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Resident’s podcast: Palliative care use amongst patients with bladder cancer

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Maria Uloko is a Urology Resident at the University of Minnesota Hospital. In this podcast she discusses the following BJUI Article of the Week:

Palliative care use amongst patients with bladder cancer

Read the full article

Abstract

Objectives

To describe the rate and determinants of palliative care use amongst Medicare beneficiaries with bladder cancer and encourage a national dialogue on improving coordinated urological, oncological, and palliative care in patients with genitourinary malignancies.

Patients and methods

Using Surveillance, Epidemiology, and End Results‐Medicare data, we identified patients diagnosed with muscle‐invasive bladder cancer (MIBC) between 2008 and 2013. Our primary outcome was receipt of palliative care, defined as the presence of a claim submitted by a Hospice and Palliative Medicine subspecialist. We examined determinants of palliative care use using logistic regression analysis.

Results

Over the study period, 7303 patients were diagnosed with MIBC and 262 (3.6%) received palliative care. Of 2185 patients with advanced bladder cancer, defined as either T4, N+, or M+ disease, 90 (4.1%) received palliative care. Most patients that received palliative care (>80%, >210/262) did so within 24 months of diagnosis. On multivariable analysis, patients receiving palliative care were more likely to be younger, female, have greater comorbidity, live in the central USA, and have undergone radical cystectomy as opposed to a bladder‐sparing approach. The adjusted probability of receiving palliative care did not significantly change over time.

Conclusions

Palliative care provides a host of benefits for patients with cancer, including improved spirituality, decrease in disease‐specific symptoms, and better functional status. However, despite strong evidence for incorporating palliative care into standard oncological care, use in patients with bladder cancer is low at 4%. This study provides a conservative baseline estimate of current palliative care use and should serve as a foundation to further investigate physician‐, patient‐, and system‐level barriers to this care.

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Article of the week: Palliative care use amongst patients with bladder cancer

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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 editorial written by a prominent member of the urological community, a video produced by the authors and a visual abstract created by Charles Scott and Nurhan Abbud. These are 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.

Palliative care use among patients with bladder cancer

Lee A. Hugar*, Samia H. Lopa*, Jonathan G. Yabes†, Justin A. Yu‡, Robert M. Turner II*, Mina M. Fam*, Liam C. MacLeod*, Benjamin J. Davies*, Angela B. Smith§¶ and Bruce L. Jacobs*

 

*Department of Urology, †Department of Medicine, ‡Department of Medicine, Section of Palliative Care and Medical Ethics, University of Pittsburgh School of Medicine, Pittsburgh, PA, §Department of Urology and Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

 

Read the full article

Abstract

Objectives

To describe the rate and determinants of palliative care use amongst Medicare beneficiaries with bladder cancer and encourage a national dialogue on improving coordinated urological, oncological, and palliative care in patients with genitourinary malignancies.

Patients and methods

Using Surveillance, Epidemiology, and End Results‐Medicare data, we identified patients diagnosed with muscle‐invasive bladder cancer (MIBC) between 2008 and 2013. Our primary outcome was receipt of palliative care, defined as the presence of a claim submitted by a Hospice and Palliative Medicine subspecialist. We examined determinants of palliative care use using logistic regression analysis.

Fig. 1. Time from diagnosis to receipt of palliative care. The timing of palliative care receipt for those patients who received palliative care (n = 262). Strata with <11 patients were suppressed in accordance with SEER‐Medicare guidelines

Results

Over the study period, 7303 patients were diagnosed with MIBC and 262 (3.6%) received palliative care. Of 2185 patients with advanced bladder cancer, defined as either T4, N+, or M+ disease, 90 (4.1%) received palliative care. Most patients that received palliative care (>80%, >210/262) did so within 24 months of diagnosis. On multivariable analysis, patients receiving palliative care were more likely to be younger, female, have greater comorbidity, live in the central USA, and have undergone radical cystectomy as opposed to a bladder‐sparing approach. The adjusted probability of receiving palliative care did not significantly change over time.

Conclusions

Palliative care provides a host of benefits for patients with cancer, including improved spirituality, decrease in disease‐specific symptoms, and better functional status. However, despite strong evidence for incorporating palliative care into standard oncological care, use in patients with bladder cancer is low at 4%. This study provides a conservative baseline estimate of current palliative care use and should serve as a foundation to further investigate physician‐, patient‐, and system‐level barriers to this care.

 

Read more Articles of the week

 

 

Video: Palliative care use amongst patients with bladder cancer

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Palliative care use amongst patients with bladder cancer

Read the full article

Abstract

Objectives

To describe the rate and determinants of palliative care use amongst Medicare beneficiaries with bladder cancer and encourage a national dialogue on improving coordinated urological, oncological, and palliative care in patients with genitourinary malignancies.

Patients and methods

Using Surveillance, Epidemiology, and End Results‐Medicare data, we identified patients diagnosed with muscle‐invasive bladder cancer (MIBC) between 2008 and 2013. Our primary outcome was receipt of palliative care, defined as the presence of a claim submitted by a Hospice and Palliative Medicine subspecialist. We examined determinants of palliative care use using logistic regression analysis.

Results

Over the study period, 7303 patients were diagnosed with MIBC and 262 (3.6%) received palliative care. Of 2185 patients with advanced bladder cancer, defined as either T4, N+, or M+ disease, 90 (4.1%) received palliative care. Most patients that received palliative care (>80%, >210/262) did so within 24 months of diagnosis. On multivariable analysis, patients receiving palliative care were more likely to be younger, female, have greater comorbidity, live in the central USA, and have undergone radical cystectomy as opposed to a bladder‐sparing approach. The adjusted probability of receiving palliative care did not significantly change over time.

Conclusions

Palliative care provides a host of benefits for patients with cancer, including improved spirituality, decrease in disease‐specific symptoms, and better functional status. However, despite strong evidence for incorporating palliative care into standard oncological care, use in patients with bladder cancer is low at 4%. This study provides a conservative baseline estimate of current palliative care use and should serve as a foundation to further investigate physician‐, patient‐, and system‐level barriers to this care.

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Article of the week: Persistent muscle-invasive BCa after neoadjuvant chemotherapy: an analysis of SEER‐Medicare data

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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 editorial written by a prominent member of the urological community. These are 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.

Persistent muscle‐invasive bladder cancer after neoadjuvant chemotherapy: an analysis of Surveillance, Epidemiology and End Results‐Medicare data

Giulia Lane*†, Michael Risk*†, Yunhua Fan*, Suprita Krishna* and Badrinath Konety*

 

*Department of Urology, University of Minnesota, and †Minneapolis Veterans Affairs Health Care System, Minneapolis, MN, USA
Read the full article

Abstract

Objectives

To evaluate whether patients with persistent muscle‐invasive bladder cancer (MIBC) after undergoing neoadjuvant chemotherapy (NAC) and radical cystectomy (RC) have worse overall survival (OS) and cancer‐specific survival (CSS) than patients with similar pathology who undergo RC alone.

Materials and Methods

Using the Surveillance, Epidemiology and End Results (SEER)‐Medicare database, we identified the records of patients with pT2‐4N0M0 disease who underwent RC, with and without NAC, for MIBC between 2004 and 2011. To evaluate survival outcomes in those with MIBC after NAC vs patients with MIBC who underwent RC alone, we used Kaplan–Meier time‐to‐event analysis and Cox proportional hazard regression modelling. Landmark analysis was conducted to mitigate immortal time bias. Propensity scoring was used to decrease the risk of selection bias.

Fig. 2. Propensity‐weighted Kaplan–Meier curves. Overall survival and cancer‐specific survival among patients with persistent pT2‐4N0M0 bladder cancer after radical cystectomy from time of diagnosis. (A) Overall survival and (B) cancer‐specific survival. Neoadjuvant chemotherapy (NAC) + radical cystectomy (RC) in red. RC alone in blue.

Results

Of the 1 886 patients with persistent pT2‐4 disease at the time of RC, 1505 underwent RC alone and 381 received NAC + RC. After adjusting for confounders, the propensity‐weighted risk of death from bladder cancer after diagnosis did not differ between the groups (hazard ratio [HR] 0.72, 95% confidence interval [CI] 0.72–1.08; P = 0.23); however, the risk of death from all causes was worse in the RC‐alone group (HR 0.79, 95% CI0.67–0.94; P = 0.006).

Conclusions

Patients who had persistent MIBC after platinum‐based NAC + RC vs RC alone derived an OS benefit but not a CSS benefit from NAC. This may represent a selection bias favouring patients who were selected for NAC; however, the OS benefit was not evident in patients with persistent pT3‐T4N0M0 disease. This study underscores the importance of future research investigating methods to identify patients who will respond to NAC for bladder cancer. It also highlights the need to consider adjuvant therapy in patients who have persistent MIBC after NAC.

Read more Articles of the week

 

 

Editorial: The bladder cancer conundrum: how do we treat the right tumour with the right treatment, at the right time?

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The bladder cancer conundrum is how to accurately determine the type of tumour, treatment and timing that is ideal for each patient? This is epitomised by the use of neoadjuvant chemotherapy (NAC) for muscle‐invasive bladder cancer (MIBC). MIBC is a deadly disease; if untreated, the 2‐year mortality rate is 85% [1] and even if treated the overall survival (OS) rate at 5 years is 50%. In this context, NAC is appealing because it may improve outcomes. In 2003, a landmark study by Grossman et al. [2] examined NAC prior to radical cystectomy (RC) for MIBC. The median survival (44 vs 77 months, P = 0.06) and pT0 rates, which equate to the best survival rates (30% vs 15%, P < 0.001), were improved with NAC. A meta‐analysis of 11 randomised control trials in >3000 patients reported an OS benefit of 5% at 5 years with platinum‐based NAC [3]. Whilst NAC improves outcomes, especially for those patients who achieve pT0, it is also important to examine outcomes for patients with persistent MIBC and to determine if NAC is helpful in those patients.

In this issue of the BJUI, Lane et al. [4] attempt to answer this question by examining outcomes for patients with persistent MIBC after RC alone or NAC followed by RC. Using Surveillance, Epidemiology, and End Results (SEER)‐Medicare data, the authors examined 1505 patients that underwent RC alone and 381 patients that received NAC and RC from 2004 to 2011. The authors report that after propensity weighted Kaplan–Meier analysis, the 5‐year OS rate was improved amongst patients that received NAC and RC as compared to patients that had RC alone if there was pT2–T4N0M0 disease on final pathology (43.5% vs 37.2%, P = 0.001). However, there was no difference in cancer‐specific survival (CSS) for NAC with RC compared to only RC (53.7% vs 58.4%, P = 0.76). After adjusting for confounders, the authors found similar results. The use of NAC and RC was found to have an OS benefit (hazard ratio [HR] 0.79, 95% confidence interval [CI] 0.67–0.94; P = 0.006) for pT2–4N0M0 patients but not a CSS benefit (HR 0.88, 95% CI 0.72–1.08; P = 0.23).

Since previous studies have established the value of NAC in patients that are down‐staged to pT0 disease, the authors also focused their subset analysis on patients not down‐staged and instead had persistent MIBC. On subset analysis, NAC and RC patients with pT2N0M0 disease had an OS but no CSS benefit. For pT3–T4N0M0 patients, there was no OS or CSS benefit. This may suggest that a subset of non‐responders, such as those with pT2 disease, may experience some benefit from NAC despite persistent disease. Lastly, it is worth noting that whilst NAC improves outcomes, is better tolerated before surgery than adjuvant therapy, and is supported by high‐quality evidence, utilisation remains suboptimal. In this study [4], 381 of 1886 patients (or only 20%) had NAC and only 55% of these received cisplatin‐based therapy. Utilisation patterns vary and updated studies may show different results though. Overall, the authors should be congratulated for a study that is relevant, thoughtful and directed at an important clinical topic.

In this study [4], one issue that is raised is the challenges of accurate preoperative staging. The authors in this paper analysed patients according to pathological stage to limit confounding, as determining the exact stage of patients prior to NAC and RC cannot be done exactly. In this study, pT2 patients had on OS benefit after NAC but pT3–4 patients did not benefit. Clinical staging relies on transurethral resection, imaging and examination under anaesthesia to establish the diagnosis. Without final staging, it is difficult to precisely parse out which patients are clinical T2 vs T3 disease before RC. Predicting which patients are non‐responders is particularly important because these patients may be exposed unnecessarily to the risks of chemotherapy and may have delays in surgery that can negatively impact their outcomes. Therefore, even if the optimal treatment is known, identifying which patients will benefit can be challenging.

Fortunately, there is an exciting future for MIBC on the horizon. First, traditionally bladder cancer staging relies on determining the depth of invasion. In the future, more refined categorisation may help better characterise tumour subtypes. Through innovative multiplatform analyses, an improved understanding of distinct subtypes in bladder cancer has emerged [5]. Consequently, better subtype recognition may herald more targeted, and effective, therapy. Next, it is essential to determine the right type of treatment. Now, NAC is the standard of care for MIBC. However, there are several exciting trials examining other effective options to be used alternatively or synergistically. For example, the use of immunotherapy in the preoperative space is being studied and may shift how we manage MIBC. Lastly, the question of timing is key. Now, the order of surgery and systemic therapy may be a new frontier and perhaps the most significant question we are trying to solve. The possibility of understanding new subtypes of tumours and having new treatment options may require new timing for specific therapies in certain patients. It is conceivable that certain subtypes would be best managed with systemic therapy immediately whilst others with upfront surgery.

Certainly, more work needs to be done. So, what can we do now? We can promote the overall well‐being of our patients. Urologists can be conduits to help patients live healthy lifestyles and engage in behaviours that will promote psychological stability and physical strength. Encouraging daily activity, increasing fruit and vegetable consumption and, if needed, weight loss are options. Smoking cessation represents an imperative opportunity where urologists can make a positive impact [6]. Prehabilitation programmes focused on preparation for surgery can be done during NAC or while waiting for surgery and incorporate these elements. In this way, waiting time is leveraged to make small but cumulative improvements – ‘a little bit at a time’ is possible.

For now, we will continue to study the bladder cancer conundrum: subtypes of tumours, various treatments, and the best timing for therapy. Regardless of these results, it is likely patients with bladder cancer will still need some combination of surgery, systematic therapy and supportive care while they heal. In the interim, promoting well‐being is one way to help patients live healthier lives whilst making them more resilient to undergo whatever treatments may emerge next.

by Matthew Mossanen and Adam S. Kibel

References

  1. Prout, GR, Marshall, VF. The prognosis with untreated bladder tumors. Cancer 1956; 9: 551– 8
  2. Grossman, HB, Natale, RB, Tangen, CM et al. Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer. N Engl J Med 2003; 349: 859– 66
  3. Advanced Bladder Cancer Overview Collaboration. Neoadjuvant chemotherapy for invasive bladder cancer. Cochrane Database Syst Rev 2005; 2: CD005246.
  4. Lane, G, Risk, M, Fan, Y, Krishna, S, Konety, B. Persistent muscle‐invasive bladder cancer after neoadjuvant chemotherapy: an analysis of Surveillance, Epidemiology and End Results‐Medicare data. BJU Int 2019; 123: 818– 25
  5. Robertson, AG, Kim, J, Al‐Ahmadie, H et al. Comprehensive molecular characterization of muscle‐invasive bladder cancer. Cell 2018; 174: 1033
  6. Mossanen, M, Caldwell, J, Sonpavde, G, Lehmann, LS. Treating patients with bladder cancer: is there an ethical obligation to include smoking cessation counseling? J Clin Oncol 2018; 36: 3189– 91

April 2017 #urojc summary: Is SABR a viable therapeutic option for managing renal tumors in patients deemed unsuitable for surgery?

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saji_author-photo5April 2017 #urojc summary: Is SABR a viable therapeutic option for managing renal tumors in patients deemed unsuitable for surgery?

In April 2017, the International Twitter-based Urology Journal Club (@iurojc) #urojc reviewed an interesting recent article by Siva et. Al reporting their experience in a prospective cohort study utilizing Stereotactic Ablative Body Radiotherapy (SABR) on inoperable primary renal cell carcinomas. The article was made freely available courtesy of BJUI for the duration of the discussion (https://onlinelibrary.wiley.com/doi/10.1111/bju.13811/full). The journal club ran for 48 hours beginning on April 2nd at 21:00 UTC. The first author of the manuscript, Dr. Shankar Siva, a radiation oncologist at the Peter MacCallum Cancer Center joined the discussion using the Twitter handle @_ShankarSiva.

The study enrolled 37 total patients (T1a n=13, T1b n=23, and T2a n=1) due to one of three reasons: (1) deemed medically inoperable (n=28 Charlson Comorbidity >6), (2) high-risk group for surgery (n=11 high risk post-surgical dialysis), (3) refused surgery (n=1). The primary outcome measured was the successful delivery of radiotherapy. Secondary outcomes included (1) adverse events of radiotherapy, (2) local progression of the disease, (3) distant progression of the disease, and (4) overall survival.

@iurojc kicked things off with a starter question

There was immediate debate regarding the validity of treating patients with inoperable tumors using alternative modalities.

@PatrickKenneyMD cited a retrospective analysis by Kutikov et. al (@uretericbud) of the SEER database on competing causes of mortality in elderly patients with localized RCC. The study reported the 5-year probability of mortality from non-cancer related etiology to be 11% while the RCC related mortality probability was 4%. The authors of the paper encourage that management decisions for localized RCC in older patients should take into account competing causes of mortality. @DrewMoghanaki argued that many patients will still suffer from the sequelae of cancer progression that could be prevented by treating with non-surgical modalities such as SABR.
@_ShankarSiva chimed in

@uretericbud questioned the comparison of two discrepant neoplasms

@_ShankarSiva explained

From Belgium, an important point was made about the question itself.

While this conversation was occurring, a lively discussion on the utility of SABR compared to other established non-surgical modalities was taking place.

@_ShankarSiva replied

Next, @CanesDavid posed a question regarding the most frequent factors of surgical disqualification in the cohort

@benchallacombe noted a limitation of the study which led to a discussion of the utility of one of the four secondary outcomes of the study- local progression.

@nickbrookMD (co-author) cited an article by Crispen et. al that characterized the growth rate of untreated solid enhancing renal masses. @Rad_Nation proposed two follow-up studies that could be conducted.

Even if these studies are conducted, there is skepticism around whether Urologists will view SBRT as a viable alternative treatment modality for RCC.

@iurojc posed an important question. What should be the overall goal of the urologist? Is it to cure cancer by all means? Or perhaps to find a balance between quality of life and management of the disease? SBRT may play a crucial role in the latter situation.

To wrap things up, @iurojc asked a summary question.

The authors of the manuscript provided a response and their thoughts on what needs to be done next.

Thank you to everyone who participated in the April 2017 #urojc. Special thanks to the authors @_ShankarSiva and @nickbrookMD for joining in on the discussion and providing further insight to their work.

Akhil Saji is a third-year medical student at New York Medical College, Valhalla, NY.

Twitter @AkhilASaji

 

References

1. Siva, Shankar, et al. “Stereotactic ablative body radiotherapy for inoperable primary kidney cancer: a prospective clinical trial.” BJU international (2017)

2. Kutikov, Alexander, et al. “Evaluating overall survival and competing risks of death in patients with localized renal cell carcinoma using a comprehensive nomogram.” Journal of Clinical Oncology 28.2 (2009): 311-317.

3. Crispen, Paul L., et al. “Predicting growth of solid renal masses under active surveillance.” Urologic Oncology: Seminars and Original Investigations. Vol. 26. No. 5. Elsevier, 2008

 

Article of the week: Nephron-sparing management vs radical nephroureterectomy

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

In addition to the article itself, there is an accompanying editorial written by 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 Dr. Jay Simhan dicsussing his paper.

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

Nephron-sparing management vs radical nephroureterectomy for low- or moderate-grade, low-stage upper tract urothelial carcinoma

Jay Simhan, Marc C. Smaldone, Brian L. Egleston*, Daniel Canter†, Steven N. Sterious, Anthony T. Corcoran, Serge Ginzburg, Robert G. Uzzo and Alexander Kutikov

Division of Urologic Oncology, Departments of Surgical Oncology, *Biostatistics, Fox Chase Cancer Center, Temple University School of Medicine, Philadelphia, PA and †Department of Urology, Emory University School of Medicine, Atlanta, GA, USA

Read the full article
OBJECTIVE

• To compare overall and cancer-specific outcomes between patients with upper tract urothelial carcinoma (UTUC) managed with either radical nephroureterectomy (RNU) or nephron-sparing measures (NSM) using a large population-based dataset.

PATIENTS AND METHODS

• Using Surveillance, Epidemiology, and End Results (SEER) data, patients diagnosed with low- or moderate-grade, localised non-invasive UTUC were stratified into two groups: those treated with RNU or NSM (observation, endoscopic ablation, or segmental ureterectomy).

• Cancer-specific mortality (CSM) and other-cause mortality (OCM) rates were determined using cumulative incidence estimators. Adjusting for clinical and pathological characteristics, the associations between surgical type, all-cause mortality and CSM were tested using Cox regressions and Fine and Gray regressions, respectively.

RESULTS

• Of 1227 patients [mean (sd) age 70.2 (11.00) years, 63.2% male] meeting inclusion criteria, 907 (73.9%) and 320 (26.1%) patients underwent RNU and NSM for low- or moderate-grade, low-stage UTUC from 1992 to 2008.

• Patients undergoing NSM were older (mean age 71.6 vs 69.7 years, P < 0.01) with a greater proportion of well-differentiated tumours (26.3% vs 18.0%, P = 0.001).

• While there were differences in OCM between the groups (P < 0.01), CSM trends were equivalent. After adjustment, RNU treatment was associated with improved non-cancer cause survival [hazard ratio (HR) 0.78, confidence interval [CI] 0.64–0.94) while no association with CSM was demonstrable (HR 0.89, CI 0.63–1.26).

CONCLUSIONS

• Patients with low- or moderate-grade, low-stage UTUC managed through NSM are older and are more likely to die of other causes, but they have similar CSM rates to those patients managed with RNU.

• These data may be useful when counselling patients with UTUC with significant competing comorbidities.

Read more articles of the week

Editorial: Upper tract urothelial carcinoma: do we really need to burn down the house?

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In this issue, Simhan et al. [1] use the Surveillance, Epidemiology, and End Results (SEER) database to compare outcomes of nephron-sparing and radical extirpative therapy for upper tract urothelial carcinoma (UTUC). Their study sheds some well-needed light on a difficult clinical dilemma.

A diagnosis of low- or moderate-grade, low-stage UTUC is akin to finding a spot of suspicious green mould on your attic drywall. The scale and potential danger of the problem may not be immediately apparent and both patient and urologist must make tough choices with incomplete information. Spot treat the problem and preserve nephrons via endoscopic or segmental resection or burn down the house with radical nephroureterectomy to minimise recurrence and progression risk? With only relatively small datasets for guidance and the uncertainty of endoscopic biopsy, many urologists have a low threshold to proceed with radical therapy, perhaps unnecessarily.

Simhan et al. [1] identified 1227 patients in the SEER dataset with low- or moderate-grade, localised, non-invasive UTUC who were treated either with nephron-sparing procedures (endoscopic resection or segmental ureterectomy) or nephroureterectomy between 1992 and 2008. For this cohort, radical therapy with nephroureterectomy imparted no advantage in cancer-specific survival. Patients undergoing nephron sparing were slightly older and did experience higher non-cancer specific mortality. This may reflect an underlying bias to offer nephron sparing to older patients with a greater burden of comorbidities and shorter life expectancy. These results corroborate another large SEER study from 2010, which documented no difference in cancer-specific mortality when comparing segmental resection with nephroureterectomy for T1–T4 N0M0 urothelial carcinoma of the ureter [2].

Population-based tumour registry studies are complementary to institutional series and are particularly valuable for rare tumours like UTUC. However, they have their limitations and these are outlined clearly in the Simhan et al. [1] article. Most notable are the lack of linked comorbidity information and the inability to separate segmental resection from endoscopic management in the nephron-sparing group. We should avoid the temptation to broaden indications for endoscopic resection to all patients with low-grade, low-stage UTUC of the renal pelvis and calyces. After all, the authors present no data on: (i) local recurrence and reoperation rates, (ii) progression to radical nephroureterectomy or (iii) correlation between endoscopic biopsy results and the ultimate pathology from nephroureterectomy specimens.

Over the past decade, there has been a progressive movement toward nephron-sparing approaches for treatment of T1 RCC, even in the context of a normal contralateral kidney. This transition has been fuelled by data showing the substantial negative impact of chronic kidney disease (CKD) on cardiovascular events and overall mortality [3]. Broader application of this philosophy to the treatment of low- or moderate-grade, low-stage UTUC would be a natural next step. This is particularly true given the advantage of maximising nephrons should disease progression necessitate platinum-based chemotherapy.

However, endoscopic resection of UTUC carries a much higher burden of local recurrence (20–85%) [4], than does partial nephrectomy for RCC. Patients with UTUC often require multiple serial endoscopic resections and years of complicated and costly surveillance. More recent data also suggests that surgically induced CKD may not carry the same risk of progression and mortality as medical CKD [5]. Perhaps burning down the house is not as potentially destructive as we once thought?

With these caveats firmly in mind, the Simhan et al. [1] study does support a growing appreciation that nephron-sparing approaches to low- or moderate-grade, low-stage UTUC do not worsen cancer-specific mortality. Although these findings are encouraging, I agree with the authors that patient selection for nephron sparing should continue to be informed by clinical judgment and adherence to published treatment guidelines [6].

Richard E. Link
Associate Professor of Urology, Director, Division of Endourology and Minimally Invasive Surgery, Scott Department of Urology, Baylor College of Medicine, Houston, TX, USA

References

  2. Jeldres C, Lughezzani G, Sun M et al. Segmental ureterectomy can safely be performed in patients with transitional cell carcinoma of the ureter. J Urol 2010; 183: 1324–1329
  3. Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med 2004; 351: 1296–1305
  4. Bagley DH, Grasso M 3rd. Ureteroscopic laser treatment of upper urinary tract neoplasms. World J Urol 2010; 28: 143–149
  5. Lane BR, Campbell SC, Demirjian S, Fergany AF. Surgically induced chronic kidney disease may be associated with a lower risk of progression and mortality than medical chronic kidney disease. J Urol 2013; 189: 1649–1655
  6. Roupret M, Zigeuner R, Palou J et al. European guidelines for the diagnosis and management of upper urinary tract urothelial cell carcinomas: 2011 update. Eur Urol 2011; 59: 584–594

 

Video: Nephron sparing vs radical nephroureterectomy for UTUC

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Nephron-sparing management vs radical nephroureterectomy for low- or moderate-grade, low-stage upper tract urothelial carcinoma

Jay Simhan, Marc C. Smaldone, Brian L. Egleston*, Daniel Canter†, Steven N. Sterious, Anthony T. Corcoran, Serge Ginzburg, Robert G. Uzzo and Alexander Kutikov

Division of Urologic Oncology, Departments of Surgical Oncology, *Biostatistics, Fox Chase Cancer Center, Temple University School of Medicine, Philadelphia, PA and †Department of Urology, Emory University School of Medicine, Atlanta, GA, USA

Read the full article
OBJECTIVE

• To compare overall and cancer-specific outcomes between patients with upper tract urothelial carcinoma (UTUC) managed with either radical nephroureterectomy (RNU) or nephron-sparing measures (NSM) using a large population-based dataset.

PATIENTS AND METHODS

• Using Surveillance, Epidemiology, and End Results (SEER) data, patients diagnosed with low- or moderate-grade, localised non-invasive UTUC were stratified into two groups: those treated with RNU or NSM (observation, endoscopic ablation, or segmental ureterectomy).

• Cancer-specific mortality (CSM) and other-cause mortality (OCM) rates were determined using cumulative incidence estimators. Adjusting for clinical and pathological characteristics, the associations between surgical type, all-cause mortality and CSM were tested using Cox regressions and Fine and Gray regressions, respectively.

RESULTS

• Of 1227 patients [mean (sd) age 70.2 (11.00) years, 63.2% male] meeting inclusion criteria, 907 (73.9%) and 320 (26.1%) patients underwent RNU and NSM for low- or moderate-grade, low-stage UTUC from 1992 to 2008.

• Patients undergoing NSM were older (mean age 71.6 vs 69.7 years, P < 0.01) with a greater proportion of well-differentiated tumours (26.3% vs 18.0%, P = 0.001).

• While there were differences in OCM between the groups (P < 0.01), CSM trends were equivalent. After adjustment, RNU treatment was associated with improved non-cancer cause survival [hazard ratio (HR) 0.78, confidence interval [CI] 0.64–0.94) while no association with CSM was demonstrable (HR 0.89, CI 0.63–1.26).

CONCLUSIONS

• Patients with low- or moderate-grade, low-stage UTUC managed through NSM are older and are more likely to die of other causes, but they have similar CSM rates to those patients managed with RNU.

• These data may be useful when counselling patients with UTUC with significant competing comorbidities.

Read more articles of the week

Editorial – Prostate cancer surgery vs radiation: has the fat lady sung?

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The current article by Sun et al. [1] representing a number of institutions involved in prostate cancer treatment provision is thought-provoking and hypothesis-generating. The authors contention when mining Surveillance, Epidemiology and End Results data for 67 000 men who had localized prostate cancer between 1988 and 2005 is that those with a life expectancy >10 years had less likelihood of prostate cancer death when treated with surgery rather than by radiotherapy or being left to observation. The Scandinavians have already shown, in the randomized study by Hugosson et al. [2], that if you have your prostate cancer removed you have less likelihood of symptomatic local recurrence, lower likelihood of metastasis and progression, and a 29% reduced likelihood of prostate cancer death. The current study asks the question ‘Is radiation therapy less likely to provide a long-term cure for prostate cancer than surgery?’ and gives an answer in the affirmative.

The current paper, in its way, neatly encapsulates the contemporary angst generated in the community when prostate cancer screening, diagnosis and therapy are discussed. The Prostate, Lung, Colorectal, and Ovarian Cancer Screening (PLCO) trial [3] allegedly shows no benefit from treatment over observation and contends perhaps that we surgeons and radiation oncologists are harm-workers, not life-savers. The PLCO has a 52% PSA contamination in its control arm [3]. That flawed trial compared screening with de facto screening and produced, in my view, a null hypothesis. How do we explain the paradox of a 44% reduction in prostate cancer-specific mortality between 1993 and 2009? How do we explain the disconnect between these trials and the facts? What do we do with the data not yet considered by the expert panels showing that early PSA testing at age <50 years is highly predictive of subsequent lethal prostate cancer? [4]

Clinicians are rapidly moving to an era of judicious risk assessment. This can only be done after biopsy is performed. We now frequently enrol patients with apparently indolent prostate cancer into surveillance protocols [5]. So the question should be ‘If the disease found on biopsy is moderate to high risk, and potentially lethal for that man, should we remove his prostate surgically or radiate it with intensity-modulated radiation therapy, brachytherapy, proton therapy, +/- hormone therapy?’.

As a surgeon I have an inherent dislike of combining hormone therapy in primary treatment. At least 50% of men in high-risk prostate cancer cohorts who receive radiation therapy also receive hormone therapy as adjuvant or neoadjuvant treatment [6]. Hormone therapy has a myriad of side effects. Even if the playing field was level between surgery and radiation therapy, the avoidance of hormone therapy as a first-line treatment gives surgery a seductive advantage.

The authors of the current report show a significant survival advantage in the cohort for surgery over radiation therapy and observation. There will never be a randomized trial between the two potentially curative treatment methods surgery and radiation. The scourge of commercial interest with spurious claims of superiority of one form of therapy over another, proton beam vs intensity-modulated radiation therapy, robotics vs high-intensity focused ultrasonography, means that we risk having our decisions regarding appropriate therapy formed by multibillion dollar technology companies with powerful marketing capacity. The current paper confirms what is self-evident: untreated localized prostate cancer can be lethal. Surgery and radiation therapy lower the morbidity and mortality from prostate cancer. Which is the better method of curative therapy is moot, but we do know that cure is very much predicated on the expertise and location of the practitioner.

We know mostly when and who to treat and what treatments work well. In my view, the prostate cancer testing debate resonates with the contemporary discussion about childhood immunization for infectious diseases. Some parents now, who clearly cannot remember the devastating epidemics of polio and other childhood illnesses, refuse to immunize their children. Prostate cancer practitioners who did not live in the quite recent era where the initial presentation of prostate cancer was bone metastasis +/− crush fracture to the vertebra and sometimes paraplegia, may be unknowingly steering us backwards.

At the recent 2013 AUA meeting, Adams et al. [7] reported on the fate of men not screened for prostate cancer, i.e. those men who presented with a PSA >100 ng/mL. There was a 3-year survival rate of 9.7%, a 19.7% cord compression rate and a 64% hospitalization rate. Those who do not learn the lessons of history are condemned to repeat them.

Anthony J. Costello
Department of Surgery, Royal Melbourne Hospital, University of Melbourne, Melbourne, Australia

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References

  1. Sun M, Sammon JD, Becker A et al. Radical prostatectomy vs radiotherapy vs observation among older patients with clinically localized prostate cancer: a comparative effectiveness evaluation. BJU Int 2014; 113: 200–208
  2. Hugosson J, Carlsson S, Aus G et al. Mortality results from the Goteborg randomised population-based prostate-cancer screening trial. Lancet Oncol 2010; 11: 725–732
  3. Andriole GL, Crawford ED, Grubb RL 3rd et al. Prostate cancer screening in the randomized Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial: mortality results after 13 years of follow-up. J Natl Cancer Inst 2012; 104: 125–132
  4. Vickers AJ, Ulmert D, Sjoberg DD et al. Strategy for detection of prostate cancer based on relation between prostate specific antigen at age 40–55 and long term risk of metastasis: case-control study. BMJ 2013; 346: f2023
  5. Evans SM, Millar JL, Davis ID et al. Patterns of care for men diagnosed with prostate cancer in Victoria from 2008 to 2011. Med J Aust 2013; 198: 540–545
  6. Cooperberg MR, Vickers AJ, Broering JM, Carroll PR. Comparative risk-adjusted mortality outcomes after primary surgery, radiotherapy, or androgen-deprivation therapy for localized prostate cancer. Cancer 2010; 116: 5226–5234
  7. Adams W, Elliott CS, Reese JH. The fate of men presenting with PSA over 100 ng/mL: what happens when we do not screen for prostate cancer? AUA 2013. Abstract 2696

 

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