transcatheter arterial chemoembolization(TACE)was opted because liver metastases were one of the prognostic factors. Four types of chemotherapy drugs(cisplatin 20 mg, docetaxel 20 mg, 5-FU 250 mg, and bevacizumab 100 mg)were infused through the right and left hepatic arteries, followed by embolization with HepaSphereTM. The liver tumors were remarkably reduced in size and the levels of tumor markers were reduced in 5 sessions. This treatment would avoid the lethal liver trouble; however, the patient died 7 months after the first session of TACE.

A 64-year-old man was diagnosed with metastatic prostate cancer (cT3bN0M1b) and treated with combined androgen blockade. After two years and three months, he developed castration-resistant prostate cancer. Multiple lung metastases appeared after the administration of five courses of docetaxel and four courses of cabazitaxel therapy. Pulmonary metastases disappeared following rechallenge with docetaxel. Enzalutamide administration was initiated because docetaxel had to be discontinued due to adverse events. Although enzalutamide lowered the prostate specific antigen value, the patient staggered while walking and developed homonymous hemianopsia. Magnetic resonance imaging revealed a brain tumor. Although the brain tumor was considered to have metastasized from the prostate cancer, it was diagnosed as a primary central nervous system lymphoma using open-ended tumor biopsy. The brain tumor was eliminated with whole-brain irradiation. Thereafter, he has been treated with enzalutamide for 3 years without clinical progression of either disease.

An 87-year-old man was referred to our hospital with a high suspicion of prostate cancer, because of high prostate-specific antigen (PSA) levels (1,500 ng/ml). The laboratory results showed a PSA level of 1, 411 ng/ml, platelet count of 7.5×104/μl, and fibrinogen level of 68 mg/dl. D-dimer and fibronogen degradation product (FDP) levels were >240 and >480 μg/m respectively. Based on the above results, the patient was diagnosed as having prostate cancer with disseminated intravascular coagulopathy (DIC score=8 points). The patient was immediately hospitalized and heparin was administered to treat the DIC. On the 5th day, a prostate biopsy was performed and treatment was started with combined androgen blockade (CAB) therapy. The pathology report confirmed the diagnosis of prostate cancer with a Gleason Score of 4+3. Multiple bone and lymph node metastases were found on magnetic resonance imaging, computed tomography and, bone scans. Based on the results, the prostate cancer was stage cT3 N1 M1b. The medication was changed from heparin to nafamostat mesylate on the 12th day, due to the presence of DIC with the malignancy. After successful treatment with CAB, denosumab, and thrombomodulin alpha, the DIC levels improved (DIC score=3 points), and the PSA levels decreased to 51.5 ng/ml on the 47th day. DIC has been known to occur during treatment for prostate cancer ; however, cases of DIC with prostate cancer without any treatment are rare.

Peritoneal metastasis of prostate cancer is extremely rare, with only a few cases reported. A 78-yearold male patient was introduced to our hospital presenting with a prostate-specific antigen (PSA) level of 94.0 ng/ml at examination. He was diagnosed with poorly differentiated adenocarcinoma of the prostate, with a Gleasonscore of 9 (5＋4) at cT3bN0M0. Intensity-modulated radiation therapy was performed after 6 months of combined-androgen blockade (CAB) therapy. Twenty-one months later, several lymph node metastases were observed. With the resumptionof CAB therapy, PSA levels dropped and the multiple lymph node metastasis disappeared ; however, peritoneal metastasis was observed after 43 months. We performed a laparoscopic biopsy and our diagnosis after pathological evaluation was metastasis of the prostate cancer. He was treated with Enzalutamide.

A 79 year-old-man visited our hospital with right back pain. Computed tomography suggested external iliac and para-aortic lymphadenopathy. Serum prostate specific antigen (PSA) increased to 335 ng/ml and prostate cancer was highly suspected. We performed transperineal prostate biopsies two times, but could not detect prostate carcinoma cells. Multiparametric magnetic resonance imaging (MRI) indicated no suspicious malignant lesions in the prostate. Laparoscopic biopsy of the right obturator lymph nodes was performed and histological examination, including immunohistochemical staining with PSA, confirmed lymphnode metastasis from prostate cancer. After endocrine therapy was started, serum PSA levels declined and lymph nodes shrunk. In cases of negative prostate biopsies despite high serum PSA levels, aggressive indication for biopsy of metastatic lesion and histological inspection is highly recommended.

Case 1 : A 65-year-old man visited withfrequent urination and dysuria. Pyuria and bacteriuria were observed and prostate specific antigen (PSA) was elevated to 5.69 ng/ml. Prostate cancer and urinary tract infection were suspected. A antibiotics were administered and prostate magnetic resonance imaging (MRI) was performed. Massive prostate cancer was strongly suspected from the MRI findings and prostate needle biopsy was performed. The pathological examination revealed nonspecific granulomatous prostatitis. Case 2 : A 69-year-old man visited withfrequent urination. Urinalysis was normal and PSA was elevated to 4.52 ng/ml. Diffuse prostate cancer was suspected from the MRI findings and prostate needle biopsy was performed. Pathological findings were similar to those in case 1. Case 3 : A 61-year-old man presented withno urinary symptoms. Urinalysis was normal and PSA was elevated to 11.64 ng/ml. Medical history was renal pelvic cancer and bladder cancer. He had undergone a transurethral resection of the bladder tumor (TURBT) and intravesical Bacillus Calmette-Guérin (BCG) immunotherapy. Prostate cancer was suspected from the MRI findings and prostate needle biopsy was performed. Pathological findings were granulomatous prostatitis. In these three cases, the structure of these prostate capsules was preserved although extensive prostate cancer was suspected from the findings of MRI T2-weighted and diffusion weighted images. Although histopathologic examination is mandatory for differential diagnosis between granulomatous prostatitis and diffuse prostate cancer, prostate MRI may help to distinguish these diseases.

We report a 60-year-old man with prostate cancer diagnosed during androgen replacement therapy (ART) for late onset hypogonadism after surgery for pituitary adenoma. He was refered to the department of urology since prostate specific antigen values were elevated after 6 months of ART. After the diagnosis of prostate cancer, ART was discontinued, and robot-asssited laparoscopic radical prostatectomy with pelvic lymphadenoctomy was performed. Pathological examination revealed Gleason score 4 + 5 prostate adenocarcinoma with seminal vesicle invasion and lymph node metastasis(pT3bN1). He has stayed biochemically and radiologically disease-free 33 months postoperatively.

A 69-year-old man who had a history of several nasal hemorrhages and transfusions presented with hereditary hemorrhagic telangiectasia. He was referred to the previous hospital due to the elevation of prostate specific antigen (PSA) to 17.2 ng/ml, and was diagnosed with prostate cancer (cT3aN0M0, Gleason 4 + 5). He was referred to our hospital for the treatment of prostate cancer. Contrast lung computed tomography and brain magnetic resonance imaging did not show arteriovenous fistula in either the lung or brain. Upper gastrointestinal endoscopy showed capillary dilatations in the gastric mucosa. Robot-assisted laparoscopic prostatectomy with Trendelenburg position under general anesthesia was performed. Tracheal intubation was made using bronchofiberscopy. A gastric tube was not inserted. Intra- and postoperative course was uneventful, and there has been no elevation of PSA during the eight months followed.

The predictive factors for biochemical recurrence (BCR) were investigated in patients with positive surgical margin of the extirpated prostate by radical retropubic prostatectomy (RRP). The records of 365 patients who underwent RRP in our hospital between January 2002 and December 2014 were retrospectively analyzed. Patients who had received additional therapy before or after RRP, who had not been followed up for more than a year after surgery, and who had pN1 lesions were excluded from the study. Positive surgical margin was observed in 112 cases. Prostate specific antigen (PSA) before surgery ≥20 ng/ml, biopsy positive core ratio ≥40%, Gleason score of the surgical specimen ≥8, and postoperative PSA nadir ≥0.01 ng/ml were identified as significant predictors of BCR.

An 84-year-old man was referred to our hospital with swollen right cervical lymph nodes. Computed tomography showed right supraclavicular and mediastinal lymph node enlargement, and fluorodeoxyglucose positronemissiontomography showed multiple areas of abnormally increased radioactivity inthe right supraclavicular and mediastinal lymph nodes, right ninth rib, and left fifth and seventh ribs. Biopsy of the right supraclavicular lymph node revealed metastatic adenocarcinoma with partial immunohistochemical staining for prostate specific antigen (PSA). Serum PSA levels were not elevated (2.01 ng/ml). An 8-core transrectal prostatic biopsy was negative. Thus, we could not determine the primary site of the adenocarcinoma. The patient was diagnosed with carcinoma of an unknown primary site and followed without chemotherapy. Four years later, he was referred to our hospital due to right hydronephrosis. Serum PSA level was 31. 1 ng/ml. The tumor was not palpable by rectal examination. A 12-core transrectal prostatic biopsy revealed a poorly differentiated adenocarcinoma. Computed tomography revealed metastases in the left axilla, para-aortic, and pelvic lymph nodes as well as in the lung. We diagnosed the patient with prostate cancer, and combined androgen blockade (CAB) was administered. Metastases in the lymph nodes, lung, and bone were reduced on imaging after 1 month of therapy. Therefore, a definitive diagnosis of prostate cancer T1cN1M1c was made. Dutasteride had been administered as a benign prostate hyperplasia treatment 2 years before his first visit, which may have made the definitive diagnosis of prostate cancer difficult. In contrast, dutasteride may have delayed the progressionof prostate cancer inthis patient.

(Objective) The prostate cancer detection rates on initial transrectal ultrasound guided prostate biopsies were investigated and the clinicopathological features of prostate cancer patients were examined. (Methods) A retrospective review was performed. From 2003 to 2015, 2,246 patients received initial prostate biopsy in Tochigi Cancer Center. Prostate cancer detection rates and clinicopathological features of the prostate cancer patients in relation to prostate-specific antigen levels were evaluated. (Results) Of the biopsies, 1,294 cases (57.6%) were diagnosed as prostate cancer. The prostate cancer detection rates were 27.8%, 39.8%, 53.6%, 67.4%, 88.4%, 100% in the groups with PSA levels 0.0-3.0, 3.1-4.0, 4.1-10.0, 10.1-20.0, 20.1-100.0, >100.0 ng/ml, respectively. Of all 1,294 cases in prostate cancer, patients rates with the low risk were 0%, 30%, 22%, 0%, 0%, 0% in the groups with PSA levels 0.0-3.0, 3.1-4.0, 4.1-10.0, 10.1-20.0, 20.1-100.0, >100.0 ng/ml, respectively. (Conclusions) From the results of the prostate cancer detection rates and the low risk rates, it seems difficult to determine diagnosis and treatment of prostate cancer only with PSA values.