Upfront Androgen Receptor-Axis-Targeted Therapies in Men with De Novo High-Volume Metastatic Hormone-Sensitive Prostate Cancer.

PURPOSE: The extent of effectiveness of upfront androgen receptor-axis-targeted therapies (ARAT) versus total androgen blockade (TAB) in improving prostate cancer-specific survival (CSS) and progression-free survival (PFS) in a real-world sample of Japanese patients with high-volume mHSPC remains unclear. We, therefore, investigated the efficacy and safety of upfront ARAT versus bicalutamide for de novo high-volume mHSPC in Japanese patients. MATERIAL AND METHODS: This was a multicenter retrospective study that analyzed CSS, clinical PFS, and adverse events (AEs) in 170 patients with newly diagnosed high-volume mHSPC. Fifty-six patients were treated with upfront ARAT, and 114 of them were prescribed bicalutamide in addition to ADT between January 2018 and March 2021. The primary and secondary endpoints were CSS and PFS, respectively. A 1:1 nearest neighbor propensity score matching (PSM) with a caliper of 0.2 was performed to match the ARAT group to TAB patients. RESULTS: During the follow-up for a median of 21.5 months, the median CSS was not reached and 37 months in the upfront ARAT and total androgen blockade (TAB) groups, respectively (log-rank test: P = 0.006) by propensity score matching (PSM). Moreover, while the PFS of ARAT was unreached, the median PFS of TAB was 9 months (log-rank test: P < 0.001). Nine patients discontinued ARAT owing to grade ≥ 3 AEs; one patient who was treated with TAB had a grade 3 AE. CONCLUSION: Upfront ARAT significantly prolonged the CSS and PFS of patients with high-volume mHSPC better than TAB, although ARAT was associated with a higher rate of grade ≥ 3 AEs. Upfront ARAT can be more beneficial for patients with de novo high-volume mHSPC than TAB.

Treatment strategy for metastatic prostate cancer with extremely high PSA level: reconsidering the value of vintage therapy.

The prognostic significance of initial prostate-specific antigen (PSA) level for metastatic prostate cancer remains uncertain. We investigated the differences in prognosis and response to hormonal therapies of metastatic prostate cancer patients according to initial PSA levels. We analyzed 184 patients diagnosed with metastatic prostate cancer and divided them into three PSA level groups as follows: low (<100 ng ml-1), intermediate (100-999 ng ml-1), and high (≥1000 ng ml-1). All patients received androgen deprivation therapy (ADT) immediately. We investigated PSA progression-free survival (PFS) for first-line ADT and overall survival (OS) within each of the three groups. Furthermore, we analyzed response to antiandrogen withdrawal (AW) and alternative antiandrogen (AA) therapies after development of castration-resistant prostate cancer (CRPC). No significant differences in OS were observed among the three groups (P = 0.654). Patients with high PSA levels had significantly short PFS for first-line ADT (P = 0.037). Conversely, patients in the high PSA level group had significantly longer PFS when treated with AW than those in the low PSA level group (P = 0.047). Furthermore, patients with high PSA levels had significantly longer PFS when provided with AA therapy (P = 0.049). PSA responders to AW and AA therapies had significantly longer survival after CRPC development than nonresponders (P = 0.011 and P < 0.001, respectively). Thus, extremely high PSA level predicted favorable response to vintage sequential ADT and AW. The current data suggest a novel aspect of extremely high PSA value as a favorable prognostic marker after development of CRPC.

Significant prognostic difference between Grade Group 4 and 5 in the 2014 International Society of Urological Pathology Grading System for High Grade Prostate Cancer with Bone Metastasis.

BACKGROUND: To investigate prognostic difference between Gleason Score (GS) 8 and 9-10, as the 2014 International Society of Urological Pathology Gleason Grading Systems proposed, in patients with prostate cancer (PCa) with bone metastasis. MATERIALS AND METHODS: We retrospectively reviewed data on 106 patients with GS 8-10 between 2006 and 2016. All patients received androgen deprivation therapy immediately. We validated biochemical recurrence, PCa-specific survival, and overall survival, and analyzed the predictive value for overall survival. RESULTS: Patients with GS 9-10 had significantly lower PCa-specific survival (50.5% vs. 83.4%, P = 0.01) and overall survival (38.8% vs. 66.3%, P = 0.04) at 5 years than those with GS 8, while biochemical recurrence rate was not significantly different (P = 0.26). Furthermore, these significant differences between GS 8 and 9-10 were also observed among high-risk groups proposed in Japan Cancer of the Prostate Risk Assessment Stratification (prostate cancer-specific survival: P = 0.03, overall survival: P = 0.04, respectively). Pathological GS 9-10 was an independent prognostic factor for overall survival (hazard ratio = 1.97, P = 0.04) in multivariable cox proportional hazard regression analysis. Among patients with GS 9-10, albumin level was an only prognostic factor for overall survival (hazard ratio = 0.33, P < 0.01). CONCLUSION: Pathological GS 9-10 predicts significantly worse outcomes than GS 8 in Japanese PCa patients with bone metastasis. Our data indicated clinical significance of discriminating the 2014 International Society of Urological Pathology Gleason Grading Group 4 and 5 among high-risk PCa patients with bone metastasis.

Outcomes of patients older than 75 years with non-metastatic prostate cancer.

OBJECTIVE: Prostate cancer in elderly patients was formerly treated with androgen deprivation therapy. Since the latter of the 1990s new technologies were introduced into treatments, then strategies have varied. We aimed to observe the outcomes of elderly patients treated during transition period and compare each stage with others. METHODS: During 2008 and 2010, 255 patients with prostate cancer older than 75 years were sequentially treated. With exception of patients with bone and/or visceral metastasis, outcomes of 199 patients with localized and locally advanced stages were examined. Complete records were obtained by the end of 2015. RESULTS: In total, 122 (61%), 28 (14%), 37 (19%) and 12 (6%) of patients were in stages T1c-T2a, T2b-c, T3 and T4, respectively. Patients generally presented with abnormal screening or lower urinary tract symptom. Seventy-one percent of patients received androgen deprivation therapy as monotherapy and 22% of the radiation-treated patients added androgen deprivation therapy. Patients in stage T1c-T2a and T2b-c showed a favorable prognosis. Some cancer death appeared in patients with T3 and T4 during observation periods. Twenty-seven percent of patients died from prostate cancer-independent complications: pneumonia, heart disease, and brain vascular disease. Tendency is similar to that of Japanese elderly male population. No remarkable side effects from androgen deprivation therapy were noticed. CONCLUSION: Elderly patients with localized prostate cancer showed favorable prognosis by androgen deprivation therapy with/without radiation, thus efficacy of androgen deprivation therapy is suitable to elderly patients with applicable stages. Prognosis of patients with locally advanced stage is serious and remains to be improved.

Treatment of locally advanced prostate cancer (Stage T3).

OBJECTIVE: Formerly, locally advanced prostate cancer exhibited poorly prognosis. In the late 1990s, new surgical and radiation technologies were introduced in combination with androgen deprivation. To evaluate respective strategies, outcomes were examined. PATIENTS AND METHODS: Between 2001 and 2010, 224 patients with T3N0M0 (10.9% of all prostate cancer cases) were treated with prostatectomy, external beam radiation therapy with/without androgen deprivation or hormone alone. Complete records were obtained by the end of 2015. RESULTS: Operation group first started without adjuvant treatment and prostate-specific antigen (PSA) relapse occurred in 39% of cases. Radiation therapy group was alternatively divided into two subgroups, that received either monotherapy or combination with androgen deprivation, and PSA relapse rates were 65 and 16%, respectively. High rates of PSA relapse in both the operation and radiation therapy groups were observed in patients without adjuvant therapy, but after relapse androgen deprivation proceeded favorable outcomes. In the radiation subgroups, PSA relapse rates were different, but both subsequent survival rates were the same. This may be due to the effect of androgen deprivation after relapse, indicating effect of delayed therapy. PSA relapse rate in the hormone therapy group was 25% and after relapse, patients applied to treatment with other hormonal and anticancer drugs. Overall survival rates were 91, 88 and 67% in the operation, radiation therapy and hormone therapy groups, respectively. CONCLUSION: Aggressive treatment with short-term androgen deprivation for locally advanced prostate cancer could be beneficial and not harmful when suitable candidates are selected. Delayed androgen deprivation was effective for no adjuvant patients after PSA relapse.

Long-term outcomes of nonpalpable prostate cancer (T1c) patients treated with radical prostatectomy.

PURPOSE: Various strategies have been used to treat patients with nonpalpable prostate cancer (T1c). As one of the treatments for this stage, a radical prostatectomy was performed and the outcomes were evaluated. METHODS: Between 1993 and 2002, 117 patients with T1c received a radical prostatectomy and their follow-up were examined by the end of 2013. Patients were classified according to risk groups using prostate-specific antigen (PSA) and Gleasson score, and outcomes of respective groups were compared. RESULTS: Approximately 60% of patients were in low risk group, and the remaining patients were grouped into the intermediate or high risks in half. In 22% insignificant cancer was detected. Biochemical failure occurred in 14%. One patient exhibited bone metastasis, but no deaths from prostate cancer ware observed. The five and ten year overall survival rates were 92% and 75%, respectively, and the biochemical failure-free survival rates were 92% and 89%, respectively. No different outcomes were observed for the different risk groups in the overall and biochemical failure-free survival rates. T1c tumors contain a certain range of various stages of tumors, but most patients experienced favorable outcomes. CONCLUSION: Radical prostatectomy as monotherapy is one of the treatment option for T1c prostate cancer patients, who have a long life span and belong to intermediate or high risk groups.

Management of men with a suspicion of prostate cancer after negative initial prostate biopsy results.

INTRODUCTION: For men with elevated prostate-specific antigen (PSA), appropriate management after negative prostate biopsy remains controversial. After determining PSA kinetics, subsequent follow-up was considered. PATIENTS AND METHODS: A total of 115 cases with negative repeat biopsy were followed by evaluating PSA kinetics and ratio of percent free PSA (F/T) and by performing second repeat biopsy. RESULTS: Eighteen cancer cases were diagnosed. Shorter PSA doubling times and faster velocities were found in cancer cases compared with cases without cancer. We observed a clear decrease in F/T among cancer cases. CONCLUSIONS: To avoid unnecessary repeat biopsies, cases with a suspicion of cancer after negative biopsy can be divided into two groups: one that requires additional biopsies and one with an average change in PSA of <1 ng/ml/year and no change in F/T, which is recommended for surveillance as stable disease without biopsy over a specified time period.

[The initial division of left renal vein in left renal cancer with intracaval tumor thrombus: a case report].

A 30-year-old female was admitted to our hospital with a 3-month history of general fatigue and one month history of left flank mass. Computed tomography revealed a huge left renal tumor (20 × 13 × 10 cm) with intracaval tumor thrombus. The tumor thrombus extended into the right atrium. The left renal vein (lt-RV) was expanded 3.5 cm in diameter by the tumor thrombus. The tumor was surrounded by a tortuous dilated capsular vein. The strategic issue was how to ligate the left renal artery (lt-RA) behind the expanded lt-RV. We first divided the lt-RV occluded by the tumor thrombus using a Linear Cutter® and then divided the lt-RA before the dissection of the tumor to avoid excessive bleeding. Even transarterial embolization of lt-RA were to be performed,the tumor was too large to dissect without division of lt-RV and lt RA. After the left kidney was removed,the lower half of the tumor thrombus was excised,clamping the inferior vena cava,three right renal arteries,two right renal veins,and the lumber vein. Finally,we removed the upper half of the tumor thrombus extending to the right atrium through atriotomy and cavotomy under an extracorporeal cardiovascular bypass. Operation time was 9 h 22 m,and total blood loss was 1670 ml. Convalescence was uneventful except for abdominal lymphocele.

Outcome of patients with localized prostate cancer treated by radiotherapy after confirming the absence of lymph node invasion.

OBJECTIVE: Management of lymph nodes in radiotherapy for prostate cancer is an issue for curative intent. To find the influence of lymph nodes, patients with T1-T3 prostate cancer and surgically confirmed negative nodes were treated with radiotherapy. METHODS: After lymphadenectomy, 118 patients received photon beam radiotherapy with 66 Gy to the prostate. No adjuvant treatment was performed until biochemical failure. After failure, hormone therapy was administered. Follow-up period was 57 months (mean). RESULTS: Biochemical failure occurred in 47 patients. Few failures were observed in patients with low (24%) and intermediate risks (14%). In contrast, 64% of high-risk patients experienced failure, 97% of whom showed until 36 months. Most patients with failure responded well to hormone therapy. After 15 months (mean), a second biochemical failure occurred in 21% of patients who had the first failure, most of them were high risk. Factors involving failure were high initial and nadir prostate-specific antigen, advanced stage, short prostate-specific antigen-doubling time and duration between radiation and first failure. Failure showed an insufficient reduction in prostate-specific antigen after radiotherapy. Factor for second failure was prostate-specific antigen-doubling time at first failure. CONCLUSIONS: Half of high-risk patients experienced biochemical failure, indicating one of the causes involves factors other than lymph nodes. Low-, intermediate- and the other half of high-risk patients did not need to take immediate hormone therapy after radiotherapy. After failure, delayed hormone therapy was effective. Prostate-specific antigen parameters were predictive factors for further outcome.

Outcome of patients with hormone-refractory prostate cancer: prognostic significance of prostate-specific antigen-doubling time and nadir prostate-specific antigen.

OBJECTIVE: Most patients with advanced prostate cancer after prostate-specific antigen (PSA) relapse following maximum androgen blockade rapidly progress to death. The present study was aimed to predict the survival of these serious patients after PSA relapse. METHODS: Sixty-eight patients with M1b and 20 patients with T3b, who relapsed and died of cancer within a short period, were studied. PSA-doubling time (PSA-DT) at PSA relapse influenced the outcome after PSA relapse [hazard ratio (CI): 2.000 (1.283-3.226)]; thus, on the basis of the median values of PSA-DT (>2 months) and additionally nadir PSA in previous treatment (2 months and nadir PSA of

Significance of prostate-specific antigen-doubling time on survival of patients with hormone refractory prostate cancer and bone metastasis: analysis on 56 cases of cancer-specific death.

OBJECTIVE: Most of the metastatic diseases initially respond to maximum androgen blockade, but then relapse and lose response, and finally die. After relapse, the disease progresses in various courses. The present study was aimed to establish the predicting factors influencing the survival period of patients at prostate-specific antigen (PSA) relapse (entering the hormone refractory state). MATERIALS AND METHODS: Fifty-six patients with prostate cancer and bone metastasis, who were treated during the entire disease period at the same hospital and died were studied. To calculate PSA-doubling time, assay of PSA was carried out every 3 months or less. RESULTS: The period between PSA relapse and death was related with PSA-doubling time at relapse, nadir PSA and the period between the start of treatment and PSA relapse. The PSA-doubling time of 2 months or less at relapse was suggestive of a poor outcome. Final PSA-doubling time was not correlated with the survival period after PSA relapse. CONCLUSION: The PSA-doubling time at relapse is one of the relevant factors for predicting the survival period after PSA relapse.