Testosterone bounce predicts favorable prognoses for prostate cancer patients treated with degarelix.

BACKGROUND: To clarify the clinical roles of changes in testosterone (T) levels with a cut-off level of 20 ng/dL as predictive factors for prostate cancer patients treated with degarelix acetate. METHODS: A total of 120 prostate cancer patients who received hormone therapies with gonadotropin-releasing hormone antagonist degarelix acetate were retrospectively analyzed. The predictive values of nadir T levels, max T levels, T bounce, and other clinical factors were evaluated for overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS). T bounce was defined as satisfying both nadir serum T levels of <20 ng/dL and max serum T levels of ≥20 ng/dL during hormone therapies. RESULTS: In 120 prostate cancer patients, 16 (13%) patients did not achieve nadir T < 20 ng/dL, and 76 (63%) patients had max T ≥ 20 ng/dL. The median times to nadir T and max T are 108 and 312 days, respectively. T bounce was shown in 60 (50%) patients and is associated with favorable prognoses both for OS (p = 0.0019) and CSS (p = 0.0013) but not for PFS (p = 0.92). While in the subgroup analyses of the patients with the progression of the first-line hormone therapies, T bounce predicts favorable OS (p = 0.0015) and CSS (p = 0.0013) after biochemical recurrence. CONCLUSIONS: The present study revealed that T bounce with cut-off levels of 20 ng/dL is a promising biomarker that predicts OS and CSS for prostate cancer patients treated with degarelix acetate.

Metastatic castration resistant prostate cancer patients' experience with Radium-223 treatment in Japan.

Aim: We aimed to determine Japanese metastatic castration resistant prostate cancer (CRPC) patients' Ra-223 treatment experience. Patients & methods: Patients answered the Cancer Therapy Satisfaction Questionnaire (CTSQ domains: Satisfaction with Therapy [SWT], Expectations of Therapy [ET], Feelings about Side Effects [FSE]), the Memorial Anxiety Scale for Prostate Cancer (MAX-PC) and the FACT-Bone Pain (FACT-BP) Questionnaire at baseline, during (vists 3 and 5) and after treatment (end of observation; EOO). Results: Data from 72 patients were included. Baseline median CTSQ scores SWT: 66.1 (IQR19.7), ET: 75.0 (IQR45), and FSE 68.8 (IQR 34.4) were unchanged during vists 3 and 5, but the SWT (-3.57 [IQR17.9]) and ET (-5.0 [IQR30]) decreased while FSE was unchanged (0.0 [IQR31.25]) at EOO. The median MAX-PC (18.0 [IQR 49]) score was unchanged (0.0, IQR 6) while the median FACT BP (54.0 [IQR13]) score decreased by -1.0 (IQR 8) at EOO. Conclusion: Japanese metastatic castration resistant prostate cancer patients' experience is stable during Ra-223 treatment.

What is this study about? We wanted to know the treatment experience with Radium-223 (Ra-223) among Japanese prostate cancer patients. Ra-223 is a radioactive molecule used for the treatment of metastatic castration resistant prostate cancer. We asked patients to answer different questionnaires on treatment satisfaction, anxiety and quality of life before, during, and after treatment with Ra-223. What were the results? Based on the patients' answers to our questionnaires, treatment satisfaction, anxiety and quality of life remain stable while the patients undergo treatment with Ra-223, but in some aspects may decline after treatment. What do the results mean? The results mean that patients' experience during Ra-223 treatment is stable but patients should share any concerns they have about their treatment with their doctors.

Clinical practice guidelines for molecular tumor marker, 2nd edition review part 2.

In recent years, rapid advancement in gene/protein analysis technology has resulted in target molecule identification that may be useful in cancer treatment. Therefore, "Clinical Practice Guidelines for Molecular Tumor Marker, Second Edition" was published in Japan in September 2021. These guidelines were established to align the clinical usefulness of external diagnostic products with the evaluation criteria of the Pharmaceuticals and Medical Devices Agency. The guidelines were scoped for each tumor, and a clinical questionnaire was developed based on a serious clinical problem. This guideline was based on a careful review of the evidence obtained through a literature search, and recommendations were identified following the recommended grades of the Medical Information Network Distribution Services (Minds). Therefore, this guideline can be a tool for cancer treatment in clinical practice. We have already reported the review portion of "Clinical Practice Guidelines for Molecular Tumor Marker, Second Edition" as Part 1. Here, we present the English version of each part of the Clinical Practice Guidelines for Molecular Tumor Marker, Second Edition.

Detection of intraductal carcinoma in prostate cancer patients with small tumor volume.

OBJECTIVES: The purpose of this study was to investigate intraductal carcinoma of the prostate (intraductal carcinoma) and significant cancer (SC) in patients with small tumor volume (<0.5 cm3 ) in prostatectomy specimens. METHODS: Data from 639 patients undergoing radical prostatectomy between April 2006 and December 2017 at Chiba University Hospital and 2 affiliated institutions were retrospectively reviewed. Tumor volume in prostatectomy specimens was measured, and with a tumor volume of less than 0.5 cm3 , the presence of intraductal carcinoma and SC was examined. SC was defined as one that did not meet the definition of pathological insignificant cancer (organ-confined cancer, Grade Group 1, tumor volume < 0.5 cm3 ). The number of patients who met four active surveillance (AS) protocols was also examined. RESULTS: A total of 83 patients with tumor volume < 0.5 cm3 were identified in this study population (SC: 43 patients [52%], intraductal carcinoma: 5 patients [6%]). The median follow-up was 34.6 months (range: 18-57 months). Four (5%) developed biochemical recurrence. The number of positive biopsy cores ≥ 2 was an independent predictor of SC in patients with tumor volume < 0.5 cm3 (hazard ratio: 4.39; 95% confidence interval: 1.67-11.56; p = 0.003). In tumor volume < 0.5 cm3 , tumor volume was significantly correlated with the International Society of Urological Pathology Grade Group (1 vs. 4-5, p = 0.002) and the presence of intraductal carcinoma (p = 0.004). In intraductal carcinoma-positive cases, four of five patients (80%) had the predictor of SC, which was two or more positive biopsy cores. Of the four AS protocols, the criteria for Prostate Cancer Research International: Active Surveillance were met most frequently in 46 cases (55%) of tumor volume less than 0.5 cm3 if targeted biopsy by magnetic resonance imaging was available. CONCLUSION: The results of the present study suggest that intraductal carcinoma was present even in cases with small tumor volumes. Grade Group and intraductal carcinoma showed a positive correlation with tumor volume.

External validation of the Candiolo nomogram for high-risk prostate cancer patients treated with carbon ion radiotherapy plus androgen deprivation therapy: a retrospective cohort study.

The aim of this study was to reclassify high-risk prostate cancer patients treated with carbon-ion radiotherapy and androgen deprivation therapy using the Candiolo nomogram and evaluate usefulness to predict the following 10-year biochemical recurrence. Six hundred seventy-two high-risk prostate cancer patients were reclassified according to the Candiolo nomogram. The cumulative incidence curves for biochemical recurrence were compared by Gray's test. Furthermore, five predictors of the Candiolo nomogram in our patients were evaluated by Fine and Gray regression hazards model. The higher the Candiolo risk, the worse the biochemical recurrence, especially in high- and very high-risk patients. Out of five predictors, age ≥70 years, cT3 stage, biopsy Gleason score ≥9 or the percentage of positive biopsy cores ≥50% had significant impacts on 10-year biochemical recurrence in our patients. The Candiolo nomogram can reclassify our high-risk prostate cancer patients treated with carbon-ion radiotherapy and androgen deprivation therapy and evaluate the biochemical recurrence preciously.

Carbon-ion radiotherapy for urological cancers.

Carbon-ions are charged particles with a high linear energy transfer, and therefore, they make a better dose distribution with greater biological effects on the tumors compared with photons and protons. Since prostate cancer, renal cell carcinoma, and retroperitoneal sarcomas such as liposarcoma and leiomyosarcoma are known to be radioresistant tumors, carbon-ion radiotherapy, which provides the advantageous radiobiological properties such as an increasing relative biological effectiveness toward the Bragg peak, a reduced oxygen enhancement ratio, and a reduced dependence on fractionation and cell-cycle stage, has been tested for these urological tumors at the National Institute for Radiological Sciences since 1994. To promote carbon-ion radiotherapy as a standard cancer therapy, the Japan Carbon-ion Radiation Oncology Study Group was established in 2015 to create a registry of all treated patients and conduct multi-institutional prospective studies in cooperation with all the Japanese institutes. Based on accumulating evidence of the efficacy and feasibility of carbon-ion therapy for prostate cancer and retroperitoneal sarcoma, it is now covered by the Japanese health insurance system. On the other hand, carbon-ion radiotherapy for renal cell cancer is not still covered by the insurance system, although the two previous studies showed the efficacy. In this review, we introduce the characteristics, clinical outcomes, and perspectives of carbon-ion radiotherapy and our efforts to disseminate the use of this new technology worldwide.

Comparison of the medical costs between active surveillance and other treatments for early prostate cancer in Japan using data from the PRIAS-JAPAN study.

OBJECTIVES: To compare the medical costs of active surveillance with those of robot-assisted laparoscopic prostatectomy, brachytherapy, intensity-modulated radiation therapy, and hormone therapy for low-risk prostate cancer. METHODS: The costs of protocol biopsies performed in the first year of surveillance (between January 2010 and June 2020) and those of brachytherapy and radiation therapy performed between May 2019 and June 2020 at the Kagawa University Hospital were analyzed. Hormone therapy costs were assumed to be the costs of luteinizing hormone-releasing hormone analogs for over 5 years. Active surveillance-eligible patients were defined based on the following: age <74 years, ≤T2, Gleason score ≤6, prostate-specific antigen level ≤10 ng/ml, and 1-2 positive cores. We estimated the total number of active surveillance-eligible patients in Japan based on the Japan Study Group of Prostate Cancer (J-CAP) study and the 2017 cancer statistical data. We then calculated the 5-year treatment costs of active surveillance-eligible patients using the J-CAP and PRIAS-JAPAN study data. RESULTS: In 2017, number of active surveillance-eligible patients in Japan was estimated to be 2808. The 5-year total costs of surveillance, prostatectomy, brachytherapy, radiation therapy, and hormone therapy were 1.65, 14.0, 4.61, 4.04, and 5.87 million United States dollar (USD), respectively. If 50% and 100% of the patients in each treatment group had opted for active surveillance as the initial treatment, the total treatment cost would have been reduced by USD 6.89 million (JPY 889 million) and USD 13.8 million (JPY 1.78 billion), respectively. CONCLUSION: Expanding active surveillance to eligible patients with prostate cancer helps save medical costs.

A qualitative research study in Japan investigating patients' experience with metastatic castration-resistant prostate cancer: from diagnosis to decision for Ra-223 treatment.

Aim: This qualitative study aimed to reveal symptoms and impacts among bone metastatic castration-resistant prostate cancer (or mCRPC) Japanese patients, prior to Radium-223 (Ra-223) treatment. Materials & Methods: Twenty-three mCRPC patients designated to receive Ra-223 and three treating physicians (Ra-223 prescribers) in Japan, were interviewed. All interview data were assessed for concept frequency, themes and saturation. Results: Forty-five percent of the patients (mean age: 75.8 years) were symptomatic at the time of enrollment. Interviews with all patients revealed 47 mCRPC symptoms, including back pain and bone-specific pain, and 45 life impacts, including worry about disease progression and the impact on daily, physical activities. Conclusion: The symptoms and impacts of living with mCRPC and the associated burden of bone metastasis and skeletal-related symptoms are varied and are important considerations for treatment.

Lay abstract Aim: This study looked at symptoms and impacts among patients with a type of prostate cancer called metastatic castration-resistant prostate cancer. This cancer has spread to other parts of the body including patients' bones. Patients' prostate-specific antigen levels continue to rise despite surgical or medical treatment and their doctors decided the next best treatment is Radium-223 (Ra-223), a radiopharmaceutical therapy. Materials & methods: Twenty-three metastatic castration-resistant prostate cancer patients designated to receive Ra-223 and three treating physicians (Ra-223 prescribers) in Japan, were interviewed. All interview data were assessed for the number of times some words or themes are mentioned by the patients. Results: Ten of the 23 patients (average age of 76 years) had symptoms when the study started. Interviewed patients talked about symptoms including back pain and pain in their bones, and how their cancer caused them to worry about their physical activities and disease progression. Conclusion: The symptoms impact on patients' daily living and the burden of bone metastasis and bone-related symptoms are varied and are important considerations for treatment.

Prognostic factors influencing overall survival in de novo oligometastatic prostate cancer patients.

BACKGROUND: Oligometastatic cancer has been suggested as an intermediate state between localized disease and wide-ranging metastases. The clinical significance of local treatment in oligometastatic prostate cancer (PCa) has been a recent topic of interest. However, standard definitions of oligometastasis are lacking. Here we studied risk factors among Japanese de novo oligometastatic patients with PCa. METHODS: We retrospectively assessed clinical data from 264 patients, including locally advanced (T3 or T4N0M0) cancer, lymph-node-positive cancer (Tany N1M0), and cancer with ≤10 bone metastases. All patients received androgen deprivation therapy only. The number of bone metastases and clinical factors were evaluated in association with overall survival (OS) and progression-free survival (PFS). The Mann-Whitney U test, Cox proportional hazard models, and Kaplan-Meier methods were used as statistical analyses. RESULTS: Median age, PSA at baseline and OS were 74 years, 55.2 ng/mL, and 129.0 months, respectively. The cutoff for the number of bone metastases having the greatest impact on OS was ≥3 (hazard ratio [HR]: 2.67; P = .0001). In multivariate analysis, non-regional lymph node (LN) metastases (HR: 2.15; P = .0222), ISUP grade group (GG) 5 (HR: 2.04; P = .0186) and ≥3 bone metastases (HR: 1.82; P = .0390) were independent predictors of OS. In risk classification based on these factors, OS and PFS were significantly classifiable into poor (2-3 factors), intermediate (1 factor), and good (no factors) risk groups (P < .0001). CONCLUSION: Not only the number of bone metastases, but also non-regional LN metastases predict OS in patients with de novo oligometastatic PCa.

Higher serum testosterone levels predict poor prognosis in castration-resistant prostate cancer patients treated with docetaxel.

BACKGROUND: The role of testosterone as a prognostic factor for castration-resistant prostate cancer treated with docetaxel in Japan was investigated. METHODS: A total of 164 patients with castration-resistant prostate cancer who received docetaxel treatment at Chiba University Hospital and an affiliated hospital were retrospectively analyzed. Testosterone and other clinical factors at the start of docetaxel treatment were evaluated with respect to overall survival and progression-free survival. RESULTS: Of the 164 patients, 69 had high-volume tumors. The median prostatic-specific antigen was 27.0 ng/mL. The median testosterone was 13.0 ng/dL. The rates of bone and visceral metastases were 80.1% and 8.8%, respectively. For progression-free survival, testosterone ≥13 ng/dL was an independent prognostic factor only on univariate analysis (hazard ratio, 1.81; P = .0108). For overall survival, testosterone ≥ 1.3 ng/dL (hazard ratio, 3.37; P < .0001), high volume (hazard ratio, 3.06; P = .0009), and prostate-specific antigen ≥ 27.0 ng/mL (hazard ratio, 2.75; P = .0013) were independent prognostic factors on multivariate analysis. When assessing related clinical factors, higher serum testosterone was associated with visceral metastasis, high volume, and prostate-specific antigen. Based on three prognostic factors (testosterone, high volume, prostate-specific antigen), a risk classification was developed. The high-risk group (3 risk factors) showed a significantly shorter overall survival compared to the moderate-risk (2 risk factors) and low-risk (0-1 risk factor) groups (P < .0001). CONCLUSIONS: The present study identified higher serum testosterone (≥13 ng/dL) as a significant prognostic factor in castration-resistant prostate cancer patients treated with docetaxel therapy.

Diagnostic Impacts of Clinical Laboratory Based p2PSA Indexes on any Grade, Gleason Grade Group 2 or Greater, or 3 or Greater Prostate Cancer and Prostate Specific Antigen below 10 ng/ml.

PURPOSE: The PROPHET (Prostate Cancer: Prostate Health Index Trial) is a prospective study to clarify the diagnostic impact of laboratory based and prostate volume adjusted p2PSA ([-2] proenzyme prostate specific antigen) related indexes on prostate cancer and clinically significant prostate cancer with prostate specific antigen less than 10 ng/ml. MATERIALS AND METHODS: Between April 2015 and March 2017, 421 men 50 to 79 years old in the prostate specific antigen range above age specific cutoffs and below 10 ng/ml were registered in the PROPHET. We investigated the diagnostic impacts of various clinical laboratory based free prostate specific antigen related and p2PSA related indexes on any grade and high Gleason grade group prostate cancer. RESULTS: Of the 363 eligible participants 179, 141 and 80 were diagnosed with any grade, and Gleason Grade Group 2-5 and 3-5 prostate cancer, respectively. The AUC-ROCs distinguishing nonprostate cancer vs prostate cancer, nonprostate cancer plus low Gleason Grade Group and low volume vs remaining prostate cancer with a higher Gleason Grade group or a higher volume on the PHI (Prostate Health Index) were significantly superior to the AUC-ROCs of prostate specific antigen and free-to-total prostate specific antigen. At 90% sensitivity in all investigated p2PSA related indexes the false-positive rate was superior to that of prostate specific antigen and free-to-total prostate specific antigen in any group comparison in terms of the Gleason Grade Group and positive biopsy cores. In 35% to 42% of men without prostate cancer and/or those with less aggressive prostate cancer the PHI would avoid unnecessary biopsy. CONCLUSIONS: Laboratory based p2PSA related indexes were significantly superior for detecting clinically significant prostate cancer compared to free-to-total prostate specific antigen. The indexes those would avoid up to 42% of prostate biopsies in men without aggressive cancer while maintaining 90% sensitivity.

Not all prostate cancer is the same - patient perceptions: an Asia-Pacific region study.

OBJECTIVE: To explore the perceptions of patients living with different stages of prostate cancer across the Asia-Pacific (APAC) region, as while extensive quantitative research has been undertaken into outcomes of treatments for prostate cancer, little in the way of qualitative research has been performed looking at subjective perceptions of patients in regard to their perceived deficits in the treatment of this condition and such research is particularly lacking in reference to the APAC region. PATIENTS AND METHODS: Initial 45-min qualitative research interrogatory interviews were conducted with 12 patients from Australia, China and Japan to identify themes that were significant to patients in the management of prostate cancer. Thereafter, 150 patients with different stages of prostate cancer underwent 30-min online (Australia) or computer-assisted/personal interviews categorised on the five key themes identified, in order to more fully clarify the nature of patient perceptions of how their prostate cancer had been treated and the issues they felt could be more fully addressed in order to improve the management of this condition. RESULTS: Interviews indicated common challenges and unmet needs among patients, including: (i) patients' feelings and emotional state change during their disease journey, (ii) patients lack of knowledge about prostate cancer and disease progression prior to diagnosis, (iii) patients felt shared decision-making was uncommon, (iv) patients have misperceptions about surgery, and (v) patients have unmet needs for greater information and support to manage their condition. CONCLUSIONS: These patient perceptions of unmet needs in prostate cancer management stand in contrast to patient awareness of other common diseases such as heart failure and diabetes. Such unmet needs vary across disease stages and between different nationalities. Patients with prostate cancer in the APAC region appear to have gaps in knowledge about their disease and wish for greater information, support and public awareness about prostate cancer.

Docetaxel-based chemotherapy combined with dexamethasone 1 mg daily oral administration for castration-resistant prostate cancer: Long-term outcomes.

OBJECTIVES: To report long-term outcome survival analysis of docetaxel-based chemotherapy combined with dexamethasone in castration-resistant prostate cancer patients (Japan-Multinational Trial Organization Pca10-01 trial). METHODS: The Japan-Multinational Trial Organization Pca10-01 phase II trial was a multicenter, prospective single-arm, phase II trial both in non-metastatic and metastatic castration-resistant prostate cancer patients that was organized by The Japan-Multinational Trial Organization. Patients received 75 mg/m2 of docetaxel (every 21 days) and 0.5 mg of dexamethasone orally twice a day continuing throughout the treatment period. The primary end-point of this additional analysis was overall survival. Secondary end-points were progression-free survival and safety. RESULTS: Between January 2011 and February 2014, a total of 76 chemotherapy-naïve castration-resistant prostate cancer patients were enrolled. The median overall survival time was 42.5 months. The median overall survival time of M1 patients was 40.5 months (M0: not reached). The median progression-free survival time was 13.2 months (M0: 15.7 months and M1: 12.3 months). The multivariate analysis predicting overall survival of M1 patients showed that time to castration-resistant prostate cancer (≥20 months) was an independent parameter (hazard ratio 0.39, P = 0.023). Regarding the safety analysis, 36 out of 74 patients (48.6%) suffered from any grade of adverse events after the protocol treatment, and 18 patients (24.3%) had grade ≥3 adverse events. CONCLUSIONS: Docetaxel-based chemotherapy combined with dexamethasone can achieve excellent survival efficacy not only in M0 castration-resistant prostate cancer patients, but also in M1 castration-resistant prostate cancer patients.

Chronological changes in epidemiological characteristics of lower urinary tract urolithiasis in Japan.

OBJECTIVES: To determine changes and trends in the annual incidence and epidemiological aspects of lower urinary tract stones in Japan. METHODS: Data about patients who had been diagnosed by urologists in 2015 with first and recurrent lower urinary tract stones were collected from 301 hospitals approved by the Japanese Board of Urology. The estimated annual incidence according to sex, age and stone composition was compared with previous nationwide surveys between 1965 and 2005. RESULTS: The incidence of lower urinary tract stones in Japan has steadily increased from 4.7 per 100 000 in 1965 to 12.0 per 100 000 in 2015. However, the age standardized annual incidence of lower urinary tract stones has remained relatively stable over the same period at 5.5 per 100 000 and 6.0 per 100 000 in 1965 and 2015, respectively. The increase in incidence was most evident among individuals aged ≥80 years. The incidence of calcium oxalate stones has steadily increased among males and females, whereas that of infection-related stones has significantly decreased from 26.2% to 14.3% among men over the past 50 years. CONCLUSIONS: Nationwide surveys suggest a steady increase in the incidence of lower urinary tract stones over a 50-year period in Japan. This trend might reflect changes in the aging population and improved Japanese medical standards.

Updated long-term outcomes after carbon-ion radiotherapy for primary renal cell carcinoma.

Long-term oncological outcomes for primary renal cell carcinoma (RCC) treated with carbon-ion radiotherapy (CIRT) are poorly understood. Patients with primary RCC were treated with 12 or 16-fraction CIRT at The Hospital of the National Institute of Radiological Sciences outside of clinical trials. Outcome data were pooled and retrospectively analyzed for toxicity, local control, and disease-free, cancer-specific, and overall survival. From 1997 to 2014, 19 RCC patients (11 with T1aN0M0, 4 with T1bN0M0, and 4 with inoperable advanced stage [T4N0M0, T3aN1M0, and T1aN0M1]) were treated with CIRT and followed up for a median of 6.6 (range, 0.7-16.5) years; 9 of these patients were inoperable because of comorbidities or advanced-stage disease. Diagnoses were confirmed by imaging in 11 patients and by biopsy in the remaining 8. In 4 of 5 patients with definitive renal comorbidities, including diabetic nephropathy, sclerotic kidney or solitary kidney pre-CIRT progressed to grade 4 chronic kidney disease (CKD). In contrast, the remaining 14 patients without definitive renal comorbidities did not progress to grade 3 or higher CKD. Furthermore, although 1 case of grade 4 dermatitis was observed, there were no other grade 3 or higher non-renal adverse events. Local control rate, and disease-free, cancer-specific, and overall survival rates at 5 years of all 19 patients were 94.1%, 68.9%, 100%, and 89.2%, respectively. This updated retrospective analysis based on long-term follow-up data suggests that CIRT is a safe treatment for primary RCC patients without definitive renal comorbidities pre-CIRT, and yield favorable treatment outcomes, even in inoperable cases.

Significance of prostate-specific antigen kinetics after three-dimensional conformal radiotherapy with androgen deprivation therapy in patients with localized prostate cancer.

BACKGROUND: To evaluate the relationship between biochemical recurrence and post-radiation prostate-specific antigen (PSA) kinetics in patients with localized prostate cancer treated by radiotherapy with various durations of androgen deprivation therapy (ADT). METHODS: We reviewed our single-institution, retrospectively maintained data of 144 patients with T1c-T3N0M0 prostate cancer who underwent three-dimensional conformal radiotherapy (3D-CRT) between December 2005 and December 2015 and 113 patients were fulfilled the inclusion criteria. In this cohort, 3D-CRT was delivered with a dose in the range from 70.0 to 72.0 Gy with ADT. All patients received ADT as concurrent regimens. Biochemical recurrence was defined on the basis of the following: "PSA nadir + 2.0 ng/ml or the clinical judgement of attending physicians". Kaplan-Meier, log-rank, and Cox regression analyses were carried out. RESULTS: The median follow-up period was 54.0 months. The median duration of ADT was 17 months (interquartile range, 10-24 months). There was a trend toward statistical significant correlation between post-radiation PSA decline rate of ≥ 90% and PSA recurrence (p = 0.056). The same correlation could be observed in D'Amico high-risk patients (p = 0.036). However, it was not observed between PSA nadir and PSA recurrence (p = 0.40) in univariate analysis. Furthermore, multivariate analysis showed that post-radiation PSA decline rate of ≥ 90% was a significant predictor of biochemical recurrence in patients who received radiotherapy with various durations of ADT (p = 0.044). CONCLUSIONS: Post-radiation PSA decline rate of ≥ 90% was a prognostic factor for biochemical recurrence in localized prostate cancer patients received 3D-CRT with various durations of ADT.

Duration of androgen deprivation therapy and nadir of testosterone at 20 ng/dL predict testosterone recovery to supracastrate level in prostate cancer patients who received external beam radiotherapy.

OBJECTIVES: To determine the predictors of testosterone recovery after termination of androgen deprivation therapy in high/intermediate-risk prostate cancer patients receiving external beam radiation therapy with neoadjuvant and adjuvant androgen deprivation therapy. METHODS: A total of 82 patients who underwent external beam radiation therapy with androgen deprivation therapy for prostate cancer were retrospectively analyzed. Serum testosterone levels after androgen deprivation therapy terminations were studied. Cox proportional hazard models and the Kaplan-Meier method were used for statistical analysis. RESULTS: Median age, baseline testosterone, nadir testosterone and duration of androgen deprivation therapy were 73 years, 456 ng/dL, 16 ng/dL and 26 months, respectively. Androgen deprivation therapy duration of 33 months (hazard ratio 0.13; P = 0.0018), nadir testosterone of 20 ng/dL (hazard ratio 0.35; P = 0.0112) and testosterone >50 ng/dL at 6 months after androgen deprivation therapy termination (hazard ratio 0.21; P = 0.0075) were significantly associated with testosterone recovery to normal levels (200 ng/dL) on multivariate analysis. Androgen deprivation therapy duration of 33 months (hazard ratio 0.31; P = 0.0023) and nadir testosterone of 20 ng/dL (hazard ratio 0.38; P = 0.0012) were significantly associated with testosterone recovery to the supracastrate level (50 ng/dL) on multivariate analysis. After dividing patients into three risk groups, the rate of testosterone recovery to the normal level after 2 years of androgen deprivation therapy termination was 100% in the low-risk group versus 20.8% in the high-risk group (P < 0.0001); the rate of testosterone recovery to the supracastrate level was 100% in the low-risk group versus 51.5% in the high-risk group (P < 0.0001). CONCLUSIONS: Duration of androgen deprivation therapy and achievement of nadir testosterone 20 ng/dL both predict testosterone recovery to the supracastrate level in prostate cancer patients undergoing external beam radiation therapy with androgen deprivation therapy.

Chronological changes in the epidemiological characteristics of upper urinary tract urolithiasis in Japan.

OBJECTIVES: To assess epidemiological and chronological trends of upper urinary tract stones in Japan in 2015. METHODS: Patients with a first episode of upper urinary tract stones in 2015 were enrolled in this nationwide survey. The study included all hospitals approved by the Japanese Board of Urology, therefore covering most of the hospitals where urologists practice in Japan. The annual incidence and composition of urolithiasis were evaluated by age and sex. These results were compared with the previous results of the nationwide surveys from 1965 to 2005 to analyze temporal trends. RESULTS: The estimated annual incidence of a first-episode upper urinary tract stone in 2015 was 137.9 (191.9 in men and 86.9 in women) per 100 000. The estimated age-standardized first-episode upper urinary tract stone incidence in 2015 was 107.8 (150.6 in men and 63.3 in women) per 100 000, which did not represent a significant increase since 2005. An equivalent incidence was observed in patients aged >50 years, whereas a reduced incidence was observed in patients aged <50 years in both sexes. The proportion of patients who received percutaneous nephrolithotomy and/or ureteroscopy increased by approximately fivefold in the past 10 years. CONCLUSIONS: The steady increase in the annual incidence of upper urinary tract stones since 1955 leveled off in 2015. The current results show novel trends in the incidence and treatment modalities in the nationwide surveys of urolithiasis in Japan.

Cancer-specific mortality of high-risk prostate cancer after carbon-ion radiotherapy plus long-term androgen deprivation therapy.

The treatment outcomes of patients with high-risk localized prostate cancer (PC) after carbon-ion radiotherapy (CIRT) combined with long-term androgen deprivation therapy (LTADT) were analyzed, and compared with those of other treatment modalities, focusing on PC-specific mortality (PCSM). A total of 1247 patients were enrolled in three phase II clinical trials of fixed-dose CIRT between 2000 and 2013. Excluding patients with T4 disease, 608 patients with high-risk or very-high-risk PC, according to the National Comprehensive Cancer Network classification system, who received CIRT with LTADT were evaluated. The median follow-up time was 88.4 months, and the 5-/10-year PCSM rates were 1.5%/4.3%, respectively. T3b disease, Gleason score of 9-10 and percentage of positive biopsy cores >75% were associated with significantly higher PCSM on univariate and multivariate analyses. The 10-year PCSM rates of patients having all three (n = 16), two (n = 74) or one of these risk factors (n = 217) were 27.1, 11.6 and 5.7%, respectively. Of the 301 patients with none of these factors, only 1 PCSM occurred over the 10-year follow-up (10-year PCSM rate, 0.3%), and significant differences were observed among the four stratified groups (P <0.001). CIRT combined with LTADT yielded relatively favorable treatment outcomes in patients with high-risk PC and very favorable results in patients without any of the three abovementioned factors for PCSM. Because a significant difference in PCSM among the high-risk PC patient groups was observed, new categorization and treatment intensity adjustment may be required for high-risk PC patients treated with CIRT.

The efficacy and safety of docetaxel-based chemotherapy combined with dexamethasone 1 mg daily oral administration: JMTO Pca 10-01 phase II trial.

OBJECTIVES: Previously, one randomized control trial (TAX327) revealed the efficacy of docetaxel-based chemotherapy combined with prednisone. On the other hand, several studies showed a high prostate specific antigen (PSA) response with low-dose dexamethasone in castration-resistant prostate cancer (CRPC) patients. The objective of this study was to evaluate the efficacy and safety of docetaxel-based chemotherapy combined with dexamethasone in CRPC patients. MATERIALS AND METHODS: This study was a single-arm multi-institutional phase II trial. Patients received 75 mg/m2 of docetaxel, and 0.5 mg of dexamethasone orally twice a day continuing throughout the treatment period. Treatment was planned for 10 cycles, and continued for at least four cycles depending on the observation of PSA flare. The primary endpoint was PSA response defined as a reduction from baseline of at least 50% that continued for at least 3 weeks. Secondary endpoints were safety, PSA flare, time to PSA failure and adherence rate to protocol treatment (10 cycles). RESULTS: Between January 2011 and February 2014, a total of 76 chemotherapy-naïve CRPC patients were enrolled. Seventy-five patients received docetaxel-based chemotherapy combined with dexamethasone. The median age and PSA level at enrollment were 71 years (53-85) and 23.2 ng/mL (2.9-852), respectively. PSA response rate was 76.8% (90% confidence interval (CI): 66.9-84.9). Of all patients, 30 patients completed 10 cycles of chemotherapy (40%). The incidence rate of PSA flare was 10.7% (eight patients). The median time to PSA failure was 369 days (95% CI: 245-369). The most frequently observed adverse event was hematotoxicity (neutropenia of G2 or greater: 100%). CONCLUSIONS: The present study showed a significantly high PSA response compared with previous reports. Most patients tolerated the protocol treatment well, whereas hematotoxicity was often observed.