lymph node dissection

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Video: Machine learning‐assisted decision‐support model to identify PCa patients requiring an extended PLND

December 25, 2019/by Yu-Dong Zhang

A machine learning‐assisted decision‐support model to better identify patients with prostate cancer requiring an extended pelvic lymph node dissection

Abstract

Objectives

To develop a machine learning (ML)‐assisted model to identify candidates for extended pelvic lymph node dissection (ePLND) in prostate cancer by integrating clinical, biopsy, and precisely defined magnetic resonance imaging (MRI) findings.

Patients and Methods

In all, 248 patients treated with radical prostatectomy and ePLND or PLND were included. ML‐assisted models were developed from 18 integrated features using logistic regression (LR), support vector machine (SVM), and random forests (RFs). The models were compared to the Memorial SloanKettering Cancer Center (MSKCC) nomogram using receiver operating characteristic‐derived area under the curve (AUC) calibration plots and decision curve analysis (DCA).

Results

A total of 59/248 (23.8%) lymph node invasions (LNIs) were identified at surgery. The predictive accuracy of the ML‐based models, with (+) or without (−) MRI‐reported LNI, yielded similar AUCs (RFs⁺/RFs⁻: 0.906/0.885; SVM⁺/SVM⁻: 0.891/0.868; LR⁺/LR⁻: 0.886/0.882) and were higher than the MSKCC nomogram (0.816; P < 0.001). The calibration of the MSKCC nomogram tended to underestimate LNI risk across the entire range of predicted probabilities compared to the ML‐assisted models. The DCA showed that the ML‐assisted models significantly improved risk prediction at a risk threshold of ≤80% compared to the MSKCC nomogram. If ePLNDs missed was controlled at <3%, both RFs⁺ and RFs⁻ resulted in a higher positive predictive value (51.4%/49.6% vs 40.3%), similar negative predictive value (97.2%/97.8% vs 97.2%), and higher number of ePLNDs spared (56.9%/54.4% vs 43.9%) compared to the MSKCC nomogram.

Conclusions

Our ML‐based model, with a 5–15% cutoff, is superior to the MSKCC nomogram, sparing ≥50% of ePLNDs with a risk of missing <3% of LNIs.

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Article of the Week: More PLND template at RP detects metastases in the common iliac region and in the fossa of Marcille

May 9, 2018/by admin Z.9

Every Month, the Editor-in-Chief selects an Article of the Month 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.

More extended lymph node dissection template at radical prostatectomy detects metastases in the common iliac region and in the fossa of Marcille

Lydia Maderthaner, Marc A. Furrer, Urs E. Studer, Fiona C. Burkhard, George N. Thalmann and Daniel P. Nguyen

Department of Urology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland

Read the full article

Abstract

Objectives

To assess the effect of adding lymph nodes (LNs) located along the common iliac vessels and in the fossa of Marcille to the extended pelvic LN dissection (PLND) template at radical prostatectomy (RP).

Patients and Methods

A total of 485 patients underwent RP and PLND at a referral centre between 2000 and 2008 (historical cohort: classic extended PLND template) and a total of 268 patients between 2010 and 2015 (contemporary cohort: extended PLND template including LNs located along the common iliac vessels and in the fossa of Marcille). Descriptive analyses were used to compare baseline, pathological, complication and functional data between the two cohorts. A logistic regression model was used to assess the template’s effect on the probability of detecting LN metastases.

Results

Of 80 patients in the historical cohort with pN+ disease, the sole location of metastasis was the external iliac/obturator fossa in 23 (29%), and the internal iliac in 18 (23%), while 39 patients (49%) had metastases in both locations. Of 72 patients in the contemporary cohort with pN+ disease, the sole location of metastasis was the external iliac/obturator fossa in 17 patients (24%), the internal iliac in 24 patients (33%), and the common iliac in one patient (1%), while 30 patients (42%) had metastases in >1 location (including fossa of Marcille in five patients). Among all 46 patients in the contemporary cohort with ≤2 metastases, three had one or both metastases in the common iliac region or the fossa of Marcille. The adjusted probability of detecting LN metastases was higher, but not significantly so, in the contemporary cohort. There were no differences between the two cohorts in complication rates and functional outcomes.

Conclusion

A more extended template detects LN metastases in the common iliac region and the fossa of Marcille and is not associated with a higher risk of complications; however, the overall probability of detecting LN metastases was not significantly higher.

Editorial: PLND during RP for PCa: extending the template in the right patients without increasing complications

May 9, 2018/by Francesco Montorsi

It took long time and consistent evidence to endorse the staging role of extended pelvic lymph node dissection (PLND) in prostate cancer (PCa). The poor performance of both conventional and functional imaging in identifying preoperative nodal status has contributed to making extended PLND the most accurate nodal staging procedure in PCa 1.

Current available guidelines recommend a standard extended PLND template that includes external, internal iliac and obturator lymph nodes 2–4; however, where does the need for a more extended template originate? Observational data suggest that a standard extended PLND template intercepts ~75% of all anatomical landing sites 4. Extending the anatomical template by adding nearby nodal stations would further minimize the risk of missing positive lymph nodes; however, it has previously been shown that a more accurate staging (i.e. a more extended template) might come at the price of longer operating time and a higher risk of procedure‐related complications 1.

According to the study by Maderthaner et al. 5, in the current issue of BJUI, an experienced academic surgical team is able to further extend the PLND template (including common iliac and the fossa of Marcille lymph nodes) without significantly increasing the risk of complications. In their study, 17% and 7% of the included men with pN+ disease had positive common iliac and fossa of Marcille lymph nodes, respectively.

Before celebrating this super‐extended template as safe and effective, however, at least three points need to be considered. First, these results were obtained by a group of skilled surgeons with longstanding experience in anatomical pelvic nodal dissection. It should not be taken for granted that this template in the hands of other surgeons would result in no additional complications, especially during the learning curve.

Second, >80% of men submitted to the super‐extended template did not have positive nodes outside the standard extended template boundaries, indicating possible overtreatment in a substantial proportion of men. Notably, extended PLND in this study was offered apparently without upfront preoperative lymph node invasion risk stratification.

Third, as a consequence, patient selection has a role to play. In other words, is super‐extended PLND appropriate for every patient? The use of available risk stratification tools in everyday clinical practice allows a more accurate decision process; this is the case for the Briganti nomogram concerning the need to perform an extended PLND 6. Could a similar approach be used in the setting of a super‐extended template to identify the best candidates? Recently, Gandaglia et al. 7 analysed data from 471 men with high‐risk PCa treated with radical prostatectomy and a super‐extended PLND including common iliac and pre‐sacral nodes in order to identify those men who really require such a super‐extended PLND. Interestingly, although not specifically designed for this task, the Briganti nomogram was able to provide a patient selection strategy: only 5% of patients with a nomogram‐derived N+ risk of <30% had positive common iliac and pre‐sacral nodes, indicating that the super‐extended PLND template should perhaps be considered exclusively in men with an N+ risk ≥30%.

In conclusion, a critical assessment of super‐extended staging PLND template would be welcome, allowing selection of the proper candidates, and a proper balance between accurate staging and the risk of treatment‐related complications.

Eugenio Vent imiglia, *†Alberto Briganti,*† and Francesco Montorsi,*†

*University Vita-Salute San Raffaele, Milan, Italy and †Division of Experimental Oncology/Unit of Urology, URI, IRCCS Ospedale San Raffaele, Milan, Italy

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References

1 Fossati N, Willemse P‐PM, Van den Broeck T et al. The benefits and harms of different extents of lymph node dissection during radical prostatectomy for prostate cancer: a systematic review. Eur Urol 2017; 72: 84–109
Crossref PubMed Web of Science®Google Scholar

2 Santis D, Henry A, Joniau S et al. Prostate Cancer EAU ESTRO SIOG Guidelines on 2017.
Google Scholar

3 Mattei A, Fuechsel FG, Bhatta Dhar N et al. The template of the primary lymphatic landing sites of the prostate should be revisited: results of a multimodality mapping study. Eur Urol 2008; 53: 118–25
Crossref PubMed Web of Science®Google Scholar

4 Joniau S, Van den Bergh L, Lerut E et al. Mapping of pelvic lymph node metastases in prostate cancer. Eur Urol 2013; 63: 450–8
Crossref PubMed Web of Science®Google Scholar

5 Maderthaner L, Furrer MA, Studer UE, Burkhard FC, Thalmann GN, Nguyen DP. More extended lymph node dissection template at radical prostatectomy detects metastases in the common iliac region and in the fossa of Marcille. BJU Int 2018; 121: 725–31
Google Scholar

6 Briganti A, Larcher A, Abdollah F et al. Updated nomogram predicting lymph node invasion in patients with prostate cancer undergoing extended pelvic lymph node dissection: the essential importance of percentage of positive cores. Eur Urol 2012; 61: 480–7
Crossref PubMed Web of Science®Google Scholar

7 Gandaglia G, Zaffuto E, Fossati N et al. Identifying the candidate for super extended staging pelvic lymph node dissection among patients with high‐risk prostate cancer. BJU Int 2018; 121: 421–7
Wiley Online Library Google Scholar

RSM Urology Winter Meeting 2017, Northstar, California

February 17, 2017/6 Comments/by Niyati Lobo

This year’s Annual RSM Urology Section Winter Meeting, hosted by Roger Kirby and Matt Bultitude, was held in Lake Tahoe, California.

A pre-conference trip to sunny Los Angeles provided a warm-up to the meeting for a group of delegates who flew out early to visit Professor Indy Gill at the Keck School of Medicine. We were treated to a diverse range of live open, endourological and robotic surgery; highlights included a salvage RARP with extended lymph node dissection and a robotic simple prostatectomy which was presented as an alternative option for units with a robot but no/limited HoLEP expertise.

On arrival to Northstar, Dr Stacy Loeb (NYU) officially opened the meeting by reviewing the social media urology highlights from 2016. Next up was Professor Joseph Smith (Nashville) who gave us a fascinating insight into the last 100 years of urology as seen through the Journal of Urology. Much like today, prostate cancer and BPH were areas of significant interest although, in contrast, early papers focused heavily on venereal disease, TB and the development of cystoscopy. Perhaps most interesting was a slightly hair-raising description of the management of IVC bleeding from 1927; the operating surgeon was advised to clamp as much tissue as possible, close and then return to theatre a week later in the hopes the bleeding had ceased!

With the promise of beautifully groomed pistes and stunning views of Lake Tahoe, it was hardly surprising that the meeting was attended by a record number of trainees. One of the highlights of the trainee session was the hilarious balloon debate which saw participants trying to convince the audience of how best to manage BPH in the newly inaugurated President Trump. Although strong arguments were put forward for finasteride, sildenafil, Urolift, PVP and HoLEP, TURP ultimately won the debate. A disclaimer: this was a fictional scenario and, to the best of my knowledge, Donald Trump does not have BPH.

The meeting also provided updates on prostate, renal and bladder cancer. A standout highlight was Professor Nick James’ presentation on STAMPEDE which summarized the trial’s key results and gave us a taste of the upcoming data we can expect to see in the next few years.

We were fortunate to be joined by prominent American faculty including Dr Trinity Bivalacqua (Johns Hopkins) and Dr Matt Cooperberg (UCSF) who provided state-of-the-art lectures on potential therapeutic targets and biomarkers in bladder and prostate cancer which promise to usher in a new era of personalized therapy.

A personal highlight was Tuesday’s session on learning from complications. It was great to hear some very senior and experienced surgeons speaking candidly about their worst complications. As a trainee, it served as a reminder that complications are inevitable in surgery and that it is not their absence which distinguishes a good surgeon but rather the ability to manage them well.

There was also plenty for those interested in benign disease, including topical discussions on how to best provide care to an increasingly ageing population with multiple co-morbidities. This was followed by some lively point-counterpoint sessions on robot-assisted versus open renal transplantation (Ravi Barod and Tim O’Brien), Urolift vs TURP (Tom McNicholas and Matt Bultitude) and HOLEP vs prostate artery embolization for BPH (Ben Challacombe and Rick Popert). Professor Culley Carson (University of North Carolina) concluded the session with a state-of-the art lecture on testosterone replacement.

In addition to the excellent academic programme, delegates enjoyed fantastic skiing with perfect weather and unparalleled views of the Sierra Nevada Mountains. For the more adventurous skiiers, there was also a trip to Squaw Valley, the home of the 1960 Winter Olympics. Another highlight was a Western-themed dinner on the shores of Lake Tahoe which culminated in almost all delegates trying their hand at line dancing to varying degrees of success! I have no doubt that next year’s meeting in Corvara, Italy will be equally successful and would especially encourage trainees to attend what promises to be another excellent week of skiing and urological education.

Miss Niyati Lobo
ST3 Urology Trainee, Brighton and Sussex University Hospitals NHS Trust

@niyatilobo

sLND for Prostate Cancer Nodal Recurrence: #urojc September 2014 summary

September 22, 2014/by admin Z.9

The September 2014 edition of the International Urology Journal Club (#urojc) returned to familiar territory – prostate cancer. In particular, the discussion focused on salvage lymph node dissection following radical prostatectomy. For the second time (first in July 2014), two journal articles were selected. Both were kindly made available to open access by The Journal of Urology (@JUrology).

The first paper from the Mayo Clinic by Karnes et al., titled ‘Salvage Lymph Node Dissection (sLND) for Prostate Cancer Nodal Recurrence Detected by ¹¹C-Choline Positron Emission Tomography/Computed Tomography (PET/CT)’, reported on a retrospective single-surgeon series of 52 men who underwent salvage lymph node dissection for nodal recurrence post radical prostatectomy. Median follow-up was 20 months. Three-year Biochemical recurrence (BCR)-free survival rate was 45.5% (PSA <0.2). Metastatic/systemic progression-free and cancer-specific survival rates were 46.9% and 92.5% respectively. They concluded that sLND may delay further progression of disease but highlighted the need for randomised controlled trials.

The second paper from German group Tilki et al., titled ‘Salvage Lymph Node Dissection for nodal recurrence of prostate cancer after Radical Prostatectomy’, also reported on a retrospective series of 58 patients who underwent sLND for nodal recurrence on PET/CT post radical prostatectomy. Median follow-up was 39 months. All but 1 patient had BCR. Five-year clinical recurrence-free and cancer-specific survival rates were 35.9% and 71% respectively. Tilki et al. concluded that while most patients had BCR, sLND may delay ADT and clinical recurrence in selected cases.

A common sentiment shared during the discussion related to the lack of randomised evidence for sLND:

There were some serious concerns about the methodology and results from the two articles:

Discussions quickly shifted away from the two articles to the actual clinical question of sLND in oligometastatic disease and delay to ADT. Matthew Katz provided useful links to the use of stereotactic radiation therapy.

Issues surrounding sLND training and the paradigm shift in recent years were also highlighted:

Opinions were divided on the question of surgical morbidity versus the potential increase in time to ADT:

Pop culture references were in vogue this month. An article by the Mayo Clinic on the ¹¹C-Choline PET scan sparked the linked exchange:

Some take home messages pertained to the uncertainty regarding patient selection and the role of sLND in the broader multidisciplinary arena of prostate cancer treatment:

The winner of the Best Tweet Prize is Brian Chapin (@ChapinMD) for his tweet above. We thank the Journal of Clinical Urology for supporting this month’s prize by way of a one year electronic subscription to their journal. We also thank the Journal of Urology for supporting this month’s discussion by way of allowing time limited open access of both articles.

Staying true to form, this month’s edition of #urojc provided a forum for lively international discussion. We look forward to next month’s installment and especially encourage trainees to make use of this excellent educational opportunity.

Isaac Thangasamy is a second year Urology Trainee currently working at the Royal Brisbane and Women’s Hospital, Brisbane, Australia. He is passionate about education and social media. Follow him on Twitter @iThangasamy

Article of the week: SEER shows no benefit from LND in RCC

January 15, 2014/by admin Z.9

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 prominent members 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 Maxine Sun discussing her paper.

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

Extent of lymphadenectomy does not improve the survival of patients with renal cell carcinoma and nodal metastases: biases associated with the handling of missing data

Maxine Sun*, Quoc-Dien Trinh*^‡, Marco Bianchi*^¶, Jens Hansen*^††, Firas Abdollah^¶, Zhe Tian*, Shahrokh F. Shariat^§, Francesco Montorsi^¶, Paul Perrotte^† and Pierre I. Karakiewicz*^†

*Cancer Prognostics and Health Outcomes Unit, ^†Department of Urology, University of Montreal Health Center, Montreal, Canada, ^‡Vattikuti Urology Institute, Henry Ford Health System, Detroit, MI, ^§Department of Urology,Weill Medical College of Cornell University, New York, NY, USA, ^¶Department of Urology, Vita-Salute San Raffaele University, Milan, Italy, and ^††Martini Clinic, Prostate Cancer Center Hamburg-Eppendorf, Hamburg, Germany

Maxine Sun and Quoc-Dien Trinh contributed equally to this study.

Read the full article

OBJECTIVE

• Previous studies showed no survival benefit with respect to performing lymph node dissection (LND) at nephrectomy, whereas a recent population-based analysis suggested otherwise, although the latter relied on imputation. To reconcile the findings of that study by critically evaluating the handling of missing data.

PATIENTS AND METHODS

• Study participants comprised patients diagnosed with non-metastatic renal cell carcinoma (RCC) of all stages who underwent LND at nephrectomy (n = 10 596).

• Multivariable Cox regression models were performed to predict cancer-specific mortality (CSM), where the primary variable of interest was the extent of LND.

• To examine differences in approaches with respect to handling missing data, separate analyses were performed: (i) imputed population; (ii) exclusion of patients with missing data; and (iii) inclusion of patients with missing data as a sub-category.

RESULTS

• Overall, 2916 (28%) patients had missing tumour grade.

• In multivariable analyses, our findings showed that increasing the extent of LND was associated with a significant protective effect on CSM in patients with pN1 after imputation (hazard ratio [HR], 0.82; P = 0.04).

• By contrast, the extent of LND was no longer significantly associated with a lower risk of CSM after excluding patients with a missing tumour grade (HR, 0.83; P = 0.1) or when including patients with missing tumour grade as a sub-category (HR, 0.82; P = 0.05).

CONCLUSIONS

• The findings of the present study failed to corroborate the association of a survival benefit with increasing extent of LND at nephrectomy.

• The different methodologies employed to account for missing data may introduce important biases.

• Such considerations are non-negligible with respect to the interpretation of results for investigators who rely on administrative cohorts.

Read Previous Articles of the Week

Editorial: Does performing LND at nephrectomy give a survival benefit or not?

January 15, 2014/by Jared Whitson

We read with interest the article by Sun et al. [1] in this issue of the BJU International. We were pleased to see another research group interested in this important aspect of the management of patients with lymph-node-positive non-metastatic RCC. The question of the benefits of lymphadenectomy in such patients could not be answered by the European Organization for Research and Treatment of Cancer randomized trial [2], as only 4% of clinically node-negative patients had micrometastatic disease.

Given some of the complexities involved in the analysis of Surveillance, Epidemiology and End Results data and the particular statistical analysis we used in showing a benefit to increasing nodal yield in patients with positive nodes [3], we were reassured that Sun et al. were able to validate our findings when replicating our data extraction and analysis. They performed two additional analyses and the four results are shown in Table 1.

While Sun et al. concluded that multiple imputation introduces bias into the findings, inspection of the estimates of the impact of lymph node dissection (the hazard ratio) appear identical. If bias is a deviation of an estimate from the truth [4], we would argue that Sun et al. found no evidence of bias introduced by the multiple imputation method. This is not to say that all four analyses are free from potential bias – the reported hazard ratios may in fact still be biased results – but that there is no more bias in the multiple imputation model than in the others. In addition, we were somewhat surprised to see the use of a missing indicator approach proposed as less likely than multiple imputation to introduce bias as studies have shown the opposite [5].

Furthermore, the CIs show that the benefit to extent of lymphadenectomy may be as great as a 34% reduction in cancer-related death, with exclusion of all but a 5% increase in death associated with the procedure. CIs provide extremely valuable information, particularly in the setting of marginally significant or nonsignificant P values. Sun et al. could have strengthened their paper on statistical considerations by discussing this further. In fact, we would argue that their additional analyses lend further support to the potential benefit of the extent of lymphadenectomy.

The most notable difference across the analyses is a drift in the P value. We would argue that this mirrors the loss in power associated with the censoring of almost 3000 patients (28%) with missing grades. In addition, grade does not appear to be missing at random, as patients with missing tumour grades were associated with larger tumours, higher local stage, increased probability of nodal involvement and increased risk of kidney cancer death. The censoring of such patients may in and of itself introduce bias, although again the hazard ratios do not seem to reflect this. The devaluation of the P value continues to be an active area of biostatistical research, although in general journals have not foregone its inclusion in favour of an entirely Bayesian approach [6]. We believe that, in this case, Sun et al. have taken a far too traditional approach to interpretation of small differences in P values, particularly in the setting of changing sample sizes.

We agree with Sun et al. that consideration of another randomized trial focused on patients at high risk of nodal involvement or with clinically apparent nodes on CT is warranted based upon our combined results.

Jared M. Whitson and Maxwell Meng
Department of Urology, Kaiser Permanente South Sacramento Medical Center, Sacramento, CA, USA

Read the full article

References

Sun M, Trinh Q-D, Bianchi M et al. Extent of lymphadenectomy does not improve survival of patients with renal cell carcinoma and nodal metastases: biases associated with handling of missing data. BJU Int 2014; 113: 36–42
Blom JH, van Poppel H, Marechal JM et al. Radical nephrectomy with and without lymph-node dissection: final results of European Organization for Research and Treatment of Cancer (EORTC) randomized phase 3 trial 30881. Eur Urol 2009; 55: 28–34
Whitson JM, Harris CR, Reese AC, Meng MV. Lymphadenectomy improves survival of patients with renal cell carcinoma and nodal metastases. J Urol 2011; 185: 1615–1620
Grimes DA, Schulz KF. Bias and causal associations in observational research. Lancet 2002; 359: 248–252
Greenland S, Finkle WD. A critical look at methods for handling missing covariates in epidemiologic regression analyses. Am J Epidemiol 1995; 142: 1255–1264
Goodman SN. Toward evidence-based medical statistics. 2: the Bayes factor. Ann Intern Med 1999; 130: 1005–1013

Video: Survival for RCC and nodal metastases

January 15, 2014/by admin Z.9

Extent of lymphadenectomy does not improve the survival of patients with renal cell carcinoma and nodal metastases: biases associated with the handling of missing data

Maxine Sun and Quoc-Dien Trinh contributed equally to this study.

Read the full article

OBJECTIVE

PATIENTS AND METHODS

• Study participants comprised patients diagnosed with non-metastatic renal cell carcinoma (RCC) of all stages who underwent LND at nephrectomy (n = 10 596).

• Multivariable Cox regression models were performed to predict cancer-specific mortality (CSM), where the primary variable of interest was the extent of LND.

RESULTS

• Overall, 2916 (28%) patients had missing tumour grade.

CONCLUSIONS

• The findings of the present study failed to corroborate the association of a survival benefit with increasing extent of LND at nephrectomy.

• The different methodologies employed to account for missing data may introduce important biases.

• Such considerations are non-negligible with respect to the interpretation of results for investigators who rely on administrative cohorts.