Diffusion of Robotics in Urology: Responsible Introduction of Surgical Innovation

The use of robotic surgery in urology began in 2001 with the advent of robot assisted radical prostatectomy (RARP). Since then, it has diffused throughout the field, providing an alternative to the open approach in numerous urologic procedures. However, the evidence for the utility and added benefits of the robotic approach is limited and varies among procedures. Given the fact that robotic-assisted procedures cost the patient an additional $1000 and the hospital nearly $100,000 annually, it is necessary to investigate the benefits of this technology and to determine for which procedures and which patients it is worth this increased cost. Furthermore, it is critical to assess whether the early introduction of this technology is safe for patients. Not only is the data supporting the use of robotics unclear, but also, in retrospect, the introduction of robotics may have led to unfavorable patient outcomes in certain settings. This blog will serve as overview of some of the early data regarding the use of robotics in the surgical management of three index cancers and will end with a brief discussion of safety during the initial diffusion of robotic prostatectomy.

    

RADICAL PROSTATECTOMY

Most of the initial data regarding RARP came from small, retrospective, single-center studies, most of which reported less blood loss, lower rates of transfusion, shorter length of stay and fewer short term complications. A recent prospective, multi-center, controlled trial from Sweden showed that RARP was associated with 500cc less blood loss, shorter length of stay by one day, and lower rates of reoperation during the initial hospital stay [1]. Therefore, at least in the short term, there seems to be good evidence for RARP improving perioperative outcomes.

Figure 1. RARP is associated with better short-term outcomes including less blood loss, shorter length of stay, and less rates of reoperation.  From Wallerstedt, et al. [1].

Data regarding long-term outcomes are more controversial. Based on numerous studies, it is difficult to interpret whether there is any benefit or drawback to achieving the "trifecta" of oncologic control, continence, and potency with robotic assistance. A recent prospective, non-randomized study from Sweden suggests that there may be some benefit to RARP with regard to potency, but no difference for oncologic control or continence [2]. Of note, the only randomized trial that sought to investigate this was terminated due to slow patient enrollment. Therefore, some evidence points to the benefits of RARP, some to its detriment, but most suggest equivalence between open and robotic.

 

PARTIAL NEPHRECTOMY

The use of robotics in partial nephrectomy (PN) is a different story. PN is the preferred surgical management of small renal masses (when technically feasible) because of its ability to preserve kidney function (i.e. nephron-sparing) with equivalent oncologic control. Minimally invasive PN has been shown to be associated with less blood loss, shorter length of stay, faster recovery, and less post-operative pain compared to the open flank incision [3]. Within the category of minimally invasive surgery, Pierorazio et al. showed that robotic assisted partial nephrectomy (RAPN) is associated with shorter operative time, less blood loss, and shorter warm ischemia time (WIT) [4]. Regarding complications, Mullins et al. found no difference in complication rates, but when stratified by Clavien grade, the RAPN cohort was more likely to have lower grade complications [5]. A meta-analysis comparing robotic vs. laparoscopic PN found no differences in operative times, blood loss, conversion rates, complications, or length of stay. However, RAPN was associated with shorter WIT, the key to renal preservation, which ultimately is the primary goal of PN [6].

Figure 2. RAPN is associated with shorter WIT.  From Aboumarzouk, et al. [6].

Robotic technology has led to an increased use of PN, due in part to the superior range of motion that aids in tumor excision and reconstruction under ischemic time constraints. This has been shown to be a real phenomenon, with a demonstrable increase in PN compared to radical nephrectomy in the years of robotic diffusion. [7] In addition, robotics has allowed urologists to tackle more complex renal tumors, such as tumors invading the large veins of the kidney and retroperitoneum (i.e. IVC thrombectomies), intrarenal, and posterior tumors, with comparable functional outcomes and less risk of conversion to radical nephrectomy [8-10].

 

RPLND

Retroperitoneal lymph node dissection (RPLND) is a treatment option for men with stage I and select stage II nonseminomatous germ cell tumors and is particularly useful for men who want to avoid long term surveillance or chemotherapy. Laparoscopic RPLND has been shown to have comparable oncologic outcomes with superior perioperative outcomes compared to open [11, 12]. The data regarding robotic RPLND is scant due to its nascency in the field, however a recent study shows that early on, robotic RPLND is comparable to laparoscopic in terms of perioperative outcomes [13]. Given the increased cost and risk of serious complications due to the intimacy with the great vessels during this procedure, the role of robotics in RPLND remains largely unknown at this point.

 

DIFFUSION AND PATIENT SAFETY

Given the variable and unclear data, particularly regarding RARP, how did robotics diffuse so rapidly and widely among urologists? First, it is important to note that in order to introduce new technology, one only needs a 510(k) clearance from the FDA. In the case of RARP, da Vinci received FDA clearance in 2000, the first RARP was in 2001, and the first population-based outcomes study was published in 2009. So many were performing RARP blindly without any population based data on efficacy or safety. Parsons et al. sought to retrospectively investigate if there was an effect on patient safety during this diffusion period using patient safety indicators (PSI). They found that in the year before the "tipping point," a set point indicating when RARP diffused from centers of excellence to more general urologists, there was a two-fold increase in PSI [14].

Figure 3. RARP during diffusion era is associated with a two-fold increase in PSI.  From Parsons, et al. [14].

These results highlight the importance of responsibility with regards to the introduction of new technology. Is a compromise to patient safety in the initial years of dissemination necessary? Does new technology always come with risk? How do we know when to stop pursuing a given technique? When is a reasonable time to assess whether it is inferior and causing more harm than good? Was RARP even worth this increased risk given its limited utility and increased cost? Finally, is the culprit here technology, or does innovation by nature have barriers at first?

 

SUMMARY

The role of robotics in urology today raises many questions regarding comparative efficacy, cost justification, and patient safety with innovation. Radical prostatectomy and partial nephrectomy illustrate a juxtaposition of results – RAPN seems to have succeeded while RARP has yet to show a demonstrable benefit other than less blood loss. It has also raised questions about patient safety during the dissemination of new technology and bears the question, how does an innovator responsibly report results while marketing and patient demand accelerate the innovation's diffusion? Moving forward, standardized training and credentialing programs as well as systematic reporting to non-industry groups could be instituted in order to diffuse innovation while keeping the patient first.

This blog was written by Kelly Harris, a medical student at Johns Hopkins Medical School.  Kelly recently finished a four-week sub-internship at the Brady Urological Institute and gave a presentation to the department on "The Diffusion of Robotic Surgery in Urology" from which this blog is inspired. Kelly is looking forward to a career in urology.

1. Wallerstedt A, Tyritzis SI, Thorsteinsdottir T, et al. Short-term Results after Robot-assisted Laparoscopic Radical Prostatectomy Compared to Open Radical Prostatectomy. Eur Urol 2015: 67:660-70
2. Haglind E, Carlsson S, Stranne J, et al. Urinary Incontinence and Erectile Dysfunction After Robotic Versus Open Radical Prostatectomy: A Prospective, Controlled, Nonrandomised Trial. Eur Urol 2015
3. Hung AJ, Cai J, Simmons MN, Gill IS. "Trifecta" in partial nephrectomy. J Urol 2013: 189:36-42
4. Pierorazio PM, Mullins JK, Eifler JB, et al. Contemporaneous comparison of open vs minimally-invasive radical prostatectomy for high-risk prostate cancer. BJU Int 2013: 112:751-7
5. Mullins JK, Feng T, Pierorazio PM, Patel HD, Hyams ES, Allaf ME. Comparative analysis of minimally invasive partial nephrectomy techniques in the treatment of localized renal tumors. Urology 2012: 80:316-21
6. Aboumarzouk OM, Stein RJ, Eyraud R, et al. Robotic versus laparoscopic partial nephrectomy: a systematic review and meta-analysis. Eur Urol 2012: 62:1023-33
7. Patel HD, Mullins JK, Pierorazio PM, et al. Trends in renal surgery: robotic technology is associated with increased use of partial nephrectomy. J Urol 2013: 189:1229-35
8. Ball MW, Gorin MA, Jayram G, Pierorazio PM, Allaf ME. Robot-assisted radical nephrectomy with inferior vena cava tumor thrombectomy: technique and initial outcomes. Can J Urol 2015: 22:7666-70
9. Harris KT, Ball MW, Gorin MA, Curtiss KM, Pierorazio PM, Allaf ME. Transperitoneal Robot-Assisted Partial Nephrectomy: A Comparison of Posterior and Anterior Renal Masses. J Endourol 2014: 28:655-9
10. Curtiss KM, Ball MW, Gorin MA, Harris KT, Pierorazio PM, Allaf ME. Perioperative outcomes of robotic partial nephrectomy for intrarenal tumors. J Endourol 2015: 29:293-6
11. Bhayani SB, Ong A, Oh WK, Kantoff PW, Kavoussi LR. Laparoscopic retroperitoneal lymph node dissection for clinical stage I nonseminomatous germ cell testicular cancer: a long-term update. Urology 2003: 62:324-7
12. Steiner H, Peschel R, Janetschek G, et al. Long-term results of laparoscopic retroperitoneal lymph node dissection: a single-center 10-year experience. Urology 2004: 63:550-5
13. Harris KT, Gorin MA, Ball MW, Pierorazio PM, Allaf ME. A Comparative Analysis of Robotic versus Laparoscopic Retroperitoneal Lymph Node Dissection for Testicular Cancer. BJU Int 2015
14. Parsons JK, Messer K, Palazzi K, Stroup SP, Chang D. Diffusion of surgical innovations, patient safety, and minimally invasive radical prostatectomy. JAMA Surg 2014: 149:845-51

Historical Contribution: 1964, Schirmer & Walton, Hypothermia and Kidney Function

1964
Schirmer HKA, Walton K. The Effet of Hypothermia upon Respiration and Anerobic Glycolysis of Dog Kidney. Invest Urol. 1964. 1;6:604-9.

 
The first deliberate partial nephrectomy for the excision of a tumor was credited to Vincenz Czerny in 1887. Numerous studies over the next decades defined the surgical anatomy and feasibility of partial nephrectomy for a variety of localized kidney processes (including cancer). Lack of early diagnostics and technical challenges prevented the operation from being widely utilized in the early 1900's. While these early researchers investigated repair mechanisms of the kidney, advances in the understanding of segmental blood supply and renal hypothermia to prevent ischemic damage were not introduced until the 1950's and 1960's.[1] 

Horst Schirmer, MD

In 1964, Horst Schirmer and Kenneth Walton of the Brady Urological Institute investigated the effects of hypothermia on the kidney. Prior work demonstrated that, with local cooling, renal function would only be temporarily depressed and irreversible damage (under normothermic conditions) could be limited. They investigated ox'ygen consumption and glycolysis in the kidneys of dogs. They found:

• With decreasing temperature, the reduction in glycolysis associated with ischemia was tempered (33% at 27C, 17% at 17C and near zero at 7C).
• After achieving hypothermia of 7C, normal function returned after 1 hour.
• Interruption of blood flow for 4 hours resulted in:
  • 75% reduction in function in the normothermic kidney
  • Unchanged function in the cooled (7C) kidney
• By examining both tissue from the cortex and medulla of the kidney, the cortex is nearly 7x more active than the medulla – providing evidence that cortical cooling is sufficient to provide effective hypothermia.

 
To read the entire manuscript: follow the link above, visit the Centennial Website or click here.

 

HISTORICAL CONTRIBUTIONS highlight the greatest academic manuscripts from the Brady Urological Institute over the past 100 years.  As the Brady Urological Institute approaches its centennial, we will present a HISTORICAL CONTRIBUTION from each of the past 100 years.  In the most recent experience, the most highly cited article from each year is selected; older manuscripts were selected based on their perceived impact on the field.  We hope you enjoy! 

[1] Herr HW.A history of partial nephrectomy for renal tumors.J Urol. 2005 Mar;173(3):705-8.

Quality of Life in the Treatment of Clinically-Localized, Small Renal Masses

There are a number of management strategies for patients with clinically-localized, small renal masses (SRM, clinical stage T1) including radical nephrectomy (RN), nephron-sparing surgery (NSS; includes partial nephrectomy, PN, and ablative technologies), and active surveillance. Fortunately survival rates are excellent regardless of treatment [1]. And with recent level I evidence indicating no difference in oncologic or renal-functional outcomes for healthy patients undergoing PN and RN,[2,3] quality-of-life (QOL) is becoming an increasingly important consideration for these patients.

This blog will review what is known regarding QOL in the management of SRM.

 

Radical Nephrectomy versus Nephron-Sparing Surgery

Most of the studies evaluating QOL in patients undergoing RN and NSS evaluate patients undergoing open surgery (in fact, there are no studies evaluating patients undergoing minimally-invasive PN). In addition, most of these studies employ a cross-sectional survey in which all patients from a given institution were sent a QOL questionnaire at some time period after surgery. Very few studies evaluate patients undergoing surgery in the more ideal, prospective fashion.

Cross-Sectional Studies

It is generally understood that patients undergoing RN and PN are very different patient populations. RN patients are often older, have more comorbidities and larger tumors. Patients undergoing PN are subjected to a higher risk surgery, but have the benefit of preservation of a kidney. 
Despite these differences, a study of the baseline QOL in patients undergoing RN and PN found no difference in general perceived health or QOL among the groups.[4] A more in-depth analysis indicating that patients undergoing PN had better QOL scores related to physical health, while patients undergoing RN had better mental health QOL scores at baseline.
A number of studies indicate that overall QOL is similar following RN and PN.[5-7] The study by Poulakis et al. indicated that patients undergoing PN had higher physical health QOL scores [7], and while the study by Clark et al. did not demonstrate a difference in QOL between RN and PN, those patients with more renal parenchyma (tissue) saved had higher QOL scores.[6] In general, these studies found that while NSS did not predict QOL, comorbidities, tumor size and renal function after surgery related strongly to overall QOL.
In contrast, a study by Ficarra et al. found that patients undergoing PN had improved QOL. Specifically they found lower rates of anxiety and depression in patients undergoing PN; and fewer patients had an impairment of their general health.[8]

Prospective Studies

In a study comparing radio-frequency ablation (RFA) to laparoscopic RN, Onishi et al. found that patients undergoing RFA were older and sicker with resultant lower QOL scores at baseline. However, over the course of six months following surgery, patients undergoing RFA had improvements in QOL while those undergoing RN had a significant detriment to physical functioning, physical health, pain and general health.[9] In the study by Parker et al., patients undergoing RN had improved cancer-related QOL (indicating less fear of cancer recurrence). However, many domains of QOL (including physical health and fear of recurrence) were related to renal function – which was significantly better in patients undergoing PN.[10]

 

Minimally-Invasive versus Open Surgery

As stated above, most studies evaluate open RN and NSS. Studies evaluating laparoscopic and open surgery indicate that patients undergoing laparoscopic surgery have a quicker return to baseline QOL, but at one year both groups achieve similar QOL.[10] A recent systematic review of this literature indicates that:

• With regard to RN, laparoscopic surgery has improved perioperative outcomes and related QOL.
• With regard to NSS, PN results in better preservation of renal function and related QOL regardless of approach. [11]

 

Active Surveillance and Watchful Waiting

Little QOL data exists in the SRM literature regarding active surveillance (AS) or watchful waiting (WW) programs. Analogous data from prostate cancer AS programs suggest that men do not fare worse in terms of their mental and physical wellbeing compared to those that choose to undergo active intervention [12-15], however there may be increased anxiety, particularly if tumor growth or progression is found.[16]
In a two-year study of patients undergoing WW, greater illness uncertainty was related to poorer general health, cancer-related QOL and higher distress. While physical health-related QOL decreased over the two-year period, intrusive thoughts and avoidance behaviors improved; and mental health-related QOL did not change with time.[17]
In an ongoing prospective study of AS and surgery for SRM, early data indicates that physical health-related QOL is significantly higher at baseline for patients who undergo surgery. While this difference persists throughout follow-up, mental health-related QOL (including depression and anxiety) is not adversely affected for patients undergoing AS over time and when compared to surgery patients.[18]

 

SUMMARY

While there are many shortcomings in the data regarding QOL in the management of SRM, the little data that exists indicates that:

• There is likely little difference in QOL for healthy patients undergoing RN and PN.
• A perceived QOL benefit to PN (and other NSS) may be related to preservation of renal function and tissue.
• While there is no long-term difference in QOL related to open or laparoscopic surgery, patients undergoing laparoscopic surgery may have a quicker return to baseline QOL on average.
• WW and AS for SRM does not appear to adversely affect mental health-related QOL.

 
This blog was written by Phillip M. Pierorazio, MD, Assistant Professor of Urology and Oncology.
 

 

 



 
[1] Patel HD, Kates M, Pierorazio PM, Hyams ES, Gorin MA, Ball MW, Bhayani SB, Hui X, Thompson CB, Allaf ME. Survival after diagnosis of localized T1a kidney cancer: current population-based practice of surgery and nonsurgical management. Urology. 2014 Jan;83(1):126-32. doi: 10.1016/j.urology.2013.08.088. Epub 2013 Nov 16.
[2] Van Poppel H, Da Pozzo L, Albrecht W, Matveev V, Bono A, Borkowski A, Colombel M, Klotz L, Skinner E, Keane T, Marreaud S, Collette S, Sylvester R. A prospective, randomised EORTC intergroup phase 3 study comparing the oncologic outcome of elective nephron-sparing surgery and radical nephrectomy for low-stage renal cell carcinoma. Eur Urol. 2011 Apr;59(4):543-52. doi: 10.1016/j.eururo.2010.12.013. Epub 2010 Dec 22.
[3] Scosyrev E, Messing EM, Sylvester R, Campbell S, Van Poppel H. Renal function after nephron-sparing surgery versus radical nephrectomy: results from EORTC randomized trial 30904. Eur Urol. 2014 Feb;65(2):372-7. doi: 10.1016/j.eururo.2013.06.044. Epub 2013 Jul 2.
[4] Arnold ML, Thiel DD, Diehl N, Wu KJ, Ames S, Parker AS. Comparison of baseline quality of life measures between renal cell carcinoma patients undergoing partial versus radical nephrectomy. BMC Urol. 2013 Oct 22;13:52. doi: 10.1186/1471-2490-13-52.
[5] Clark PE, Schover LR, Uzzo RG, Hafez KS, Rybicki LA, Novick AC. Quality of life and psychological adaptation after surgical treatment for localized renal cell carcinoma: impact of the amount of remaining renal tissue. Urology. 2001 Feb;57(2):252-6.
[6] Gratzke C, Seitz M, Bayrle F, Schlenker B, Bastian PJ, Haseke N, Bader M, Tilki D, Roosen A, Karl A, Reich O, Khoder WY, Wyler S, Stief CG, Staehler M, Bachmann A. Quality of life and perioperative outcomes after retroperitoneoscopic radical nephrectomy (RN), open RN and nephron-sparing surgery in patients with renal cell carcinoma. BJU Int. 2009 Aug;104(4):470-5. doi: 10.1111/j.1464-410X.2009.08439.x. Epub 2009 Feb 23.
[7] Poulakis V, Witzsch U, de Vries R, Moeckel M, Becht E. Quality of life after surgery for localized renal cell carcinoma: comparison between radical nephrectomy and nephron-sparing surgery. Urology. 2003 Nov;62(5):814-20.
[8] Ficarra V, Novella G, Sarti A, Novara G, Galfano A, Cavalleri S, Artibani W. Psycho-social well-being and general health status after surgical treatment for localized renal cell carcinoma. Int Urol Nephrol. 2002-2003;34(4):441-6.
[9] Onishi T, Nishikawa K, Hasegawa Y, Yamada Y, Soga N, Arima K, Yamakado K, Hoshina A, Sugimura Y. Assessment of health-related quality of life after radiofrequency ablation or laparoscopic surgery for small renal cell carcinoma: a prospective study with medical outcomes Study 36-Item Health Survey (SF-36). Jpn J Clin Oncol. 2007 Oct;37(10):750-4. Epub 2007 Oct 17.
[10] Parker PA, Swartz R, Fellman B, Urbauer D, Li Y, Pisters LL, Rosser CJ, Wood CG, Matin SF. Comprehensive assessment of quality of life and psychosocial adjustment in patients with renal tumors undergoing open, laparoscopic and nephron sparing surgery. J Urol. 2012 Mar;187(3):822-6. doi: 10.1016/j.juro.2011.10.151. Epub 2012 Jan 15.
[11] MacLennan S, Imamura M, Lapitan MC, Omar MI, Lam TB, Hilvano-Cabungcal AM, Royle P, Stewart F, MacLennan G, MacLennan SJ, Dahm P, Canfield SE, McClinton S, Griffiths TR, Ljungberg B, N'Dow J; UCAN Systematic Review Reference Group; EAU Renal Cancer Guideline Panel. Systematic review of perioperative and quality-of-life outcomes following surgical management of localised renal cancer. Eur Urol. 2012 Dec;62(6):1097-117. doi: 10.1016/j.eururo.2012.07.028. Epub 2012 Jul 20.
[12] Vasarainen H, Lokman U, Ruutu M, Taari K, Rannikko A. Prostate cancer active surveillance and health-related quality of life: results of the Finnish arm of the prospective trial. BJU international. Jun 2012;109(11):1614-1619.
[13] Wilcox CB, Gilbourd D, Louie-Johnsun M. Anxiety and health-related quality of life (HRQL) in patients undergoing active surveillance of prostate cancer in an Australian centre. BJU international. Mar 2014;113 Suppl 2:64-68.
[14] Daubenmier JJ, Weidner G, Marlin R, et al. Lifestyle and health-related quality of life of men with prostate cancer managed with active surveillance. Urology. Jan 2006;67(1):125-130.
[15] van den Bergh RC, Essink-Bot ML, Roobol MJ, et al. Anxiety and distress during active surveillance for early prostate cancer. Cancer. Sep 1 2009;115(17):3868-3878.
[16] Johansson E, Steineck G, Holmberg L, et al. Long-term quality-of-life outcomes after radical prostatectomy or watchful waiting: the Scandinavian Prostate Cancer Group-4 randomised trial. The lancet oncology. Sep 2011;12(9):891-899.
[17] Parker PA, Alba F, Fellman B, Urbauer DL, Li Y, Karam JA, Tannir N, Jonasch E, Wood CG, Matin SF. Illness uncertainty and quality of life of patients with small renal tumors undergoing watchful waiting: a 2-year prospective study. Eur Urol. 2013 Jun;63(6):1122-7. doi: 10.1016/j.eururo.2013.01.034. Epub 2013 Feb 9.
[18] Pierorazio PM, McKiernan JM, Allaf ME. Quality of Life on Active Surveillance for a Small Renal Masses versus Immediate Intervention: Interim Analysis of the DISSRM (Delayed Intervention And Surveillance For Small Renal Masses) Registry. AUA Annual Meeting, 2013. https://www.auanet.org/university/abstract_detail.cfm?id=633&meetingID=13SAN

Urologic Oncology in the Middle East

The Emirates Oncology Conference and Pan-Arab Cancer Congress 2014 was held in Abu Dhabi, UAE as a joint program of the SEHA Health System in conjunction with Johns Hopkins International and its affiliate Tawam Hospital. While the conference covered a wide range of malignancies, there was a palpable focus on cancer care in the Middle East. In urologic oncology, the prevalence of renal cell, prostate and bladder cancers is different depending on the country and region – therefore, the treatments and outcomes can vary dramatically.

This blog will discuss differences in Renal Cell Carcinoma, Prostate Cancer and Bladder Cancer in countries of the Middle East. 

The incidence and mortality of urologic malignancies in the Middle East (Western Asia) and the more developed regions of the world including the United States and Europe.

RENAL CELL CARCINOMA

According to the WHO GLOBOCAN program, the annual incidence of RCC (renal cell carcinoma) is 213,924 people, with 90,802 deaths per year leaving a 5-year prevalence of 580,700 people. RCC is age-related (i.e. more common in older patients) and is most common in the more developed countries of the world like the United States and countries of Europe. In the United States, the ASR (age-specific rate) of RCC is 12.0 per 100,000 people (see Table below). While Israel has an ASR for RCC of 10.0, most Arab countries of the Middle East have rates between 2.0 and 3.0. Turkey has the highest ASR of 5.6 for RCC. 

The 20 highest age-specific rates of kidney cancer (per 100,000) in the countries of Western Asia from WHO GLOBOCAN.

Most of the figures are likely inaccurate and underestimate the true incidence of RCC as data in not consistently shared among countries and institutions within countries.  To address the shortcomings of systematic data collection in these countries, the Africa Middle-East Collaborative RCC Epidemiology Project was started as a cancer registry, collecting data from a number of countries including Algeria, Egypt, Jordan, Lebanon, Libya, Morocco, and Saudi Arabia. For instance, GLOBOCAN estimates the incidence of RCC in Lebanon to be approximately 2 per 100,000, while the actual data from the collaborative registry indicates the incidence in Lebanon is closer to 4.3 per 100,000.

Similar to other countries around the world, most RCC are low-grade, early stage tumors, however the significant proportion of patients that present with high-stage or metastatic disease mirrors the 20-30% seen globally.

 

PROSTATE CANCER

The prostate cancer data mirrors the data for RCC. The US has an ASR of 98.2 per 100,000 men; Turkey has the highest ASR of 40.6 in the Middle East. 

The 20 highest age-specific rates of prostate cancer (per 100,000) in the countries of Western Asia from WHO GLOBOCAN.

Interestingly, Lebanon has seen a dramatic rise in the incidence of prostate cancer due to a national screening campaign using PSA several years ago.

The increasing trends in prostate cancer in Lebanon coincide with a national PSA screening campaign.
From Shamseddine etal. [1]

In the United Arab Emirates, prostate cancer is the 3^rd most common malignancy. Most patients (77%) present with advanced disease and only approximately 20% receive radical local treatment (16.6% radiation treatment, 5.5% radical prostatectomy).[2] However, over the past decade there has been a tremendous shift toward a multidisciplinary approach to prostate cancer including oncology, urologic oncologists, robotic surgery, radiation oncology and cancer nursing. There are now approximately 30 daVinci Robotic Surgery Systems in the Middle East, with 12 in Saudi Arabia.

 

BLADDER CANCER

The ASR trends in bladder cancer are similar to those observed in RCC and prostate cancer. 

The 20 highest age-specific rates of bladder cancer (per 100,000) in the countries of Western Asia from WHO GLOBOCAN.

One of the more interesting trends in bladder cancer are the decreasing rates of schisosomiasis related squamous cell carcinomas of the bladder in Egypt (read more about schistosomiasis-related cancer of the bladder in our previous blog or click here). Control of schistosomiasis through antibilharzial campaigns have led to dramatic decreases in infestation rates and subsequent bladder cancer incidence. For instance, in Egypt the overall prevalence of schistosomiasis infection decreased from 37-48% to 3%, with a subsequent decrease in the proportion of bladder cancers from 31% to 12% of total cancers in the country.[3,4]

The second interesting trend in bladder cancer is the increasing incidence of cancers related to increasing rates of tobacco smoke. For instance, in Lebanon, the incidence of bladder cancer (13.7%) approaches that of prostate cancer (16.4%) – unheard of in most other countries! Recent data indicate that differences in the prevalence of drug metabolizing enzymes (S-transferases, N-acetyltransferases, and cytochromes P-450) in a number of ethnic groups may explain the susceptibility to bladder cancer in this population.[5]

	Age-specific Rate (per 100,000 population)
	Renal Cancer	Prostate Cancer	Bladder Cancer	Testis Cancer
United States of America	12.0	98.2	11.6	5.0
State of Palestine	3.1	15.2	7.6	1.6
Iraq	2.9	8.7	11.4	1.1
Israel	10.0	84.3	12.6	4.9
Jordan	3.2	15.3	7.1	1.7
Kuwait	2.2	14.5	5.5	0.6
Lebanon	3.2	37.2	16.6	2.4
Oman	2.1	10.2	4.8	0.4
Qatar	3.5	13.2	5.3	0.5
Saudi Arabia	2.3	9.5	3.6	0.6
Syrian Arab Republic	3.1	11.9	9.6	1.4
Turkey	5.6	40.6	15.2	3.2
United Arab Emirates	2.3	10.0	4.3	0.4
Yemen	0.6	2.7	1.8	0.1

 

SUMMARY

• The most common urologic malignancies (RCC, prostate and bladder cancer) are disease of older populations and more common in the most developed countries of the world.
• The incidence of these cancers is lower in all countries of the Middle East, although the true incidence may be underestimated by difficulties in gathering and sharing cancer data.
• A number of interesting trends in the incidence of urologic malignancies make the Middle East a fascinating frontier for investigating cancers of the genitourinary system.

 
This blog was inspired by the lecture, "Overview of Genito Urinary Malignancies in The MENA Region," by Professor Marwan Ghosn of Lebanon.
 
[1] Shamseddine A, Saleh A, Charafeddine M, Seoud M, Mukherji D, Temraz S, Sibai AM. Cancer trends in Lebanon: a review of incidence rates for the period of 2003-2008 and projections until 2018. Popul Health Metr. 2014 Mar 4;12(1):4. doi: 10.1186/1478-7954-12-4.
[2] Ghafoor M, Schuyten R, Bener A. Epidemiology of prostate cancer in United Arab Emirates. Med J Malaysia. 2003 Dec;58(5):712-6.
[3] Ministry of Health and Population, Department of Endemic Diseases, Prevalence of schistosomiasis in Egypt over time, Egypt, 2004.
[4] I. Gouda, N. Mokhtar, D. Bilal, T. El-Bolkainy, N.M. El-Bolkainy. Bilharziasis and bladder cancer: a time trend analysis of 9843 patients. J Egypt Natl Canc Inst, 19 (2) (2007), pp. 158–162
[5] Dhaini HR, Kobeissi L. Toxicogenetic profile and cancer risk in Lebanese. J Toxicol Environ Health B Crit Rev. 2014;17(2):95-125. doi: 10.1080/10937404.2013.878679.

 

Robotics in Urologic Oncology: Partial Nephrectomy for Kidney Cancer

Robotic surgery is the latest evolution in laparoscopic surgery. Traditional laparoscopic surgery was and is performed with rigid instruments, a two-dimensional view with the surgeon at the patient's bedside and an assistant controlling the camera (or view) of the operation. Robotic surgery makes use of a three-dimensional, dual-camera system; instruments that mimic natural hand motions leading to improved ergonomics, and while the surgeon sits at a console away from the patient, he or she has full control of the camera and view of the operation. The robotic systems used today are termed "master-slave" systems where the robot transforms human movements into scaled robotic movements, but the robotic instruments cannot function independently or autonomously.

The most widely-used robotic system is the daVinci system by Intuitive Surgical. This system was first cleared by the FDA in 1997 for surgical assistance, for radical prostatectomy in 2001 and broad urological surgery in 2005. There are currently over 2,000 daVinci units in use in the United States and nearly 1,000 additional units worldwide. Urology and urologic oncology as specialties represent a major proportion of the utilization of robotic surgery. For many diseases and operations, robotic technology has improved perioperative and long-term outcomes – for other operations the benefit is marginal at best. In this series of blog entries, we will review the utilization and impact of robotic technology on a number of urologic oncology disease states.

The first blog in this series will focus on kidney cancer and the use of robotic partial nephrectomy.

 

THE HISTORY OF LAPAROSCOPIC NEPHRECTOMY AND PARTIAL NEPHRECTOMY

The first laparoscopic radical nephrectomy was performed in 1991 by Dr. Clayman and colleagues at the Washington University School of Medicine, St Louis.[1] Unlike appendectomy (appendix removal) and cholecystectomy (gallbladder removal) in general surgery, the adoption of laparoscopic nephrectomy was slow in the US with only 30% of nephrectomies being performed laparoscopically by 2005.[2] In comparison, 70% of gallbladders were removed laparoscopically 15 years after the first laparoscopic cholecystectomy. During the same time period, partial nephrectomy (PN, or removal of just a kidney tumor and the surrounding normal kidney tissue) was historically underutilized in the US. In the 1990's and early 2000's, only approximately 10% of kidney surgeries were PN – and most of these were performed at large, academic, urban and teaching hospitals.[3] While the rates oif both laparoscopy and PN increased during the 2000's, the majority of PN were performed through an open incision, once again in large urban and teaching hospitals.[4]

 
In the late 2000's, a number of national and worldwide trends changed the way kidney surgery was performed. First, robotic technology was taking off – the daVinci system was approved for radical prostatectomy in 2001 and over the next decade hospitals all over the US were acquiring robots. As the number of robotic prostatectomies and surgeries increased nationwide, surgeons became more comfortable with robotic technology and began looking for more uses. In addition, in 2009, the AUA (American Urological Association) released the "Guidelines for the Management of the Clinical Stage 1 Renal Mass." The Guideline states that "Nephron-sparing surgery should be considered in all patients with a clinical T1 renal mass as an overriding principle," and within a year of releasing the Guidelines, the utilization of PN increased from 27% to 32% nationwide.[5]

 
Data from Johns Hopkins and the State of Maryland indicate that the rate of PN increased from 9% to 27% from 2000 to 2010. The proportion of open PN decreased by 1/3^rd and robotic and other minimally-invasive PN increased to nearly 60% of all PN. Importantly, after 2008 (a time period which robotic technologies were widely disseminated), being treated at a university hospital was no longer a predictor of PN – PN was finally becoming widespread!![6] 

The increasing using of robotic and minimally-invasive partial
nephrectomy in the State of Maryland. From Patel et al. [6]

This local trend was reflected in national data, indicating modest increases in open PN (8%) but dramatic increases in robotic PN (45%) in the National Inpatient Sample (a large all-payer inpatient care database cataloguing over 7 million inpatient hospitalizations).[7]

 

COMPARATIVE OUTCOMES FOR ROBOTIC PARTIAL NEPHRECTOMY: 

DO THE DATA SUPPORT THIS TREND?

In general, the increasing use of robotic PN is supported by data and represents one of the true "success stories" for robotic surgery. Robotic surgery is beneficial to patients undergoing PN as the wristed robotic instruments and three-dimensional views facilitate better and faster removal of tumors and reconstruction of the kidney.  The video below is a representative example of a robotic PN: the artery is temporarily clamped to facilitate a bloodless resection and reconstruction (ischemia time), the tumor is resected and the kidney is reconstructed.

In a systematic review of eight studies comparing robotic PN to open PN, robotic PN was associated with:

• Longer operative time (+40.89 minutes ; p = 0.002)
• Lower perioperative complication rate (19.3% for RPN and 29.5% for OPN)
  • Odds ratio: 0.53; 95%CI, 0.42–0.67; p<0.001
• Shorter hospital stay (−2.78 days; p<0.00001)
• Less estimated blood loss (−106.83mL; p = 0.003)

There was no difference observed in transfusions, conversion to radical nephrectomy, ischemia time, estimated GFR change (kidney function), surgical margin status, or overall cost.[8]
Comparing robotic to laparoscopic PN in a systematic review of 12 studies and over 700 patients, demonstrated no difference in operative times, estimated blood loss, conversion rates, length of hospital stay, complications, or positive margins between the surgeries. In fact, the only notable difference was that robotic PN was associated with less warm ischemic time (quicker removal of the tumor and reconstruction of the kidney). It should be noted that laparoscopic surgery was performed by fewer, but expert surgeons while robotic PN was performed by a greater variety of surgeons of varying experience level.[9]

When comparing our data at Johns Hopkins, we found that robotic PN was associated with improved operative parameters (operative time, blood loss, ischemia time) and fewer serious complications.[10] In addition, we determined that the learning curve for robotic PN was much quicker than laparoscopic surgery – about 25 patients.[11]

While long-term oncologic data is lacking, surrogate oncologic measure (i.e. surgical margin status) and short-term recurrence and survival data indicate that robotic PN is equivalent to open and laparoscopic surgery with regards to oncology outcomes, and likely superior with regard to perioperative outcomes.

 

SUMMARY

• The emergence of robotic technology dramatically changed the management of kidney cancer in the United States, with more patients undergoing partial nephrectomy now than ever before.
• The comparative data demonstrates improved outcomes for many peri-operative and surrogate oncologic outcomes. Longer-term data will likely confirm robotic PN as the standard-of-care for small renal masses requiring treatment.

 

 

This blog was adapted from a lecture titled "Robotics in Urologic Oncology," given by Phillip M. Pierorazio, MD, Assistant Professor of Urology and Oncology, at the Emirates Oncology Conference, 2014 in Abu Dhabi.

 

 

1. Clayman et al. Laparoscopic Nephrectomy. N Engl J Med 1991; 324:1370-1371May 9, 1991. http://www.nejm.org/doi/full/10.1056/NEJM199105093241918
2. Miller, D. C. et al. JAMA 2006;295:2480-2482
3. Hollenbeck, Urology, Volume 67, Issue 2, 2006, 254 - 259
4. Patel et al., J Urol, Volume 187, Issue 3, 2012, 816 - 821
5. Bjurlin et al., Urology, Volume 82, Issue 6, 2013, 1283 - 1290
6. Patel et al., J Urol, 2013 Apr;189(4):1229-35.
7. Ghani et al., J Urol, Volume 191, Issue 4, 2014, 907 - 913
8. Wu etal. PLoS One. 2014; 9(4): e94878.
9. Aboumarzouka etal. Eur Urol. 2012 Dec;62(6):1023-33.
10. Mullins etal. Urology. 2012 Aug;80(2):316-21.
11. Pierorazio et al., Urology, 78 (2011), p. 813

Oncocytoma: A Benign Kidney Tumor Often Confused for Cancer

Upwards of 15-20% of kidney tumors may be benign lesions. While physicians and surgeons can use patient information, radiographic imaging and biopsy to provide information, the definitive diagnosis of cancer or benign tumor is established only after the tumor has been removed. For instance, smaller tumors, female sex and age are associated with benign tumors - younger women are nearly twice as likely as age-matched men to have benign masses.[1-5] While certain characteristics are indicative of benign tumors (i.e. fat always indicates an angiomyolipoma), many other benign tumors – like oncocytoma – can appear similar to renal cell carcinoma (RCC) on CT scan and biopsy.

This blog will review oncocytoma, one of the most common benign tumors of the kidney.

Epidemiology and Etiology

Renal oncocytoma is one of the most common of benign renal masses, accounting for 3-7% of kidney tumors.[6] Oncocytomas appear as enhancing renal masses and are often indistinguishable from clear-cell RCC on CT scans (see Diagnosis below). Both oncocytomas and clear-cell RCC pick up contrast material and enhance brightly. However, oncocytoma is a distinct entity from RCC with unique cell of origin and cytogenetic abnormalities.[7-8]

Oncocytomas are more common in older patients with small, incidentally discovered renal masses. [4,9] Generally, they are more common in men than women (2:1 ratio), present in the 4th to 6th decade of life and can present bilaterally, multifocally or recur in 6-13% of cases.[10] Patients with the rare, Birt-Hogg-Dubé, genetic syndrome can present with oncocytomatosis – the presence of multiple oncocytomas in both kidneys. [11] Oncocytomas are benign tumors and rare case reports of metastatic oncocytoma represent either malignant degeneration, coexistence of RCC or pseudometastases (not really metastatic disease).[12]

Diagnosis

In general, oncocytoma appear similar to RCC on imaging. However, a number of characteristic radiographic findings are common in oncocytoma:

• On CT scan, bright, rapidly-enhancing pattern and a central stellate scar [13]
• On angiography, a spoke wheel pattern of feeding arteries may be present
• On MRI, a well-defined capsule, central stellate scar, and distinctive pattern on T1 and T2 images may indicate oncocytoma.[14,15]

The similar appearance of clear-cell RCC and oncocytoma on contrast-enhanced CT scan.

The Houndsfield Unit (HU) -based enhancement patterns for clear-cell RCC and oncocytoma are overlapping on CT scan. [13]

Renal biopsy has a limited role in the diagnosis of oncocytoma, particularly because it can be difficult to distinguish from chromophobe RCC (see our blog entry on Renal Cell Carcinoma: Implications of Histology for more information about chromophobe RCC), the eosinophilic-variant of clear-cell RCC (a rare and potentially aggressive form of kidney cancer) and may be co-exist with RCC in 7-32% of cases. However, surgical series indicate that if oncocytoma is present with RCC in the same tumor, the tumor is often low-grade and indolent (benign-behaving).[16]

Histology and Pathology

Oncocytomas appear grossly as tan, homogenous tumors with a distinct border (composed of a well-formed pseudocapsule) and typically have a central stellate scar. Microscopically, cells are derived from distal tubules, are rounded and highly-eosinophlic (pink) due to an abundance of mitochondria (the energy producing portion of the cell). As stated above, it can extremely difficult to distinguish oncocytoma from chromophobe RCC or the eosinophilic-variant of clear-cell RCC under the microscope. Cells are typically arranged in a nested pattern and can demonstrate perinephric extension, pleomorphism (variability in size and shape), prominent nucleoli and atypia, making the distinction between RCC difficult.[17,18] On a percutaneous renal biopsy, where only a portion of tumor is present and cellular architecture is incomplete, distinguishing oncocytoma from RCC can be extremely challenging.

From pathologyatlas.com

To distinguish ococytoma from RCC, a number of features can be examined. Chromosomal abnormalities associated with RCC are not present in oncocytoma, and oncocytoma will commonly present with loss of chromosome 1p, loss of Y- or 14q- and rearrangements of 11q13. [7,8] Hale's colloidal iron stain has traditionally been used to identify oncoctyoma, however can have nonspecific staining patterns leading to difficult interpretation.[19] One of the distinguishing cellular features of oncocytoma is uniform, round mitochondria with lamellar cristae – in chromphobe RCC, mitochondria are variable in size and shape with tubulocystic cristae; and in eosinophilic-variant of clear-cell RCC, mitochondria are pleomorphic and have attenuated cristae.[20] Researchers at Johns Hopkins are taking advantage of differences in mitochondria among oncocytoma and RCC to come up with a better, preoperative diagnostic test to distinguish oncocytoma before a sending a patient to surgery.

Electron micropscopy of oncocytoma with uniform, round mitochondria (left) and chromophobe RCC with the pale area around the nucleus is predominantly occupied by microvesicles and irregular mitochondria (right).[20]

Management

Most often oncocytoma are clinically assumed to be RCC and have the same management strategies available including active surveillance, radical nephrectomy (for large tumors of uncertain etiology) and nephron-sparing surgeries including partial nephrectomy and thermal ablation. Oncocytomas under active surveillance can demonstrate rapid growth and are often the fastest growing tumors in active surveillance studies! Therefore, growth rate is not able to distinguish oncocytoma from RCC during periods of AS.[21,22] When the diagnosis of oncocytoma is known or highly-suspected, nephron-sparing approaches should be employed due to the benign nature of these lesions. At Johns Hopkins, partial nephrectomy is preferred to thermal ablation as a definitive diagnosis can be made from analysis of the tumor rather than biopsy specimens.

This blog is adapted from the Handbook of Urology, Chapter 24: Angiomyolipoma, Oncocytoma and Retroperitoneal Fibrosis, by Phillip M. Pierorazio, MD; Edited by John Kellogg Parsons, John B. Eifler, and Misop Han available from Wiley.


 

1. Kutikov A, Fossett LK, Ramchandani P, et al.: Incidence of benign pathologic findings at partial nephrectomy for solitary renal mass presumed to be renal cell carcinoma on preoperative imaging. Urology 2006; 68(4): 737-40.
2. Kouba E, Smith A, McRackan D, Wallen EM, Pruthi RS: Watchful waiting for solid renal masses: insight into the natural history and results of delayed intervention. J Urol 2007; 177(2): 466-70; discussion 470.
3. Pierorazio PM, Murphy AM, Benson MC, McKiernan JM: Gender discrepancies in the diagnosis of renal cortical tumors. World J Urol 2007; 25(1): 81-5.
4. Cao Y, Paner GP, Perry KT, Flanigan RC, Campbell SC, Picken MM: Renal neoplasms in younger adults: analysis of 112 tumors from a single institution according to the new 2004 World Health Organization classification and 2002 American Joint Committee on Cancer Staging System. Arch Pathol Lab Med 2005; 129(4): 487-91.
5. Snyder ME, Bach A, Kattan MW, Raj GV, Reuter VE, Russo P: Incidence of benign lesions for clinically localized renal masses smaller than 7 cm in radiological diameter: influence of sex. J Urol 2006; 176(6 Pt 1): 2391-5; discussion 2395-6.
6. Morra MN, Das S: Renal oncocytoma: a review of histogenesis, histopathology, diagnosis and treatment. J Urol 1993; 150(2 Pt 1): 295-302.
7. Lindgren V, Paner GP, Omeroglu A, et al.: Cytogenetic analysis of a series of 13 renal oncocytomas. J Urol 2004; 171(2 Pt 1): 602-4.
8. Paner GP, Lindgren V, Jacobson K, et al.: High incidence of chromosome 1 abnormalities in a series of 27 renal oncocytomas: cytogenetic and fluorescence in situ hybridization studies. Arch Pathol Lab Med 2007; 131(1): 81-5.
9. Skolarus TA, Serrano MF, Berger DA, et al.: The distribution of histological subtypes of renal tumors by decade of life using the 2004 WHO classification. J Urol 2008; 179(2): 439-43; discussion 443-4.
10. Minor LD, Picken MM, Campbell SC: Benign renal tumors. AUA Update 2003; 22: 170-175.
11. Al-Saleem T, Cairns P, Dulaimi EA, Feder M, Testa JR, Uzzo RG: The genetics of renal oncocytosis: a possible model for neoplastic progression. Cancer Genet Cytogenet 2004; 152(1): 23-8.
12. Oxley JD, Sullivan J, Mitchelmore A, Gillatt DA: Metastatic renal oncocytoma. J Clin Pathol 2007; 60(6): 720-2.
13. Pierorazio PM1, Hyams ES, Tsai S, Feng Z, Trock BJ, Mullins JK, Johnson PT, Fishman EK, Allaf ME. Multiphasic enhancement patterns of small renal masses (≤4 cm) on preoperative computed tomography: utility for distinguishing subtypes of renal cell carcinoma, angiomyolipoma, and oncocytoma. Urology. 2013 Jun;81(6):1265-71. doi: 10.1016/j.urology.2012.12.049. Epub 2013 Apr 17.
14. Licht MR: Renal adenoma and oncocytoma. Semin Urol Oncol 1995; 13(4): 262-6.
15. Harmon WJ, King BF, Lieber MM: Renal oncocytoma: magnetic resonance imaging characteristics. J Urol 1996; 155(3): 863-7.
16. Ginzburg S, Uzzo R, Al-Saleem T, Dulaimi E, Walton J, Corcoran A, Plimack E, Mehrazin R, Tomaszewski J, Viterbo R, Chen DY, Greenberg R, Smaldone M, Kutikov A. Coexisting hybrid malignancy in a solitary sporadic solid benign renal mass: implications for treating patients following renal biopsy. J Urol. 2014 Feb;191(2):296-300. doi: 10.1016/j.juro.2013.07.059. Epub 2013 Jul 27.
17. Amin MB, Crotty TB, Tickoo SK, Farrow GM: Renal oncocytoma: a reappraisal of morphologic features with clinicopathologic findings in 80 cases. Am J Surg Pathol 1997; 21(1): 1-12.
18. Perez-Ordonez B, Hamed G, Campbell S, et al.: Renal oncocytoma: a clinicopathologic study of 70 cases. Am J Surg Pathol 1997; 21(8): 871-83.
19. Leroy X, Moukassa D, Copin MC, Saint F, Mazeman E, Gosselin B: Utility of cytokeratin 7 for distinguishing chromophobe renal cell carcinoma from renal oncocytoma. Eur Urol 2000; 37(4): 484-7.
20. Tickoo SK, Lee MW, Eble JN, Amin M, Christopherson T, Zarbo RJ, Amin MB. Ultrastructural observations on mitochondria and microvesicles in renal oncocytoma, chromophobe renal cell carcinoma, and eosinophilic variant of conventional (clear cell) renal cell carcinoma. Am J Surg Pathol. 2000 Sep;24(9):1247-56.
21. Kawaguchi S, Fernandes KA, Finelli A, Robinette M, Fleshner N, Jewett MA: Most renal oncocytomas appear to grow: observations of tumor kinetics with active surveillance. J Urol 2011; 186(4): 1218-22.
22. Siu W, Hafez KS, Johnston WK, 3rd, Wolf JS, Jr.: Growth rates of renal cell carcinoma and oncocytoma under surveillance are similar. Urol Oncol 2007; 25(2): 115-9.

Active Surveillance for Kidney Cancer: Questions and Details

Active surveillance is the least invasive option for managing a kidney tumor. At Johns Hopkins, "active surveillance" is preferred to terms like "observation" or "watchful waiting," as these indicate a passive approach where we wait for something bad to happen. Active surveillance is, by definition, an involved process where patients and tumors are watched very closely, where tumor size and growth characteristics are monitored, and the need for treatment is reassessed on a regular basis.

Why active surveillance?

Kidney tumors are biologically heterogeneous – this means they come in all shapes, sizes and behaviors. Some are completely benign tumors, some are cancers that behave like benign tumors and some can be very aggressive. Most small kidney tumors (less than or equal to 4cm) are either benign or behave like benign tumors. The bigger a tumor gets, the more likely it is a dangerous cancer and conversely, the smaller a tumor is, the more likely it is benign or behaves in a benign fashion. While Hopkins is an expert center for kidney surgery, not all patients need to undergo surgery – especially if they have a benign or benign-behaving tumor.

Who is a good patient for active surveillance?

Several patient characteristics make active surveillance an attractive option:

• Tumor size: the smaller the tumor, the higher likelihood of having a benign or benign-behaving cancer.
• Tumors less than or equal to 4cm can safely undergo active surveillance, although the risk of cancer spreading from a tumor is smaller for tumors less than 3cm and is <1% for tumors <2cm. 
• Older patients who are medically fragile: Since the risk that the small kidney tumor spreads is low, in patients with a short life expectancy (<10years) a discussion regarding active surveillance may be prudent. Many of these patients die WITH the kidney tumor rather than OF the kidney tumor.
• Patients with poor kidney function: Since any intervention on the kidney can cause further deterioration of kidney function, these patients may be better off selecting active surveillance. In some patients, further decline in kidney function puts the patient at risk of needing dialysis. Dialysis, while life-saving, may be associated with poor outcomes and a low quality of life. Ask your doctor about your creatinine level which is an indicator of kidney function (normal is around 1.0 mg/dl).
• Patients with hereditary forms of kidney cancer: This includes patients with Von-Hippel-Lindau (VHL), Birt-Hogg-Dube (BHD), or other conditions in which patients are at risk of having multiple and recurrent tumors in both kidneys. These tumors are typically placed on active surveillance until they reach 3cm or larger.
• Patients who are experiencing or recovering from an active serious medical problem: 
• Active, serious medical issues can include patients with heart failure and/or significant vascular disease. These patients are excellent candidates for active surveillance as these chronic medical conditions increase the risks of surgery.
• An example of a recovering medical issue is patients who have drug eluting heart stents or patients who temporarily need to be on a blood thinner like warfarin (Coumadin). Kidney surgery/intervention can result in severe bleeding in these patients and thus a period of active surveillance until they can come off the blood thinners may be helpful to avoid a potential serious complication. A period of active surveillance until things stabilize should be entertained.
• Patients who are extremely anxious about having surgery or do not wish to have treatment: While urologists at Johns Hopkins are expert surgeons who perform a large number and variety of kidney surgeries safely, these surgeries are not without risks. Surgery is not for everyone. 

What does active surveillance involve?

The initial evaluation includes a complete history and consideration of other health risks, a thorough staging evaluation (imaging of the chest, abdomen, and pelvis) to make sure the tumor is confined to the kidney, blood work and urine tests to evaluate kidney function. After the initial evaluation, repeat imaging is recommended every six months for the first two years, and annually thereafter. However, active surveillance is often tailored to the patient and the protocol can be customized for each patient.

It is preferred that the first image is a CT scan or MRI with contrast (if the patient can receive contrast). After the first image, ultrasound is the recommended follow-up as there is no radiation, costs are relatively cheap and ultrasound is easy to perform. Tumor size and growth rates are evaluated with each image to determine if the tumor is changing in size or quality. Tumors are expected to change over time – the goal is to catch the dangerous ones before they grow too large or leave the kidney!!

Can these tumors be biopsied?

Percutaneous renal mass biopsy is an option for patients considering both surgery and active surveillance. Biopsy can often provide information regarding the malignant or benign nature of the mass. However, we expect most small renal masses to be low-grade, benign-behaving tumors and renal biopsy is not very good at telling the "good" cancers from the "bad." Researchers at Johns Hopkins are working right now to improve the performance of renal biopsy. Therefore, we decide on an individual basis, with each patient, if biopsy will be helpful.

What are the "triggers" for intervention?

Most renal masses grow at a slow and unpredictable rate. The average growth rate is about 1 millimeter per year, however some tumors can grow faster and some tumors can shrink away! The biggest trigger for intervention is overall tumor size. The risk of spread from the kidney increases from <1% at 2cm, to 2-3% at 3cm and 5-10% for tumors 4cm or larger.[1] Growth rate (centimeters per year) is also a consideration and tumors that grow >0.5cm/year may indicate aggressive growth. With each active surveillance image, the need for intervention is reconsidered.

Can the tumor spread while on active surveillance?

The answer to this is unfortunately, YES. However, for a well-selected patient the risk of this occurring on surveillance is very low (<2%).[2] Each patient and tumor are unique and this risk should be discussed with your urologist.

In patients who elect for delayed intervention, are the results compromised?

A study by Johns Hopkins urologists showed that a period of active surveillance did not alter results. In this study, patients delayed treatment of their small kidney mass by over 1 year. All were eventually treated with minimally invasive surgery successfully.[3]

Does Johns Hopkins have an active surveillance program for kidney tumors?

Yes. In 2009, Johns Hopkins urologists Mohamad Allaf, MD and Phillip M. Pierorazio, MD started the DISSRM (Delayed Intervention and Surveillance for Small Renal Masses) Registry. The DISSRM Registry now catalogues over 200 patients undergoing active surveillance at Johns Hopkins, Columbia University in New York, and Beth-Israel Deaconess Hospital in Boston. For more details, see our prior blog: Active Surveillance Proving Safe for Patients with Small Renal Masses.  Patients in the program are followed in an identical fashion to patients who choose not to enroll in the program (see "What does active surveillance involve?" above). The program involves regular check-ups and questionnaires regarding quality of life, anxiety, and general well-being. In addition, patients have the option of contributing blood and urine samples to look for a blood or urine marker to detect kidney cancer and answer some other important questions for this disease. Benefits to enrolling in the DISSRM Registry include help with decision-making throughout the surveillance process, the gathering of data to help the next patient with a small renal mass, ensuring follow-up with the research team at Hopkins and, lastly, is extremely easy study in which to participate. After talking with an urologist at Hopkins, a patient can sign consent forms and enroll in the study. A designated DISSRM clinic meets monthly to follow patients enrolled in the study. However, not all patients need to remain at Hopkins and some patients can follow-up remotely – so long as imaging and blood work are sent to Hopkins.


For more information regarding management of Kidney Cancer or the DISSRM Registry contact Dr. Mohamad Allaf, Dr. Phillip Pierorazio, or Tina Driscoll, the study coordinator at 410-955-0163.



[1] Thompson RH, Hill JR, Babayev Y, Cronin A, Kaag M, Kundu S, Bernstein M, Coleman J, Dalbagni G, Touijer K, Russo P. Metastatic renal cell carcinoma risk according to tumor size. J Urol. 2009 Jul;182(1):41-5. doi: 10.1016/j.juro.2009.02.128. Epub 2009 May 17.
[2] Smaldone MC, Kutikov A, Egleston BL, Canter DJ, Viterbo R, Chen DY, Jewett MA, Greenberg RE, Uzzo RG. Small renal masses progressing to metastases under active surveillance: a systematic review and pooled analysis. Cancer. 2012 Feb 15;118(4):997-1006. doi: 10.1002/cncr.26369. Epub 2011 Jul 15.
[3] Rais-Bahrami S, Guzzo TJ, Jarrett TW, Kavoussi LR, Allaf ME. Incidentally discovered renal masses: oncological and perioperative outcomes in patients with delayed surgical intervention. BJU Int. 2009 May;103(10):1355-8