Six-year outcomes of robot-assisted radical prostatectomy versus volumetric modulated arc therapy for localized prostate cancer: A propensity score-matched analysis.

BACKGROUND: Although robot-assisted radical prostatectomy (RARP) and intensity-modulated radiotherapy are the leading respective techniques of prostatectomy and radiotherapy for localized prostate cancer, almost no study has directly compared their outcomes; none have compared mortality outcomes. METHODS: We compared 6­year outcomes of RARP (n = 500) and volumetric modulated arc therapy (VMAT, a rotational intensity-modulated radiotherapy, n = 360) in patients with cT1-4N0M0 prostate cancer. We assessed oncological outcomes, namely overall survival (OS), cancer-specific survival (CSS), radiological recurrence-free survival (rRFS), and biochemical recurrence-free survival (bRFS), using propensity score matching (PSM). We also assessed treatment-related complication outcomes of prostatectomy and radiotherapy. RESULTS: The median follow-up duration was 79 months (> 6 years). PSM generated a matched cohort of 260 patients (130 per treatment group). In the matched cohort, RARP and VMAT showed equivalent results for OS, CSS, and rRFS: both achieved excellent 6­year outcomes for OS (> 96%), CSS (> 98%), and rRFS (> 91%). VMAT had significantly longer bRFS than RARP, albeit based on different definitions of biochemical recurrence. Regarding complication outcomes, patients who underwent RARP had minimal (2.6%) severe perioperative complications and achieved excellent continence recovery (91.6 and 68.8% of the patients achieved ≤ 1 pad/day and pad-free, respectively). Patients who underwent VMAT had an acceptable rate (20.0%) of grade ≥ 2 genitourinary complications and a very low rate (4.4%) of grade ≥ 2 gastrointestinal complications. CONCLUSION: On the basis of PSM after a 6-year follow-up, RARP and VMAT showed equivalent and excellent oncological outcomes, as well as acceptable complication profiles.

Advantages of enhanced recovery after surgery program in robot-assisted radical cystectomy.

Radical cystectomy is a gold-standard treatment for muscle-invasive bladder cancer. We recently introduced robot-assisted radical cystectomy (RARC) with perioperative enhanced recovery after surgery (ERAS). The medical records of patients with bladder cancer who underwent open radical cystectomy (ORC) or RARC/ERAS at NTT Medical Center Tokyo were retrospectively reviewed to compare the surgical outcomes, hospital stay, and medical costs between groups. Multidisciplinary full ERAS items were provided for the RARC/ERAS group. The median estimated blood losses in the ORC and RARC/ERAS groups were 650 and 100 mL, and the median operative times were 312 and 445 min, respectively. In addition, the median times to liquid food intake in these groups were 6 and 0 days, the median times to first flatus and first defecation were 2 and 1 day, and 3 and 1.5 days, respectively. The rates of postoperative ileus in the ORC and RARC/ERAS groups were 27.5% and 4.5%, and the median postoperative hospital stays was 26.5 and 12 days, respectively. Medical costs excluding surgery were significantly lower in the RARC/ERAS group. In conclusion, RARC/ERAS represents a safe treatment option for muscle-invasive bladder cancer with decreased perioperative complications and lower medical costs.

Subclassification of pT3 upper tract urothelial carcinoma: a multicenter retrospective study.

PURPOSE: The prognosis of patients with pT3 upper tract urothelial carcinoma (UTUC) varies. The current study aimed to further classify patients with pT3 UTUC into different survival outcome groups based on tumor location and site of invasion. METHODS: This retrospective study included 323 patients with pT3 UTUC who underwent nephroureterectomy at 11 hospitals in Japan. Histological and clinical data were obtained via a chart review. Univariate and multivariate Cox proportional hazards analyses showed the effect of different variables on recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS). RESULTS: The median age of the patients was 72 years. Patients with pT3 UTUCs were divided into two groups: those with renal parenchymal invasion only (pT3a, n = 95) and those with peripelvic or periureteral fat invasion (pT3b, n = 228). pT3b UTUC was significantly associated with hydronephrosis, low preoperative estimated glomerular filtration rate (eGFR), histological nodal metastasis, nuclear grade 3, lymphovascular invasion (LVI), carcinoma in situ, and positive surgical margin. Based on the univariate analyses, patients with pT3b UTUC had a significantly lower 5-year RFS (42.4% vs. 70.1%, p < 0.0001), 5-year CSS (54.3% vs. 80.0%, p = 0.0002), and 5-year OS (47.8% vs. 76.8%, p < 0.0001) than those with pT3a UTUC. According to the multivariate analyses, nodal metastasis, LVI, adjuvant chemotherapy, preoperative eGFR, nuclear grade (RFS only), surgical margin (RFS only), and Charlson comorbidity index (OS only), but not pT3b stage, were associated with survival. CONCLUSION: Compared with pT3a UTUC, pT3b UTUC was significantly associated with worse histological features, consequently resulting in unsatisfactory survival outcomes.

A case of sepsis-induced cardiomyopathy successfully treated with venoarterial extracorporeal membrane oxygenation.

Introduction: Sepsis with concomitant acute pyelonephritis, secondary to urolithiasis, is common. We report a case of sepsis-induced cardiomyopathy with acute pyelonephritis, successfully managed with venoarterial extracorporeal membrane oxygenation. Case presentation: A 64-year-old woman presented with fever and disturbed consciousness. Abdominal computed tomography revealed right hydronephrosis with ipsilateral ureteral stone. Despite ureteral stent placement and antibiotic treatment, her hemodynamics worsened. She was diagnosed with sepsis-induced cardiomyopathy and underwent venoarterial extracorporeal membrane oxygenation. Her hemodynamics improved rapidly; venoarterial extracorporeal membrane oxygenation was withdrawn on postoperative day-3. She was discharged from our hospital after sufficient antibiotic treatment. Conclusion: Venoarterial extracorporeal membrane oxygenation may be initiated in patients with sepsis-induced cardiomyopathy. Evaluation of left ventricular ejection fraction via echocardiography is important to determine the indication for venoarterial extracorporeal membrane oxygenation.

Clinical features and treatment outcomes of Fournier's gangrene in a single tertiary emergency hospital: Simplified Fournier's Gangrene Severity Index score is a predictor for death.

To assess the predictive reliability of the Simplified Fournier's Gangrene Severity Index Score (SFGSI) for mortality in Japanese patients with Fournier's gangrene (FG), we compared the clinical features and outcomes of a patient sample with the SFGSI. The medical records of 36 patients diagnosed with FG at our hospital between October 2007 and September 2022 were reviewed retrospectively. Clinical and laboratory variables, including SFGSI, were evaluated and predictive factors for fatality were investigated using multivariate logistic regression analysis. The median age and body mass index were 65 and 24.2, respectively. Eight patients had cooccurring chronic kidney disease and 23 had diabetes. None were taking sodium-glucose co-transporter-2 (SGLT-2) inhibitors. The causative organisms were diverse, and no specific trends in causative organisms were observed. 26 patients underwent debridement of necrotic tissue including eight colostomies, two orchiectomies, and one cystectomy. Multivariate logistic regression analysis revealed that SFGSI alone was an independent predictor of case fatality, with an odds ratio of 20.167 (95% CI: 1.66-245.53). In conclusion, the fatality rate was 19.4%, which was comparable to that reported in other studies. The SFGSI was an independent predictor of mortality in this study.

Effect of M2-like macrophages of the injured-kidney cortex on kidney cancer progression.

Chronic kidney disease (CKD) affects kidney cancer patients' mortality. However, the underlying mechanism remains unknown. M2-like macrophages have pro-tumor functions, also exist in injured kidney, and promote kidney fibrosis. Thus, it is suspected that M2-like macrophages in injured kidney induce the pro-tumor microenvironment leading to kidney cancer progression. We found that M2-like macrophages present in the injured kidney promoted kidney cancer progression and induced resistance to anti-PD1 antibody through its pro-tumor function and inhibition of CD8+ T cell infiltration. RNA-seq revealed Slc7a11 was upregulated in M2-like macrophages. Inhibition of Slc7a11 with sulfasalazine inhibited the pro-tumor function of M2-like macrophages and synergized with anti-PD1 antibody. Moreover, SLC7A11-positive macrophages were associated with poor prognosis among kidney cancer patients. Collectively, this study dissects the characteristic microenvironment in the injured kidney that contributed to kidney cancer progression and anti-PD1 antibody resistance. This insight offers promising combination therapy with anti-PD1 antibody and macrophage targeted therapy.

Mammary-type myofibroblastoma of the perineum: Typical or rare location?

Introduction: Mammary-type myofibroblastoma is a rare benign tumor, mainly arising along the embryonal mammary ridge. We report a rare case of mammary-type myofibroblastoma of the perineum. Case presentation: A 37-year-old Japanese man presented with a 20 mm, progressively-growing painless mass in the right perineum. Computed tomography showed a subcutaneous tumor with a strong contrast effect. Upon total resection, pathology showed a spindle-cell tumor positive for desmin but negative for CD34. Further immunohistochemistry showed loss of Rb expression, leading to differential diagnosis. We could not evaluate the exact rarity of the perineal location due to categorization in past reports. Conclusion: Due to the similarities between mammary and anogenital tissue, we suggest that tallying perineal and vulvar areas separately from the embryonic mammary ridge sites may be beneficial in gaining insight into the pathophysiology of this tumor.

Smaller decline of renal function after nephroureterectomy predicts poorer prognosis of upper tract urothelial carcinoma: a multicentre retrospective study.

PURPOSE: Renal function is frequently impaired in the patients with upper tract urothelial carcinoma. We aimed to evaluate the impact of renal function and its change after surgery on survival rates in patients with upper tract urothelial carcinoma after nephroureterectomy. METHODS: The study cohort comprised 755 patients with upper tract urothelial carcinoma who underwent nephroureterectomy between 1995 and 2016 at nine hospitals in Japan. Estimated glomerular filtration rate was calculated using the three-variable Japanese equation for glomerular filtration rate estimation from serum creatinine level and age. Outcomes were recurrence-free, cancer-specific and overall survivals. Univariate and multivariate Cox proportional hazards regression analyses were used. RESULTS: Median patients' age was 72 years old. Pre- and post-surgical median estimated glomerular filtration rate were 55.5 and 42.9 ml/min/1.73 m2, respectively. Median estimated glomerular filtration rate decline after surgery, which represents function of the affected side kidney, was 13.1 ml/min/1.73 m2. The 5-year recurrence-free, cancer-specific and overall survivals were 68.3, 79.4 and 74.0%, respectively. Multivariate analysis indicated that lower preoperative estimated glomerular filtration rate and estimated glomerular filtration rate decline were associated with poorer recurrence-free, cancer-specific and overall survivals, but post-operative estimated glomerular filtration rate was not. Estimated glomerular filtration rate decline was more significant poor-prognosticator than preoperative estimated glomerular filtration rate. Proportions of the patients with estimated glomerular filtration rate <60 ml/min/1.73 m2 before surgery were 50.6 and 73.2% in organ-confined disease and locally advanced disease, respectively (P < 0.0001). After surgery, they were 91.6 and 89.8%, respectively (P = 0.3896). CONCLUSIONS: Lower preoperative renal function, especially of the affected side kidney, was significantly associated with poor prognosis after nephroureterectomy for upper tract urothelial carcinoma. Many patients with locally advanced disease have reduced renal function at diagnosis and even more after surgery.

Comparison of major definitions of sarcopenia based on the skeletal muscle index in patients with urothelial carcinoma.

For the past decade, sarcopenia has been actively investigated in various cancers, including urothelial carcinoma (UC). Although skeletal muscle index (SMI) is the main parameter used to evaluate sarcopenia in oncology, the optimal definition of SMI-based sarcopenia is not entirely standardized. We recently highlighted the potential limitations of current definitions of SMI-based sarcopenia in another journal. In this study, we reviewed studies that assessed sarcopenia in UC patients. We then performed a comparative validation of three major SMI-based definitions of sarcopenia, including Prado's, the international and Martin's definitions in metastatic UC patients. We believe that the standardization of the sarcopenia definition is an urgent issue in oncology, and this paper discusses a possible new direction to address this issue.

Transient acute kidney injury observed immediately after robot-assisted radical prostatectomy but not after open radical prostatectomy.

Acute kidney injury (AKI) is a serious postoperative complication that occurs following laparoscopic surgery. However, its association with robot-assisted radical prostatectomy (RARP), the gold standard surgery for prostate cancer, is controversial. The current cohort included 257 patients with prostate cancer who underwent either RARP (n=187) or open radical prostatectomy (ORP; n=70). Patient serum creatinine concentration was measured at the following six time points: Prior to surgery, on postoperative day 0 (immediately after surgery), on postoperative day 1, 3 months after surgery, 1 year after surgery and 2 years after surgery. AKI was diagnosed according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. A total of 25 RARP and 0 ORP patients met the KDIGO criteria on postoperative day 0. On postoperative day 1, 3 RARP and 2 ORP patients met the criteria, suggesting that AKI after RARP was a transient phenomenon. At 1 and 2 years after surgery, 5 of 257 patients exhibited a significant increase in serum creatinine concentrations from baseline results. Clinicians should be aware of transient AKI occurring after RARP, rather than ORP, to ensure better perioperative management in patients undergoing radical prostatectomy.

Quantification of the individual risk of each Gleason pattern, including tertiary Gleason pattern 5, after radical prostatectomy: development of the modified Gleason grade grouping (mGGG) model.

BACKGROUND: While the new Gleason grade grouping (GGG), which started in 2016, has been widely validated in prostate cancer, it does not incorporate the concept of tertiary Gleason pattern 5. Furthermore, no study has "quantified" the individual risk of each Gleason pattern, including tertiary Gleason pattern 5, after radical prostatectomy. METHODS: We reviewed 1022 men with adjuvant-treatment-naïve prostate cancer who underwent radical prostatectomy between 2005 and 2017. The primary endpoint was biochemical recurrence-free survival, defined as two consecutive prostate-specific antigen measurements ≥0.2 ng/ml after surgery. The individual quantitative risk score (IQRS) of each amount (primary/secondary/tertiary) of each Gleason pattern (3/4/5) was calculated using the Cox regression model. On the basis of the IQRS, the modified Gleason grade grouping (mGGG) model was developed. As a robustness analysis of the mGGG model, salvage treatment-free survival was also assessed. RESULTS: During a median follow-up of 45 months, 229 of 1022 (22.4%) patients developed biochemical recurrence. The IQRS of each Gleason pattern was as follows: primary 5, 1.81 points (hazard ratio [HR] 6.13); secondary 5, 1.37 points (HR 3.92); tertiary 5, 0.87 points (HR 2.39); primary 4, 1.07 points (HR 2.91); secondary 4, 0.79 points (HR 2.21); and any Gleason pattern 3, 0 points (HR 1). Based on the IQRS, the mGGG model was developed, which classified patients into the following five groups: I (3 + 3 or less); II (3 + 4); III (4 + 3); IV (3 + 4 + t5, 4 + 3 + t5, 3 + 5, 5 + 3, and 4 + 4); V (4 + 4 + t5, 4 + 5, 5 + 4, and 5 + 5). The c-index for biochemical recurrence-free survival was significantly improved from 0.655 of the original GGG model to 0.672 of the mGGG model (P < 0.05). In the robustness analysis, the c-index for salvage treatment-free survival was also significantly improved from 0.619 of the original GGG model to 0.638 of the mGGG model (P < 0.05). CONCLUSIONS: The quantitative risk of tertiary (< 5%) Gleason pattern 5 is slightly higher than that of secondary (5-50%) Gleason pattern 4. Our newly developed mGGG model more accurately predicts outcomes after radical prostatectomy than the original GGG model.

Robot-assisted radical prostatectomy versus volumetric modulated arc therapy: Comparison of front-line therapies for localized prostate cancer.

BACKGROUND: Although radical prostatectomy and external beam radiotherapy are recognized as comparable treatment options for localized prostate cancer, robot-assisted radical prostatectomy (RARP) and volumetric modulated arc therapy (VMAT) as the leading respective techniques have yet to be compared. METHODS: We retrospectively analyzed 860 patients with cT1-4N0M0 prostate cancer who underwent RARP (n = 500) or VMAT (n = 360) between 2011 and 2016. Biochemical recurrence-free survival (bRFS; two consecutive prostate-specific antigen measurements ≥0.2 ng/ml for RARP and Phoenix definition for VMAT) and radiological recurrence-free survival (rRFS; radiologically diagnosed distant metastasis or local recurrence) were compared between the two modalities. Cox proportional hazards model was used for multivariate analysis. RESULTS: The median follow-up durations were 30 and 47.5 months, and median ages were 67 and 71 years (both P < 0.0001) in the RARP and VMAT groups, respectively. VMAT patients had significantly better bRFS than RARP patients, though their definitions of biochemical recurrence differed. If a unified definition of biochemical recurrence (two consecutive prostate-specific antigen measurements ≥0.2 ng/ml) was applied, RARP patients had significantly better bRFS than VMAT patients. Regarding rRFS, RARP patients had significantly better outcomes than VMAT patients, however, multivariate analysis together with D'Amico's risk classification, age-adjusted Charlson's comorbidity index, and concomitant androgen-deprivation therapy, demonstrated no significant difference between RARP and VMAT. CONCLUSIONS: The rRFS outcomes of RARP and VMAT after a medium-term follow-up period were similar, despite their different patient backgrounds. Further studies with a longer follow-up period are needed to compare these techniques in terms of cancer-specific and overall survivals.

Prognostic significance of neutrophil-to-lymphocyte ratio in collecting duct carcinoma.

Collecting (Bellini) duct carcinoma of the kidney is a rare lethal tumor, and its prognostic factors remain unclear. The present study investigated the prognostic significance of neutrophil-to-lymphocyte ratio, which has recently been recognized as a readily available prognostic marker in various malignancies, in patients with collecting duct carcinoma. Of 11 patients who were pathologically diagnosed with collecting duct carcinoma at our institution, nine died of collecting duct carcinoma, one died of a postoperative complication, and one was alive, with a median follow-up period of 6 (range: 0-97) months. Both univariate and multivariate analyses associated neutrophil-to-lymphocyte ratio ≥4 (median) with worse cancer-specific survival. Notably, the sole surviving patient maintained a low neutrophil-to-lymphocyte ratio (<4) both at the initial diagnosis and at the time of distant recurrence. These results suggest that neutrophil-to-lymphocyte ratio might serve as a useful biomarker for collecting duct carcinoma as well as other malignancies.

Preoperative chronic kidney disease is predictive of oncological outcome of radical cystectomy for bladder cancer.

PURPOSE: To evaluate the impact of preoperative chronic kidney disease (CKD) on oncological outcomes after radical cystectomy (RC) for bladder cancer. METHODS: We reviewed the medical records of patients with urothelial bladder carcinoma who underwent RC with curative intent at seven hospitals between 1990 and 2013. After excluding patients with a history of upper urinary tract urothelial cancer or neoadjuvant chemotherapy, we analyzed 594 cases for the study. Preoperative estimated glomerular filtration rate (eGFR) was calculated using the three-variable Japanese equation for GFR estimation from serum creatinine level and age. Patients were divided into four groups of different CKD stages based on eGFR values (mL/min/1.73 m2), i.e., ≥ 60 (CKD stages G1-2), 45-60 (G3a), 30-45 (G3b), and < 30 (G4-5). Survival was estimated using the Kaplan-Meier method. Univariate and multivariate Cox proportional hazards regression analyses addressed survivals after RC. RESULTS: Median age of patients was 67 years. Patients were classified into CKD stages: G1-2 (n = 388; 65.3%), G3a (n = 122; 20.5%), G3b (n = 51; 8.6%), and G4-5 (n = 33; 5.6%). During a median follow-up of 4.0 years, 200 and 164 patients showed cancer progression and died of bladder cancer, with the 5-year progression-free survival (PFS) and cancer-specific survival (CSS) of 64.9 and 70.2%, respectively. On multivariate analyses, CKD stages of G3b or greater, advanced pT stage, lymph node metastasis, and positive lymphovascular invasion were independent poor prognostic factors for PFS and CSS. CONCLUSIONS: We demonstrated that the advanced preoperative CKD stage was significantly associated with poor oncological outcomes of the bladder cancer after RC.

Efficacy of post-nephroureterectomy cisplatin-based adjuvant chemotherapy for locally advanced upper tract urothelial carcinoma: a multi-institutional retrospective study.

PURPOSE: To evaluate the efficacy of adjuvant systemic chemotherapy for locally advanced (pT3-4pN0/xM0) upper tract urothelial carcinoma (UTUC). MATERIALS AND METHODS: We retrospectively reviewed the medical records of 109 patients with pT3-4pN0/xM0 UTUC who had undergone radical nephroureterectomy between 1996 and 2013 at our four institutions. The patients were divided into two groups: those who received adjuvant chemotherapy (AC group) and those who did not (surgery-alone: SA group). All chemotherapy regimens were cisplatin-based. Cox proportional hazards regression models addressed the associations between clinicopathological factors and recurrence-free survival (RFS) and cancer-specific survival (CSS). RESULTS: Forty-three (39.5%) out of the 109 patients underwent one to four cycles of adjuvant chemotherapy after nephroureterectomy. Median follow-up was 46.5 months. There were no significant differences in the background characteristics of the two groups, except for age. Recurrence developed in 11 (25.6%) and 29 (43.9%) patients in the AC and SA groups, respectively. Ultimately, six (14.0%) and 18 (27.3%) patients in the AC and SA groups, respectively, died of disease progression. On univariate analysis, hydronephrosis, nuclear grade, lymphovascular invasion, and adjuvant chemotherapy were significantly associated with both RFS and CSS. Charlson comorbidity index was associated only with CSS. On multivariate analysis, adjuvant chemotherapy was the only independent factor associated with improved RFS (p = 0.0178, HR = 0.41). Moreover, adjuvant chemotherapy (p = 0.0375, HR = 0.33), lower nuclear grade (p = 0.0070), and the absence of hydronephrosis (p = 0.0493) were independently associated with better CSS. CONCLUSION: Locally advanced (pT3-4pN0/xM0) UTUC patients who underwent cisplatin-based adjuvant chemotherapy demonstrated better RFS and CSS than those without adjuvant chemotherapy.

Prognostic significance of serum neuron-specific enolase in small cell carcinoma of the urinary bladder.

PURPOSE: Small cell carcinoma of the urinary bladder (SCCB) is known for its aggressive clinical features and poor prognosis. No prognostic factor has been established so far. The aim of this study was to assess the significance of possible prognostic factors, including serum neuron-specific enolase (NSE), an established biomarker for small cell lung carcinoma. METHODS: We retrospectively reviewed 31 patients with primary SCCB treated at our eight affiliate institutions between 2001 and 2014. The association of various clinicopathological factors at diagnosis, including the serum NSE value, with cancer-specific survival (CSS) was assessed. The log-rank test and Cox proportional hazards model were used for univariate and multivariate analyses, respectively. RESULTS: Nineteen (61.3 %) died of SCCB during the follow-up, with a median survival time of 12.7 months. Prognostic factors were analyzed for the 25 patients after excluding six with missing data. Univariate analysis demonstrated that stage (extensive disease) and serum NSE ≥25 ng/ml were significantly associated with worse CSS. Multivariate analysis identified increased serum NSE value as a sole independent predictor of CSS (hazard ratio 18.52, p = 0.0022). CONCLUSIONS: Serum NSE value at diagnosis was an independent prognostic factor for primary SCCB and may serve as a useful biomarker in the management of SCCB.

Optimal timing of salvage radiotherapy for biochemical recurrence after radical prostatectomy: is ultra-early salvage radiotherapy beneficial?

BACKGROUND: The optimal timing of salvage radiotherapy for biochemical recurrence after radical prostatectomy is controversial. In particular, the prognostic significance of salvage radiotherapy delivered before a current definition of biochemical recurrence, i.e. ultra-early salvage radiotherapy, is unclear. METHODS: We reviewed 76 patients with pT2-3N0M0 prostate cancer who underwent salvage radiotherapy for post-prostatectomy biochemical recurrence at the following three timings: ultra-early salvage radiotherapy (n = 20) delivered before meeting a current definition of biochemical recurrence (two consecutive prostate-specific antigen [PSA] values ≥0.2 ng/mL); early salvage radiotherapy (n = 40) delivered after meeting the definition but before PSA reached 0.5 ng/mL; and delayed salvage radiotherapy (n = 16) delivered after PSA reached 0.5 ng/mL. The primary endpoint was failure of salvage radiotherapy, defined as a PSA value ≥0.2 ng/mL. The log-rank test and Cox proportional hazards model were used for univariate and multivariate analyses, respectively. RESULTS: During the follow-up period (median: 70 months), four of 20 (20 %), nine of 40 (23 %) and seven of 16 (44 %) patients failed biochemically in the ultra-early, early and delayed salvage radiotherapy groups, respectively. On univariate analyses, the outcome of delayed salvage radiotherapy was worse than the others, while there was no significant difference between ultra-early and early groups. Multivariate analysis demonstrated the presence of Gleason pattern 5, perineural invasion and delayed salvage radiotherapy as independent predictors of poorer survival. CONCLUSIONS: No survival benefit of ultra-early salvage radiotherapy was demonstrated, whereas delayed salvage radiotherapy was associated with worse outcome as reported in previous studies. Our results may support the current recommendations that salvage radiotherapy should be undertaken after two consecutive PSA values ≥0.2 ng/mL and before reaching 0.5 ng/mL.

Impact of Gleason pattern 5 including tertiary pattern 5 on outcomes of salvage treatment for biochemical recurrence in pT2-3N0M0 prostate cancer.

BACKGROUND: Gleason pattern 5 (GP5), including tertiary GP5, at radical prostatectomy has reportedly been associated with poorer clinical outcome. However, it is undetermined how tertiary GP5 is handled in the new Gleason grade grouping starting in 2016, and its prognostic value in patients undergoing salvage treatment for postoperative biochemical recurrence (BCR) remains unclear. METHODS: We retrospectively reviewed 116 patients with pT2-3N0M0 prostate cancer (PC) who received salvage treatment for BCR after radical prostatectomy between 2003 and 2014. The primary endpoint was failure of salvage treatment, defined as a single prostate-specific antigen (PSA) value ≥0.2 ng/ml after PSA nadir following salvage treatment. Associations of various clinicopathological factors, including GP5, with failure-free survival were assessed. Cox proportional hazards model was used for multivariate analysis. RESULTS: Patients received salvage treatment with either radiotherapy (n = 48), androgen-deprivation therapy (n = 61), or both (n = 7) for BCR. Twenty-three patients (19.8 %) experienced failure of salvage treatment, with a median follow-up period of 79 months. Univariate analysis associated GP5, Gleason score-based parameters, lymphovascular invasion, and PSA doubling time <6 months with poorer failure-free survival. Receiver operating characteristic curve analyses identified the area under the curve for GP5 (0.654) as the largest among those parameters (P = 0.0060). Multivariate analysis demonstrated that GP5 was the only independent predictor of poor outcome. CONCLUSIONS: The presence of GP5 is an independent predictor of poor prognosis in patients with pT2-3N0M0 PC undergoing salvage treatment for BCR after radical prostatectomy. GP5 may thus be a more useful marker than conventional Gleason score in this setting.