Radical prostatectomy vs radiation therapy and androgen-suppression therapy in high-risk prostate cancer

Study Type – Therapy (retrospective cohort analysis) Level of Evidence 2b What's known on the subject? and What does the study add? Prostate cancer is generally considered to be high risk when the prostate‐specific antigen (PSA) concentration is >20 ng/mL, the Gleason score is ≥8 or the American Joint Commission on Cancer (AJCC) tumour (T) category is ≥2c. There is no consensus on the best treatment for men with prostate cancer that includes these high‐risk features. Options include external beam radiation therapy (EBRT) with androgen suppression therapy (AST), treatment with a combination of brachytherapy, EBRT and AST termed combined‐modality therapy (CMT) or radical prostatectomy (RP) followed by adjuvant RT in cases where there are unfavourable pathological features, e.g. positive surgical margin, extracapsular extension and seminal vesicle invasion. While outcomes for both approaches have been published independently these treatments have not been compared in the setting of a prospective RCT where confounding factors related to patient selection for RP or CMT would be minimised. These factors include age, known prostate cancer prognostic factors and comorbidity. RCTs that compare RP to radiation‐based regimens have been attempted but failed to accrue.

OBJECTIVE

• ? To assess the risk of prostate cancer‐specific mortality after therapy with radical prostatectomy (RP) or combined‐modality therapy (CMT) with brachytherapy, external beam radiation therapy (EBRT) and androgen‐suppression therapy (AST) in men with Gleason score 8–10 prostate cancer.

PATIENTS AND METHODS

• ? Men with localised high‐risk prostate cancer based on a Gleason score of 8–10 were selected for study from Duke University (285 men), treated between January 1988 and October 2008 with RP or from the Chicago Prostate Cancer Center or within the 21st Century Oncology establishment (372) treated between August 1991 and November 2005 with CMT.
• ? Fine and Gray multivariable regression was used to assess whether the risk of prostate cancer‐specific mortality differed after RP as compared with CMT adjusting for age, cardiac comorbidity and year of treatment, and known prostate cancer prognostic factors.

RESULTS

• ? As of January 2009, with a median (interquartile range) follow‐up of 4.62 (2.4–8.2) years, there were 21 prostate cancer‐specific deaths.
• ? Treatment with RP was not associated with an increased risk of prostate cancer‐specific mortality compared with CMT (adjusted hazard ratio [HR] 1.8, 95% confidence interval [CI] 0.6–5.6, P= 0.3).
• ? Factors associated with an increased risk of prostate cancer‐specific mortality were a PSA concentration of <4 ng/mL (adjusted HR 6.1, 95% CI 2.3–16, P < 0.001) as compared with ≥4 ng/mL, and clinical category T2b, c (adjusted HR 2.9; 95% CI 1.1–7.2; P= 0.03) as compared with T1c, 2a.

CONCLUSION

• ? Initial treatment with RP as compared with CMT was not associated with an increased risk of prostate cancer‐specific mortality in men with Gleason score 8–10 prostate cancer.

     

Microstaging of pT1 transitional cell carcinoma of the bladder: identification of subgroups with distinct risks of progression

Objectives. To evaluate microstaging by means of quantifying the depth of invasion of the subepithelial connective tissue in pT1 transitional cell carcinoma (TCC) of the bladder for its additional prognostic value with respect to disease recurrence and progression.Methods. We reviewed the pathologic findings of a consecutive series of 124 patients with pT1 tumors entered in a prospective randomized multicenter trial comparing mitomycin C and bacillus Calmette-Guérin treatment, with at least 3 years of follow-up and clinical outcome hidden from reviewers. The depth of invasion was established by identifying submucosal tumor invasion up to, in, or beyond the muscularis mucosae or vascular plexus and classified as pT1a, pT1b, or pT1c, respectively. In addition to tumor grade, the presence of carcinoma in situ (CIS) near the primary tumor or in biopsy specimens taken from abnormal looking mucosa was taken into account. The risks of recurrence and progression were calculated using Kaplan-Meier curves and modeled with proportional hazard models.Results. pT1 subclassification was possible in more than 90% of the specimens. The 3-year risk of recurrence was not different in any of the subgroups. By contrast, the Kaplan-Meier 3-year risk for progression was 6%, 33%, and 55% for pT1a, pT1b (hazard ratio [HR] 5.51), and pT1c (HR 12.35) tumors, respectively (log-rank test P < 0.001). The Kaplan-Meier 3-year risk of progression was 9% versus 39% (HR 5.62) for the absence or presence of CIS in the tumor (P = 0.001) and 8% versus 49% (HR 6.72) for CIS in biopsy specimens (P < 0.001). Tumor grade had no statistically significant prognostic value with respect to progression, nor had tumor volume or multifocality. The combination of the parameters (pT1c and CIS) increased the risk of progression by a factor of 27 (P < 0.0001) compared with the absence of pT1c and CIS.Conclusions. These data show that the extent of lamina propria invasion (pT1a, pT1b, pT1c) is a clinically relevant prognostic factor for progression of pT1 TCC of the bladder. With the combination of this pT1 subclassification and the presence of CIS subgroups, distinct risks of progression can be identified that may give additional information for follow-up and treatment policies.     

Endocrine therapy with or without radical prostatectomy for T1b-T3N0M0 prostate cancer

BACKGROUND: We retrospectively compared the 5-year survival rates of T1b-T3N0M0 prostate cancer patients treated either by endocrine therapy plus radical prostatectomy or endocrine therapy alone. METHODS: Clinical T1b-T3N0M0 prostate cancer patients were enrolled at 104 institutions in Japan. They were assigned to study 1 (n = 176), if they were indicated to prostatectomy, if not indicated, they were assigned to study 2 (n = 151). The indication of prostatectomy was based on the clinical judgement of physicians and/or patients. Those assigned to study 1 underwent prostatectomy and adjuvant endocrine therapy with or without preoperative androgen deprivation. Those assigned to study 2 were treated with leuprorelin acetate with or without chlormadinone acetate. They were followed-up every 3 months until death or for 5 years and over. RESULTS: Those assigned to study 1 were younger (mean age 67.2 vs 75.7 years), less advanced in clinical stage, and had lower prostate specific antigen levels (mean 43.8 vs 103.6 ng/mL). Death for any reason was observed less frequently in study 1 (n = 29, 16%) than study 2 (n = 50, 33%), and the 5-year overall survival rate was higher in study 1 (87 vs. 68%). However, prostate cancer deaths were comparatively seldom (9% in study 1 and 7% in study 2), resulting in the identical 5-year cause specific survival rate in both study groups (91%). In both study groups the overall survival was almost equal to the natural survival of age-matched men. CONCLUSIONS: Endocrine therapy offers a reasonable survival rate in T1b-T3 prostate cancer patients within a 5-year follow-up. Observation will be extended to determine 10-year outcomes.     

Radical prostatectomy for high-risk prostate cancer: Biochemical outcome

Objectives:   To determine the biochemical outcome following radical prostatectomy alone in patients with high-risk prostate cancer.
Methods:   Between January 2002 and August 2007, 252 patients underwent radical retropubic prostatectomy. Those who received neoadjuvant hormone therapy were excluded from this analysis. Based on pre-operative data, we stratified the patients into low, intermediate, and high-risk groups according to the risk criteria of the National Comprehensive Cancer Network in 2003, respectively. Prostate-specific antigen (PSA) failure was defined as any detectable PSA level higher than 0.2 ng/mL.
Results:   The PSA failure-free survival rate for the high-risk group ( n  = 46) was 64.5% after a median follow-up period of 39 months. Among patients with high-risk disease, none with pathologically organ-confined cancer ( n  = 19) and a negative surgical margin had PSA failure. The PSA failure-free rate in patients with non organ-confined cancer ( n  = 27) was 39.5%. Among the pretreatment variables, a positive biopsy core percentage (the number of positive biopsy cores/total biopsy core) ≥30 was a significant independent predictor of extra prostatic extension.
Conclusions:   Radical prostatectomy is feasible in high-risk prostate cancer patients, only if they have a pathologically organ-confined disease.     

l-Arginine Administration During Reperfusion Improves Pulmonary Function

Background. Nitric oxide is crucial to the maintenance of vascular homeostasis. Because nitric oxide levels decline upon lung reperfusion, infusion of l-arginine, a nitric oxide precursor, during reperfusion might prove effective at ameliorating reperfusion injury.Methods. Neonatal piglet heart-lung blocks were preserved with Euro-Collins solution for 12 hours, rewarmed at room temperature for 1 hour, and reperfused for 10 minutes with either whole blood (n = 5), whole blood containing l-arginine (10 mmol/L; n = 6), or leukocyte-depleted blood (n = 6) on an isolated, blood-perfused, working heart-lung circuit. After the initial 10 minutes, all blocks received whole blood for 4 hours. Control blocks were continuously perfused on the circuit without intervening ischemia (n = 6).Results. The partial pressure of oxygen in the whole blood group (113.8 ± 33.1 mm Hg) was significantly less than in controls (417.3 ± 6.2 mm Hg; p < 0.01). Lung compliance was significantly less in the whole blood group (0.8 ± 0.2 mL/cm H₂O) than in controls (2.9 ± 0.4 mL/cm H₂O; p < 0.01). The l-arginine and leukocyte-depleted blood groups showed no significant difference from controls.Conclusions. l-Arginine infusion during reperfusion improves pulmonary function, making it a simple alternative to leukocyte depletion.     

Adjuvant versus salvage radiation therapy for prostate cancer and the risk of death

Study Type – Therapy (case series)
Level of Evidence 4

OBJECTIVE

To investigate whether salvage radiation therapy (RT) for prostate‐specific antigen (PSA) failure can provide the same result as adjuvant RT, which decreases the risk of all‐cause mortality (ACM) for men with positive margins (R1), or extra‐capsular or seminal vesicle extension (pT3).

METHODS

We studied 1638 men at Duke University who underwent radical prostatectomy for unfavourable‐risk prostate cancer and whose postoperative PSA was undetectable. Cox regression was used to evaluate whether salvage vs adjuvant RT in men with a rapid (<10 months) or slow (≥10 months) PSA doubling time (DT) was associated with the risk of ACM, adjusting for adverse features (pT3, R1, Gleason score 8–10), age, preoperative PSA level, comorbidity and hormonal therapy use.

RESULTS

Despite fewer men with two or more adverse features (61 vs 82%; P = 0.016), salvage for a rapid PSA DT vs adjuvant RT increased the risk of ACM [adjusted hazard ratio (AHR) = 3.42; 95% confidence interval (CI) = 1.27–9.20; P = 0.015]. There was no difference (AHR = 1.39; 95% CI = 0.50–3.90; P = 0.53) in the risk of ACM among men who received salvage for a slow PSA DT or adjuvant RT. Nearly all (90%) men with a slow PSA DT had Gleason score ≤7 and the majority (59%) had at most pT3 or R1 disease.

CONCLUSION

Radiation therapy after PSA failure as compared with adjuvant RT was not associated with an increased risk of ACM in men with Gleason score ≤7 and pT3R0 or pT2R1 disease.     

A long-term study of the efficacy of treatment of localized prostate cancer

This paper presents a retrospective comparison of patients undergoing treatment for clinically localized prostate cancer. We reviewed the age, grade, and stage at diagnosis as well as the survival and recurrence rates of 222 patients treated for carcinoma of the prostate with either radical prostatectomy (RP) or radiotherapy (XRT) at four Army medical centers. Mean follow-up was 8.02 years (range 0.026–32.5 years). Stage and grade were similar in patients receiving either RP or XRT. Kaplan-Meier estimates showed that patients who underwent RP had a significantly greater disease-specific survival (p = 0.0001) and a significantly lower rate of distant metastases (p = 0.006) than did those who received XRT. There was no significant difference in the rate of local progression (p = 0.276) or in the mean time to local progression (XRT = 3.5, RP = 4.0 years) or to distant metastases (XRT = 3.79, RP = 4.52 years). Cox proportional hazards model incorporating age, stage, grade, and treatment type demonstrated that those patients who received XRT had more than two times the risk of dying of their disease than did those who underwent RP (risk ratio = 2.37; 95% confidence interval = 1.49–3.76). These data in similar groups of patients suggest that metastasis-free survival is improved in those who receive RP compared with XRT and that this translates into an enhanced survival advantage. Further study of larger groups of patients stratified by risk factors in randomized, prospective trials with longer follow-up will improve our ability to determine the best treatment for clinically localized prostate cancer.     

Salvage radical prostatectomy for recurrent prostate cancer after radiation therapy

Salvage radical prostatectomy is considered for patients with locally recurrent prostate cancer after external beam radiotherapy. Between 2001 and 2004, 32 men treated with curative intent with radiotherapy for prostate cancer were subsequently treated with salvage surgery for clinically localized prostate cancer. We assessed the morbidity associated with this procedure and the outcome of the patients. Thirty-two patients underwent salvage radical prostatectomy. Initial pre-radiation median prostate-specific antigen was 13 ng/ml. Pre-radiation disease was clinical stage T1b in five cases, T2a in 10, T2b in 10 and T3a in seven. Mean operative time was 122 minutes, intraoperative blood loss was 550 ml and hospital stay and catheterization time were 5 and 12 days, respectively. There was biochemical failure in eight patients after salvage radical prostatectomy and 24 patients are biochemical non evidence of disease (bNED). In recurrent prostate local disease with prostate-specific antigen <10 ng/ml and life expectancy greater than 10 years, salvage radical prostatectomy is a reasonable treatment option.     

Feasibility and safety of robot-assisted salvage prostatectomy for recurrent prostate cancer following radiation therapy

We report a comparison of perioperative complications and pathologic outcomes in patients with locally radiorecurrent prostate cancer treated by open radical retropubic or robot-assisted prostatectomy. The results of our study demonstrate that both surgical approaches were feasible and safe without any significant perioperative complications (death, rectal injury) with comparable short-term outcomes.     

bcl-2/bax ratio as a predictive marker for therapeutic response to radiotherapy in patients with prostate cancer

Objectives. Markers predictive of therapeutic response of prostatic tumors to radiotherapy may have major significance in optimizing effective treatment of prostate cancer. Because inherent cellular radioresistance plays a critical role in the failure of radiotherapy, in this study, we investigated whether there is a correlation between the ratio of two apoptosis regulators, bcl-2 (apoptosis suppressor) and bax (apoptosis inducer) in prostatic tumors and the clinical response to radiotherapy in patients with localized prostate cancer.Methods. A retrospective review of records of 41 patients who underwent external beam radiotherapy for prostate cancer was conducted. On the basis of post-treatment prostate biopsy and prostate-specific antigen (PSA) criteria, the cancers of 20 patients were classified as radiation nonresponders and 21 as radiation responders. Immunohistochemical analysis was performed on paraffin-embedded prostate sections to determine the level of expression of the two apoptotic proteins, bcl-2 and bax, in tumor cells.Results. bcl-2 immunoreactivity was significantly higher in prostatic tumors not responsive to radiotherapy (38.6 ± 4.1), compared with the radiation responders (24.1 ± 4.6) (P <0.001). Expression of bax protein was lower in nonresponders, but values were not significantly different from the responders. The resulting significantly higher bcl-2/bax ratio (P <0.01) correlated with poor therapeutic responsiveness of prostate cancer to radiotherapy (1.12 ± 0.12 and 0.56 ± 0.13, for nonresponders and responders, respectively). This correlation (r = 0.67) was independent of age, PSA, and Gleason score.Conclusions. These findings suggest that patients with an elevated bcl-2/bax ratio are at increased risk of their cancer failing to respond to radiotherapy. This study suggests a predictive value for the bcl-2/bax ratio as a potential molecular marker for predicting radioresistance of prostatic tumors.     

The role of surgery in high-risk localised prostate cancer

? The optimal management of high-risk localised prostate cancer is a major challenge for urologists and oncologists. It is clear that multimodal therapy including radical local treatment is needed in these men to achieve the best outcomes. ? External beam radiotherapy (EBRT) is an essential component of therapy either as a primary or adjuvant treatment. However, the role of radical prostatectomy (RP) is more controversial. Both methods are currently valid therapy options. ? There have been many individual studies of EBRT and RP in high-risk disease, but no good quality large prospective randomized trials. ? In EBRT, combination with neoadjuvant plus long-term adjuvant androgen-deprivation therapy (ADT) has been conclusively shown to improve outcomes and is widely considered the standard of care. ? However, the role of RP has achieved recent prominence with several important studies. Published data from prospective randomized trials in patients after RP have shown that in men with adverse pathological features at surgery, the addition of adjuvant RT improves biochemical-free and progression-free survival. ? More recently, studies from large-volume centres comparing EBRT and RP have provided intriguing suggestions of better outcomes with RP as the primary treatment. ? An important question therefore, is which of the two methods provides the best outcome in men with localised high-risk disease. Crucially, does the combination of RP and selective adjuvant EBRT provide clinically significant better outcomes compared with EBRT alone? ? In this review we discuss the current evidence for the role of RP for high-risk localised prostate cancer and define the parameters and urgent need for a prospective trial to test the role of surgery for this group of patients.     

Robot‐assisted laparoscopic prostatectomy is not associated with early postoperative radiation therapy

OBJECTIVE

To compare open radical prostatectomy (RP) and robot‐assisted laparoscopic prostatectomy (RALP), and to determine whether RALP is associated with a higher risk of features that determine recommendations for postoperative radiation therapy (RT).

PATIENTS AND METHODS

Patients undergoing RP from 2003 to 2007 were stratified into two groups: open RP and RALP. Preoperative (PSA level, T stage and Gleason score), pathological factors (T stage, Gleason score, extracapsular extension [ECE] and the status of surgical margins and seminal vesicle invasion [SVI]) and early treatment with RT or referral for RT within 6 months were compared between the groups. Multivariate analysis was used to control for selection bias in the RALP group.

RESULTS

In all, 904 patients were identified; 368 underwent RALP and 536 underwent open RP (retropubic or perineal). Patients undergoing open RP had a higher pathological stage with ECE present in 24.8% vs 19.3% in RALP (P = 0.05) and SVI in 10.3% vs 3.8% (P < 0.001). In the RALP vs open RP group, there were positive surgical margins in 31.5% vs 31.9% (P = 0.9) and there were postoperative PSA levels of ³ 0.2 ng/mL in 5.7% vs 6.3% (P = 0.7), respectively. On multivariate analysis to control for selection bias, RALP was not associated with indication for RT (odds ratio (OR) 1.10, P = 0.55), or referral for RT (OR 1.04, P = 0.86).

CONCLUSION

RALP was not associated with an increase in either indication or referral for early postoperative RT.     

Robotic radical prostatectomy as the initial step in multimodal therapy for men with high-risk localised prostate cancer: initial experience of 160 men

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? The choice of therapy with high‐risk localised prostate cancer is difficult and, in the stark absence of any randomised trials, comparative retrospective analyses of case series continue to be necessary. Radical surgery has been considered by many to be inferior to a combination of radiotherapy (RT) and androgen deprivation therapy (ADT), but this changing perhaps coincidentally with the widespread acceptance of robot‐assisted laparoscopic prostatectomy surgery (RALP). Further evidence has now described the long‐term toxicities related to ADT, and this has strengthened a desire amongst many to at least defer, if not avoid, ADT unless absolutely necessary. This article presents a single‐centre experience of RALP in the setting of high‐risk localised disease, and concludes that RALP incorporating the use of post‐operative RT represents a strong perhaps optimum management strategy.

OBJECTIVES

• ? To report the outcome of robotic‐assisted laparoscopic radical prostatectomy (RALP) for men with localised high‐risk prostate cancer at diagnosis.
• ? Although commonly managed by radiotherapy (RT) with prolonged androgen‐deprivation therapy (ADT), we hypothesize that initiation of multimodal therapy with RALP is oncologically efficacious and may allow many men to avoid ADT.

PATIENTS AND METHODS

• ? Between December 2003 and September 2010, 1480 men underwent RALP of whom 160 fulfilled the National Comprehensive Control Network criteria for high‐risk disease (prostate‐specific antigen (PSA) >20 ng/mL and/or clinical stage, cT ≥ 3 and/or biopsy Gleason score ≥8).
• ? Biochemical recurrence (postoperative PSA ≥ 0.2) was used to assess outcome after RALP monotherapy.
• ? Treatment failure was defined as either a rising PSA level after salvage RT or the initiation of ADT.

RESULTS

• ? The mean age ± standard deviation was 63.1 ± 6.3 years. Median PSA level was 9.95 ng/mL (interquartile range 6.0–21.4).
• ? Analysis of prostatectomy specimen showed Gleason 8–10 cancers in 65 (41%), and extracapsular disease, pT ≥ 3, in 96 (60%) of which seminal vesicle invasion was evident in 36 (23%). Downgrading by prostatectomy occurred in 64 (40% of total group) and five (3%) were downstaged to pT2 disease. By contrast, any upgrading occurred in 29 (18% of total group) and upstaging occurred in 68 (43%). The overall positive surgical margin rate was 38%, correlating with stage pT2 (15%) or pT3 (53%).
• ? With median follow‐up of 26.2 months (interquartile range 5.5–37.3), two non‐cancer‐related deaths have occurred (overall survival 98.8%; cancer‐specific survival 100%), and biochemical recurrence has occurred in 53 men (33%). RALP surgery has served as monotherapy (n= 117, 73%), or has been followed by salvage RT (n= 24, 15%) and/or ADT (n= 43, 27%). Overall 2‐year and 3‐year treatment failure was 31 and 41%, respectively.
• ? Serum PSA level was the only independent predictor of overall treatment failure (hazard ratio [HR] 1.02, P= 0.001) although a strong trend was observed for both clinical stage (HR 1.22, P= 0.058) and the number of positive biopsy cores on transrectal biopsy (HR 1.06, P= 0.057).

CONCLUSIONS

• ? RALP incorporating the use of postoperative RT is a good multimodal management strategy for men with this aggressive variant of prostate cancer.
• ? At median follow‐up in excess of 2 years, we found low rates of treatment failure enabling a high proportion of men to remain free of ADT.

     

The role of extended pelvic lymphadenectomy with radical prostatectomy for high-risk prostate cancer

IntroductionThe role of pelvic lymph node dissection (PLND) during radical prostatectomy (RP) for prostate cancer (PCa) is controversial. Despite extensive research in both patterns of lymphatic drainage and the clinical effect of lymph node involvement, the exact role of PLND in PCa is yet to be defined.MethodsA systematic search of the MEDLINE database was performed, and all relevant articles were reviewed in depth.ResultsWe included 84 relevant articles in our review and subdivided the information into the following categories: preoperative patient evaluation, procedure/extent of dissection, complications, and robotic surgery era. Most authors agree that the greatest benefit is seen in patients with high-risk PCa undergoing RP. Multiple imaging modalities have been evaluated for assistance in patient selection, but the use of preoperative nomograms appears to be the most helpful selection tool. The role of limited PLND vs. extended PLND (e-PLND) is yet to be defined, though many authors agree that e-PLND is preferred in the setting of high-risk PCa. Although PLND is associated with a higher incidence of complications, especially lymphocele formation, it is unclear whether e-PLND leads to more complications than limited PLND. The introduction of minimally invasive surgery may have had a negative effect on implementation of PLND in the appropriate patients undergoing RP.ConclusionDespite a lack of prospective, randomized trials evaluating PLND in RP, there does appear to be a consistent benefit in patients with high-risk disease.     

Early salvage radiation therapy does not compromise cancer control in patients with pT3N0 prostate cancer after radical prostatectomy: results of a match-controlled multi-institutional analysis

Background

Previous randomised trials demonstrated that adjuvant radiation therapy (aRT) improves cancer control in patients with pT3 prostate cancer (PCa). However, there is currently no evidence supporting early salvage radiation therapy (eSRT) as equivalent to aRT in improving freedom from biochemical recurrence (BCR) after radical prostatectomy (RP).

Objective

To evaluate BCR-free survival for aRT versus observation followed by eSRT in cases of relapse in patients undergoing RP for pT3pN0, R0–R1 PCa.

Design, setting, and participants

Using a European multi-institutional cohort, 890 men with pT3pN0, R0–R1 PCa were identified.

Intervention

All patients underwent RP. Subsequently, patients were stratified into two groups: aRT versus initial observation followed by eSRT in cases of relapse.

Outcome measurements and statistical analyses

Propensity-matched analysis was employed, and patients were stratified into two groups: aRT versus observation and eventual eSRT, defined as RT given at a postoperative serum prostate-specific antigen (PSA) ≤0.5 ng/ml at least 6 mo after RP. BCR, defined as PSA >0.20 ng/ml and rising after administration of RT, was compared between aRT and initial observation followed by eSRT in cases of relapse using Kaplan-Meier and Cox regression methods.

Results and limitations

Overall, 390 (43.8%) and 500 (56.2%) patients were treated with aRT and initial observation, respectively. Within the latter group, 225 (45.0%) patients experienced BCR and underwent eSRT. In the postpropensity-matched cohort, the 2- and 5-yr BCR-free survival rates were 91.4% and 78.4% in aRT versus 92.8% and 81.8% in patients who underwent initial observation and eSRT in cases of relapse, respectively (p = 0.9). No differences in the 2- and 5-yr BCR-free survival rates were found, even when patients were stratified according to pT3 substage and surgical margin status (all p ≥ 0.4). These findings were also confirmed in multivariable analyses (p = 0.6). Similar results were achieved when the cut-off to define eSRT was set at 0.3 ng/ml (all p ≥ 0.5).

Conclusions

The current study suggests that timely administration of eSRT is comparable to aRT in improving BCR-free survival in the majority of pT3pN0 PCa patients. Therefore, eSRT may not compromise cancer control but significantly reduces overtreatment associated with aRT.     

Midterm outcomes of four-port extraperitoneal laparoscopic radical prostatectomy for high-risk prostate cancer within Asian population

ObjectiveAsian patients tend to have higher stage prostate cancer at diagnosis compared with patients of other races. This article aims to investigate the use of four-port extraperitoneal laparoscopic radical prostatectomy (EPLRP) as the first step in a multimodality treatment strategy for Asian patients with high-risk prostate cancer (HRPC).Materials and methodsA cohort of 202 patients underwent EPLRP between January 2006 to January 2016, of whom 122 (60.3%) had HRPC as defined by D'Amico classification: clinical T stage ≥ cT2c or PSA level ≥ 20 ng/mL or biopsy Gleason sum ≥ 8). All patients underwent proper preoperative staging. The median age was 68 years (48–82), PSA level 17.8 ng/mL (3.3–191.1), and biopsy Gleason sum 7 (6–10). All patients underwent pelvic lymphadenectomy, and some underwent neurovascular bundle preservation according to their risk category.ResultsPerioperative outcomes included a median operative time of 185 min (65–380), total blood loss 150 ml (30–500), postoperative hospitalization 10 days (6–25), and urethral catheterization time 7 days (4–22). No patient was converted to open surgery. Median specimen weight was 42 g (19–124), lymph node yield was 10 (0–35) with 11.5% positivity and a positive surgical resection margin rate of 28.7%. The median follow-up period was 37 months (6–129). 96.7% of patients achieved continence and 53.8% of the 39 potent patients prior to surgery maintained their sexual potency at one year after EPLRP. The 5-year cancer-specific, overall, and biochemical recurrence-free survival rates were 98.8%, 92.2%, and 68.7%, respectively.ConclusionExtraperitoneal laparoscopic radical prostatectomy has low morbidity, and can provide fair functional and oncological outcomes as the first step of a multimodality treatment strategy for high-risk prostate cancer in Asian.     

Impact of performance status on efficacy of systemic therapy for prostate cancer: a meta-analysis

Objective

To evaluate the efficacy of systemic therapies in patients with worse performance status (PS) treated for high-risk non-metastatic prostate cancer (PCa), metastatic hormone-sensitive PCa (mHSPC), and non-metastatic/metastatic castration-resistant PCa (nmCRPC/mCRPC), as there is sparse pooled data showing the effect of PS on oncological outcomes in patients with PCa.

Methods

Three databases were queried in June 2022 for randomised controlled trials (RCTs) analysing patients with PCa treated with systemic therapy (i.e., adding androgen receptor signalling inhibitor [ARSI] or docetaxel [DOC] to androgen-deprivation therapy [ADT]). We analysed the oncological outcomes of patients with PCa with worse PS, defined as Eastern Cooperative Oncology Group PS ≥ 1, treated with combination therapies and compared these to patients with good PS. The main outcomes of interest were overall survival (OS), metastasis-free survival (MFS), and progression-free survival.

Results

Overall, 25 and 18 RCTs were included for systematic review and meta-analyses/network meta-analyses, respectively. In all clinical settings, combination systemic therapies significantly improved OS in patients with worse PS as well as in those with good PS, while the MFS benefit from ARSI in the nmCRPC setting was more pronounced in patients with good PS than in those with worse PS (P = 0.002). Analysis of treatment ranking in patients with mHSPC revealed that triplet therapy had the highest likelihood of improved OS irrespective of PS; specifically, adding darolutamide to DOC + ADT had the highest likelihood of improved OS in patients with worse PS. Analyses were limited by the small proportion of patients with a PS ≥ 1 (19%–28%) and that the number of PS 2 was rarely reported.

Conclusions

Among RCTs, novel systemic therapies seem to benefit the OS of patients with PCa irrespective of PS. Our findings suggest that worse PS should not discourage treatment intensification across all disease stages.