Tag Archive for: radical prostatectomy

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Article of the Week: 68Ga-PSMA has high detection rate of PCa recurrence after RP

Every Week the Editor-in-Chief selects an Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an accompanying editorial written by a prominent member of the urological community. This blog is intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation.

If you only have time to read one article this week, it should be this one.

68Ga-PSMA has high detection rate of prostate cancer recurrence outside the prostatic fossa in patients being considered for salvage radiation treatment

 

Pim J. van Leeuwen*, Phillip Stricker*, George Hruby§, Andrew Kneebone§Francis Ting*, Ben Thompson, Quoc Nguyen, Bao Ho** and Louise Emmett**,††

 

*St Vincents Prostate Cancer Centre, St Vincents Clinic, Sydney, NSWAustralian Prostate Cancer Research Centre – New South Wales, Garvan Institute of Medical Research/Kinghorn Cancer Centre, Sydney, NSWRadiation Oncology Department, Northern Sydney Cancer Centre, Royal North Shore Hospital, St Leonards, NSW§University of Sydney, Sydney, NSWNorthern Clinical School, University of Sydney, St Leonards, NSW, **Department of Diagnostic Imaging, St Vincents Public Hospital, Sydney, NSW, and ††University of New South Wales, Sydney, NSW, Australia

 

Objectives

To examine the detection rates of 68Ga-PSMA-positron emission tomography (PET)/computed tomography (CT) in patients with biochemical recurrence (BCR) after radical prostatectomy (RP), and also the impact on their management.

Materials and Methods

A total of 300 consecutive patients with prostate cancer (PCa) who underwent 68Ga-PSMA-PET/CT between February and July 2015 were prospectively included in the Prostate Cancer Imaging (ProCan-I) database. For the present analysis, we included patients with BCR (prostate-specific antigen [PSA] level ≥0.05 and <1.0 ng/mL) after RP, who were being considered for salvage radiation therapy (RT) according to the Faculty of Radiation Oncology Genito-Urinary Group (FROGG) guidelines. Two readers assessed each 68Ga-PSMA-PET/CT, and all positive lesions were assigned to an anatomical location. For each patient, the clinical and pathological features were recorded, their association with pathological 68Ga-PSMA uptake was investigated, and detection rates were determined according to PSA level.

AOTWMAY

Results

A total of 70 patients were included, and 53 positive 68Ga-PSMA lesions were detected in 38 (54%) patients. Among patients with PSA levels 0.05–0.09 ng/mL, 8% were definitely positive; the corresponding percentages for the other PSA ranges were as follows: PSA 0.1–0.19 ng/mL, 23%; PSA 0.2–0.29 ng/mL, 58%; PSA 0.3–0.49 ng/mL, 36%; and PSA 0.5–0.99 ng/mL, 57%. Eighteen of 70 patients (27%) had pathological 68Ga-PSMA uptake in the prostatic fossa, 11 (14.3%) in the pelvic nodes, and five (4.3%) in both the fossa and pelvic lymph nodes. Finally, there was uptake outside the pelvis with or without a lesion in the fossa or pelvic lymph nodes in four cases (8.6%). As a result of the 68Ga-PSMA findings there was a major management change in 20 (28.6%) patients.

Conclusions

68Ga-PSMA appears to be useful for re-staging of PCa in patients with rising PSA levels who are being considered for salvage RT even at PSA levels <0.5 ng/mL. These results underline the need for further prospective trials to evaluate the changes in RT volume or management attributable to 68Ga-PSMA findings.

Editorial: PSMA-targeted imaging of PCa – the best is yet to come

In recent years there has been increasing interest in imaging recurrent or metastatic prostate cancer with positron-emission tomography (PET) radiotracers targeting prostate-specific membrane antigen (PSMA [1]). The majority of this work has been performed using urea-based small molecules labelled with gallium-68 (68Ga). Within this class of radiotracers, 68Ga-PSMA-11 (also known as 68Ga-PSMA-HBED-CC) has been the most widely studied. In this month’s edition of BJUI, van Leeuwen et al. [2] report on the clinical utility of 68Ga-PSMA-11 PET/CT in men with rising PSA levels after radical prostatectomy being considered for salvage radiation therapy. In their study, 70 patients with negative conventional imaging findings and a median PSA of 0.2 ng/mL (all <1 ng/mL) were imaged with 68Ga-PSMA-11 PET/CT prior to initiating treatment. On PSMA-targeted PET/CT, 53 lesions were detected in 38 (54%) patients. Perhaps most significant among their findings was that 28.6% of men had radiotracer uptake outside of the prostatic fossa leading to a major change in clinical management. In total, these data demonstrate the great potential of PSMA-targeted imaging, particularly in men with biochemically recurrent prostate cancer.

While a great deal of encouraging data with 68Ga-PSMA-11 has appeared in the medical literature, it is worth noting that several other small molecules that offer potential advantages over this agent have seen early clinical development. For example, PSMA-617 makes use of the DOTA chelation moiety in place of HBED-CC, allowing for a scaffold that can accommodate both diagnostic 68Ga and therapeutic lutetium-177 (177Lu) [3]. Additionally, our group has focused on fluorine-18 (18F)-labelled urea-based small molecules targeting PSMA, most recently 18F-DCFPyL [4]. 18F-labelled small molecules offer several potential advantages over those labelled with 68Ga. These include more favourable dosimetry allowing for higher injected radiotracer doses and lower-energy emitted positrons that have shorter path lengths to annihilation and therefore higher intrinsic spatial resolution [5]. Notably, a recent direct comparison of 68Ga-PSMA-11 and 18F-DCFPyL performed by Dietlein et al. [6] seems to confirm these advantages, having observed a higher rate of lesion detection as well as superior mean tumour-to-background ratios with the radiofluorinated compound. An additional advantage of 18F-labelled compounds is related to their longer half-life for radionuclide decay (109 vs 68 min for 68Ga). Given this difference, agents incorporating 68Ga typically require an on-site generator for radiotracer production, whereas 18F-based radiotracers can be produced en masse at a central site with a cyclotron and then delivered to remote locations via pre-existing distribution infrastructure (e.g. PETNET in the USA). Table 1 summarizes several relevant differences in the physical properties of 68Ga and 18F.

Table 1. Comparison of gallium-68 and fluorine-18
Radionuclide 68Ga 18F
Half-life, min 68 109
Method of production Generator Cyclotron
Average positron energy, keV 836.0 249.3
Average path length in soft tissue, mm 8.1 2.4
Positron yield per 100 disintegrations 89.14 96.86

 

In summary, these are exceptionally exciting times for the study of PSMA-targeted imaging of prostate cancer. With continued radiotracer development and accompanying well-designed clinical trials, there is no doubt we can drastically improve the care of men with prostate cancer.

Michael A. Gorin*, Martin G. Pomper† and Steven P. Rowe

 

*The James Buchanan Brady Urological Institute and Department of Urology, and Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA

 

References

 

 

Article of the Week: Recourse to RP and associated short-term outcomes in Italy

Every Week the Editor-in-Chief selects an Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an accompanying editorial written by a prominent member of the urological community. This blog is intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation.

Finally, the third post under the Article of the Week heading on the homepage will consist of additional material or media. This week we feature a video from Mr. Julian Hanske, discussing his editorial. 

If you only have time to read one article this week, it should be this one.

Recourse to radical prostatectomy and associated short-term outcomes in Italy: a country-wide study over the last decade

Giacomo Novara, Vincenzo Ficarra*, Filiberto Zattoni and Ugo Fedeli

 

Department of Surgery, Oncology, and Gastroenterology, Urology Clinic, University of Padova, Padova, *Department of Experimental and Clinical Medical Sciences, Urologic Clinic, University of Udine, Udine, and †Epidemiological Department, Veneto Region, Italy

 

OBJECTIVE

To estimate time trends in the recourse to radical prostatectomy (RP) and associated short-term outcomes after RP in Italy, as population-based data on RP adoption and outcomes are available mainly from Northern America and Northern Europe.

PATIENTS AND METHODS

All RPs for prostate cancer performed between 2001 and 2010 were extracted from the Italian national archive of hospital discharge records. Age-specific and age-standardised RP rates were computed. The effect of procedural volume on in-hospital mortality, complications, and length of stay (LOS) was estimated by multilevel regression models.

RESULTS

In all, 144 432 RPs were analysed. Country-wide RP rates increased between 2001 and 2004, and thereafter remained stable, with large differences between geographical areas. The mean hospital volume increased in the first study years, without centralisation but due to increasing RP numbers at the population level. The median LOS declined from 10 to 8 days over the study period (mean from 11.7 to 9.2 days). In-hospital mortality declined from 0.16% in 2001 to 0.07% in 2010. In-hospital mortality, LOS, and the prevalence of complications increased with age, and decreased with year of surgery. Compared with very low-volume hospitals, procedures performed in high-volume hospitals were associated with decreased in-hospital mortality, in-hospital complications, and LOS.

CONCLUSIONS

The study adds evidence on rapidly changing trends in RP rates in Italy, on improving in-hospital outcomes, and on their association with procedural volume.

Editorial: How Can We Improve Surgical Outcomes?

How to improve surgical outcomes for all is a long-standing health policy/services research question. There are generally two perspectives to the debate. One reasonable approach would be to regionalise, or centralise, the performance of a procedure, in this case radical prostatectomy (RP), to ‘specialised’ surgeons or institutions. Data from the USA show that regionalisation of prostate cancer care initially occurred in the late 1990s and even further more recently after the introduction of robotic surgery. The improvement of surgical outcomes after RP in the USA has been partially attributed to such phenomena [1]. Conversely, it may be impossible to centralise a common procedure, such as RP, to a small number of hospitals, concerns that were raised in an review on improving surgical care by Hollenbeck et al. [2]. Alternatively, large state or national quality improvement initiatives, with incremental advances in process-of-care adoption/compliance, may improve the care of prostate cancer for all. This collaborative and inclusive approach is, for example, employed by the Michigan Urological Surgery Improvement Collaborative (MUSIC). However, one has to factor in that this type of approach demands funding, collaboration and patience. Regardless, there is little doubt that both approaches, enforced by health policy or not, are needed in large and diverse countries such as the USA.

In this issue of BJU International, Novara et al. [3] examine the trends in RP utilisation within Italy. The authors have to be commended for their efforts to raise awareness of the need for concerted cancer registries and centralised treatments. They corroborated previous studies on the relationship between hospital volume and perioperative outcomes, such as in-hospital mortality, complications and length of stay [4]. They also found an improvement in perioperative outcomes over time. Although their study design may only allow us to speculate on the reasons for these improvements, they are likely to be the result of many factors, such as improved surgical technique, improved perioperative medical/anaesthetic care and regionalisation of care. For surgical technique, the only significant advance over the past decade was the introduction of robot-assisted RP. Given the late adoption of robotic surgery in Italy and the controversy about its benefits, this is unlikely to be the major driver behind the recorded trends. On perioperative medical/anaesthetic care, the past decade has seen major advances and standardisation of thromboembolic prevention, perioperative care of patients with pre-existing heart conditions and significant comorbidities. Finally, centralisation of care may have played an important role in the decreasing rates of adverse outcomes after RP. Although the authors specify that there was no policy-driven regionalisation of RP care in Italy (relative to the UK, for example), the increase in average hospital volume should translate into better outcomes, as discussed above [4]. Further regionalisation should be expected in Italy with the adoption of robotic surgery, as only a few centres have the means and logistics to support a da Vinci system [5].

Julian Hanske *, Christian P. Meyer†‡ and Quoc-Dien Trinh

 

*Department of Urology, Marien Hospital, Ruhr-University Bochum, Herne, Germany, Division of Urologic Surgery and Center for Surgery and Public Health, Brigham and WomenHospital, Harvard Medical School, Boston, MA, USA and Department of Urology, University Medical Centre HamburgEppendorf, Hamburg, Germany

 

References

 

 

2 Hollenbeck BK, Miller DC, Wei JT, Montie JE. Regionalization of care:centralizing complex surgical procedures. Nat Clin Pract Urol 2005; 2: 461

 

 

4 Trinh QD, Bjartell A, Freedland SJ et al. A systematic review of the volumeoutcome relationship for radical prostatectomy. Eur Urol 2013; 64: 78698

 

5 Makarov DV, Yu JB, Desai RA, Penson DF, Gross CP. The association between diffusion of the surgical robot and radical prostatectomy rates. Med Care 2011; 49: 3339

 

Video: How Can We Improve Surgical Outcomes?

Recourse to radical prostatectomy and associated short-term outcomes in Italy: a country-wide study over the last decade

Giacomo Novara, Vincenzo Ficarra*, Filiberto Zattoni and Ugo Fedeli

 

Department of Surgery, Oncology, and Gastroenterology, Urology Clinic, University of Padova, Padova, *Department of Experimental and Clinical Medical Sciences, Urologic Clinic, University of Udine, Udine, and †Epidemiological Department, Veneto Region, Italy

 

OBJECTIVE

To estimate time trends in the recourse to radical prostatectomy (RP) and associated short-term outcomes after RP in Italy, as population-based data on RP adoption and outcomes are available mainly from Northern America and Northern Europe.

PATIENTS AND METHODS

All RPs for prostate cancer performed between 2001 and 2010 were extracted from the Italian national archive of hospital discharge records. Age-specific and age-standardised RP rates were computed. The effect of procedural volume on in-hospital mortality, complications, and length of stay (LOS) was estimated by multilevel regression models.

RESULTS

In all, 144 432 RPs were analysed. Country-wide RP rates increased between 2001 and 2004, and thereafter remained stable, with large differences between geographical areas. The mean hospital volume increased in the first study years, without centralisation but due to increasing RP numbers at the population level. The median LOS declined from 10 to 8 days over the study period (mean from 11.7 to 9.2 days). In-hospital mortality declined from 0.16% in 2001 to 0.07% in 2010. In-hospital mortality, LOS, and the prevalence of complications increased with age, and decreased with year of surgery. Compared with very low-volume hospitals, procedures performed in high-volume hospitals were associated with decreased in-hospital mortality, in-hospital complications, and LOS.

CONCLUSIONS

The study adds evidence on rapidly changing trends in RP rates in Italy, on improving in-hospital outcomes, and on their association with procedural volume.

Article of the Week: Predicting pathological outcomes in patients undergoing RARP for high-risk prostate cancer

Every Week the Editor-in-Chief selects an Article of the Week from the current issue of BJUI. The abstract is reproduced below and you can click on the button to read the full article, which is freely available to all readers for at least 30 days from the time of this post.

In addition to the article itself, there is an accompanying editorial written by a prominent member of the urological community. This blog is intended to provoke comment and discussion and we invite you to use the comment tools at the bottom of each post to join the conversation.

Finally, the third post under the Article of the Week heading on the homepage will consist of additional material or media. This week we feature a video from Dr. Firas Abdollah, discussing his paper. 

If you only have time to read one article this week, it should be this one.

Predicting Pathologic Outcomes in Patients Undergoing Robot-Assisted Radical Prostatectomy for High Risk Prostate Cancer:  A Preoperative Nomogram

Firas Abdollah, Dane E. Klett, Akshay Sood, Jesse D. Sammon, Daniel PucherilDeepansh Dalela, Mireya Diaz, James O. Peabody, Quoc-Dien Trinh* and Mani Menon

 

Vattikuti Urology Institute, Center for Outcomes Research Analytics and Evaluation, Henry Ford Health System, Detroit, MI, and *Division of Urologic Surgery/Center for Surgery and Public Health, Brigham and Womens Hospital, Harvard Medical School, Boston, MA, USA

 

OBJECTIVE

To identify which high-risk patients with prostate cancer may harbour favourable pathological outcomes at radical prostatectomy (RP).

PATIENTS AND METHODS

We evaluated 810 patients with high-risk prostate cancer, defined as having one or more of the following: PSA level of >20 ng/mL, Gleason score ≥8, clinical stage ≥T2c. Patients underwent robot-assisted RP (RARP) with pelvic lymph node dissection, between 2003 and 2012, in one centre. Only 1.6% (13/810) of patients received any adjuvant treatment. Favourable pathological outcome was defined as specimen-confined disease (SCD; pT2–T3a, node negative, and negative surgical margins) at RARP-specimen. Logistic regression models were used to test the relationship among all available predicators and harbouring SCD. A logistic regression coefficient-based nomogram was constructed and internally validated using 200 bootstrap resamples. Kaplan–Meier method estimated biochemical recurrence (BCR)-free and cancer-specific mortality (CSM)-free survival rates, after stratification according to pathological disease status.

RESULTS

Overall, 55.2% patients harboured SCD at RARP. At multivariable analysis, PSA level, clinical stage, primary/secondary Gleason scores, and maximum percentage tumour quartiles were all independent predictors of SCD (all P < 0.04). A nomogram based on these variables showed 76% discrimination accuracy in predicting SCD, and very favourable calibration characteristics. Patients with SCD had significantly higher 8-year BCR- (72.7% vs 31.7%, P < 0.001) and CSM-free survival rates (100% vs 86.9%, P < 0.001) than patients with non-SCD.

CONCLUSIONS

We developed a novel nomogram predicting SCD at RARP. Patients with SCD achieved favourable long-term BCR- and CSM-free survival rates after RARP. The nomogram may be used to support clinical decision-making, and aid in selection of patients with high-risk prostate cancer most likely to benefit from RARP.

Editorial: More Nomograms or Better Lymph node dissection – What do we need in Prostate Cancer?

The publication of nomograms to predict radical prostatectomy (RP) outcome using preoperative parameters were important steps in urological oncology. Abdollah et al. [1], in this issue of BJU International, present a new nomogram to predict specimen-confined disease (SCD; pT2–3a, pN0 R0) in men with high-risk prostate cancer undergoing pelvic lymph node dissection (PLND) and robot-assisted RP (RARP). They used statistical logistic regression to measure the impact of various preoperatively available clinicopathological parameters on the likelihood of pathological outcome and tumour recurrence. The final nomogram accurately identified SCD (pT2–3a, pN0 R0) in 76% of the patients. It is intuitive that these patients have good long-term oncological outcomes after surgery. Consequently, Abdollah et al. found excellent 8-year cancer-specific survival rates in these patients. Because nomograms provide individualised risk prediction for patients in an easily applicable manner, they have become very popular among clinicians. Nomograms are now being applied for almost every aspect of prostate cancer. These are freely available and both patients and physicians are encouraged to use them.

Although nomograms undoubtedly have improved our perspective of disease behaviour and individual patient prediction, several key questions remain. First, how good are the input data to a nomogram? Abdollah et al. [1] evaluated 810 patients with high-risk prostate cancer treated in a single large centre between 2003 and 2012. Impressively, more than half of the patients (55%) harboured SCD at RARP. Such a high chance of having SCD will probably encourage many physicians and patients to choose surgery, even without using a nomogram, because this approach may avoid the need for hormonal treatment, which is obligatory for radiation therapy in high-risk prostate cancer. Second, is the predictive accuracy safe within clinical practice? Most nomograms using clinicopathological data generate predictive accuracies within the range of 75–90% (including the nomogram presented by Abdollah et al. [1]). It is of special importance to consider that 64/447 (14%) of the patients with SCD in the series reported by Abdollah et al. [1] received salvage treatment, which was initiated after a median (interquartile range, IQR) of 4.8 (1.4–9.3) months, and the indication to initiate this salvage therapy was PSA recurrence. Obviously, these patients did not have specimen confined disease and were misclassified. In this case, one might postulate a persistence of nodal disease, given an inadequate extent of PLND. Abdollah et al. [1] reported on a median (IQR) of 5 (3.0–11.0) lymph nodes removed.

In their landmark paper on extended PLND (ePLND) in cadavers, Weingartner et al. [2] demonstrated that a mean lymph node yield of 20 serves as a guideline for sufficient ePLND. More than 10 years ago, Heidenreich et al. [3] reported on a 15% higher rate of lymph node metastasis detection when comparing ePLND with the standard LND (obturator). Bader et al. [4] provided further evidence that an ePLND is needed to provide adequate clinical staging and potential therapeutic benefit. Of 365 patients with clinically localised prostate cancer, 88 (24%) had positive lymph nodes. In this series, a pelvic LND that spared the internal iliac bed would have left 58% of patients with positive nodes with residual disease and 19% would have been incorrectly staged as lymph node-negative for cancer. These data were recently confirmed by several authors when analysing retrospective series. Furthermore, Seiler et al. [5] updated their series of 88 patients and recently reported on the long-term outcome after a median follow-up of 15.6 years. They showed that 18% of those patients with one positive node remained biochemical recurrence free, 28% showed biochemical recurrence only, and 54% had clinical progression. Of these 39 patients, 57% never required deferred androgen-deprivation therapy. In contrast, patients with multiple positive nodes are likely to experience rapid progression and, thus, may benefit from early adjuvant therapies. International clinical practice guidelines recommend the performance of an anatomically ePLND at RP in men with high-risk prostate cancer, for both staging and therapeutic purposes.

Nowadays, most urologists claim to perform an ePLND. However, a recent analysis among 50 671 men who were surgically treated with RP from 2010 to 2011 in the USA showed that, overall, only 69.3% of the high-risk patients underwent concomitant PLND [6]. Surgical approach and hospital characteristics were associated with treatment with PLND and detection of lymph node metastasis. More specifically, patients with prostate cancer undergoing open RP or surgically treated at high-volume centres were more likely to undergo PLND than those undergoing RARP or surgically treated at low-volume centres.

Despite the strong evidence that ePLND positively affects survival in men with limited lymph node involvement, this procedure is not commonly performed. The reasons for this are multiple and include expertise, stage migration and functional and oncological outcomes, as well as economics and the introduction of laparoscopic and laparoscopic RARP. However, this is no reason not to offer the patient, if possible, an operation which has the highest chance of cure

Martin Spahn
Department of Urology, University Hospital Bern , InselspitalBern, Switzerland

 

References

 

 

Video: Predicting pathological outcomes in patients undergoing RARP for high-risk prostate cancer: A Preoperative Nomogram

Predicting Pathologic Outcomes in Patients Undergoing Robot-Assisted Radical Prostatectomy for High Risk Prostate Cancer:  A Preoperative Nomogram

Firas Abdollah, Dane E. Klett, Akshay Sood, Jesse D. Sammon, Daniel PucherilDeepansh Dalela, Mireya Diaz, James O. Peabody, Quoc-Dien Trinh* and Mani Menon

 

Vattikuti Urology Institute, Center for Outcomes Research Analytics and Evaluation, Henry Ford Health System, Detroit, MI, and *Division of Urologic Surgery/Center for Surgery and Public Health, Brigham and Womens Hospital, Harvard Medical School, Boston, MA, USA

 

OBJECTIVE

To identify which high-risk patients with prostate cancer may harbour favourable pathological outcomes at radical prostatectomy (RP).

PATIENTS AND METHODS

We evaluated 810 patients with high-risk prostate cancer, defined as having one or more of the following: PSA level of >20 ng/mL, Gleason score ≥8, clinical stage ≥T2c. Patients underwent robot-assisted RP (RARP) with pelvic lymph node dissection, between 2003 and 2012, in one centre. Only 1.6% (13/810) of patients received any adjuvant treatment. Favourable pathological outcome was defined as specimen-confined disease (SCD; pT2–T3a, node negative, and negative surgical margins) at RARP-specimen. Logistic regression models were used to test the relationship among all available predicators and harbouring SCD. A logistic regression coefficient-based nomogram was constructed and internally validated using 200 bootstrap resamples. Kaplan–Meier method estimated biochemical recurrence (BCR)-free and cancer-specific mortality (CSM)-free survival rates, after stratification according to pathological disease status.

RESULTS

Overall, 55.2% patients harboured SCD at RARP. At multivariable analysis, PSA level, clinical stage, primary/secondary Gleason scores, and maximum percentage tumour quartiles were all independent predictors of SCD (all P < 0.04). A nomogram based on these variables showed 76% discrimination accuracy in predicting SCD, and very favourable calibration characteristics. Patients with SCD had significantly higher 8-year BCR- (72.7% vs 31.7%, P < 0.001) and CSM-free survival rates (100% vs 86.9%, P < 0.001) than patients with non-SCD.

CONCLUSIONS

We developed a novel nomogram predicting SCD at RARP. Patients with SCD achieved favourable long-term BCR- and CSM-free survival rates after RARP. The nomogram may be used to support clinical decision-making, and aid in selection of patients with high-risk prostate cancer most likely to benefit from RARP.

Controversies in management of high-risk prostate and bladder cancer

CaptureRecently, there has been substantial progress in our understanding of many key issues in urological oncology, which is the focus of this months BJUI. One of the most substantial paradigm shifts over the past few years has been the increasing use of radical prostatectomy (RP) for high-risk prostate cancer and increasing use of active surveillance for low-risk disease [1,2]
Consistent with these trends, this months BJUI features several useful articles on the management of high-risk prostate cancer. The rst article by Abdollah et al. [3] reports on a large series of 810 men with DAmico high-risk prostate cancer (PSA level >20 ng/mL, Gleason score 810, and/or clinical stage T2c) undergoing robot-assisted RP (RARP). Despite high-risk characteristics preoperatively, 55% had specimen-conned disease at RARP, which was associated with higher 8-year biochemical recurrence-free (72.7% vs 31.7%, P < 0.001) and prostate cancer-specic survival rates (100% vs 86.9%, P < 0.001). The authors therefore designed a nomogram to predict specimen-conned disease at RARP for DAmico high-risk prostate cancer. Using PSA level, clinical stage, maximum tumour percentage quartile, primary and secondary biopsy Gleason score, the nomogram had 76% predictive accuracy. Once externally validated, this could provide a useful tool for pre-treatment assessment of men with high-risk prostate cancer. 
Another major controversy in prostate cancer management is the optimal timing of postoperative radiation therapy (RT) for patients with high-risk features at RP. In this months BJUI, Hsu et al. [4] compare the results of adjuvant (6 months after RP with an undetectable PSA level), early salvage (administered while PSA levels at 1 ng/mL) and late salvage RT (administered at PSA levels of >1 ng/mL) in 305 men with adverse RP pathology from the USA Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) registry. At 6.2 years median follow-up, late salvage RT was associated with signicantly higher rates of metastasis and/or prostate cancer-death. By contrast, there was no difference in prostate cancer mortality and/or metastasis between early salvage vs adjuvant RT. A recent study from the USA National Cancer Data Base reported infrequent and declining use of postoperative RT within 6 months for men with adverse RP pathology, from 9.1% in 2005 to 7.3% in 2011 [5]. As we await data from prospective studies comparing adjuvant vs early salvage RT, the results of Hsu et al. [4] are encouraging, suggesting similar disease-specic outcomes if salvage therapy is administered at PSA levels of <1 ng/mL. 
Finally, this issues Article of the Month by Baltaci et al. [6] examines the timing of second transurethral resection of the bladder (re-TURB) for  high-risk non-muscle-invasive bladder cancer (NMIBC). The management ofbladder cancer at this stage is a key point to improve the overall survival of bladder cancer. Re-TURB is already recommended in the European Association of Urology guidelines [7], but it remains controversial as to whether all patients require re-TURB and what timing is optimal. The range of 26 weeks after primary TURB was established based on a randomised trial assessing the effect of re-TURB on recurrence in patients treated with intravesical chemotherapy [8], but it has not been subsequently tested in randomised trial. Baltaci et al. [6], in a multi-institutional retrospective review of 242 patients, report that patients with high-risk NMIBC undergoing early re-TURB (1442 days) have better recurrence-free survival vs later re-TURB (73.6% vs 46.2%, P < 0.01). Although prospective studies are warranted to conrm their results, these novel data suggest that early re-TURB is signicantly associated with lower rates of recurrence and progression.
 
 
References

 

 

 

4 Hsu CC , Paciorek AT, Cooperberg MR, Roach M 3rd, Hsu IC, Carroll PRPostoperative radiation therapy for patients at high-risk of recurrence after radical prostat ectomy: does timing matter? BJU Int 2015; 116: 71320

 

5 Sineshaw HM, Gray PJ, Efstathiou JA, Jemal A. Declining use of radiotherapy for adverse features after radical prostatectomy: results from the National Cancer Data Base. Eur Urol 2015; [Epub ahead of print]. DOI: 10.1016/ j.eururo.2015.04.003

 

 

7 Babjuk M, Bohle A, Burger M et al. European Association of Urology Guidelines on Non-Muscle-Invasive Bladder Cancer (Ta, T1, and CIS). Available at: https://uroweb.org/wp-content/uploads/EAU-Guidelines- Non-muscle-invasive-Bladder-Cancer-2015-v1.pdf. Accessed September 2015

 

 

Stacy Loeb – Department of Urology, Population Health, and the Laura and Isaac Perlmutter Cancer Center, New York University, New York City, NY, USA

 

Maria J. Ribal – Department of Urology, Hospital Clinic, University of Barcelona, Barcelona, Spain

 
 

Clever surgeons and challenging study endpoints

CaptureIntraoperative in vivo tracking of a periprostatic nerve with multiphoton microscopy in rat model.

In the last 6 months, the BJUI editorial team has evaluated an average of 59 urological oncology papers per month with an average acceptance rate of 16%. We receive additional papers for our ‘Translational Science’ section. Studies with high-quality methods are given the highest priority. Other papers compete well if they are highly applicable to clinical practice (i.e. comparative, multicentre, multi-surgeon design) and/or show us new ideas in surgical technique, re-designed study endpoints, or explore new sources of data. For translational science, the best candidates are studies that look at new diagnostic tests in humans and beyond simple immunostaining techniques. We want to evaluate biomarkers likely to be validated and translated into a clinical test. Clinical impact will be even higher if a biomarker is linked to a therapy outcome rather than just a risk estimate. We want our papers to guide us to better outcomes for our patients, hopefully control healthcare costs, and, yes, be well-cited in the literature.

Our review process is tough but fair, and we congratulate and highlight three authorship groups for acceptance into this month’s issue of BJUI. The theme of ‘clever surgeons and challenging study endpoints’ is well illustrated by all three groups. Zargar et al. [1] report on an exclusive database of high-volume minimally invasive surgeons who have tackled the partial nephrectomy option for small renal masses. The comparison is simple in concept and retrospective in design, but what they have done is to significantly increase the outcome measures into a ‘trifecta’ concept in perioperative outcomes (previously reported) with an even more stringent ‘optimal outcome’ endpoint that includes renal function preservation. With a database of 1185 robotic and 646 laparoscopic cases, the robotic procedures showed superior trifecta results (70% vs 33%), complication rates (14.8% vs 20.9%), positive surgical margin rates (3.2% vs 9.7%), and warm ischaemia time (18 vs 26 min). The optimal outcome endpoint included a minimum 90% estimated GFR (eGFR) preservation and no chronic kidney disease upstaging. Only the robotic cohort had sufficient data available and the rate was 38.5%. The latter figure is an interesting challenge, as defining such a high threshold for success challenges surgical technique and allows more room to identify incremental advancement. This may be the largest study of its kind, but non-randomised and with limitations discussed in peer review such as the learning curve influence, use of eGFR as an endpoint with two kidneys, and incomplete data. The definitions used are of interest and the field could use some uniformity moving forward in measuring perioperative and long-term benchmarks of quality.

Durand et al. [2] give us a glimpse into the future of surgery, a science fiction world of prostate surgery where nerves and prostatic glands can be colour coded and seen at a microscopic level in real time. The pictures stand for themselves, especially Fig. 1. If such imaging can be integrated into technique decisions, and perhaps future instrument designs, then perhaps we will have a whole new wave of studies possible on linking surgical technique to improved functional and oncological outcomes after radical prostatectomy. The paper has a nice depth in detail, methods, results, as well as narratives in solving technical problems with novel technology.

This issue’s ‘Article of the Month’ by Gavin et al. [3] is a different look at the question of morbidity after localised prostate cancer treatments, specific to long-term care at >2 years from treatment. The database is from a cancer registry and they have an impressive 54% response rate from a population that is 2–18 years from diagnosis. Rather than Likert-like scales of symptom severity, they simply look at ‘current’ vs ‘ever had’ symptoms and look at the total burden including multiple/overlapping symptoms. Although this may not be as robust and validated as the Expanded Prostate Cancer Index Composite (EPIC) instrument, the simple phrasing of ‘current’ vs ‘ever had’ is probably capturing a very high proportion of symptoms rather than dismissing them if minor or in the past. Again, we see more erectile dysfunction after radical prostatectomy and radiation with hormonal therapy, and more bowel symptoms after radiation therapy. Hormone therapy patients have hot flashes and fatigue, and watchful-waiting patients have some advantages but are certainly not free of symptoms. The burden of symptoms is interesting, nine of 10 reported at least one of seven key symptoms at some point and three of four are current. Therefore, as the authors indicate, ≈75% of prostate cancer survivors will have ongoing symptoms needing follow-up care. This is a significant database resource adding to our understanding of long-term outcomes of patients with prostate cancer and supporting the significance of the Durand et al. [2] study that may show the way forward towards reducing such burdens of disease treatment.

 

References

 

 

3 Gavin AT, Drummond FJ, Donnelly C, OLeary E, Sharp L, Kinnear HRPatient-reported ever had and current long-term physical symptoms after prostate cancer treatments. BJU Int 2015; 397406

John W. Davis, MD
Associate Editor, BJUI

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