Tag Archive for: active surveillance

Posts

The USPSTF Changes Course: a “C” rating for PSA screening in ages 55-69. I did not see this coming.

It should surprise no one that I never agreed with the 2012 United States Preventive Services Task Force to give PSA a “D” rating that has led to decreases in U.S. rates of PSA testing, biopsies, and diagnosis of low- through high-risk cancer. I take care of men with prostate cancer in a multidisciplinary clinic at a dedicated cancer hospital. I perform robotic surgeries and manage over a 1,000 men on active surveillance. If you search the BJUI blogs, you can find the often viewed (>80K) “Melbourne Consensus Statement on Prostate Cancer Testing” that included 15 authors who produced 5 consensus statements on the topic. There are 62 comments—comment #5 is a fairly famous one that equates the panel to “a group of 10 pig-farmers telling us we should eat more bacon.” So yes, I think I count as a pig farmer here. My maternal grandfather and great uncle farmed pigs in Western Tennessee, so it does run in the family.


USPSTF PSA screening: Pig farming or roboticsFigure 1: It was either this or robotics

That said, it always seemed odd, that as a large country and major healthcare market, we rolled out PSA screening in the 1990s with wild enthusiasm and without data on benefit, only to then try and roll it back in when faced with two conflicting level 1 evidence studies. Meanwhile, the American Urological Association guidelines recommended PSA screening (with the “shared decision making caveat”)—mostly mirroring the European study—for men ages 55-69 (also consensus statement 1 from the Melbourne consensus). However, a recent fact struck me during a conference talk—Urologists in the U.S. are estimated to order <10% of all PSA tests, and a vast majority are from primary care physicians. So in essence it doesn’t matter as much what we think of one guideline versus another, it’s what the primary care specialties think that matters. As the USPSTF is targeted at primary care, their D rating did have an effect—fewer PSA tests, biopsies, and diagnosis of all grades of cancer (not just Gleason 6). We have heard stories over the years that specialty exams in primary care were starting to feature PSA screening questions, and the “don’t screen” answer was the one you got credit for. But I was also never convinced that most primary care physicians were comfortable with abandoning screening either. They must have seen what we saw—real cancers presenting later stage.

Some memorable quotes along these years of debate:

“There is no evidence prostate carcinogenesis has declined.” Joel Nelson, J Urol 2015

“I believe the USPSTF recommendations have created confusion at the patient and primary physician level, and that this confusion did not likely result in more informed, shared decision making, but instead avoidance of the issue.” Samir Taneja, J Urol.

Amen. So now it’s 2017 and the USPSTF has looked at the data again. They’ve had their “analysis” methods on the web for a while so we know something was planned. I can’t find authorship credits anywhere—we always complained that no prostate cancer experts were involved in the past, and now wondering who is driving this ship. The take home messages are:

  1. Offer PSA screening to ages 55-69 with shared decision making. The narrative is not “do screening.” It’s a full paragraph with the often told caveats of individualized decisions, potential harms and benefits. It’s limited to the reduction in mortality way of thinking, i.e. no thought to preventing metastatic progression, palliative care, etc.
  2. Don’t screen in men ages 70 and older. From an evidence standpoint—hard to argue and the AUA guidelines are similar. The Melbourne Consensus is at least polite enough to point out that not all men over age 70 are going to drop dead any minute, and maybe some of them should be screened if very healthy (level of evidence = CS for common sense).
  3. We recognized that men with a family history of prostate cancer or African American race are higher risk, but we don’t have evidence to support a different screening policy. Again—hard to argue with the evidence and the AUA says the same.

So really that’s it—3 main concepts. This is likely to be a significant impact in the U.S., depending upon whether or not primary care physicians change practice (and their exam questions are the same with a different correct answer).

Probably what is on your mind now is “why the change.” It does not appear to be one thing—not even recent publications revealing a more significant pattern of PSA contamination in the PLCO trial. The checklist seems to include: 1) PCLO “issues”, 2) more data from ERSPC and its subsets, 3) more data on treatment benefit, and 4) increased use of active surveillance in low-risk disease. So the balance tipped in favor of a “C” although they state the benefits and harms are still close. Fair enough.

As I re-read the 2013 Melbourne Consensus and compare to the 2017 USPSTF statement, there is a lot of overlap now. So congrats to the Melbourne group for getting it right in the first place. I, myself, did not see this coming—just another example of why I don’t invest in individual stocks or otherwise pretend to know the future.

I apologize as I re-read this, as I realize we Americans think the world revolves around us. Many of you certainly live in countries that are against routine screening and manage to get by. By all means, please sound off on what you think this means for the international picture of men’s health.

USPSTF PSA screening: Scenic Melbourne at duskFigure 2: Scenic Melbourne at dusk

 

John W. Davis is BJUI Associate Editor for oncology. @jdhdavis

 

 

Comments on this blog have been closed due to high levels of spam.

 

 

Article of the Week: 3-Tesla mpMRI and TRUS-Bx in PCa patients on AS

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

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

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

Value of 3-Tesla multiparametric magnetic resonance imaging and targeted biopsy for improved risk stratification in patients considered for active surveillance

Rodrigo R. Pessoa*, Publio C. Viana, Romulo L. Mattedi, Giuliano B. Guglielmetti*, Mauricio D. Cordeiro*, Rafael F. Coelho*, William C. Nahas* and Miguel Srougi*

 

Departments of *Urology, Diagnostic and Interventional Radiology, and Department of Pathology, Instituto do Cancer, Universidade de Sao Paulo Faculdade de Medicina Hospital das Clinicas, Sao Paulo, SP, Brazil
Read the full article

Abstract

Objective

To evaluate the role of multiparametric magnetic resonance imaging (mpMRI) of the prostate and transrectal ultrasonography guided biopsy (TRUS-Bx) with visual estimation in early risk stratification of patients with prostate cancer on active surveillance (AS).

Patients and Methods

Patients with low-risk, low-grade, localised prostate cancer were prospectively enrolled and submitted to a 3-T 16-channel cardiac surface coil mpMRI of the prostate and confirmatory biopsy (CBx), which included a standard biopsy (SBx) and visual estimation-guided TRUS-Bx. Cancer-suspicious regions were defined using Prostate Imaging Reporting and Data System (PI-RADS) scores. Reclassification occurred if CBx confirmed the presence of a Gleason score ≥7, greater than three positive fragments, or ≥50% involvement of any core. The performance of mpMRI for the prediction of CBx results was assessed. Univariate and multivariate logistic regressions were performed to study relationships between age, prostate-specific antigen (PSA) level, PSA density (PSAD), number of positive cores in the initial biopsy, and mpMRI grade on CBx reclassification. Our report is consistent with the Standards of Reporting for MRI-targeted Biopsy Studies (START) guidelines.

apr-aotw-1-results

Results

In all, 105 patients were available for analysis in the study. From this cohort, 42 (40%) had PI-RADS 1, 2, or 3 lesions and 63 (60%) had only grade 4 or 5 lesions. Overall, 87 patients underwent visual estimation TRUS-Bx. Reclassification among patients with PI-RADS 1, 2, 3, 4, and 5 was 0%, 23.1%, 9.1%, 74.5%, and 100%, respectively. Overall, mpMRI sensitivity, specificity, positive predictive value, and negative predictive value for disease reclassification were 92.5%, 76%, 81%, and 90.5%, respectively. In the multivariate analysis, only PSAD and mpMRI remained significant for reclassification (P < 0.05). In the cross-tabulation, SBx would have missed 15 significant cases detected by targeted biopsy, but SBx did detect five cases of significant cancer not detected by targeted biopsy alone.

Conclusion

Multiparametric magnetic resonance imaging is a significant tool for predicting cancer severity reclassification on CBx among AS candidates. The reclassification rate on CBx is particularly high in the group of patients who have PI-RADS grades 4 or 5 lesions. Despite the usefulness of visual-guided biopsy, it still remains highly recommended to retrieve standard fragments during CBx in order to avoid missing significant tumours.

Read more articles of the week

Editorial: An end to the phenomenon of ‘upgrading’ in early prostate cancer?

The phenomenon of ‘upgrading’ in early prostate cancer is one of those unusual events that is both useful to us on the one hand and undesirable on the other; useful because the phenomenon gifts us a direct measure of the precision of our risk stratification methods for men recently diagnosed, and undesirable because the perfect pathway should, ideally, be free of any upgrading.

Upgrading occurs in a number of settings. We see it at play to some degree when an unreliable test is re-applied in the same subject. The REDUCE study [1] showed us that just under one fifth of men will convert from a status of ‘cancer-free’ to one of ‘cancer-present’ as a result of a second exposure to the same test; that is, TRUS-guided biopsy. We see it in full play when an unreliable test is followed by a more accurate test. Shaw et al. [2] have reminded us once again – as have a number of others – of our limited ability to risk-stratify patients with early prostate cancer. They reported a 50% upgrading when they compared the results of TRUS biopsy against the final pathology at radical prostatectomy. In other words, half the patients went on to their definitive therapy with an incorrect grade attribution [2].

It would be a great pity if, in the modern era, the only route available to patients who wanted to be sure of their risk status was to agree to surgical removal of the prostate. Surely, the value of accurate risk stratification is derived from using it to allocate appropriate and effective care. Risk stratification needs to be linked to or closely follow diagnosis if it is to be put to work for patients.

Nowhere is this need greater than in men whose treatment preference is tissue preservation. The study, in this issue of BJUI, by Pessoa et al. [3] adds to our knowledge on the subject and equips us with a strategy to mitigate some of the errors that are inherent to the standard diagnostic pathway.

In the present study, the authors evaluated the role of a single exposure to MRI (and the opportunity that resulted to undertake a targeted biopsy of an MRI-derived abnormality as well as systematic sampling) in 105 men who had been attributed a diagnosis of low-risk prostate cancer – and, as a result, were deemed to be suitable for active surveillance. The authors used prostate imaging reporting and data system (PIRADS) scoring to interpret and communicate MRI risk. In summary, men attributed a low PIRADS score (PIRADS 1–3) had a low probability of being re-classified to a higher risk. In contrast, men attributed PIRADS score 4 or 5 had a probability of 70–100% of being re-classified. The authors calculated a sensitivity of 93% for MRI to predict ‘re-classification’. This equates to a 93% sensitivity to predict the presence of clinically significant disease as re-classification occurred when there was a transition from low-risk to higher-risk disease.

These results concur with those of others who are working in this area [4] and are in line with current recommendations [5]. One observation that is worth highlighting – because it is a current controversy in the field – relates to the utility of the systematic (or semi-random) biopsies as a component of the confirmatory biopsy. Whilst targeted biopsy was superior to systematic biopsy at identifying clinically significant disease, omission of the systematic biopsies would have resulted in five significant cancers being overlooked. The less perfect the targeted biopsy, the greater the reliance on the systematic. In the present study, the lesion generation and the targeting may have been compromised by one or two issues. Using TRUS biopsy as the authors did (as opposed to transperineal biopsy) to access all areas of the prostate is always going to be a challenge. To do so without image registration makes it even harder. To use PIRADS – as opposed to a Likert scale – as a method of interpreting and communicating MRI outputs will, very likely, lead to an under-reporting of the smaller, high-grade lesions [6]. This is because PIRADS 2.0 is triggered by a volume threshold towards the upper end of the scale. Such lesions might be more prevalent in an apparently ‘low-risk’ population such as the one under scrutiny. If this is the case, they will not be identified as ‘targets’ by virtue of a high PIRADS score. As a consequence they cannot be identified by targeting but might be picked up by the random fall of the needles.

Mark Emberton
Division of Surgery and Interventional Science, University College London, London, UK
Read the full article
References

1 Andriole GL, Bostwick DG, Brawley OW et al. Rittmaster RS; REDUCE Study Group. Effect of dutasteride on the risk of prostate cancer. N Engl Med 2010; 362: 1192202

 

2 Shaw GL, Thomas BC, Dawson SN et al. Identication of pathologically insignicant prostate cancer is not accurate in unscreened men. Br Cancer 2014; 110: 240511

 

4 Nassiri N, Margolis DJ, Natarajan S et al. Targeted biopsy to detect Gleason score upgrading during active surveillance for men with low- vs. intermediate-risk prostate cancer. J Urol 2016; [Epub ahead of print]. doi: 10.1016/j.juro.2016.09.070.

 

5 Moore CM, Giganti F, Albertsen P et al. Reporting magnetic resonance imaging in men on active surveillance for prostate cancer: the PRECISE recommendations-a report of a European school of oncology task force. Eur Urol 2016; [Epub ahead of print]. doi: 10.1016/j.eururo.2016.06.011.

 

 

The optimal treatment of patients with localized prostate cancer: the debate rages on

The widely anticipated results of the ProtecT study have now been published. Unfortunately, the results do little to advance our understanding as to whether surgery or radiation provides better outcomes.

 

In summary

The study followed oncologic and functional outcomes of 545 patients randomized to active monitoring (surveillance), 553 to radical prostatectomy, and 545 to radiotherapy. With a median follow-up of 10 years, the authors report no significant differences in prostate cancer specific (p=0.48) or overall survival (p=0.87) among the three treatment groups. They did demonstrate an increase in disease progression and metastasis among men managed with surveillance.

In an accompanying manuscript, the authors examined patient reported outcome measures out to 6 years following treatment. The authors report worse urinary continence and erectile function following surgery and worse voiding symptoms and bowel function following radiotherapy.

 

What do we take from this?

The investigators and participating patients should be congratulated for successfully completing this study. Numerous authors have documented their failure to adequately accrue to randomized studies of surgery versus radiotherapy in localized prostate cancer (including MRC PR06 and SPIRIT). The failure of these trials, among others, prompted Dr. Wilt to ask “Can randomized treatment trials in early stage prostate cancer be completed?” These authors have unequivocally proven that the answer is “yes”.

However, there are many caveats in applying these results to our patients:

 

(1) Study power

The study was clearly underpowered to evaluate the primary outcome of prostate-cancer specific mortality.  Drs. Roobol and Bokhorst eloquently described important limitations of the ProtecT study. The authors designed the study assuming prostate cancer mortality of 15% at a median follow-up of 10 years. This was later adjusted downwards to 10% based on updated UK data. In the end, rates were closer to 1%. The conclusions of the primary analysis are based on a total of 17 (17!!) deaths.

 

(2) Study cohort – enriched with low risk disease

Among the randomized patients, the median PSA was 4.6 ng/mL, 76% had clinical stage T1c disease, and 77% had Gleason score 6 disease. These patients would almost certainly be considered most suitable for active surveillance, rather than active therapy, if seen in clinic today. Clinically meaningful decisions between surgery and radiotherapy are in the realm of treatment of intermediate and high-risk localized prostate cancer and these comprise a small group in this study.  Based on this baseline distribution, it will be unlikely that any significant differences will be found in future follow-up studies.

 

(3) Outcomes for active surveillance

Perhaps the most notable findings of this study involve the significantly higher rates of progression, metastasis and prostate cancer specific mortality for patients treated on the surveillance protocol as compared to those treated actively, though statistical significance was not reached for PCSM. The manuscript does not provide further details regarding the pathologic characteristics of these patients. Relevantly, what was the Gleason score for these patients? This is of particularly importance as many surveillance proponents are advocating an expanding role of AS.

 

(4) Treatments administered

RCTs typically require significant periods of accrual, follow-up and analysis. As a result, they may be out of date prior to completion. This is certainly true of the ProtecT study. This most prominently affects patients allocated to radiotherapy. In the study protocol, patients received 3D conformal radiotherapy at 74 Gy, not the IMRT which has now become widely used. Thus, proponents of radiotherapy will likely to discount any findings which do not favour radiotherapy.

In addition, the current day relevance of the surgical treatment provided is questionable. First, the vast majority of patients in the surgical arm underwent open RP. More concerning is the quality of surgery provided: 93 patients (24%) of the cohort had positive surgical margins. In contemporary series, the average rate is under 15% with centers of excellence approaching 5%. While PSM rates clearly affect oncologic outcomes, they likely are also a surrogate of surgical quality which may affect functional outcomes.

 

 (5) Comparison of active treatments

In the accompanying editorial, Dr. D’Amico comments on a “trend favouring radiation and ADT over surgery” and suggests that “one may consider radiation and ADT as a preferred option”. The basis for this conjecture is 5 deaths in the surgery group and 4 in the radiotherapy group, hardly a convincing sample. In contrast to these data, there was a higher number of patients with metastasis among those treated with radiotherapy (16 vs 13). These discordant results would certainly suggest that any preference for radiotherapy is premature. Indeed, with additional follow-up one would expect the patients with metastasis to die of prostate cancer, thus favouring those treated surgically.

On a methodological note, while the inclusion of active surveillance is a strength of the study, it poses analytic difficulties. The primary analysis assesses a null hypothesis assuming equality across all study interventions. Thus, as this was non-significant, pairwise testing of surgery and radiotherapy, and each with surveillance, is inappropriate and conclusions on these comparisons should not be drawn.

 

(6) Functional outcomes and treatment-related complications

Most clinicians are well aware that many complications other than erectile function and urinary incontinence may affect that life trajectory of patients following prostate cancer treatments. ProtecT offers the opportunity to examine the risks of secondary malignancy, repeat urologic and gastrointestinal interventions, surgeries and hospitalizations following treatment. However, these are not currently included in the published data.

Further, the PCOS studies have clearly shown that differences in patient reported urinary, sexual and bowel function change over time with convergence after long term follow-up (15 years). With ongoing maturity, it will be interesting to see if a similar pattern emerges in ProtecT.

 

In conclusion

The ProtecT study may raise more questions than it answers. Among a low risk group of patients, it has shown that active treatment of PSA-detected prostate cancer can reduce the progression to metastatic disease. Assessment of prostate cancer specific and overall mortality, as well as the comparative efficacy of surgery and radiotherapy, is not possible due to power limitations.

Will you be changing you patient counselling based on these results?

 

cw-head-shot-smallChristopher Wallis, MD
Resident,
Division of Urology,
Department of Surgery,
University of Toronto
Doctoral Student in Clinical Epidemiology and Health Care Research, Institute of Health Policy, Management & Evaluation
University of Toronto
nam_drrobert_portrait-2010-small

 

 

 

 

 

 


Robert Nam
, MD MSc FRCSC
Ajmera Family Chair in Urologic Oncology
Professor,
Division of Urology,
Department of Surgery
University of Toronto
Head, Genitourinary Cancer Site
Odette Cancer Centre
Sunnybrook Health Sciences Centre

 

 

 

 

Article of the Week: Complications after serial prostate biopsies in men on AS

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

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

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

 

Complications after prostate biopsies in men on active surveillance and its effects on receiving further biopsies in the Prostate cancer Research International: Active Surveillance (PRIAS) study

Leonard P. Bokhorst*, Inari Lepisto†, Yoshiyuki Kakehi‡, Chris H. Bangma*, Tom Pickles§, Riccardo Valdagni¶, Arnout R. Alberts*, Axel Semjonow**, Petra Str
olin††, Manuel F. Montesino‡‡, Viktor Berge§§, Monique J. Roobol* and Antti Rannikko†

*Department of Urology, Erasmus University Medical Center, Rotterdam, The Netherlands,
†Department of Urology, Helsinki University Central Hospital, Helsinki, Finland,
‡ Department of Urology, Kagawa University Faculty of Medicine, Kagawa, Japan,
§Department of Radiation Oncology, British Columbia Cancer Agency, Vancouver, BC, Canada,
¶Prostate Cancer Program and Radiation Oncology 1, Fondazione IRCSS Istituto Nazionale dei Tumori, Milan, Italy,
**Department of Urology, Prostate Center, University Hospital Muenster, Muenster,
††Department of Urology, Martini Klinik, Hamburg, Germany,
‡‡Department of Urology, Hospital Virgen del Camino, Pamplona, Spain, and
§§Department of Urology, Oslo University Hospital, Oslo, Norway

 

Read the full article

 

Objective

To study the risk of serial prostate biopsies on complications in men on active surveillance (AS) and determine the effect of complications on receiving further biopsies.

Patients and methods

In the global Prostate cancer Research International: Active Surveillance (PRIAS) study, men are prospectively followed on AS and repeat prostate biopsies are scheduled at 1, 4, and 7 years after the diagnostic biopsy, or once yearly if prostate-specific antigen-doubling time is <10 years. Data on complications after biopsy, including infection, haematuria, haematospermia, and pain, were retrospectively collected for all biopsies taken during follow-up in men from several large participating centres. Generalised estimating equations were used to test predictors of infection after biopsy. Competing risk analysis was used to compare the rates of men receiving further biopsies between men with and without previous complications.

Results

In all, 2 184 biopsies were taken in 1 164 men. Infection was reported after 55 biopsies (2.5%), and one in five men reported any form of complication. At multivariable analysis, the number of previous biopsies was not a significant predictor of infection (odds ratio 1.04, 95% confidence interval 0.76–1.43). The only significant predictor for infection was the type of prophylaxis used. Of all men with a complication at the diagnostic or first repeat biopsy, 21% did not have a repeat biopsy at the time a repeat biopsy was scheduled according to protocol, vs 12% for men without a previous biopsy complication.

aotwsept-1

Conclusion

In our present cohort of men on AS, we found no evidence that repeat prostate biopsy in itself posed a risk of infection. However, complications after biopsy were not uncommon and after a complication men were less likely to have further biopsies. We should aim to safely reduce the amount of repeat biopsies in men on AS.

 

Read the full article

Editorial: Active surveillance for prostate cancer: is it too active?

The wide dissemination of prostate cancer screening has increased the number of men diagnosed with low-risk, indolent cancers that are better managed with active surveillance (AS) rather than immediate treatment. During the past decade, the number of men managed with AS has increased from <10% to 40% in community based practice registries [1]. Prostate needle biopsy has a central role in diagnosis and reclassification of cancer for men on AS, and the number of these procedures has increased on an individual patient level and overall in the population. The rise of prostate biopsies repeated in the same patients has mirrored the increased rate of biopsy related infectious complications. An association between the number of repeat prostate biopsies and risk of infectious complications was reported in a single-centre observational study [2].

In this issue of BJUI, Bokhort et al. [3] report the risk of complications of serial prostate biopsies in men on AS in the multi-institutional Prostate cancer Research International Active Surveillance (PRIAS) study. Although they did not identify the number of previous biopsies as an independent predictor of infection, the type of prophylactic antibiotic was associated with risk of infection. Overall, one in five men reported any complication during AS and the rate of infectious complications was 2.5%. These figures are more relevant if we consider that men in whom an infection occurred were twice as likely to discontinue AS. Although the rate of attrition may have confounded the association of repeat biopsies on infectious complications or guided a more augmented antibiotic prophylaxis regimen, the most important finding of this study remains the significant morbidity associated with AS.

In the PRIAS study, institutions are guided to perform surveillance biopsies at 1, 4, and 7 years after the diagnostic biopsy. However, the schedule of biopsies varies significantly globally across institutions. In some academic centres, prostate biopsies are taken annually for men on AS, while other experts in AS have discussed taking biopsies every 5 years [4, 5]. As more studies emerge demonstrating the oncological safety of AS, we must address how ‘active’ AS should be and develop individualised recommendations based on tumour characteristics. A barrier to AS remains the burden of morbidity associated with prostate biopsies and efforts to reduce these procedures will contribute to further reducing the overtreatment of men with low-risk prostate cancer. In addition, the patient costs associated with serial office visits and the burden on physicians and healthcare systems stemming from the increased clinical volume following these patients remain an unmet need for the future.

Read the full article

 

Behfar Ehdaie
Department of Surgery, Urology Service, and Department of Epidemiology and Biostatistics, Center of Health Policy and Outcomes, Memorial Sloan Kettering Cancer Center, New York, NY, USA

 

References

1. Cooperberg MR, Carroll PR. Trends in management for patients with localized prostate cancer, 1990–2013. JAMA 2015; 314: 802

 

Controversies in management of high-risk prostate and bladder cancer

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

 

 

 

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

 

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

 

 

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

 

 

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

 

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

 
 

Article of the Month: Indications for Intervention During Active Surveillance of Prostate Cancer

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 Dr. Max Kates discussing his paper. 

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

Indications for Intervention During Active Surveillance of Prostate Cancer: A Comparison of the Johns Hopkins and PRIAS Protocols

Max Kates, Jeffrey J. Tosoian, Bruce J. Trock, Zhaoyong Feng, H. Ballentine Carter and Alan W. Partin
James Buchanan Brady Urological Institute, Johns Hopkins Medical Institutions, Baltimore, MD, USA
Read the full article
OBJECTIVE

To analyse how patients enrolled in our biopsy based surveillance programme would fare under the Prostate Cancer Research International Active Surveillance (PRIAS) protocol, which uses PSA kinetics.

PATIENTS AND METHODS

Since 1995, 1125 men with very-low-risk prostate cancer have enrolled in the AS programme at the Johns Hopkins Hospital (JHH), which is based on monitoring with annual biopsy. The PRIAS protocol uses a combination of periodic biopsies (in years 1, 4, and 7) and prostate-specific antigen doubling time (PSADT) to trigger intervention. Patients enrolled in the JHH AS programme were retrospectively reviewed to evaluate how the use of the PRIAS protocol would alter the timing and use of curative intervention.

RESULTS

Over a median of 2.1 years of follow up, 38% of men in the JHH AS programme had biopsy reclassification. Of those, 62% were detected at biopsy intervals corresponding to the PRIAS criteria, while 16% were detected between scheduled PRIAS biopsies, resulting in a median delay in detection of 1.9 years. Of the 202 men with >5 years of follow-up, 11% in the JHH programme were found to have biopsy reclassification after it would have been identified in the PRIAS protocol, resulting in a median delay of 4.7 years to reclassification. In all, 12% of patients who would have undergone immediate intervention under PRIAS due to abnormal PSA kinetics would never have undergone reclassification on the JHH protocol and thus would not have undergone definitive intervention.

CONCLUSIONS

There are clear differences between PSA kinetics-based AS programmes and biopsy based programmes. Further studies should address whether and how the differences in timing of intervention impact subsequent disease progression and prostate cancer mortality.

Read more articles of the week

 

Editorial: How active should active surveillance be?

 Many investigators, including those from Johns Hopkins University (JHU) and the Prostate cancer Research International: Active Surveillance project (PRIAS), have provided meaningful data to strongly support the increasing use of active surveillance (AS) across the world. There are a multitude of strategies to minimise excessive rates of prostate cancer over detection and overtreatment. After the diagnosis of prostate cancer, the single best is AS for appropriately selected men.

 For decades, the concept of not treating a prostate cancer in otherwise healthy men, even if low-grade and low-volume was typically considered nihilistic and heretical, particularly in the USA. Thankfully, data have largely made this line of thinking anachronistic. The era of sensibly applied AS is upon us, and single-institution series with intermediate-term follow-up are excellent, with exceedingly low rates of metastasis or cancer-related death. However, we await longer-term (>10 years) outcomes from the contemporary PSA screening era.

 The ‘success’ of AS is largely dependent on the entry criteria, follow-up strategies, and indications for curative intervention. Highly restrictive inclusion criteria, rigorous biopsy based follow-up and strict definitions of reclassification triggering treatment have produced superb outcomes. Critics appropriately argue these criteria exclude a significant proportion of men with a low rate of requiring treatment or having metastases, if allowed on AS. Conversely, other programmes with looser entry criteria, more lax follow-up, and relaxed indications for intervention will be more inclusive and have lower rates of immediate or delayed intervention but must be counterbalanced against the expected higher rate of metastases or death.

 The current study [1] evaluates two different AS follow-up strategies from JHU and PRIAS. In general, JHU uses annual biopsies with progression defined as a new PSA density >0.15 ng/mL/mL or increasing tumour volume or grade beyond a certain threshold, while PRIAS recommends less frequent biopsies (years 1, 4, and 7) while relying on serological (PSA doubling time, PSADT) alongside histological indicators for defining progression and recommending treatment.

 Not surprisingly, different strategies lead to varying expected outcomes. Among the JHU patients, 38% were reclassified at a median of 2.1 years. Nearly two-thirds of the reclassified would have been identified at the PRIAS year 1 or triennial biopsies with 16% identified between PRIAS biopsies at a median delay of 1.9 years. The unanswerable but incredibly important question is whether this delay is essentially a non-issue, perhaps a favourable attribute (more AS time without compromising cure rates), or clinically disastrous (patients no longer curable).

 PRIAS relies heavily on PSA kinetics, which can be a double-edged sword. Among men in the JHU programme with >5 years follow-up, 11% would have delayed reclassification compared with PRIAS at a median time of 4.7 years. Additionally, 12% would have undergone intervention due to PRIAS-defined PSADT but not progressed based on the JHU protocol. It is convenient and perhaps intuitive that PSA kinetics should predict progression and meaningful clinical events for men on AS; however, the data from multiple studies have simply not supported this concept [2, 3].

 The JHU programme has restrictive entry rules compared with most other programmes, a rigorous biopsy based follow-up protocol, and strict criteria to treat, which is exactly why no metastasis or death have been reported among 769 men, some with up to 15 years follow-up[4]. Guidelines are needed but should not be overly prescriptive or rigid. For example, a surveillance biopsy showing a single core of Gleason 6 encompassing 60% of the total core or three cores of Gleason 6 with total cancer length of 3 mm would lead to a recommendation of treatment according to published JHU criteria. Many of us would not be phased with these biopsy reports and comfortably recommend ongoing AS.

 Data from AS series are very encouraging but it is highly likely we can do even better. For example, 10-year cancer-specific survival is 97% in the Sunnybrook AS experience and all five cancer-related deaths occurred in patients that would not meet most contemporary AS entry criteria [5, 6]. I am hopeful and confident that emerging data incorporating MRI imaging, serum biomarkers (e.g. prostate health index), or tissue-based biomarkers (e.g. Prolaris, Oncotype Dx) will provide us with a more comprehensive understanding of these men’s cancer such that tailored, evidence-based recommendations can be even more accurate.

 There is much yet to be learned about AS and this study [1] adds to our knowledge. Surveillance for prostate cancer is definitely active, but it is also dynamic and evolving.

Read the full article
Scott Eggener
Associate Professor of Surgery, University of Chicago, Chicago, IL, USA

 

References

 

 

Video: Indications for Intervention During Active Surveillance of Prostate Cancer: A Comparison of the Johns Hopkins and PRIAS Protocols

Indications for Intervention During Active Surveillance of Prostate Cancer: A Comparison of the Johns Hopkins and PRIAS Protocols

Max Kates, Jeffrey J. Tosoian, Bruce J. Trock, Zhaoyong Feng, H. Ballentine Carter and Alan W. Partin
James Buchanan Brady Urological Institute, Johns Hopkins Medical Institutions, Baltimore, MD, USA
Read the full article
OBJECTIVE

To analyse how patients enrolled in our biopsy based surveillance programme would fare under the Prostate Cancer Research International Active Surveillance (PRIAS) protocol, which uses PSA kinetics.

PATIENTS AND METHODS

Since 1995, 1125 men with very-low-risk prostate cancer have enrolled in the AS programme at the Johns Hopkins Hospital (JHH), which is based on monitoring with annual biopsy. The PRIAS protocol uses a combination of periodic biopsies (in years 1, 4, and 7) and prostate-specific antigen doubling time (PSADT) to trigger intervention. Patients enrolled in the JHH AS programme were retrospectively reviewed to evaluate how the use of the PRIAS protocol would alter the timing and use of curative intervention.

RESULTS

Over a median of 2.1 years of follow up, 38% of men in the JHH AS programme had biopsy reclassification. Of those, 62% were detected at biopsy intervals corresponding to the PRIAS criteria, while 16% were detected between scheduled PRIAS biopsies, resulting in a median delay in detection of 1.9 years. Of the 202 men with >5 years of follow-up, 11% in the JHH programme were found to have biopsy reclassification after it would have been identified in the PRIAS protocol, resulting in a median delay of 4.7 years to reclassification. In all, 12% of patients who would have undergone immediate intervention under PRIAS due to abnormal PSA kinetics would never have undergone reclassification on the JHH protocol and thus would not have undergone definitive intervention.

CONCLUSIONS

There are clear differences between PSA kinetics-based AS programmes and biopsy based programmes. Further studies should address whether and how the differences in timing of intervention impact subsequent disease progression and prostate cancer mortality.

Read more articles of the week
© 2022 BJU International. All Rights Reserved.