Genome gender diversity in affected sib-pairs with familial vesico-ureteric reflux identified by single nucleotide polymorphism linkage analysis

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Despite a lack of randomised controlled trials, most men with locally advanced prostate cancer are recommended to undergo external beam radiotherapy (EBRT), often combined with long‐term androgen‐deprivation therapy (ADT). Many of these men are not offered radical prostatectomy (RP) by their treating urologist. Additionally, it is know that EBRT with long‐term ADT does provide good cancer control (88% at 10 years). We have previously published intermediate‐term follow‐up of a large series of men treatment with RP for cT3 prostate cancer. We report long‐term follow‐up of a large series of men treated with RP as primary treatment for cT3 prostate cancer. Our study shows that with long‐term follow‐up RP provides excellent oncological outcomes even at 20 years. While most men do require a multimodal treatment approach, many men can be managed successfully with RP alone.

OBJECTIVE

• ? To present long‐term survival outcomes after radical prostatectomy (RP) for patients with cT3 prostate cancer, as the optimal treatment for patients with clinical T3 prostate cancer is debated.

PATIENTS AND METHODS

• ? We identified 843 men who underwent RP for cT3 tumours between 1987 and 1997.
• ? Survival was estimated using the Kaplan–Meier method.
• ? Cox proportional hazards regression models were used to evaluate the association of clinicopathological features with outcome

RESULTS

• ? The median (range) postoperative follow‐up was 14.3 (0.1–23.5) years.
• ? Down‐staging to pT2 disease occurred in 26% (223/843) at surgery.
• ? Local recurrence‐free, systemic progression‐free and cancer‐specific survival for men with cT3 prostate cancer after RP was 76%, 72%, and 81%, respectively, at 20 years.
• ? On multivariate analysis, increasing RP Gleason score (hazard ratio [HR] 1.8; P= 0.01), non‐diploid chromatin content (HR 1.8; P= 0.01), positive surgical margins (HR 2.1; P= 0.007), and seminal vesicle invasion (HR 2.1; P= 0.005) were associated with a significant risk of prostate cancer death, while a more recent year of surgery was associated with a decreased risk of cancer‐specific mortality (HR 0.88; P= 0.01)

CONCLUSIONS

• ? RP affords accurate pathological staging and may be associated with durable cancer control for cT3 prostate cancer, with 20 years of follow‐up presented here.
• ? RP as part of a multimodal treatment strategy therefore remains a viable treatment option for patients with cT3 tumours.

     

Biochemical outcome after high-dose-rate intensity modulated brachytherapy with external beam radiotherapy: 12 years of experience

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Biochemical control from series in which radical prostatectomy is performed for patients with unfavorable prostate cancer and/or low dose external beam radiation therapy are given remains suboptimal. The treatment regimen of HDR brachytherapy and external beam radiotherapy is a safe and very effective treatment for patients with high risk localized prostate cancer with excellent biochemical control and low toxicity.

OBJECTIVE

• ? To investigate the long‐term oncological outcome, during the PSA era, of patients with prostate cancer who were treated using high‐dose‐rate (HDR) brachy therapy (BT) combined with external beam radiation therapy (EBRT).

PATIENTS AND METHODS

• ? From June 1998 to April 2007, 313 patients with localized prostate cancer were treated with 46 Gy of EBRT to the pelvis with a HDR‐BT boost.
• ? The mean (median) follow‐up was 71 (68) months.
• ? Toxicity was reported according to the Common Toxicity Criteria for Adverse Event, V.4.

RESULTS

• ? The 10‐year actuarial biochemical control was 100% for patients with no high‐risk criteria, 88% for patients with two intermediate‐risk criteria, 91% with one high‐risk criterion and 79% for patients with two to three high‐risk criteria (P= 0.004).
• ? The 10‐year cancer‐specific survival was 97% (standard deviation ±1%).
• ? The multivariate Cox regression analyses identified, Gleason score and T stage as independent prognostic factors for biochemical failure.
• ? Gleason score was the only factor to significantly affect distant metastases.
• ? Grade ≥3 late toxicity was not detected.

CONCLUSION

• ? The 10‐year results confirm the feasibility and effectiveness of EBRT with conformal HDR‐BT boost for patients with localised prostate cancer.

     

Prediction of outcomes after radical prostatectomy in patients diagnosed with prostate cancer of biopsy Gleason score ≥ 8 via contemporary multi (≥ 12)-core prostate biopsy

Study Type – Prognostic (case series) Level of Evidence 4 What’s known on the subject? and What does the study add? Currently, controversy continues with regards to the efficacy of performing radical prostatectomy (RP) and the potential predictor of outcome after surgery in patients with prostate cancers of higher biopsy Gleason score. Among contemporary patients with biopsy Gleason score ≥8 who underwent RP alone, patients with pathologically organ‐confined disease demonstrated significantly better biochemical outcome than others. Serum PSA level and maximum tumour length in a biopsy core, independent predictors of organ‐confined disease, would be useful in the selection of candidates for RP among patients presenting with biopsy Gleason score ≥8.

OBJECTIVE

• ? To investigate the outcome of patients who underwent radical prostatectomy (RP) for prostate cancer of biopsy Gleason score ≥ 8 diagnosed via contemporary prostate biopsy.

PATIENTS AND METHODS

• ? We reviewed records of 151 patients who underwent RP for prostate cancer of biopsy Gleason score ≥ 8 detected via multi (≥12)‐core prostate biopsy without any neoadjuvant or adjuvant treatment.
• ? Preoperative predictors of pathologically organ‐confined disease along with biochemical recurrence‐free survival were analyzed via multivariate logistic regression and Cox proportional hazards model.

RESULTS

• ? For 151 total subjects, 5‐year estimated biochemical recurrence‐free survival rate was 41.0%. Patients with pathologically organ‐confined disease were observed to have much higher 5‐year biochemical recurrence‐free survival rate than those otherwise (72.1 vs 31.5%, P < 0.001).
• ? Serum PSA level (P= 0.031) and maximum tumour length in a biopsy core (P= 0.005) were observed to be significant preoperative predictors of having pathologically organ‐confined disease.
• ? As for biochemical recurrence‐free survival following RP, serum PSA (P= 0.023), biopsy Gleason score (P= 0.032), and percent of total tumour length in biopsy cores (P < 0.001) were observed be significant preoperative predictors on multivariate analysis.

CONCLUSION

• ? Among contemporary patients with biopsy Gleason score ≥ 8 who underwent RP alone, patients with pathologically organ‐confined disease demonstrated significantly better biochemical outcome than others. Serum PSA level and maximum tumour length in a biopsy core, independent predictors of organ‐confined disease, would be useful in the selection of candidates for RP among patients presenting with biopsy Gleason score ≥ 8.

     

Pathological stage distribution in patients treated with radical prostatectomy reflecting the need for protocol-based active surveillance: results from a contemporary European patient cohort

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Low‐risk prostate cancer is frequently diagnosed in the context of PSA screening or during a routine check‐up. For those patients, to avoid possible overtreatment AS is an increasingly chosen treatment option. However, the concept of AS could possibly misclassify potentially dangerous PCa as a low‐risk disease resulting in inferior cancer control outcomes. In the present study, we could demonstrate that the histopathological results of patients treated by RP in course of AS are significantly better if the selection criteria for AS are entirely fulfilled. Our findings underline the importance of a strict and precise admittance procedure for patients with early prostate cancer who are willing to undergo an AS programme.

OBJECTIVE

• ? To compare the histopathological outcomes of patients treated with radical prostatectomy (RP) after an initial active surveillance (AS) for localized, low‐risk prostate cancers (PCa) among men who fulfilled the Epstein criteria at diagnosis with those who did not.

PATIENTS AND METHODS

• ? In all, 283 patients with localized PCa were initially managed at our institution with AS.
• ? In all, ≈50% originated from the European Randomized Study of Screening for Prostate Cancer (ERSPC) participants from Switzerland: 75 (26.5%) patients underwent treatment during follow‐up and 61 were treated with RP (21.6%).
• ? These patients were stratified into those who did (n= 39) vs those who did not (n= 22) entirely fulfil AS inclusion criteria according to Epstein et al. at PCa diagnosis.

RESULTS

• ? Patients who did completely fulfil the AS inclusion criteria had significantly lower prostate‐specific antigen (PSA)‐values (4.9 vs 7.8 ng/mL; P= 0.02), a significantly lower PSA density at diagnosis (0.09 vs 0.2 ng/mL/ccm; P= 0.007) and at RP, a higher proportion of organ‐confined cancers (89.7% vs 59.1%, P= 0.02) and fewer positive surgical margins (25.6% vs 40.9%).
• ? However, the rate of favourable histopathological outcome, defined as organ‐confined disease with negative surgical margins, was statistically significantly higher in the group fulfilling AS criteria (69.2% vs 40.9%; P= 0.03).

CONCLUSIONS

• ? In our AS series, 26.5% of the patients underwent definitive therapy.
• ? Most patients treated with RP had organ‐confined disease in the majority of cases, especially when the Epstein criteria were rigorously fulfilled at PCa diagnosis.
• ? This underlines the importance of a strict and precise per protocol AS for patients with early PCa, otherwise there is a risk of missing more significant disease.

     

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.

     

Long‐term radical prostatectomy outcomes among participants from the European Randomized Study of Screening for Prostate Cancer (ERSPC) Rotterdam

Study Type – Therapy (cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Radical prostatectomy was previously shown to improve long‐term outcomes among men with clinically‐detected prostate cancer. Our data suggests that radical prostatectomy is also associated with improved outcomes in men with screen‐detected prostate cancer.

OBJECTIVE

• ? To examine the long‐term outcomes of radical prostatectomy (RP) among men diagnosed with prostate cancer from the screening and control arms of the Rotterdam section of the European Randomized Study of Screening for Prostate Cancer (ERSPC).

PATIENTS AND METHODS

• ? Among 42 376 men randomised during the period of the first round of the trial (1993–1999), 1151 and 210 in the screening and control arms were diagnosed with prostate cancer, respectively.
• ? Of these men, 420 (36.5%) screen‐detected and 54 (25.7%) controls underwent RP with long‐term follow‐up data (median follow‐up 9.9 years).
• ? Progression‐free (PFS), metastasis‐free (MFS) and cancer‐specific survival (CSS) rates were examined, and multivariable Cox proportional hazards models were used to determine whether screen‐detected (vs control) was associated with RP outcomes after adjusting for standard predictors.

RESULTS

• ? RP cases from the screening and control arms had statistically similar clinical stage and biopsy Gleason score, although screen‐detected cases had significantly lower prostate‐specific antigen (PSA) levels at diagnosis.
• ? Men from the screening arm had a significantly higher PFS (P= 0.003), MFS (P < 0.001) and CSS (P= 0.048).
• ? In multivariable models adjusting for age, PSA level, clinical stage, and biopsy Gleason score, the screening group had a significantly lower risk of biochemical recurrence (hazard ratio [HR] 0.43, 95% confidence interval [CI] 0.23–0.83, P= 0.011) and metastasis (HR 0.18, 95% CI 0.06–0.59, P= 0.005).
• ? Additionally adjusting for tumour volume and other RP pathology features, there was no longer a significant difference in biochemical recurrence between the screening and control arms.
• ? Limitations of the present study include lead‐time bias and non‐randomised treatment selection.

CONCLUSIONS

• ? After RP, screen‐detected cases had significantly improved PFS, MFS and CSS compared with controls within the available follow‐up time.
• ? The screening arm remained significantly associated with lower rates of biochemical recurrence and metastasis after adjusting for other preoperative variables.
• ? However, considering also RP pathology, the improved outcomes in the screening group appeared to be mediated by a significantly lower tumour volume.

     

Magnetic resonance imaging does not improve the prediction of misclassification of prostate cancer patients eligible for active surveillance when the most stringent selection criteria are based on the saturation biopsy scheme

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

OBJECTIVE

• ? To investigate the role of magnetic resonance imaging (MRI) in selecting patients for active surveillance (AS).

PATIENTS AND METHODS

• ? We identified prostate cancers patients who had undergone a 21‐core biopsy scheme and fulfilled the criteria as follows: prostate‐specific antigen (PSA) level ≤10 ng/mL, T1–T2a disease, a Gleason score ≤6, <3 positive cores and tumour length per core <3 mm.
• ? We included 96 patients who underwent a radical prostatectomy (RP) and a prostate MRI before surgery.
• ? The main end point of the study was the unfavourable disease features at RP, with or without the use of MRI as AS inclusion criterion.

RESULTS

• ? Mean age and mean PSA were 62.4 years and 6.1 ng/mL, respectively. Prostate cancer was staged pT3 in 17.7% of cases.
• ? The rate of unfavourable disease (pT3–4 and/or Gleason score ≥4 + 3) was 24.0%. A T3 disease on MRI was noted in 28 men (29.2%).
• ? MRI was not a significant predictor of pT3 disease in RP specimens (P = 0.980), rate of unfavourable disease (P = 0.604), positive surgical margins (P = 0.750) or Gleason upgrading (P = 0.314).
• ? In a logistic regression model, no preoperative parameter was an independent predictor of unfavourable disease in the RP specimen.
• ? After a mean follow‐up of 29 months, the recurrence‐free survival (RFS) was statistically equivalent between men with T3 on MRI and those with T1–T2 disease (P = 0.853).

CONCLUSION

• ? The results of the present study emphasize that, when the selection of patients for AS is based on an extended 21‐core biopsy scheme, and uses the most stringent inclusion criteria, MRI does not improve the prediction of high‐risk and/or non organ‐confined disease in a RP specimen.

     

Prognostic value of insulin-like growth factor II mRNA binding protein 3 in patients treated with radical prostatectomy

Study Type – Prognosis (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Insulin‐like growth factor II mRNA binding protein 3 (IMP3) is associated with poor outcomes in a variety of malignancies. The role of IMP3 in protate cancer remains poorly understood. IMP3 expression was associated with features of aggressive biology and aggressive prostate cancer recurrence after surgery. Although IMP3 is differentially expressed in patients with features of biologically aggressive prostate cancer, it does not have independent prognostic value in patients treated with RP.

OBJECTIVE

• ? To evaluate the association of insulin‐like growth factor II mRNA binding protein 3 (IMP3) with pathological features and outcomes in patients treated with radical prostatectomy (RP).

PATIENTS AND METHODS

• ? Immunohistochemical staining for IMP3 was performed on archival tissue microarray specimens from 232 consecutive patients treated with RP for clinically localized disease.
• ? None of the patients received neoadjuvant or adjuvant radiation or hormone therapy.
• ? IMP3 expression was histologically categorized as normal or abnormal.
• ? Disease recurrence was classified as aggressive if metastases were present, post‐recurrence prostate‐specific antigen (PSA) doubling time was less than 10 months, or if the patients failed to respond to salvage local radiation therapy.

RESULTS

• ? The median follow‐up was 69.8 months (interquartile range [IQR]: 40.1–99.5).
• ? IMP3 expression was abnormal in 42 (18.1%) of 232 patients.
• ? IMP3 expression was associated with extracapsular extension (P= 0.020), seminal vesicle invasion (P= 0.024), lymphovascular invasion (P= 0.036) and a high pathological Gleason score (P= 0.009).
• ? The 5‐year PSA recurrence‐free survival for IMP3‐negative patients was 83% (standard error [SE]= 3) vs 67% (SE = 8) in IMP3‐positive patients (log‐rank test, P= 0.015).
• ? In a multivariable analysis that adjusted for the effects of surgical margins, extracapsular extension and seminal vesicle invasion, PSA (hazard ratio [HR]: 1.04, P= 0.013), lymph node metastasis (HR: 16.7, P < 0.001) and a high pathological Gleason score (HR 4.3, P= 0.008) were significantly associated with PSA recurrence‐free survival, whereas IMP3 expression was not (P= 0.11). Similarly, IMP3 expression was only associated with aggressive recurrence (HR 3.2, P= 0.006).

CONCLUSION

• ? IMP3 expression is abnormal in approximately one‐fifth of prostate cancers. Although IMP3 is differentially expressed in patients with features of biologically aggressive prostate cancer, it does not have an independent prognostic value in patients treated with RP.

     

Overactive bladder syndrome: an underestimated long‐term problem after treatment of patients with localized prostate cancer?

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? In this study we observed courses of micturition symptoms and differentiated degrees of symptoms for each point in time while also considering the impact of bothersomeness. Our data show that not only significantly more patients who have undergone BT suffer from OAB than those who have undergone RP, but also that those affected show significantly higher values for severity of OAB symptoms throughout the whole observation period of 36 months. Our data analysis further shows that variability of OAB symptoms as well as fluctuation of severity of OAB symptoms vary to a significantly higher degree after BT than after RP. Looking only at mean figures at a given point in time clearly underestimates the underlying problem. This fact is not reflected in the literature.

OBJECTIVE

• ? To look at individual courses of postoperative micturition symptoms, especially urgency, in patients treated either with radical prostatectomy (RP) or with brachytherapy (BT).

PATIENTS AND METHODS

• ? In a prospective longitudinal study we investigated individual changes in micturition symptoms before treatment, and 6, 12, 24 and 36 months after treatment.
• ? All patients received the European Organization for the Research and Treatment of Cancer quality‐of‐life questionnaire, QLQ‐C30, and the International Continence Society male questionnaire at each assessment.
• ? We looked at long‐term results as well as changes in time using repeated measures analysis of variance. We further analysed fluctuation of symptoms using sum of changes.

RESULTS

• ? Of the 389 patients treated consecutively in our clinic over the last few years, 99 patients with a mean (sd ) age of 65 (6.3) years had completed all five questionnaires and thus were further analysed. Of these, 66 (66.7%) were treated with RP and 33 (33.3%) with BT.
• ? With the exception of age, no significant difference was found between the treatment groups either in physical functioning or in prevalence and severity of overactive bladder (OAB) symptoms.
• ? Adjusted for age and pretreatment symptoms in analysis of covariance, we found that there were statistically more symptoms of OAB 36 months after BT compared with those patients treated with RP (P < 0.025). Whereas 30% of patients complained about severe symptoms of urgency after BT, only 11% did so after RP.
• ? Changes of severity of OAB symptoms over the course of time (P < 0.007) using analysis of repeated measures as well as variability of OAB symptoms (P < 0.033) using the two‐sided Wilcoxon t‐test were significantly higher in patients treated with BT than in patients treated with RP.

CONCLUSIONS

• ? Independently of age and physical functioning, BT is significantly associated with higher rates of long‐term urgency symptoms, even after 3 years.
• ? Repeated measurements show that OAB symptoms are highly fluctuating and that in patients treated with BT, severity of symptoms as well as variability of symptoms was significantly higher than in those patients treated with RP.
• ? Persistent OAB seems to be an underestimated problem after treatment for localized prostate cancer, especially in patients treated with BT.

     

Impact of surgical margin status on prostate‐cancer‐specific mortality

Study Type – Diagnostic (exploratory cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Surgical margin status at radical prostatectomy (RP) has been shown to be a predictor of disease progression and the strongest predictor of benefit from adjuvant therapy, but the impact of a positive surgical margin (PSM) on long‐term prostate‐cancer‐specific survival is unknown. The PSM rate is dependent on the pathological stage of the cancer. In a recent multicentre nomogram for 15‐year prostate‐cancer‐specific mortality (PCSM) after RP, PSM was not significantly associated with PCSM, while Gleason score and pathological stage were the only significant predictors. This has not been validated in a single centre, and PSM has been shown to vary greatly with surgical technique. This is the first study on the impact of PSM on PCSM in a single surgeon's cohort. In other centres, the decision to administer adjuvant therapy may be influenced by surgical margin status. In this cohort, men routinely did not receive adjuvant therapy, affording the unique opportunity to study the long‐term implications of a PSM.

OBJECTIVE

• ? To examine the relative impact of a positive surgical margin (PSM) and other clinicopathological variables on prostate‐cancer‐specific mortality (PCSM) in a large retrospective cohort of patients undergoing radical prostatectomy (RP).

PATIENTS AND METHODS

• ? Between 1982 and 2011, 4569 men underwent RP performed by a single surgeon.
• ? Of the patient population, 4461 (97.6%) met all the inclusion criteria.
• ? The median (range) age was 58 (33–75) years and the median prostate‐specific antigen (PSA) was 5.4 ng/mL; RP Gleason score was ≤6 in 2834 (63.7%), 7 in 1351 (30.3%), and 8–10 in 260 (6.0%) patients; PSMs were found in 462 (10.4%) patients.
• ? Cox proportional hazards models were used to determine the impact of a PSM on PCSM.

RESULTS

• ? At a median (range) follow‐up of 10 years (1–29), 187 men (4.3%) had died from prostate cancer.
• ? The 20‐year prostate‐cancer‐specific survival rate was 75% for those with a PSM and 93% for those without.
• ? Compared with those with a negative surgical margin, men with a PSM were more likely to be older (median age 60 vs 58 years) and to have undergone RP in the pre‐PSA era (36.6% vs 11.8%). Additionally, they were more likely to have a higher PSA level (median 7.6 vs 5.2 ng/mL), a Gleason score of ≥7 (58.7% vs 33.7%), and a non‐organ‐confined tumour (90.9% vs 30.6% [P < 0.001 for all]).
• ? In a univariate model for PCSM, PSM was highly significant (hazard ratio [HR] 5.0, 95% confidence interval [CI] 3.7–6.7, P < 0.001).
• ? In a multivariable model, adjusting for pathological variables and RP year, PSM remained an independent predictor of PCSM (HR 1.4, 95% CI 1.0–1.9, P= 0.036) with a modest effect relative to RP Gleason score (HR 5.7–12.6) and pathological stage (HR 2.2–11.0 [P < 0.001]).

CONCLUSION

• ? Although a PSM has a statistically significant adverse effect on prostate‐cancer‐specific survival in multivariable analysis, Gleason grade and pathological stage were stronger predictors.

     

Irbesartan promotes erection recovery after nerve‐sparing radical retropubic prostatectomy: a retrospective long‐term analysis

Study Type – Therapy (retrospective cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Erectile dysfunction following radical prostatectomy (RP) is among the most common and dreaded adverse effects of the surgery. Multiple studies confirm the potential benefit of various drug classes to accelerate the return of erectile function (EF) after RP. There is pre‐clinical evidence supporting the use of angiotensin‐receptor blockers (ARBs) for this purpose, although this has not been studied in humans. The present study shows that there may be a benefit in the recovery of EF post‐RRP in patients taking a daily dose of irbesartan, an ARB, following RRP. In addition, the use of irbesartan may curb the loss of stretched penile length which occurs postoperatively. Further study in the form of prospective, randomized, placebo‐controlled clinical trials are necessary to confirm these findings.

OBJECTIVE

• ? To evaluate retrospectively the potential benefit of administering irbesartan, an angiotensin‐receptor blocker, to improve erectile function (EF) recovery after nerve‐sparing radical retropubic prostatectomy (RRP).

PATIENTS AND METHODS

• ? Before surgery potent patients who underwent nerve‐sparing RRP between April and December 2009 elected to start daily oral irbesartan 300 mg on postoperative day 1 (n= 17). A contemporaneously clinically matched cohort consisting of patients who declined irbesartan use served as the control group (n= 12).
• ? Postoperative ‘on demand’ use of erectile aids (phosphodiesterase type 5 [PDE5] inhibitors and intracavernous injections) was adopted.
• ? Potency was monitored by the administration of International Index of Erectile Function‐5 (IIEF‐5) questionnaires before surgery and at early (3 months) and long‐term (12 and 24 months) postoperative intervals.
• ? Stretched penile length (SPL) was measured both immediately and 3 months after surgery.

RESULTS

• ? EF status was no different between groups at baseline (P > 0.05).
• ? While the IIEF‐5 scores at 24 months after surgery were statistically similar between the two groups (control = 15.2 ± 2.0, irbesartan = 14.1 ± 3.1, P= 0.77), at 12 months the IIEF‐5 scores of the irbesartan group were significantly higher than those of the control group (14 ± 2.6 vs. 7.2 ± 1.6, P < 0.05).
• ? The proportional loss of SPL after RRP was less in the irbesartan than in the control group at 3 months (–0.9 ± 1.5% vs –5.6 ± 1.5, P < 0.05).

CONCLUSION

• ? Regular irbesartan use after nerve‐sparing RRP in patients with normal preoperative erectile function could improve EF recovery after surgery and mitigate early loss of SPL.

     

The impact of nerve sparing on incidence and location of positive surgical margins in radical prostatectomy

Study Type – Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Nerve sparing radical prostatectomy has been associated with increased risk of positive surgical margins due to the close anatomical relationship of the neurovascular bundle to the posterolateral aspect of the prostatic fascia. Our study of 945 men who underwent radical prostatectomy be one experienced surgeon found no increased risk of positive surgical margins, whether the cancer was organ confined or extracapsular extension was present.

OBJECTIVE

• ? To examine whether nerve‐sparing surgery (NSS) is a risk factor for positive surgical margins (PSMs) in patients with either organ‐confined prostate cancer or extracapsular extension (ECE).

PATIENTS AND METHODS

• ? Clinicopathological outcome data on 945 consecutive patients treated with radical prostatectomy (RP) were prospectively collected.
• ? All patients underwent RP (bilateral, unilateral or non‐NSS) by one surgeon between 2002 and 2007.
• ? Risk of PSMs and their locations with respect to NSS was determined by multivariate logistic regression analysis adjusting for preoperative risk factors for PSMs within pT2, pT3a and pT3b tumours.

RESULTS

• ? Overall a PSM was identified in 19.6% of patients in an unscreened population with mean prostate‐specific antigen (PSA) level of 8.1 ng/mL.
• ? There was no significant difference in rates of PSMs between NSS groups on multivariate analysis (P= 0.147).
• ? There was no significant difference in pT2 (P= 0.880), pT3a (P= 0.175) or pT3b (P= 0.354) tumours.
• ? The only significant predictor of PSMs was preoperative PSA level (risk ratio 1.289, P= 0.006).
• ? There was no significant difference in the location of PSMs except for the pT3a group, where the patients that had bilateral NSS were at higher risk of a posterolateral PSM (P= 0.028).

CONCLUSIONS

• ? With appropriate selection of patients, NSS does not increase the risk of PSMs, whether the cancer is organ confined or ECE is present.
• ? The adverse impact of the NSS procedure in the hands of an experienced surgeon is minimal and is a realistic compromise to obtain the increase in health‐related quality of life offered by NSS.

     

Comparison of the rate, location and size of positive surgical margins after laparoscopic and robot-assisted laparoscopic radical prostatectomy

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

OBJECTIVE

• ? To review and compare the rate, location and size of positive surgical margins (PSMs) after pure laparoscopic radical prostatectomy (LRP) and robot‐assisted laparoscopic radical prostatectomy (RALP).

PATIENTS AND METHODS

• ? The study comprised 200 patients who underwent RALP and 200 patients who underwent LRP up to January 2008.
• ? We compared patient age, body mass index, preoperative prostate‐specific antigen (PSA), preoperative stage and grade, prostate size, pathological stage and grade and neurovascular bundle preservation, as well as PSM rate, size and location.
• ? Continuous and categorical data were compared using Student’s t‐test and Pearson’s chi‐squared test.
• ? Multivariate regression analyses were used to identify preoperative and intraoperative predictors of PSMs.

RESULTS

• ? Although the PSM rate was similar between the two groups (LRP: 12% vs RALP: 13.5%; P= 0.76), location and size were not. PSMs after LRP were mostly at the apex (58.3%; P= 0.038), while most PSMs after RALP were posterolateral ([PL] 48%; P= 0.046).
• ? In addition, the median margin size after RALP was significantly smaller than after LRP (RALP: 2 mm vs LRP: 3.5 mm; P= 0.041).
• ? In univariate and multivariate analyses, tumour‐node‐metastasis (TNM) stage and preoperative PSA were the only independent preoperative predictors of PSMs (P= 0.044 and P= 0.01, respectively).

CONCLUSION

• ? The PSM risk is dependent on TNM stage and preoperative PSA and not the surgical technique, when comparing LRP with RALP.

     

Age‐related changes in prostate zonal volumes as measured by high‐resolution magnetic resonance imaging (MRI): a cross‐sectional study in over 500 patients

Study Type – Diagnosis (case series) Level of Evidence 4 What's known on the subject? and What does the study add? Benign prostatic hyperplasia is the most common symptomatic disorder of the prostate and its severity varies greatly in the population. Various methods have been used to estimate prostate volumes in the past including the digital rectal examination and ultrasound measurements. High‐resolution T2 weighted MRI can provide accurate measurements of zonal volumes and total volumes, which can be used to better understand the etiology of lower urinary tract symptoms of men.

OBJECTIVE

• ? To use ability of magnetic resonance imaging (MRI) to investigate age‐related changes in zonal prostate volumes.

PATIENTS AND METHODS

• ? This Institutional Review Board approved, Health Insurance Portability and Accountability Act‐compliant study consisted of 503 patients who underwent 3 T prostate MRI before any treatment for prostate cancer.
• ? Whole prostate (WP) and central gland (CG) volumes were manually contoured on T2‐weighted MRI using a semi‐automated segmentation tool. WP, CG, peripheral zone (PZ) volumes were measured for each patient.
• ? WP, CG, PZ volumes were correlated with age, serum prostate‐specific antigen (PSA) level, International Prostate Symptom Score (IPSS), Sexual Health Inventory for Men (SHIM) scores.

RESULTS

• ? Linear regression analysis showed positive correlations between WP, CG volumes and patient age (P < 0.001); there was no correlation between age and PZ volume (P= 0.173).
• ? There was a positive correlation between WP, CG volumes and serum PSA level (P < 0.001), as well as between PZ volume and serum PSA level (P= 0.002).
• ? At logistic regression analysis, IPSS positively correlated with WP, CG volumes (P < 0.001).
• ? SHIM positively correlated with WP (P= 0.015) and CG (P= 0.023) volumes.
• ? As expected, the IPSS of patients with prostate volumes (WP, CG) in first decile for age were significantly lower than those in tenth decile.

CONCLUSIONS

• ? Prostate MRI is able to document age‐related changes in prostate zonal volumes.
• ? Changes in WP and CG volumes correlated inversely with changes in lower urinary tract symptoms.
• ? These findings suggest a role for MRI in measuring accurate prostate zonal volumes; have interesting implications for study of age‐related changes in the prostate.

     

Positive predictive value of prostate biopsy indicated by prostate‐specific‐antigen‐based prostate cancer screening: trends over time in a European randomized trial*

Study Type – Diagnosis (validating cohort) Level of Evidence 1b What's known on the subject? and What does the study add? The European Randomized study of Screening for Prostate Cancer (ERSPC) showed a reduction in prostate cancer mortality of 21% for PSA‐based screening at a median follow‐up of 11 years. In the ERSPC, men are screened at 4‐year intervals. A prostate biopsy is recommended for men with a PSA level ≥3.0 ng/mL. The study shows that the positive predictive value (PPV) of a prostate biopsy indicated by PSA‐based screening remains equal throughout consecutive screening rounds in men without a previous biopsy. In men who have previously had a benign biopsy, the PPV drops considerably, but 20% of the cancers detected still show aggressive characteristics.

OBJECTIVE

• ? To assess the positive predictive value (PPV) of prostate biopsy, indicated by a prostate‐specific antigen (PSA) threshold of ≥3.0 ng/mL, over time, in the Rotterdam section of the European Randomized study of Screening for Prostate Cancer (ERSPC).

PATIENTS AND METHODS

• ? In the Rotterdam section of the ERSPC, a total of 42 376 participants, aged 55–74 years, identified from population registries were randomly assigned to a screening or control arm.
• ? For the ERSPC men undergo PSA screening at 4‐year intervals. A total of three screening rounds were evaluated; therefore, only men aged 55–69 years at the first screening were eligible for the present study.

RESULTS

• ? PPVs for men without previous biopsy remained equal throughout the three subsequent screenings (25.5, 22.3 and 24.8% respectively).
• ? Conversely, PPVs for men with a previous negative biopsy dropped significantly (12.0 and 15.2% at the second and third screening, respectively).
• ? Additionally, in men with and without previous biopsy, the percentage of aggressive prostate cancers (clinical stage >T2b, Gleason score ≥7) decreased after the first round of screening from 44.4 to 23.8% in the second (P < 0.001) and 18.6% in the third round (P < 0.001).
• ? Repeat biopsies accounted for 24.6% of all biopsies, but yielded only 8.6% of all aggressive cancers.

CONCLUSIONS

• ? In consecutive screening rounds the PPV of PSA‐based screening remains equal in previously unbiopsied men.
• ? In men with a previous negative biopsy the PPV drops considerably, but 20% of cancers detected still show aggressive characteristics.
• ? Individualized screening algorithms should incorporate previous biopsy status in the decision to perform a repeat biopsy with the aim of further reducing unnecessary biopsies.

     

Lower urinary tract symptoms and urinary incontinence in a geriatric cohort – a population‐based analysis

Study Type – Symptom prevalence (prospective cohort) Level of Evidence 1b What's known on the subject? and What does the study add? Prevalence and severity of urinary incontinence and lower urinary tract symptoms increase with age and have a considerable negative influence on quality of life. As a result of demographic changes the proportion of octogenarians will increase in the next decades substantially, yet the literature on urinary incontinence and lower urinary tract symptoms of the oldest old is scant. This population‐based study of 85‐year‐old subjects sheds new light on this topic.

OBJECTIVES

• ? To assess prevalence and severity of lower urinary tract function in 85‐year‐old men and women.
• ? Little is known on the prevalence of lower urinary tract dysfunction in this geriatric age group, which is now the fastest growing sector of the population worldwide.

PATIENTS AND METHODS

• ? The Vienna Trans‐Danube Aging study (VITA) is a longitudinal, population‐based study initiated in 2000 that included men/women aged 75 years living in a well‐defined area in Vienna.
• ? The main purpose of the VITA study was to identify risk factors for incident Alzheimer's disease.
• ? All study participants alive in 2010 were contacted by mail to complete a detailed questionnaire on various aspects of lower urinary tract symptoms (LUTS) and urinary incontinence (UI).

RESULTS

• ? The response rate was 68%, resulting in a total of 262 questionnaires available for analysis (men n= 96; women n= 166). All study participants were 85 years of age.
• ? Urinary incontinence defined as any involuntary loss during the past 4 weeks was reported by 24% of men and 35% of women (P= 0.04). Stress UI was more frequent in women (39%) than in men (14%, P < 0.01), the difference for urge UI (women 35%, men 25%) was on the border of statistical significance (P= 0.05). Only four individuals (1.5%) needed permanent catheterization.
• ? Urgency (women 56%, men 54%) and daytime frequency (women 70%, men 74%) were equally distributed (P > 0.05). Nocturia more often than twice was more prevalent in men (69%) than in women (49%) (P= 0.02). Overactive bladder, according to International Continence Society criteria, was present in 55% of women and 50% of men.
• ? No difference regarding quality of life impairment as the result of LUTS and UI was noticed between sexes. A few co‐morbidities were identified to correlate with UI and storage symptoms.

CONCLUSIONS

• ? These data provide insights into the prevalence and severity of LUTS and UI in individuals in their eighties, to our knowledge the largest population‐based study in this age group.
• ? Demographic changes in upcoming decades underline the importance of a thorough understanding of lower urinary tract dysfunction in a geriatric population.

     

Contrast-enhanced ultrasonography with contrast-tuned imaging technology for the detection of prostate cancer: comparison with conventional ultrasonography

Study Type – Diagnostic (exploratory cohort) Level of Evidence 2b What's known on the subject? and What does the study add? The present study was to perform contrast‐tuned imaging (CnTI) technology to detect prostate cancer and compare the use of CnTI technology for the detection of prostate cancer with conventional ultrasonography. The preliminary data from our study suggested that targeted biopsy of the prostate with CnTI technology could improve the cancer detection and detect higher grade prostate cancers.

OBJECTIVES

• ? To perform contrast‐enhanced ultrasonography (CEUS) using contrast‐tuned imaging (CnTI) technology to detect prostate cancer.
• ? To evaluate the detection of prostate cancer with CnTI compared with conventional grey‐scale and power Doppler ultrasonography.

PAIENTS AND METHODS

• ? In all, 150 patients referred for prostate biopsy were evaluated using transrectal grey‐scale, power Doppler and CnTI ultrasonography.
• ? Biopsy was performed at 10 sites in each patient. If an abnormality was found at any of these three ultrasonography examinations, a biopsy specimen was targeted towards from the corresponding site.
• ? The performances of the three ultrasonography techniques for prostate cancer detection were compared.

RESULTS

• ? Prostate cancer was detected at 383 sites from 73 patients. The combination of these three examinations detected more patients with prostate cancer than grey‐scale (P= 0.002), power Doppler (P= 0.001) or baseline imaging (the combination of grey‐scale and power Doppler; P= 0.031) alone.
• ? By biopsy site, CnTI had higher sensitivity and accuracy (73.1% and 83.7%) than grey‐scale (50.9%; P < 0.001 and 78.8%; P < 0.001) or power Doppler (48.3%; P < 0.001 and 77.7%; P < 0.001), while the specificity was similar for grey‐scale (88.4%), power Doppler (87.8%) and CnTI (87.3%; P > 0.05 in each case). CnTI had higher sensitivity (73.1% vs 62.9%; P < 0.001), specificity (87.3% vs 82.1%; P < 0.001) and accuracy (83.7% vs 77.2%; P < 0.001) than baseline imaging.
• ? The mean Gleason score of CnTI‐positive cases was significantly higher than CnTI‐negative cases (7.1 vs 6.3; P= 0.002).

CONCLUSIONS

• ? CEUS using CnTI technology enables a visualization of the microvasculature associated with prostate cancer.
• ? CnTI technology could be used to guide biopsy and improve the detection rate of prostate cancer.
• ? CnTI technology was able to detect higher grade prostate cancers.

     

Impact of a tertiary Gleason pattern 4 or 5 on clinical failure and mortality after radical prostatectomy for clinically localised prostate cancer

Study Type – Prognosis (case series) Level of Evidence 4 What's known on the subject? and What does the study add? It is known that a tertiary Gleason grade pattern 4 or 5 found in RP specimens has a negative impact on recurrence rate regarding biochemical relapse after radical prostatectomy. This is the first publication addressing clinical outcome in patients with a tertiary Gleason grade pattern 4 or 5 showing a negative influence on clinical failure rates.

OBJECTIVE

• ? To investigate the impact of a tertiary Gleason grade (TGG) pattern 4 or 5 on clinical failure, as the presence of a TGG pattern 4 or 5 in radical prostatectomy (RP) specimens has been associated with biochemical failure.

PATIENTS AND METHODS

• ? In all, 151 consecutive patients undergoing RP between 1985 and 2006 were reviewed, and 148 patients met study inclusion criteria.
• ? The RP specimens were pathologically re‐examined and the presence of a TGG pattern 4 or 5 was recorded.
• ? The endpoint was clinical failure defined as local recurrence and/or development of metastasis at a mean follow‐up of 108 months.
• ? Univariate analyses were performed using the Kaplan–Meier method. Multivariate analyses were performed using Cox proportional hazards regression.

RESULTS

• ? Clinical failure was more likely among men with presence of a TGG pattern 4 or 5 than in men without a TGG pattern 4 or 5 (P= 0.006). In the subgroup of patients with Gleason score 7 the presence of a TGG 5 was significantly associated with clinical failure rate (P= 0.002).
• ? In patients with Gleason score <7 or >7, a TGG pattern 4 or 5 was not associated with increased failure rates.
• ? Multivariate Cox regression analyses in patients with Gleason score 7 showed that a TGG pattern 5 was a statistically significant predictor of clinical failure when adjusting for pathological stage, surgical margin status, extraprostatic extension and seminal vesicle invasion (hazard ratio 4.03, 95% confidence interval 1.72–9.46; P= 0.001).
• ? Further subgroup analyses showed that a TGG pattern 5 was associated with statistically higher clinical progression rates in patients with Gleason score 3 + 4 (P= 0.03).
• ? In patients with Gleason score 4 + 3, a TGG pattern 5 was associated with a trend towards a higher clinical progression rate, although this was not statistically significant (P= 0.189).

CONCLUSION

• ? A TGG pattern 4 or 5 is associated with decreased clinical recurrence‐free survival in Gleason score 7.

     

Preoperative characteristics of high-Gleason disease predictive of favourable pathological and clinical outcomes at radical prostatectomy

Study Type – Diagnostic (exploratory cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Men with high‐risk prostate cancer experience recurrence, metastases and death at the highest rate in the prostate cancer population. Pathological stage at radical prostatectomy (RP) is the greatest predictor of recurrence and mortality in men with high‐grade disease. Preoperative models predicting outcome after RP are skewed by the large proportion of men with low‐ and intermediate‐risk features; there is a paucity of data about preoperative criteria to identify men with high‐grade cancer who may benefit from RP. The present study adds comprehensive biopsy data from a large cohort of men with high‐grade prostate cancer at biopsy. By adding biopsy parameters, e.g. number of high‐grade cores and >50% involvement of any core, to traditional predictors of outcome (prostate‐specific antigen concentration, clinical stage and Gleason sum), we can better inform men who present with high‐grade prostate cancer as to their risk of favourable or unfavourable disease at RP.

OBJECTIVE

• ? To investigate preoperative characteristics that distinguish favourable and unfavourable pathological and clinical outcomes in men with high biopsy Gleason sum (8–10) prostate cancer to better select men who will most benefit from radical prostatectomy (RP).

PATIENTS AND METHODS

• ? The Institutional Review Board‐approved institutional RP database (1982–2010) was analysed for men with high‐Gleason prostate cancer on biopsy; 842 men were identified.
• ? The 10‐year biochemical‐free (BFS), metastasis‐free (MFS) and prostate cancer‐specific survival (CSS) were calculated using the Kaplan–Meier method to verify favourable pathology as men with Gleason <8 at RP or ≤ pT3a compared with men with unfavourable pathology with Gleason 8–10 and pT3b or N1.
• ? Preoperative characteristics were compared using appropriate comparative tests.
• ? Logistic regression determined preoperative predictors of unfavourable pathology.

RESULTS

• ? There was favourable pathology in 656 (77.9%) men. The 10‐year BFS, MFS and CSS were 31.0%, 60.9% and 74.8%, respectively.
• ? In contrast, men with unfavourable pathological findings had significantly worse 10‐year BFS, MFS and CSS, at 4.3%, 29.1% and 52.3%, respectively (all P < 0.001).
• ? In multivariable logistic regression, a prostate‐specific antigen (PSA) concentration of >10 ng/mL (odds ratio [OR] 2.24, 95% confidence interval [CI] 1.38–3.62, P= 0.001), advanced clinical stage (≥ cT2b; OR 2.55, 95% CI 1.55–4.21, P < 0.001), Gleason pattern 9 or 10 at biopsy (OR 2.55, 95% CI 1.59–4.09, P < 0.001), increasing number of cores positive with high‐grade cancer (OR 1.16, 95% CI 1.01–1.34, P= 0.04) and >50% positive core involvement (OR 2.25, 95% CI 1.17–4.35, P= 0.015) were predictive of unfavourable pathology.

CONCLUSIONS

• ? Men with high‐Gleason sum at biopsy are at high risk for biochemical recurrence, metastasis and death after RP; men with high Gleason sum and advanced pathological stage (pT3b or N1) have the worst prognosis.
• ? Among men with high‐Gleason sum at biopsy, a PSA concentration of >10 ng/mL, clinical stage ≥ T2b, Gleason pattern 9 or 10, increasing number of cores with high‐grade cancer and >50% core involvement are predictive of unfavourable pathology.

     

Comparison of oncological outcomes of transperitoneal and retroperitoneal laparoscopic radical nephrectomy for the management of clear‐cell renal cell carcinoma: a multi‐institutional study

Study Type – Therapy (case series)
Level of Evidence 4 What’s known on the subject? and What does the study add? Laparoscopic radical nephrectomy (LRN) can be performed by a retroperitoneal approach with similar efficacy compared to the transperitoneal approach. However, the oncological acceptance of LRN has been based on studies which have been carried out primarily by transperitoneal approach, and oncological results of the retroperitoneal approach alone are lacking. Our study confirmed that retroperitoneal laparoscopic radical nephrectomy is oncologically‐equivalent to transperitoneal approach in homogeneous group with the final pathological diagnosis of clear cell RCC.

OBJECTIVE

• ? To investigate the oncological efficacy of retroperitoneal laparoscopic radical nephrectomy (RLRN) compared with transperitoneal laparoscopic radical nephrectomy (TLRN) for the management of clear‐cell renal cell carcinoma (RCC).

PATIENTS AND METHODS

• ? With emphasis on survival and disease recurrence, a retrospective analysis was made of 580 patients who underwent TLRN (472 patients) or RLRN (108 patients) at 23 institutions between January 1997 and December 2007.
• ? Inclusion criteria were clear‐cell RCC, stage pT1 to pT2 without any nodal involvement, and metastasis.
• ? Overall survival and recurrence‐free survival curves were estimated using the Kaplan–Meier method.
• ? To assess the association between the surgical approach and survival outcomes, Cox proportional hazard models were constructed.

RESULTS

• ? The median follow‐up was 30 months in the TLRN group and 35.6 months in the RLRN group. Both groups were comparable regarding age, gender, body mass index (BMI), Fuhrman’s grade, size of tumours and stage.
• ? Kaplan–Meier curves and the log‐rank test showed no significant difference between the TLRN and RLRN groups in 5‐year overall (92.6% vs 94.5%; P = 0.669) and recurrence‐free survival (92.0% vs 96.2%; P = 0.244).
• ? In a Cox regression model with age, gender, Eastern Cooperative Oncology Group performance status, BMI, nuclear grade and T‐stage adjusted variables, no significant difference was found between the two surgical approaches.

CONCLUSION

• ? The present study is the largest oncological analysis for laparoscopic radical nephrectomy (LRN) comparing transperitoneal and retroperitoneal approaches. The data from it provide the objective evidence to suggest similar oncological outcomes for both approaches to LRN.