Journal Club


New User? Register for a Journal Club Account

Already logged in? Click the button to join in with the latest journal club discussion ——>

You need to log in to create posts and topics.

Journal Club 23/01/2020 - Five-year Outcomes for a Prospective Randomised Controlled Trial Comparing Laparoscopic and Robot-assisted Radical Prostatectomy

Total number = 9

BethCReply

Hi everyone

 

Won5:57 pm

Hello, I'm Won Young

 

leah.argus5:57 pm

Hi there, I'm Leah

 

dianaomari5:58 pm

Hi, I am DIana

 

dianaomari5:58 pm

Diana*

 

Dr Kirolos Michael5:59 pm

Hi everyone! We'll start in a few minutes once more people have joined

 

Americos Argyriou6:01 pm

Could everyone please write down you name, Year of study, Hospital and email for our records and for Certificates of Attendance!

 

Americos Argyriou6:02 pm

Hey guys, I'm Americos, Intercalator 3rd/4th year, MRI, amerikos.argyriou@student.manchester.ac.uk

 

Won6:02 pm

I'm Won Young, Year 2, won.yoon@student.manchester.ac.uk

 

BethC6:02 pm

Beth, Year 4 Salford Royal, bethan.clayton@student.manchester.ac.uk

 

dianaomari6:03 pm

Hello, I'm Diana Al-Omari, 3rd year, MRI, diana.omari@student.manchester.ac.uk

 

leah.argus6:03 pm

Leah, 4th year, MFT Wytheshawe, leah.argus@student.manchester.ac.uk

 

BethC6:04 pm

Has everyone read the paper? Was it an okay read?

 

dianaomari6:04 pm

Yes it was quite interesting

 

leah.argus6:04 pm

It's quite clear in its aims and outcomes

 

Dr Kirolos Michael6:05 pm

I'm Kirolos, FY2 doctor at stepping hill

 

Dr Kirolos Michael6:05 pm

is everyone ready to make a start?

 

nmp246:05 pm

Nora, 4th year, SRFT, eleanor.palmer-2@student.manchester.ac.uk

 

leah.argus6:06 pm

I'm happy to get started

 

dianaomari6:06 pm

Me too

 

Dr Kirolos Michael6:06 pm

So the aim of these sessions is to give a taster into the world of medical research. Each session, we will look a different surgical speciality.

 

Dr Kirolos Michael6:07 pm

This week, I have chosen urology and selected a paper that looks at comparing robot-assisted vs. laparoscopic prostatectomy in terms of the 5yr outcome

 

Dr Kirolos Michael6:08 pm

Hopefully if was an interesting topic

 

Dr Kirolos Michael6:08 pm

Can anyone summarise the aim of the study?

 

leah.argus6:09 pm

It seems to be a prospective randomised study (1 year of data collection, n=120 patients, 5 years of follow up), comparing functional, oncological and patient satisfaction outcomes of robot assisted versus laparoscopic radical prostatectomy, finding improvement in functional outcomes for RARP

 

Dr Kirolos Michael6:10 pm

great

 

Dr Kirolos Michael6:12 pm

So a bit of background. Radical prostatectomy involves resecting the entirety of the prostate for localised prostate cancer, with curative intent. In the past, this used to be done as an open surgery, then laparoscopic surgery became favoured and most recently, robot-assisted prostatectomy is currently the Gold-standard. We even have a robot in urology centres like Stepping Hill where I work

 

Dr Kirolos Michael6:12 pm

What were the functional, oncological & patient satisfaction outcomes that they assessed?

 

dianaomari6:13 pm

continence, potency, PSA, were functional

 

dianaomari6:13 pm

satisfaction and general health status

 

dianaomari6:13 pm

and survival rates for the oncological aspect?

 

dianaomari6:13 pm

I think

 

Americos Argyriou6:14 pm

PSA would come under oncological too I think

 

leah.argus6:14 pm

they assessed biochemical recurrence free survival as a parameter

 

Dr Kirolos Michael6:14 pm

Good. So functional measures were continence and potency (i.e. ability to achieve a satisfactory erection)

 

Dr Kirolos Michael6:14 pm

How well things function afterwards

 

Dr Kirolos Michael6:15 pm

The PSA is more of an oncological marker of recurrence, that is the biochemical marker of recurrence

 

dianaomari6:15 pm

Makes sense

 

Dr Kirolos Michael6:16 pm

After surgery, follow up would involve prostate specific antigen levels (PSA). If they start rising, it is an indicator of recurrence.

 

Dr Kirolos Michael6:16 pm

We've already touched a little on the study type. Would someone like to summarise the methodology?

 

dianaomari6:17 pm

120 patients with prostate cancer were enrolled and randomly assigned to RARP or LRP

 

dianaomari6:18 pm

The same surgeon performed all the operations

 

Americos Argyriou6:18 pm

Single centre, single surgeon as well

 

Americos Argyriou6:18 pm

yeah

 

dianaomari6:18 pm

Yes

 

Dr Kirolos Michael6:19 pm

Very good.

 

leah.argus6:19 pm

That's a bit of a limitation

 

Americos Argyriou6:19 pm

They also set guidelines for the type of stage tumour they're including into the trial

 

Dr Kirolos Michael6:19 pm

So the key point is that this was a randomised-controlled trial. Single centre. Single surgeon.

 

Dr Kirolos Michael6:19 pm

So which tumours were only included?

 

Americos Argyriou6:20 pm

As in only T1-2 N0 M0

 

Dr Kirolos Michael6:20 pm

I agree about the limitation Leah, we'll come onto that in a little bit

 

Dr Kirolos Michael6:20 pm

That's right Americos. Does anyone know what that TNM staging means?

 

sharanniyan6:20 pm

grade, nodal involvement and distant metastasis?

 

Dr Kirolos Michael6:21 pm

That's correct. But in terms of a T1-2, N0, M0 etc.?

 

sharanniyan6:22 pm

they didn't have nodal involvement or distant metastasis and were fairly small tumours?

 

sharanniyan6:22 pm

small-medium size perhaps

 

Dr Kirolos Michael6:22 pm

absolutely

 

leah.argus6:22 pm

T1-2 means no extraprostatic involvement i think

 

Won6:22 pm

T1-2 would be 2cm, N0 would be negative lymph nodes, and M0 would be no distant metastases

 

Dr Kirolos Michael6:23 pm

They were confined to the prostate

 

leah.argus6:24 pm

Was this determined clinically or pathologically (pT) in the study?

 

Dr Kirolos Michael6:24 pm

So Won, the T in the TNM staging of prostate cancer doesn't involve size. It is to do with if it is confined to the prostate or locally invasive into nearby structures or organs etc. The T is different for different cancers. In some it is to with the size of the tumour etc.

 

Won6:25 pm

Sure

 

Dr Kirolos Michael6:25 pm

Good question Leah. So int he study design, it says it was pathologically confirmed

 

Dr Kirolos Michael6:26 pm

So required a biopsy (usually transperineal these days, but transrectal in the past)

 

BethC6:26 pm

Are we ready to start?

 

BethC6:27 pm

Sorry my laptop hadn't refreshed at all

 

Ashka6:27 pm

Hi it's Ashka. Sorry for being late. Traffic was really bad from wigan

 

Americos Argyriou6:27 pm

hahaha

 

Americos Argyriou6:27 pm

(sorry Beth)

 

Dr Kirolos Michael6:27 pm

haha I thought I got the wrong start time for a second🙈

 

Dr Kirolos Michael6:27 pm

Shall we move on to the results

 

Dr Kirolos Michael6:28 pm

so does anyone have any questions about the study design & aims etc.?

 

BethC6:28 pm

Of course, sorry about that

 

Dr Kirolos Michael6:29 pm

can anyone summarise the functional differences?

 

leah.argus6:29 pm

Were variables like blood loss and length of hospital stay recorded? These could affect the superiority of either

 

sharanniyan6:30 pm

continence was significant

 

Dr Kirolos Michael6:30 pm

That's right, continence was significant. Does any one have any numbers to hand, maybe can explain what they mean?

 

dianaomari6:31 pm

the probability of achieving continence over time was more than doubled in the RARP group compared to the LRP group (odds ratio [OR] 2.47; 95% confidence interval [CI] 1.15–5.31; p = 0.021).

 

Dr Kirolos Michael6:31 pm

Fantastic

 

sharanniyan6:31 pm

potency was doubled as well

 

leah.argus6:32 pm

Odds ratio here implies that patients undergoing RARP were 2.47x more likely to achieve continence, right?

 

sharanniyan6:32 pm

slightly more than doubled in fact

 

Dr Kirolos Michael6:32 pm

Is everyone up to date with what an odds ratio is?

 

sharanniyan6:32 pm

2.35x

 

Dr Kirolos Michael6:32 pm

Exactly

 

Dr Kirolos Michael6:32 pm

How do we calculate the odds ratio generally speaking?

 

leah.argus6:33 pm

Mantel-Cox regression is one way of doing it

 

BethC6:34 pm

I'm not entirely sure actually, could you explain if that's okay?

 

Dr Kirolos Michael6:34 pm

That's one way of analysing a hazard ratio not an odds ratio

 

Dr Kirolos Michael6:34 pm

So essentially

 

Americos Argyriou6:35 pm

Simplifying it down you can just do the fraction of those with continence in one arm and divide it by the fraction of those with continence in the other

 

Americos Argyriou6:35 pm

That'll give you the OR

 

Dr Kirolos Michael6:36 pm

To calculate an odds ratio, you calculate the probability of event in group A and the probability of event in group B (odds of the event in each group). Then you divide the odds of your intervention group over the comparator group

 

Dr Kirolos Michael6:37 pm

So that is correct Americos

 

BethC6:37 pm

That makes sense thank you!

 

Americos Argyriou6:37 pm

I think you put it more clearly

 

sharanniyan6:37 pm

How is that different from a hazard ratio?

 

Ashka6:37 pm

Thank you

 

Dr Kirolos Michael6:37 pm

So as everyone has said, you are >2x more likely to be continent & potent with RARP vs LRP

 

Dr Kirolos Michael6:39 pm

So the hazard ratio is time dependent. It's a time to event analysis that a little more complicated compared to the odds ratio. You are essentially seeing at a chosen point in time, what is the likely hood of the event occurring up to that particular time. The odds ratio doesn't like at time. It is just the probability of it happening at all if that makes sense

 

sharanniyan6:39 pm

Oh I see, thank you

 

leah.argus6:39 pm

Thanks for clarifying

 

Dr Kirolos Michael6:40 pm

Great

 

Dr Kirolos Michael6:40 pm

How about in terms of the oncological outcomes like survival. Were there any differences between the two?

 

Americos Argyriou6:40 pm

Strange how the overall contience OR is only 2.47 when at certain time points like 36 months its as high as 14.49

 

Dr Kirolos Michael6:41 pm

That's because the odds doesn't factor time I guess

 

BethC6:42 pm

There was no impact on overall survival from what I read, though functionally RARP was much better

 

BethC6:42 pm

In terms of quality of life post-treatment

 

Dr Kirolos Michael6:42 pm

That's right Beth. There was no difference in the overall survival

 

Dr Kirolos Michael6:46 pm

Also Americos, those ORs in the table are relative to the OR at 1 month. So this isn't the absolute odds ratio, it's a relative odds ratio (compared to at 1 month etc)

 

Dr Kirolos Michael6:47 pm

How about satisfaction?

 

sharanniyan6:49 pm

RARP group were happier

 

Dr Kirolos Michael6:49 pm

Great

 

sharanniyan6:49 pm

Due to the better continency and potency most likely

 

Dr Kirolos Michael6:49 pm

So that summarises the results

 

Dr Kirolos Michael6:49 pm

Shall we start listing the positives of this study?

 

Dr Kirolos Michael6:49 pm

If everyone can think of one positive thing about this study

 

dianaomari6:50 pm

Control of variables e.g. same surgeon, same technique

 

Dr Kirolos Michael6:50 pm

Very good

 

sharanniyan6:50 pm

Its an RCT with a fairly sizeable n number

 

leah.argus6:50 pm

The cohorts were very comparable in terms of stage of disease

 

BethC6:51 pm

The study period being 5 years allowed a good follow up period to accurately assess patient satisfaction and long-term side effects/complications if any

 

Dr Kirolos Michael6:51 pm

All very good points

 

leah.argus6:51 pm

^Which is an uncommon occurrence according to their literature review Beth

 

Dr Kirolos Michael6:51 pm

so going back to the size of the study, is it large?

 

dianaomari6:51 pm

I wouldn't say large

 

sharanniyan6:51 pm

I don't think large enough

 

Ashka6:52 pm

It is not large (just 120 patients)

 

Americos Argyriou6:52 pm

I think thats actually a pitfall of this study... 120 is not enough for a comparison between 2 operations where the negative outcomes are really rare

 

leah.argus6:52 pm

For example they needed to do Fisher's exact instead of Chi^2 in their statistics, which usually is the result of not enough data for a Chi^2

 

leah.argus6:52 pm

(I think)

 

BethC6:52 pm

^^good point

 

Dr Kirolos Michael6:52 pm

I agree. 120 is quite small. But you can argue that if you want to control a lot of factors for example making sure everyone is operated on by the same surgeon, you are going to have to live with a small sample size etc.

 

dianaomari6:53 pm

That's true

 

Dr Kirolos Michael6:53 pm

so there are trade-offs here

 

sharanniyan6:53 pm

Would a multi centre RCT have been a better alternative?

 

leah.argus6:53 pm

I think that would give a better representation of real-life outcomes

 

Dr Kirolos Michael6:53 pm

good point about the fisher exact test suggesting it wasn't a large enough sample size for a chi square

 

Dr Kirolos Michael6:54 pm

so in the discussion, did anyone notice anything about a bigger study?

 

sharanniyan6:55 pm

No significant difference found in that bigger study

 

sharanniyan6:55 pm

For continence

 

Dr Kirolos Michael6:55 pm

Absolutely, so in a retrospective study that compared 1,377 LRP vs 1,009 RARP patients, they found no difference in continence...

 

leah.argus6:56 pm

However they didn't mention the Cochrane review from September 2017 which tend to demonstrate good quality evidence

 

Dr Kirolos Michael6:56 pm

It raises questions. Can we apply the findings of this study to the wider population of patients with prostate cancer confined to the prostate?

 

Dr Kirolos Michael6:56 pm

Can you tell us about this Cochrane review Leah?

 

BethC6:57 pm

I believe the study definitely justifies possibly a larger study into RARP vs LRP as it shows no negative impact on survival

 

BethC6:58 pm

But i'm not sure if the study is strong enough to change guidelines

 

BethC6:58 pm

I may be wrong though!

 

Dr Kirolos Michael6:59 pm

I completely agree. So if we are looking at just this one study in isolation, it looks very promising, but with a sample of 120, you probably wouldn't be changing national guidelines based on this one study

 

leah.argus7:00 pm

So I found the Cochrane review when I had a quick browse of the EAU guidelines on the subject of radical prostectomy (https://www.ncbi.nlm.nih.gov/pubmed/28895658) It seems to confirm the notion that high-quality evidence on the LRP vs RARP is scarce, but previous evidence shows no difference including for continence and potency

 

leah.argus7:00 pm

Sorry, took me a minute to type

 

sharanniyan7:00 pm

Further, it would also depend on the centre to have the ability to do a RARP in the first place before considering changing of guidelines

 

Dr Kirolos Michael7:01 pm

Great point Leah

 

dianaomari7:01 pm

True it's very expensive

 

Dr Kirolos Michael7:01 pm

Absolutely, these Da Vinci robots are very expensive and costly for maintenance

 

Dr Kirolos Michael7:01 pm

and require a surgeon who is we trained in robotic assisted prostatectomies

 

Americos Argyriou7:02 pm

I agree with Beth and also, if a larger multicentre study found no difference in continence then we need to consider whether this surgeon's technique is the factor causing these results

 

leah.argus7:02 pm

A finding of "non-inferiority" of RARP in terms of survival, oncological outcomes, functional outcomes etc can be a useful finding on it's own too

 

Dr Kirolos Michael7:02 pm

The technical skills of the surgeon are going to play a role here and factors like how many of these operations are being performed by each centre. The bigger centres will have more experience, perhaps better outcomes etc.

 

Sacha Chiuta7:02 pm

I was going to ask, if the larger multi centre study found no difference does it not call into question whether this study’s results are reliable

 

Sacha Chiuta7:03 pm

It was a relatively small cohort of patients

 

Sacha Chiuta7:03 pm

Same surgeon same centre

 

BethC7:03 pm

Good point Leah, even though the study can't confirm which is superior, the lack of negative impact on those factors can be taken as a step forward

 

Dr Kirolos Michael7:03 pm

That's a good point as well Leah. Perhaps there are other advantages to RARP compared to laparoscopic that were not assessed in this study

 

Dr Kirolos Michael7:03 pm

Absolutely Sacha

 

Americos Argyriou7:04 pm

True. I think a big issue with comparing 2 techniques where 1 is super recent is that it means that surgeons are more experienced with the Lap technique so results will always favor it until more centres develop more experience with using it in their Teams

 

Dr Kirolos Michael7:04 pm

It could mean that this particular surgeon just has very good outcomes with RARP

 

Americos Argyriou7:04 pm

Yeah I agree with that

 

Dr Kirolos Michael7:04 pm

Again another very good point Americos

 

sharanniyan7:05 pm

This particular type of patient cohort could also be well suited for an RARP

 

Dr Kirolos Michael7:05 pm

This is a newer technique compared to laparoscopic prostatectomy

 

sharanniyan7:05 pm

Compared to those with further disease progression

 

Dr Kirolos Michael7:06 pm

The final point I wanted to make with regards to patient satisfaction

 

Dr Kirolos Michael7:06 pm

The patients having the RARP are told that this is the newest and latest technique. Perhaps this could influence their satisfaction, knowing that they have had the cutting edge surgical technique.

 

Americos Argyriou7:08 pm

They didn't attempt to blind the intervention. Possibly that could have been done.

 

Americos Argyriou7:08 pm

The patients knowing might definitely affect their morale/satisfaction post-op

 

Dr Kirolos Michael7:09 pm

In summary, NICE guidelines are now recommending RARP to be used increasingly and have issued suggestions about things like which centres should use them, minimum number of procedures to be done per centre in order to continue with this type of surgery. So it is being increasingly adopted. And like I said, even in DGHs that have urology centres like Stepping Hill perform robot-assisted radical prostatectomies on a weekly basis.

 

BethC7:09 pm

How can you control for the placebo effect in surgical trials? Is it possible

 

Dr Kirolos Michael7:09 pm

From an ethical point of view, can you consent a patient to blindly have one operation or the other?

 

Dr Kirolos Michael7:09 pm

Would you get approval from an ethics committee for blinding of that nature?

 

BethC7:10 pm

Consent would be null and void, it's a difficult one to justify

 

Dr Kirolos Michael7:10 pm

I don't think it would ever be possible

 

Ashka7:10 pm

Yo

 

Ashka7:10 pm

Sorry

 

Ashka7:10 pm

I was typing

 

Dr Kirolos Michael7:10 pm

Any more comments before we wrap up?

 

Americos Argyriou7:10 pm

if both procedures have the same risk profiles then you could consent them for both no?

 

Americos Argyriou7:10 pm

I thought that could be done

 

Dr Kirolos Michael7:11 pm

No because you have to consent specifically for the surgery that you are doing. It has to be specific and you can't really deviate too much

 

Americos Argyriou7:11 pm

But I see the issues raised...

 

Americos Argyriou7:11 pm

I see

 

BethC7:12 pm

Thank you for talking us through the paper Kirolos! It was an interesting one to start off with

 

Americos Argyriou7:12 pm

Yup, it was an interesting paper!

 

Dr Kirolos Michael7:12 pm

And patients should have the right to know what they're having even if they consented to be randomly allocated. Furthermore, after the operation, even if you could somehow blind ethically, they would need to find out what they have had done and that may impact satisfaction etc.

 

leah.argus7:12 pm

Thank you! Great discussion points Dr Michael

 

Ashka7:12 pm

Thank you very much! That was very interesting and informative

 

dianaomari7:13 pm

Thank you !!!

 

Dr Kirolos Michael7:13 pm

Thanks very much guys. I was very impressed with discussion. I think you've all hit all the main points. I hope you found it interesting. Like I said, I'm trying to choose papers with an interesting theme. They aren't necessarily the best studies etc.

 

sharanniyan7:13 pm

Very interesting paper and discussion, thanks Dr Michael

 

Sacha Chiuta7:13 pm

Thank you so much Dr. Michael such an interesting discussion

 

Dr Kirolos Michael7:13 pm

See you all next time. I send you guys some feedback forms for the next session

 

Won7:13 pm

Thank you so much!

 

Sacha Chiuta7:13 pm

Thank you Beth and LEAH

 

Dr Kirolos Michael7:14 pm

And please call me Kirolos

 

sharanniyan7:15 pm

Forgot to put my email in, Sharanniyan Ragavan, 2nd year, sharanniyan.ragavan@student.manchester.ac.uk