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Editorial: Bone Metastases in Prostate Cancer: Which Scan?

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In this issue of BJUI, Poulsen et al. [1] present a prospective comparison of 18F-fluoride (NaF) and 18F-choline (FCH) positron emission tomography (PET)/CT with planar whole-body bone scintigraphy (WBS) using spinal MRI, including short tau inversion recovery (STIR), T1 and T2 sequences, as the reference standard in 50 hormone-naïve patients with confirmed bone metastases on WBS. They found that both PET/CT methods were significantly more sensitive and accurate than WBS and that FCH PET/CT was more specific than NaF PET/CT.

It has become increasingly recognised that planar WBS is no longer the most accurate method of assessing the skeleton for metastases and that novel imaging methods, including PET/CT, single-photon emission CT (SPECT)/CT and whole-body MRI offer advantages [2].

What is surprising in the presented results is that NaF PET/CT shows poor specificity (54%), a result that is discordant with previous literature [3, 4]. Compared with PET alone, using the CT component of hybrid PET/CT reduces false-positive interpretation of NaF uptake in benign lesions [3]. This raises the question as to whether the CT component of the PET/CT acquisition was used to full effect in the present study. The use of spinal MRI as a reference standard is also a possible limitation that is recognised by the authors, as this limits the comparison to only the spine, and MRI in itself is a method with known limitations. All patients had abnormal WBS for entry into the trial and whilst the PET methods were more sensitive on a lesion basis, a patient-based comparison was therefore not possible; however, the results imply that PET methods may identify metastatic disease in patients with normal WBS, as has been previously reported [3, 5].

Nevertheless, the authors should be congratulated in reporting valuable data from a prospective study where all imaging was performed in hormone-naïve patients, minimising confounding treatment-related effects, and within a small time window of 30 days; however, some questions remain. WBS is no longer state of the art for imaging the skeleton with radiolabelled bisphosphonates, such as 99mTc-methylene diphosphonate (MDP). Although NaF PET/CT has been shown to be superior to planar WBS augmented with SPECT [3], there have not been head-to-head comparisons with 99mTc-MDP SPECT/CT, where the potential advantages of the pharmacokinetics of NaF and the superior spatial resolution of PET compared with SPECT may not be as great. This may be particularly important given the difference in costs and availability of the two methods.

Despite the results from the present study, which show superiority of FCH PET/CT compared with NaF PET/CT with regard to specificity, taking the available literature as a whole, it remains unresolved as to what the best test for staging the skeleton in patients with high-risk prostate cancer should be at diagnosis. The different mechanisms of uptake of the PET tracers should be noted. NaF uptake reflects the local bone osteoblastic reaction to tumour within the bone marrow, whereas FCH uptake reflects metabolic activity within the tumour cells themselves. In prostate cancer, where the predominant effect is an increase in osteoblastic activity in the adjacent bone, the bone-specific tracers such as 99mTc-MDP and NaF have shown high sensitivity; however, direct imaging of tumour cell metabolism, such as increased choline kinase activity and cell membrane synthesis with FCH, may be advantageous in detecting metastases in the bone marrow before an osteoblastic reaction has occurred [6]. It is possible that both PET tracers may be required to provide optimum diagnostic accuracy and of course FCH PET/CT also provides valuable data on nodal and visceral metastatic disease. In patients with recurrent disease, better specificity has been reported with FCH [4], NaF possibly being limited by non-specific treatment-related effects such as osteoblastic flare. For similar reasons it may be that the more tumour-specific imaging methods, such as FCH PET/CT or diffusion-weighted MRI, may be better in assessing the treatment response of skeletal metastases. Questions therefore remain as to the best imaging test at different times in the management of patients with metastatic prostate cancer. 99mTc-MDP SPECT/CT deserves a full assessment, but perhaps the recent advent of PET/MRI and the potential synergies available from this hybrid technique may help resolve some of the remaining issues.

Read the full article

Gary Cook*† and Vicky Goh*‡

*Division of Imaging Sciences and Biomedical Engineering, King’s College London, † Clinical PET Centre, and ‡ Department of Radiology, Guy’s and St Thomas’ Hospitals NHS Foundation Trust, London, UK

References

1 Poulsen MH, Petersen H, Høilund-Carlsen PF et al. Spine metastases in prostate cancer: comparison of [99mTc]MDP wholebody bone scintigraphy, [18F]choline PET/CT, and [18F]NaF PET/CT. BJU Int 2014; 114: 818–23

2 Fogelman I, Blake GM, Cook GJ. The isotope bone scan: we can do better. Eur J Nucl Med Mol Imaging 2013; 40: 1139–40

3 Even-Sapir E, Metser U, Mishani E et al. The detection of bone metastases in patients with high-risk prostate cancer: 99mTc-MDP Planar bone scintigraphy, single- and multi-field-of-view SPECT, 18F-fluoride PET, and 18F-fluoride PET/CT. J Nucl Med 2006; 47: 287–974

4 Langsteger W, Balogova S, Huchet V et al. Fluorocholine (18F) and sodium fluoride (18F) PET/CT in the detection of prostate cancer: prospective comparison of diagnostic performance determined by masked reading. Q J Nucl Med Mol Imaging 2011; 55: 448–57

5 Kjölhede H, Ahlgren G, Almquist H et al. Combined 18F-fluorocholine and 18F-fluoride positron emission tomography/computed tomography imaging for staging of high-risk prostate cancer. BJU Int 2012; 110: 1501–6

6 Beheshti M, Vali R, Waldenberger P et al. Detection of bone metastases in patients with prostate cancer by 18F fluorocholine and 18F fluoride PET-CT: a comparative study. Eur J Nucl Med Mol Imaging 2008; 35: 1766–74

 

Video: Bimanual Examination Of The Retrieved Specimen And Regional Hypothermia During Robot-Assisted Radical Prostatectomy: A Novel Technique For Reducing Positive Surgical Margin And Achieving Pelvic Cooling

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Bimanual examination of the retrieved specimen and regional hypothermia during robot-assisted radical prostatectomy: a novel technique for reducing positive surgical margin and achieving pelvic cooling

Wooju Jeong, Akshay Sood, Khurshid R. Ghani, Dan Pucheril, Jesse D. Sammon, Nilesh S. Gupta*, Mani Menon and James O. Peabody

Vattikuti Urology Institute and *Department of Pathology, Henry Ford Health System, Detroit, MI, USA

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OBJECTIVE

To describe a novel method of achieving pelvic hypothermia during robot-assisted radical prostatectomy (RARP) and a modification of technique allowing immediate organ retrieval for intraoperative examination and targeted frozen-section biopsies.

PATIENTS AND METHODS

Intracorporeal cooling and extraction (ICE) consists of a modification of the standard RARP technique with the use of the GelPOINT™ (Applied Medical, Rancho Santa Margarita, CA, USA), a hand access platform, which allows for delivery of ice-slush and rapid specimen extraction without compromising pneumoperitoneum.

RESULTS

The ICE technique reproducibly achieves a temperature of 15 °C in the pelvic cavity with no obvious body temperature change. Adopting this technique during RARP, there was an absolute risk reduction by 26.6% in positive surgical margin rate in patients with pT3a disease when compared with similar patients undergoing conventional RARP (P = 0.04).

CONCLUSIONS

The ICE technique eliminates the potential handicap of decreased tactile sensation for oncological margins, especially in the high-risk patients. This technique allows the surgeon to immediately examine the surgical specimen after resection, and with the aid of frozen-section pathology determine if further resection is required. A prospective trial is underway in our centre to evaluate the effects of this novel technique on postoperative outcomes.

 

Article of the Week: Radical prostatectomy – postoperative statin use and risk of biochemical recurrence

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Every week the Editor-in-Chief selects the 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 Emma Allott discussing her paper. 

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

Postoperative statin use and risk of biochemical recurrence following radical prostatectomy: results from the Shared Equal Access Regional Cancer Hospital (SEARCH) database

Emma H. Allott, PhD 1, 2, 3, Lauren E. Howard, BA 3, 4, Matthew R. Cooperberg, MD 5, Christopher J. Kane, MD 6, William J. Aronson, MD 7, 8, Martha K. Terris, MD 9, 10, Christopher L. Amling, MD 11 and Stephen J. Freedland, MD 1, 3, 12

1 Division of Urology, Department of Surgery, 4 Department of Biostatistics and Bioinformatics, 12 Department of Pathology, Duke University School of Medicine, 2 Cancer Prevention, Detection and Control Program, Duke Cancer Institute, 3 Division of Urology, Veterans Affairs Medical Center Durham, NC, 5 Department of Urology, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, 6 Urology Department, University of California San Diego Health System, San Diego, 7 Urology Section, Department of Surgery, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, 8 Department of Urology, UCLA School of Medicine, Los Angeles, CA, 9 Section of Urology, Veterans Affairs Medical Center, Augusta, 10 Department of Urology, Georgia Regents University, Augusta, GA, 11 Department of Urology, Oregon Health Sciences University, Portland, OR, USA

Read the full article
OBJECTIVE

To investigate the effect of statin use after radical prostatectomy (RP) on biochemical recurrence (BCR) in patients with prostate cancer who never received statins before RP.

PATIENTS AND METHODS

We conducted a retrospective analysis of 1146 RP patients within the Shared Equal Access Regional Cancer Hospital (SEARCH) database. Multivariable Cox proportional hazards analyses were used to examine differences in risk of BCR between post-RP statin users vs nonusers. To account for varying start dates and duration of statin use during follow-up, post-RP statin use was treated as a time-dependent variable. In a secondary analysis, models were stratified by race to examine the association of post-RP statin use with BCR among black and non-black men.

RESULTS

After adjusting for clinical and pathological characteristics, post-RP statin use was significantly associated with 36% reduced risk of BCR (hazard ratio [HR] 0.64, 95% confidence interval [CI] 0.47–0.87; P = 0.004). Post-RP statin use remained associated with reduced risk of BCR after adjusting for preoperative serum cholesterol levels. In secondary analysis, after stratification by race, this protective association was significant in non-black (HR 0.49, 95% CI 0.32–0.75; P = 0.001) but not black men (HR 0.82, 95% CI 0.53–1.28; P = 0.384).

CONCLUSION

In this retrospective cohort of men undergoing RP, post-RP statin use was significantly associated with reduced risk of BCR. Whether the association between post-RP statin use and BCR differs by race requires further study. Given these findings, coupled with other studies suggesting that statins may reduce risk of advanced prostate cancer, randomised controlled trials are warranted to formally test the hypothesis that statins slow prostate cancer progression.

Read more articles of the week

Editorial: Statins and biochemical recurrence after radical prostatectomy – who benefits?

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In the present issue of the BJUI Allott et al. [1] report results from a study where they used the Shared Equal Access Regional Cancer Hospital (SEARCH) database to explore the risk of biochemical recurrence (BCR) after radical prostatectomy (RP) among men who used statins after RP. They report improved BCR-free survival among statin users, especially among men with high-risk disease at baseline. The results provide some new insights into the current discussion on statins and prostate cancer outcomes.

Statins have recently shown promise as chemotherapeutic agents against prostate cancer. There is conflicting evidence on the effect on overall prostate cancer risk, but most studies able to evaluate the risk by tumour stage have reported lowered risk of advanced prostate cancer among statin users compared with the non-users [2], and lowered prostate cancer-specific mortality [3].

Taken together, these epidemiological findings suggest that statins may not strongly lower the risk of initiation of prostate cancer, but may be able to slow down the progression of the most dangerous form of the disease. In vitro studies support this by reporting growth inhibition and lower metastatic activity of prostate cancer cells after statin treatment [4].

Despite this, there has been recent controversy on statins’ effect on BCR of prostate cancer after radical treatment. A recent meta-analysis concluded that statin users may have a lower risk of BCR after external beam radiation therapy, but not after RP [5]. This could be due to statins acting as radiation sensitizers. Reports of improved BCR-free survival in statin users after brachytherapy would support this [6].

However, there are also differences in the characteristics of patients managed with RP or radiation therapy. Men undergoing RP have localised disease, which usually means low- to medium-grade tumours (Gleason ≤7), as high-grade disease (Gleason 8–10) progresses early and is more often locally advanced or already metastatic at diagnosis, leading to the choice of radiation therapy with neoadjuvant androgen deprivation instead of RP if curative treatment is still deemed possible.

This leads to the question whether the differing association between statins and BCR by treatment method is explained by patient selection, and whether statins are most effective against progression of high-grade disease. The study reported by Allott et al. [1] in this issue of the BJUI certainly suggests so. They report lowered risk of BCR among men who used statins after RP. They were able to study the effect of statin usage occurring after RP, not just usage at the time of RP. When the analysis was stratified by tumour characteristics, the improvement in relapse-free survival was strongest among men with high-risk disease (Gleason score ≥4 + 3; positive surgical margins).

The present study [1] supports the notion that statins could target a mechanism that is essential for progression of high-risk prostate cancer. This would be in concordance with the previously reported lowered risk of advanced prostate cancer and decreased prostate cancer mortality among statin users, as high-grade/high-risk cancer is the type progressing into advanced and fatal stages. On the other hand, if statins do not affect low-grade prostate cancer, this could explain why many RP series have not observed differences in biochemical relapses by statin use, as patients in these studies often have low-grade disease.

As always, statins’ benefits against prostate cancer are not really proven until verified in randomised clinical trials properly designed and powered to detect a difference in cancer endpoints. Designers of such trials should consider targeting the statin intervention to men with high-grade and/or high-risk prostate cancer for efficient study design.

Read the full article

Teemu J. Murtola*†

*School of Medicine, University of Tampere, and † Department of Urology, Tampere University Hospital, Tampere, Finland

References

1 Allott EH, Howard LE, Cooperberg MR et al. Postoperative statin use and risk of biochemical recurrence following radical prostatectomy: results from the Shared Equal Access Regional Cancer Hospital (SEARCH) database. BJU Int 2014; 114: 661–6

2 Bansal D, Undela K, D’Cruz S, Schifano F. Statin use and risk of prostate cancer: a meta-analysis of observational studies. PLoS ONE 2012; 7:e46691

3 Yu O, Eberg M, Benayoun S et al. Use of statins and the risk of death in patients with prostate cancer. J Clin Oncol 2014; 32: 5–11

4 Brown M, Hart C, Tawadros T et al. The differential effects of statins on the metastatic behaviour of prostate cancer. Br J Cancer 2012; 106: 1689–96

5 Park HS, Schoenfeld JD, Mailhot RB et al. Statins and prostate cancer recurrence following radical prostatectomy or radiotherapy: a systematic review and meta-analysis. Ann Oncol 2013; 24: 1427–34

6 Moyad MA, Merrick GS, Butler WM et al. Statins, especially atorvastatin, may improve survival following brachytherapy for clinically localized prostate cancer. Urol Nurs 2006; 26: 298–303

 

Video: Postoperative statin use and risk of biochemical recurrence following radical prostatectomy. Results from the Shared Equal Access Regional Cancer Hospital (SEARCH) database.

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Postoperative statin use and risk of biochemical recurrence following radical prostatectomy: results from the Shared Equal Access Regional Cancer Hospital (SEARCH) database

Emma H. Allott, PhD 1, 2, 3, Lauren E. Howard, BA 3, 4, Matthew R. Cooperberg, MD 5, Christopher J. Kane, MD 6, William J. Aronson, MD 7, 8, Martha K. Terris, MD 9, 10, Christopher L. Amling, MD 11 and Stephen J. Freedland, MD 1, 3, 12

1 Division of Urology, Department of Surgery, 4 Department of Biostatistics and Bioinformatics, 12 Department of Pathology, Duke University School of Medicine, 2 Cancer Prevention, Detection and Control Program, Duke Cancer Institute, 3 Division of Urology, Veterans Affairs Medical Center Durham, NC, 5 Department of Urology, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, 6 Urology Department, University of California San Diego Health System, San Diego, 7 Urology Section, Department of Surgery, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, 8 Department of Urology, UCLA School of Medicine, Los Angeles, CA, 9 Section of Urology, Veterans Affairs Medical Center, Augusta, 10 Department of Urology, Georgia Regents University, Augusta, GA, 11 Department of Urology, Oregon Health Sciences University, Portland, OR, USA

Read the full article
OBJECTIVE

To investigate the effect of statin use after radical prostatectomy (RP) on biochemical recurrence (BCR) in patients with prostate cancer who never received statins before RP.

PATIENTS AND METHODS

We conducted a retrospective analysis of 1146 RP patients within the Shared Equal Access Regional Cancer Hospital (SEARCH) database. Multivariable Cox proportional hazards analyses were used to examine differences in risk of BCR between post-RP statin users vs nonusers. To account for varying start dates and duration of statin use during follow-up, post-RP statin use was treated as a time-dependent variable. In a secondary analysis, models were stratified by race to examine the association of post-RP statin use with BCR among black and non-black men.

RESULTS

After adjusting for clinical and pathological characteristics, post-RP statin use was significantly associated with 36% reduced risk of BCR (hazard ratio [HR] 0.64, 95% confidence interval [CI] 0.47–0.87; P = 0.004). Post-RP statin use remained associated with reduced risk of BCR after adjusting for preoperative serum cholesterol levels. In secondary analysis, after stratification by race, this protective association was significant in non-black (HR 0.49, 95% CI 0.32–0.75; P = 0.001) but not black men (HR 0.82, 95% CI 0.53–1.28; P = 0.384).

CONCLUSION

In this retrospective cohort of men undergoing RP, post-RP statin use was significantly associated with reduced risk of BCR. Whether the association between post-RP statin use and BCR differs by race requires further study. Given these findings, coupled with other studies suggesting that statins may reduce risk of advanced prostate cancer, randomised controlled trials are warranted to formally test the hypothesis that statins slow prostate cancer progression.

Read more articles of the week

Step-by-Step. Real time TRUS-guided free-hands technique for focal cryoablation of the prostate

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Real-time transrectal ultrasonography-guided hands-free technique for focal cryoablation of the prostate

Andre Luis de Castro Abreu, Duke Bahn*, Sameer Chopra, Scott Leslie, Toru Matsugasumi, Inderbir S. Gill and Osamu Ukimura

USC Institute of Urology, Catherine and Joseph Aresty Department of Urology, Center for Prostate Cancer Focal Therapy, Keck School of Medicine, University of Southern California, Los Angeles, and *Prostate Institute of America, Community Memorial Hospital, Ventura, CA, USA

How to Cite: de Castro Abreu, A. L., Bahn, D., Chopra, S., Leslie, S., Matsugasumi, T., Gill, I. S. and Ukimura, O. (2014), Real-time transrectal ultrasonography-guided hands-free technique for focal cryoablation of the prostate. BJU International, 114: 784–789. doi: 10.1111/bju.12795

Read the full article

Objectives

To describe, step-by-step, our hands-free technique for focal cryoablation of prostate cancer.

Materials and Methods

After detailed discussion of its limitations and benefits, consent was obtained to perform focal cryoablation in patients with biopsy-proven unilateral low- to intermediate-risk prostate cancer. The procedure was performed transperineally, using a hands-free technique (without an external grid template) under real-time bi-plane transrectal ultrasonography (TRUS) guidance, using an argon/helium-gas-based third generation cryoablation system. Follow-up consisted of validated questionnaires, physical examination, PSA measures, multiparametric TRUS and/or magnetic resonance imaging (MRI) and mandatory biopsy.

Results

The important steps for achieving safety, satisfactory oncological and functional outcomes included: patient selection, including TRUS/MRI fusion target biopsy; thermocouple and cryoprobe placement with a hands-free technique, allowing delivery in unrestricted angulations according to the prostatic contour, the course of the neurovascular bundle and the rectal wall angle; and hands-free bi-plane TRUS probe manipulation to facilitate real-time monitoring of anatomical landmarks at the ideal angle of the image plane. To achieve a lethal temperature in the known cancer area, while preserving the urinary sphincter, neurovascular bundle, urethra and rectal wall, continuous intraoperative control of the thermocouple temperatures was necessary, as were real-time TRUS monitoring of ice-ball size, control of the energy delivered and the use of a warming urethral catheter.

Conclusion

We have described step-by-step the focal cryoablation of prostate cancer using a hands-free technique. This technique facilitates the effective delivery of cryoprobes and the intra-operative real-time quick manipulation of the TRUS probe.

 

Article of the Week: Assessing extranodal extension and the size of the largest lymph node metastasis after RP

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Every week the Editor-in-Chief selects the 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.

Prognosis of patients with pelvic lymph node metastasis following radical prostatectomy: value of extranodal extension and size of the largest lymph node metastasis

Niccolo M. Passoni, Harun Fajkovic*, Evanguelos Xylinas†, Luis Kluth‡, Christian Seitz*, Brian D. Robinson§, Morgan Rouprêt¶, Felix K. Chun‡, Yair Lotan**, Claus G. Roehrborn**, Joseph J. Crivelli§, Pierre I. Karakiewicz††, Douglas S. Scherr§, Michael Rink‡, Markus Graefen‡, Paul Schramek*, Alberto Briganti, Francesco Montorsi, Ashutosh Tewari§ and Shahrokh F. Shariat*§**

Department of Urology, Urological Research Institute, University Vita-Salute San Raffaele, Milan, Italy, *Department of Urology, Medical University of Vienna, Vienna, Austria, †Department of Urology, Cochin Hospital, Assistance Publique-Hôpitaux de Paris, University Paris Descartes, ¶Academic Department of Urology of la Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Faculté de medicine Pierre et Marie Curie, University Paris VI, Paris, France, ‡Medical Centre Hamburg-Eppendorf, Martini Clinic, Prostate Cancer Center at University Medical Center Hamburg-Eppendorf, Hamburg, Germany, §Department of Urology and Pathology, Weill Cornell Medical College, New York Presbyterian Hospital, New York, NY, **Department of Urology, Southwestern Medical Center, University of Texas, Dallas, TX, USA, and ††Department of Urology, University of Montreal, Montreal, QC, Canada

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OBJECTIVE
  • To assess the prognostic role of extranodal extension (ENE) and the size of the largest lymph node (LN) metastasis in predicting early biochemical relapse (eBCR) in patients with LN metastasis after radical prostatectomy (RP).
PATIENTS AND METHODS
  • We evaluated BCR-free survival in men with LN metastases after RP and pelvic LN dissection performed in six high-volume centres.
  • Multivariable Cox regression tested the role of ENE and diameter of largest LN metastasis in predicting eBCR after adjusting for clinicopathological variables.
  • We compared the discrimination of multivariable models including ENE, the size of largest LN metastasis and the number of positive LNs.
RESULTS
  • Overall, 484 patients were included. The median (interquartile range, IQR) follow-up was 16.1 (6–27.5) months. The median (IQR) number of removed LNs was 10 (4–14), and the median (IQR) number of positive LNs was 1 (1–2).
  • ENE was present in 280 (58%) patients, and 211 (44%) had their largest metastasis >10 mm. Patients with ENE and/or largest metastasis of >10 mm had significantly worse eBCR-free survival (all P < 0.01).
  • On multivariable analysis, number of positive LNs (≤2 vs >2) and the diameter of LN metastasis (≤10 vs >10 mm), but not ENE, were significant predictors of eBCR (all P < 0.003).
  • ENE and diameter of LN metastasis increased the area under the curve of a baseline multivariable model (0.663) by 0.016 points.
CONCLUSIONS
  • The diameter of the largest LN metastasis and the number of positive LNs are independent predictors of eBCR.
  • Considered together, ENE and the diameter of the largest LN metastasis have less discrimination than the number of positive LNs.
Read more articles of the week

Editorial: Extent of lymph node metastases

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The role of prostatectomy in lymph node metastasized prostate cancer has been subject to changing opinions. Classically, a nodal dissection was performed as the initial step in the procedure and prostatectomy was avoided in men with cryosection-proven metastases. Biochemical recurrence during the first 3 years occurs in the majority of men with pN1 disease [1]. Early data from randomized trials shows only a 50% prostate cancer-specific survival 12 years after prostatectomy and nodal metastases without immediate adjuvant treatment [2]. Recently, Passoni et al. [3] showed a higher 10-year overall survival of 82.8% in men with nodal metastases, of whom the majority were treated with adjuvant androgen ablation and/or radiotherapy. This percentage is remarkably similar to the treatment arm of the earlier-mentioned study reported by Messing et al. [2], which showed a 10-year disease-specific survival of >80%. At 10 years about half the patients who died, did so from prostate cancer; therefore, although reasonable intermediate range survival can be obtained in men with nodal metastases of prostate cancer, the major cause of death remains prostate cancer when surgery is applied at the age of 65 years. Although adjuvant androgen ablation may improve survival, as suggested by the above-mentioned observations, some men may not experience recurrence after resection of nodal metastases and would experience the toxicity of androgen ablation unnecessarily. The identification of these men would reduce costs and toxicity.

Passoni et al. [3] presented a multicentre study on prognostic factors after prostatectomy for node-positive disease. The number of removed nodes (median 10) seems relatively low compared with the 17 reported in their earlier single-centre study, but may be a good reflection of urological practice in general. By comparison, the percentage of men who underwent adjuvant radiotherapy in the multicentre study was low (16%). Data from da Pozzo et al. [4] suggest that adjuvant radiotherapy may be of benefit in men with limited nodal metastases. It would be of interest to study whether men with a later biochemical recurrence would be those that did experience recurrence only locally and therefore would be those most likely to benefit from adjuvant (or salvage) radiotherapy.

In the current study by Passoni et al. [1] in the BJUI, the follow-up was relatively short (16 months). Earlier data from this author group showed that number of positive nodes and lymph node density were good predictors of cancer-specific survival after prostatectomy. This earlier observation is now confirmed in a multicentre analysis with a different endpoint: biochemical recurrence. What is notable is the fact that this confirmation was obtained in a series of patients with fewer nodes removed. The value of the marker ≤2 positive nodes becomes limited with the observation that this group contained 85% of men in their series. The second marker found, the size of the node, showed a more general distribution but as a single marker had no predictive value. The differences in Harrel’s c values from the base model containing other clinical characteristics are limited and reproducibility of measures needs attention. Still, the observation that extent of nodal metastases is of prognostic value after surgery is notable.

Ideally, markers could predict the absence of further disease progression in men after prostatectomy for nodal metastasized prostate cancer. None of the studied characteristics fulfill this need because at 36 months after prostatectomy the majority of men, even those in the best prognostic group, do experience biochemical recurrence that will result in prostate cancer-related death. Gleason score is a strong predictor of the presence of nodal metastases [5], and some have suggested that nodal Gleason grade is of prognostic value in men with pN+ disease. Until these markers have been further evaluated, it remains important to address the fact that reported cancer-specific survival in most men with pN+ disease is >10 years [6]. Although tempting to speculate that prostatectomy and (extended) lymph node dissection plays a role in this, the almost inevitable development of biochemical recurrence reported in the current study by Passoni et al. [1], even in patients in the best prognostic group, stresses the systemic nature of this disease which will require a multimodality approach in most men at some point.

Read the full article

Henk G. van der Poel

Department of Urology, Netherlands Cancer Institute, Amsterdam, The Netherlands

References

1 Passoni N, Fajkovic H, Xylinas E. Prognosis of patients with pelvic lymph node metastasis following radical prostatectomy: value of extranodal extension and size of the largest lymph node metastasis. BJU Int 2014; 114: 503–10

2 Messing EM, Manola J, Yao J et al. Immediate versus deferred androgen deprivation treatment in patients with node-positive prostate cancer after radical prostatectomy and pelvic lymphadenectomy. Lancet Oncol 2006; 7: 472–9

3 Passoni NM, Abdollah F, Suardi N et al. Head-to-head comparison of lymph node density and number of positive lymph nodes in stratifying the outcome of patients with lymph node-positive prostate cancer submitted to radical prostatectomy and extended lymph node dissection. Urol Oncol 2013; 29: 29.e21–8

4 Da Pozzo LF, Cozzarini C, Briganti A et al. Long-term follow-up of patients with prostate cancer and nodal metastases treated by pelvic lymphadenectomy and radical prostatectomy: the positive impact of adjuvant radiotherapy. Eur Urol 2009; 55: 1003–11

5 Ross HM, Kryvenko ON, Cowan JE, Simko JP, Wheeler TM, Epstein JI. Do adenocarcinomas of the prostate with Gleason score (GS)</=6 have the potential to metastasize to lymph nodes? Am J Surg Pathol 2012; 36: 1346–52

6 Touijer KA, Mazzola CR, Sjoberg DD, Scardino PT, Eastham JA. Long-term outcomes of patients with lymph node metastasis treated with radical prostatectomy without adjuvant androgen-deprivation therapy. Eur Urol 2013; 65: 20–5

Videos: Avoiding breaches of the histological boundaries of the prostate in open radical prostatectomy

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Assessing the extirpative quality of a radical prostatectomy technique: categorisation and mapping of technical errors

Christian Barré, Matthieu Thoulouzan*, Geneviève Aillet† and Jean-Michel Nguyen‡
Department of Urology, Jules Verne Clinic, Nantes, *Department of Urology, Rangueil University Hospital, Toulouse, †Institute of Histo-Pathology, and ‡Department of Epidemiology and Biostatistics, UMR 892, University Hospital, Nantes, France

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Objective

  • To examine the extirpative quality of an open radical prostatectomy (RP) technique by first categorising and mapping all intraprostatic incisions into benign tissue and then determining a cumulative technical error rate given by all intraprostatic incisions into benign and malignant tissue.

Patients and Methods

  • We performed a retrospective review of prospectively collected data relating to 1065 men with clinically localised prostate cancer who underwent open retropubic RP (70.6% nerve-sparing surgery [NSS]) by a single surgeon (January 2005 to December 2011).
  • We recorded all intraprostatic incisions: (i) iatrogenic positive surgical margins (PSMs), (ii) deep or superficial benign capsular incisions (BCIs), (iii) incisions into benign prostate glands at the prostate apex or bladder neck (benign glandular tissue incisions [BGTIs]), and determined incision location, length and nature (solitary/multiple).
  • We evaluated: (i) associations between benign incisions, NSS and PSMs, (ii) significant predictors for PSM risk by multivariate analysis, (iii) postoperative biochemical recurrence (BCR)-free survival (Kaplan–Meier method).

Results

  • Intraprostatic incision rates were 2.3% pT2 PSMs, 6.0% BCIs and 5.4% BGTIs. There were slight variations in rate over time and with NSS technique. Benign incisions were located as follows: 46.8% right posterolateral, 37.5% left posterolateral, and 15.7% bilateral for BCIs; 58.6% bladder neck and 41.4% apical for BGTIs.
  • The median (range) incision length, for solitary and multiple incisions respectively, was 4 (1–13) and 9 (2–25) mm for BCIs and 1 (1–5) and 2 (2–6) mm for BGTIs.
  • BCI rate, but not BGTI rate, was significantly associated with NSS (P = 0.004) and PSM (P = 0.005), and increased PSM risk 3.6-fold.
  • A PSM increased BCR risk two-fold (odds ratio 2.078, 95% confidence interval 1.383–3.122).
  • BCR-free survival decreased significantly even for short PSMs (<1 mm; P < 0.001).

Conclusions

  • Although the pT2 PSM rate was low (2.3%), the cumulative technical error rate (patients with at least one pT2 PSM, BCI or BGTI) was five-fold higher (12.5%).
  • Categorising and mapping intraprostatic incisions is a tool surgeons can use in self-audits to identify areas of potential improvement, reduce errors, and improve surgical skills.

 

Are You Teaming Up for Movember?

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Urology, Social Media, and Prostate Cancer Controversies

The past couple of years have witnessed a rapid rise in the number of urologists engaging in conversation using social media. Urologists across the globe are now participating in the International Urology Journal Club on Twitter (#UROJC), tweeting at conferences, and using social media to build personal and professional relationships. As a result, providers with a passion for men’s health, who may never previously met in real life, are sharing ideas and experience with respect to issues in urology and patient care.

This uptick in the use of social media comes at a time when when prostate cancer screening and the optimal care of the prostate cancer patient are being hotly debated.  More research is clearly needed to settle many of the debates currently taking place both in traditional media and on social media. It, therefore, makes sense for the global urology community to partner with organizations that have a similar passion for advancing and promoting men’s health through scientific research.

Movember – Raising Awareness and Funding for Men’s Health Initiatives

Movember is a movement that began in Melbourne, Australia, in 2003. Since that time, it has spread to more than 20 other countries around the world. Each November, participants raise awareness and money for men’s health by growing a moustache. As the month goes on, and the mustache takes shape, these men become walking and talking men’s health billboards. Participants use their mustache to facilitate conversations about a wide variety of men’s health issues including prostate cancer, testicular cancer, and men’s mental health. They also actively raise money for the Movember Foundation by asking family and friends to donate to their efforts.

Movember is not just for men. Women (Mo Sistas), through encouragement, conversation, fundraising, and, in some cases, sheer tolerance, are a critical part of Movember’s success. Mo Sistas do everything Mo Bros do – they just don’t grow a moustache. Since Movember started, more than 4 million Mo Bros and Mo Sistas around the world have participated. In the process over $556 million dollars has been raised for the Movember Foundation.

Funding Cancer Research in Urology

 

Since its very inception, the Movember Foundation has supported ongoing research in men’s health. Currently the Movember Foundation is funding more than 832 men’s health programs worldwide. In 2010, Movember created a Global Action Plan to improve the clinical tests and treatments used for men with prostate and testicular cancer. Currently, Movember is funding prostate cancer research in four areas:

1. Developing more accurate blood, urine and tissue tests to differentiate between low risk and aggressive forms of prostate cancer.

2. Developing new imaging techniques that enable the earlier detection of metastatic prostate cancer.

3. Optimizing the management of men with low risk prostate cancer.

4. Understanding how increasing physical activity might improve the quality of life and survival of prostate cancer patients.

Movember’s criteria for research support encourages national and international collaboration. Working collaboratively, research groups are able to pool experience, streamline cost, and avoid duplication, in an effort to accelerate the  bench-to-bedside development of new investigations and treatments.

Disrupting the Status Quo

In the past, many different men’s health initiatives have come and gone. Movember’s innovative approach is unique in that each year, for a full month, the movement puts important men’s health issues – such as prostate cancer, testicular cancer and men’s mental health – back into the public spotlight.  The effect of the movement has been to not only energize men, but also healthcare, and even government.

One great example of this is the Prostate Cancer of Australia Specialist Nurse Program. The program, initially funded by Movember in 2011 with AU $3.6m, placed full time specialty nurses in every Australian state to help fill a gap in prostate cancer support and delivery. The pilot program was so successful that the Australian government invested AU $7.2m to allow the program to further expand. Movember has also created a variety of unexpected domino effects in the men’s health community. This year, our American colleagues, Dr. Jamin Brahmbhatt and Dr. Sijo Parekattil, inspired in part by the success of the Movember movement, started the Drive for Men’s Health. There are likely many others who, if asked, would tip their hats in the direction of Movember for their inspiration.

When Urologists Participate, Patients Benefit

Urologists by their very nature are both competitive and cooperative. The Movember movement is a unique opportunity for urologists across continents to join with other individuals and organizations that are passionate about improving the health and quality of life of men.  Movember is also an opportunity for colleagues, who may have only met via social media, to cooperate and/or compete all in an effort to raise awareness and money for men’s health research.  Last year, for example, Canadian urologist Dr. Rajiv Singal, assembled an international Movember team of Canadian and American urologists, patient advocates, and other healthcare providers to raise money and awareness for men’s health. Working together, the team raised nearly CA $50,000 dollars for the Movember Foundation.

An Invitation to Team Up

In the spirit of collaboration and friendly competition, this November we invite our urology colleagues from around the world to start their own local Movember Team, or to join our international team as we attempt to better our fundraising performance from last year.

 

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