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

Historical Contribution: 1942, Jewett, New Method of Ureteral Reimplantation

1942
Jewett. A new method of ureteral transplantation for cancer of the bladder. Journal of Urology, 1942: (48), 489-513.

 
In the early 1940's, the mortality for extirpative bladder cancer surgery and reconstruction hovered around 50%. The mainstay for urinary diversion was the ureterosigmoidostomy, which was fraught with complications related to obstruction of the freshly implanted ureter. In the discussion, Dr. Lawrence Wharton comments that, "in spite of 65 or so techniques now available, [ureteral anastomosis] is still a dangerous operation and should never be done…" However, it was recognized that there are several circumstances, including iatrogenic ureteral injuries in addition to bladder cancer, where no other option is left and foregoing urinary diversion condemned the patient to certain death.

 
In this manuscript, Dr. Hugh J. Jewett describes 15 cases of a two-stage ureterosigmoidostomy. Without a viable option for urinary divesion, Jewett knew that patients would succumb to renal failure or be so debilitated by chronic obstruction and infection that they would be unable to survive radical cystectomy. For this operation, Jewett expanded upon a two-stage surgical technique from the 1930's – and developed a special cutting electrode to facilitate the operation. Briefly, the operation included:

Stage 1: submucosal implantation of both ureters into the sigmoid colon without a lumen-to-lumen connection. This preserved ureteral blood supply and allowed the ureter to safely anastamose to the colon. Importantly, Jewett covered the ureterocolonic anastomoses in omentum and peritoneum to preserve/enhance blood supply and healing.

 
Stage 2: Maturation of the ureterosigmoidostomies. Three or four weeks later, Jewett would take the patient back to the operating room to complete the ureterosigmoidostomy. The distal ureter was divided, giving Jewett access to the anastomosis of the ureters to the colon. Using his cutting electrode, the lumen of the bowel could be joined to the ureter, completing the anastomosis in a safe, well-vascularized fashion.

 
Outcomes
All patients had invasive urothelial cancer of the bladder. Thirteen of the fifteen patients proceeded to cystectomy after urinary diversion. Nine of the 15 were alive 1.5 years after surgery. Three died during the recovery period and three died after discharge from the hospital. All of the patients, except one, died with adequate urinary drainage and good renal function. One patient, who Jewett attributed to a technical error, died of urinary obstruction as an early electrode caused significant damage to the anastomosis. Four patients required subsequent operations due to: bowel complications, urine leak and/or abdominal infection. No patient developed an ascending pyelonephritis.

 
While recognizing that his operation carried significant morbidity and mortality, Jewett noted in his conclusions,

"In the cases which I have reported, the condition of the majority of the patients was considered hopeless, and every form of therapy had been tried elsewhere before the patient was subjected to transplantation of the ureters. In a group of patients representing better surgical risks, I believe the mortality could be considerably reduced."

 
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! 


 

Radiation Therapy after Prostate Surgery: The Guidelines Say Yes, My Doctor Says No

Some men prostate cancer are faced with the realization that treatment of their prostate cancer may require multimodal treatment including some combination of surgery, radiation therapy and/or hormone therapy. The combined ASTRO/AUA (American Society for Therapeutic Radiology and Oncology/American Urological Association) Guideline for "Adjuvant and Salvage Radiotherapy after Radical Prostatectomy" makes a number of statements regarding the use of radiation therapy after surgery that can be confusing to patients and practitioners.

In this blog we review the statements from the ASTRO/AUA Guideline regarding adjuvant radiation therapy and the data supporting them.

 

THE STUDIES

The Guidelines are supported, mostly, by the data from three randomized trials of adjuvant radiation therapy (ART) versus observation for patients after radical prostatectomy (RP). The SWOG trial began first in 1988 followed by the EORTC and most recently the ARO trial. However, the EORTC trial had more than double the sample size compared to the other two trials. All three trials enrolled patients with pathologic stage, pT3, disease and/or positive surgical margins. However, they differed in that the ARO trial excluded men with a persistently elevated PSA after RP, whereas these patients were included in the other two trials.
All three trials used a relatively low radiation dose of 60 Gray (most radiation oncologist argue that adequate, contemporary treatment of prostate cancer requires 80 Gray), and only the more recent ARO trial used modern 3-dimensional treatment planning. Central pathology review was available for the majority, but not all, patients in the 3 trials. The primary endpoint was metastasis-free survival in the SWOG study, versus progression-free survival in the other 2 trials. Finally, because it began earlier, the initial SWOG publication and a more recent update had longer follow-up than in the other trials.

 

Vital Statistics:

SWOG 8794

Thompson et al. JAMA 2006; 296: 2329.
Thompson et al. JUrol 2009; 181: 956.
Initiated: 1988
Sample Size: 425
Inclusion Criteria: pT3* and/or SM+ (Positive Surgical Margin); 15.7% pT2*
Patients with Persistent PSA Elevation following Surgery: Approximately 1/3^rd
Radiation Therapy Dose: 60-64 Gray
Primary Endpoint: Metastases-Free Survival
Median Follow-up: 12.6 years

EORTC 22911

Bolla et al. Lancet 2005; 366: 572.
Van der Kwast et al. JCO 2006; 26: 4178.
Bolla et al. Lancet. 2012 Dec 8;380(9858):2018-27
Initiated: 1992
Sample Size: 1,005
Inclusion Criteria: pT3* and/or SM+ (>1/3^rd pT2*)
Patients with Persistent PSA Elevation following Surgery: 11%
Radiation Therapy Dose: 60 Gray
Primary Endpoint: clinical or biochemical Progression-Free Survival (PFS)
Median Follow-up: 10.6 years

ARO 96-02/ AUO 09/95
Wiegel et al. JCO 2009; 27: 2898.
Initiated: 1997
Sample Size: 388
Inclusion Criteria: pT3* with or without SM+ (No Lymph Node Metastases)
Patients with Persistent PSA Elevation following Surgery: 20%, were excluded
Radiation Therapy Dose: 60 Gray (using modern 3-D conformal techniques)
Primary Endpoint: biochemical Progression-Free Survival (PFS)
Median Follow-up: 4.5 years


**DEFINITIONS 
pT2: organ-confined prostate cancer at RP
pT3: non-organ confined disease at RP (includes pT3a: extraprostatic extension and pT3b: seminal vesicle invasion)
SM+: positive surgical margins


 

THE GUIDELINE STATEMENTS

Guideline Statement 1.

• Patients who are being considered for management of localized prostate cancer with radical prostatectomy should be informed of the potential for adverse pathologic findings that portend a higher risk of cancer recurrence and that these findings may suggest a potential benefit of additional therapy after surgery. (Clinical Principle)

Guideline Statement 2.

• Patients with adverse pathologic findings including seminal vesicle invasion, positive surgical margins, and extraprostatic extension should be informed that adjuvant radiotherapy, compared to radical prostatectomy only, reduces the risk of biochemical (PSA) recurrence, local recurrence, and clinical progression of cancer.
• They should also be informed that the impact of adjuvant radiotherapy on subsequent metastases and overall survival is less clear; one of two randomized controlled trials that addressed these outcomes indicated a benefit but the other trial did not demonstrate a benefit. However, the other trial was not powered to test the benefit regarding metastases and overall survival. (Clinical Principle)
  

Guideline Statement 3.

• Physicians should offer adjuvant radiotherapy to patients with adverse pathologic findings at prostatectomy including seminal vesicle invasion, positive surgical margins, or extraprostatic extension because of demonstrated reductions in biochemical recurrence, local recurrence, and clinical progression. (Standard; Evidence Strength: Grade A)

 

THE DATA SUPPORTING EACH STATEMENT

Biochemical Recurrence or Progression Free Survival

All three studies demonstrate a higher proportion of men experiencing a biochemical (PSA) recurrence after RP and ART. The risk of recurrence was decreased approximately 50% in meta-analysis data from all three trials including in the guideline indicating that ART reduces the risk of biochemical (PSA) recurrence in men with high-risk of recurrence after radical prostatectomy.

	Biochemical Progression-Free Survival
	Follow-up	RP+ART	RP alone	Hazard Ratio
SWOG8794	10 years	53.0%	26.0%	0.43, P<0.01
EORTC22911	10 years	60.6%	41.1%	0.49, P<0.01
ARO96-02	5 years	72%	54%	0.53, P=0.002

Locoregional and Metastatic Recurrence or Recurrence-Free Survival

This statistic refers to the proportion of patients who develop nodal metastasis or evidence of prostate cancer in the pelvis that can be treated with curative radiation. These numbers are expectedly low, even for patients with advanced disease. The ARO96-02 trial did not report locoregional recurrence, but both the SWOG and EORTC studies demonstrated a benefit for ART with regard to locoregional relapse.

	Local Relapse-Free Survival
	Follow-up	RP+ART	RP alone	Hazard Ratio
SWOG8794	10 years	8%	22%	NR, P<0.01
EORTC22911	10 years	8.4%	17.3%	0.45, p<0.01
ARO96-02	5 years	Not Reported

 
Metastatic recurrence refers to the proportion of patients who develop recurrent prostate cancer outside of the pelvis, are therefore not curable by local treatments like radiation and require systemic treatment like androgen deprivation and/or chemotherapy. The results for metastatic recurrence (and metastasis-free survival, MFS) are less clear with conflicting results among the studies. The SWOG study demonstrated a benefit to ART, while the EORTC did not and ARO96-02 has too few events at current follow-up. In the SWOG study, MFS was defined as the presence of metastases or death from any cause. In the SWOG study, 72% of the deaths occurred in men without metastases and there were only 5 more cancer deaths in the observation group – perhaps leading to the significant finding in this study.[1]

	Metastases and Metastases-Free Survival (MFS)
	Follow-up	RP+ART	RP alone	Hazard Ratio
SWOG8794	10 years	9.3%	17.5%	MFS:0.71, P=0.016
EORTC22911	10 years	10.1%	11%	MFS: 0.99, P=0.94
ARO96-02	4.5 years	2.7%	3.1%	NR

 

Overall Survival

Overall Survival (OS) was improved for patients receiving ART in the SWOG study, but not the EORTC or ARO96-02 studies. Mirroring the MFS data, there are conflicting results for OS among the studies.

	Deaths and Overall Survival (OS)
	Follow-up	RP+ART	RP alone	Hazard Ratio
SWOG8794	10 years	OS: 74%	66%	0.72, P=0.023
EORTC22911	10 years	OS: 76.9%	80.7%	1.18, P=0.2
ARO96-02	4.5 years	Deaths: 3.4%	5.0%	NR

SUBGROUP ANALYSES

All three studies consisted of a heterogeneous group of patients including patients with low-, intermediate- and high-risk features and variation in Gleason score, SM+ and pathological stage. When looking at these subgroups, ART appears to have the most benefit for patients with:

• Positive Surgical Margins (SM+)
• Gleason Sum ≥ 7

Other than biochemical (PSA) recurrence-free survival, the benefit to ART is unclear in patients with:

• Gleason 6
• Extraprostatic extension in the absence of SM+
• Seminal vesicle invasion (pT3)

A future blog will discuss the subgroup analyses in greater detail.

SUMMARY

• Adjuvant radiation therapy (ART) is an option for men with advanced prostate cancer and adverse features after radical prostatectomy.
• The ASTRO/AUA Guidelines are based on the data from three large, randomized clinical trials:
  • SWOG 8794
  • EORTC 22911
  • ARO 96-02/ AUO 09/95
• Patients who undergo ART will have an improvement in biochemical (PSA) and locoregional recurrence.
  • The impact of ART on distant metastases and overall survival is less clear.
• Subgroup analyses indicate that patients with positive surgical margins and Gleason Score ≥ 7 are most likely to benefit from ART.
  • The benefit of ART is unclear in patients with Gleason 6, extraprostatic extension or seminal vesicle invasion.

 

This blog was written by Mark W. Ball, MD. This blog is the first of a series on "Radiation Therapy after Prostate Surgery."  Dr. Ball is a 5^th year urology resident at the Brady Urological Institute at Johns Hopkins and looking forward to a career in urologic oncology.


 

 

 


[1] Cheng et al J Urol 182: 2531, 2009

Retroperitoneal Fibrosis (RPF): Insidious Obstructor of the Ureters

From http://www.baus.org.uk/

Retroperitoneal fibrosis (RPF) is a benign condition in which the proliferation of fibrotic and inflammatory tissue obstructs retroperitoneal structures including one or both ureters. While RPF is most often managed by nephrologists, it represents a benign proliferation of tissue that may require evaluation and management by urology.  This blog will review the basics of RPF.

Epidemiology and Etiology

In large, cross-sectional studies RPF is a rare disease, presenting in only 0.1 to 1 per 100,000 to 200,000 people.[1, 2] It is more common in men than women (ratio 2-3:1) and typically presents later in life - in the 6^th-7^th decade - although has been found in both the pediatric and elderly populations.[3, 4] While an inheritance pattern has not been documented, RPF is linked to a number of autoimmune disorders and the HLA-DRB1*03 allele which is linked to multiple sclerosis and rheumatoid arthritis.[5]


The etiology of RPF is not well understood and a number of theories exist. Possible causes include a vasculitis (inflammation) of the small vessels associated with the aorta,[6] immunologic dysregulation that produces an antibody reaction to fibroblasts or a B-cell disorder,[7, 8] or reactive inflammation in response to environmental toxins. As such, a number of medications, chemicals, radiation treatment, local and systemic diseases are associated with the development of RPF (Table).[7, 9] However, a specific etiology is identified in only 30% of RPF cases.[10] Malignancy is associated with 8-10% of RPF cases and should always be considered during initial work-up.[11]  Breast and prostate cancers are historically the cancers that can create a retroperitoneal mass similar to RPF.

Autoimmune Disorders		Medications (cont.)
Amyloidosis		Hydralazine
Ankylosing Spondylitis		LSD
Glomerulonephritis		Methyldopa
Pancreatitis		Methysergide
Primary Biliary Cirrhosis		Pergolide
Psoriasis		Phenacetin
Rheumatoid Arthritis		Reserpine
Sclerosing Cholangitis		Retroperitoneal Disease, Trauma or Surgery
Thyroid Disease		Aortic or iliac artery aneurysm; repair thereof
Uveitis		Ascending lymphangitis
Vasculitis, small- or medium-sized vessels		Collagen vascular disease
Chemicals		Endometriosis
Avitene		Hemorrhage
Asbestosis		Henoch-Schonlein purpura with hemorrhage
Methyl methacrylate		Inflammatory response to advanced atherosclerosis
Talcum powder		Ruptured viscera
Infection		Retroperitoneal Malignancy
Chronic urinary tract infection		Lymphoma
Gonorrhea		Renal Cell Carcinoma
Syphilis		Testicular
Tuberculosis		Urothelial Carcinoma
Medications		Metastases
Amphetamines		Any radiation or chemotherapy thereof
β Blockers		Systemic Disease
Bromocriptine		Inflammatory Bowel Disease
Ergotamine alkaloids		Sarcoidosis
Haloperidol		Erdheim-Chester disease

Diagnosis

From http://www.consultantlive.com/

RPF is an insidious, slowly developing disease.  Because it develops so slowsly, symptoms are often imperceivable.  Therefore, patients are often asymptomatic or present in an advanced stage when symptoms of ureteral or vascular obstruction occur.[11] Non-specific signs and symptoms may be related to the underlying etiology. Back, abdominal or flank pain have been described, as have constitutional symptoms (weight loss, anorexia, malaise), low-grade fever, hypertension or lower extremity edema related to chronic vascular obstruction. Blood tests may reveal changes in acute phase reactants (erythrocyte sedimentation rate, c-reactive protein) are elevated in 80-100% of patients and serum creatinine, hypergammaglobulinemia, anemia and autoimmune factors (antinuclear antibody, rheumatoid factor, etc.) may be abnormal but, in general, are not specific for RPF.[7, 12]


Typical findings on imaging include hydronephrosis (swelling of the renal pelvis and ureter), medial deviation of the ureter(s) and a smooth, well-demarcated retroperitoneal mass that surrounds the aorta, inferior vena cava (IVC), iliac vessels and ureters. CT and MRI are excellent modalities for establishing a diagnosis although ultrasound and intravenous pyelography can be used as adjuncts.[11, 13, 14] The retroperitoneal mass may involve one or both sides of the retroperitoneum. If unilateral, the mass may progress to cross the midline and involve bilateral structures (i.e. ureters) over time.

Histology and Pathology

RPF appears as a fibrous, white plaque that encases the major retroperitoneal vessels and structures. Most commonly it involves the aorta, inferior vena cava, major branches of both great vessels and the ureters. The plaque usually extends cranially from the renal hilum to the pelvic brim caudally, although has been demonstrated to extend into the pelvis or mediastinum. Histologically the plaque is composed of fibrotic cellular material (myofibroblasts, type-1 collagen) and a chronic inflammatory infiltrate (lymphocytes, macrophages, plasma cells and eosinophils).[8]

Management

Biopsy is required for the diagnosis of RPF and to exclude malignancy. Core biopsy is preferred to fine needle aspiration; open or laparoscopic biopsy can be performed during ureterolysis if indicated. If histologic findings are consistent with RPF, the first step is to stop all potentially inciting agents or exposures (Table). However, if obstructive uropathy is present, primary therapy should be directed at relieving the obstruction and maintaining renal function prior to initiating a biopsy for diagnosis or medical treatment. Retrograde ureteral stents are often easily passed in patients with RPF, however stents can paradoxically obstruct narrowed ureters associated with RPF. Alternatively, percutaneous nephrostomy tubes offer a reliable drainage method if stenting is not possible or unsuccessful.

Dr. Paul Scheel, MD

Once the urinary obstruction is relieved and a tissue diagnosis is obtained, medical therapy is the preferred initial treatment. Primary treatment is directed at assumed autoimmune and inflammatory etiologies of RPF, initially with a prolonged course of corticosteroids. Using prednisolone or prednisone, a number of dosing regimens are demonstrated to be initially effective in 67-89% of patients with follow-up extending from 15-55 months.[15-17] Azathioprine, colchicines, cyclophosphamide, mycophenolate mofetil and tamoxifen have been used to treat patients with severe RPF or RPF refractory to steroids.[16, 18-21] Importantly, no randomized, prospective studies exist addressing the utility of varying medical treatments or the initial use of medical versus surgical treatment for RPF. Dr. Paul Scheel, MD and Director of the Division of Nephrology at the Johns Hopkins Hospital, is a world expert and leader in the management of RPF. You can visit Dr. Scheel's website by clicking here or on the link below.

In patients refractory or unable to undergo medical treatment, ureterolysis can be performed to relieve ureteral obstruction. Ureterolysis involves completely freeing the ureters from the retroperitoneal mass. It can be performed via an open, laparoscopic or robot-assisted laparoscopic approach.[22, 23]  See the video below for robot-assisted laparoscopic ureterolysis.  Principles of ureterolysis include: biopsy of the fibrotic lesion, initiation of dissection in an area free of disease, avoidance of devascularization of the ureter, lateralization of the ureter, stenting for 6-8 weeks and enclosure within peritoneum or omentum to preserve ureteral vascularity and prevent recurrence.[24] In addition, bilateral ureterolysis should be performed in all cases (even if only a unilateral process is evident during evaluation) as disease can progress to involve both sides and reoperative surgery can be technically challenging. Successful treatment has been reported in 66-100% of surgical series with variable follow-up extending over many years.[22, 25, 26] However, ureterolysis is a complicated, challenging, rare surgery and should only be performed as a last resort. Therefore long-term follow-up is required with serial axial imaging and renal functional studies for an indefinite period of time.






Link: Retroperitoneal Fibrosis at Johns Hopkins Medicine.

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.    Uibu, T., et al., Asbestos exposure as a risk factor for retroperitoneal fibrosis. Lancet, 2004. 363(9419): p. 1422-6.

2.    Debruyne, F.M., M.J. Bogman, and A.F. Ypma, Retroperitoneal fibrosis in the scrotum. Eur Urol, 1982. 8(1): p. 45-8.

3.    Wu, J., E. Catalano, and D. Coppola, Retroperitoneal fibrosis (Ormond's disease): clinical pathologic study of eight cases. Cancer Control, 2002. 9(5): p. 432-7.

4.    Miller, O.F., et al., Presentation of idiopathic retroperitoneal fibrosis in the pediatric population. J Pediatr Surg, 2003. 38(11): p. 1685-8.

5.    Martorana, D., et al., Chronic periaortitis and HLA-DRB1*03: another clue to an autoimmune origin. Arthritis Rheum, 2006. 55(1): p. 126-30.

6.    Baker, L.R., Auto-allergic periaortitis (idiopathic retroperitoneal fibrosis). BJU Int, 2003. 92(7): p. 663-5.

7.    Vaglio, A., C. Salvarani, and C. Buzio, Retroperitoneal fibrosis. Lancet, 2006. 367(9506): p. 241-51.

8.    Corradi, D., et al., Idiopathic retroperitoneal fibrosis: clinicopathologic features and differential diagnosis. Kidney Int, 2007. 72(6): p. 742-53.

9.    Kavoussi, L.R., et al., eds. Campbell-Walsh Urology. 10 ed. Vol. 2. 2012, Elsevier Saunders: Philadelphia, PA. 1108-1112.

10.    Koep, L. and G.D. Zuidema, The clinical significance of retroperitoneal fibrosis. Surgery, 1977. 81(3): p. 250-7.

11.    Amis, E.S., Jr., Retroperitoneal fibrosis. AJR Am J Roentgenol, 1991. 157(2): p. 321-9.

12.    Monev, S., Idiopathic retroperitoneal fibrosis: prompt diagnosis preserves organ function. Cleve Clin J Med, 2002. 69(2): p. 160-6.

13.    Mulligan, S.A., et al., CT and MR imaging in the evaluation of retroperitoneal fibrosis. J Comput Assist Tomogr, 1989. 13(2): p. 277-81.

14.    Vivas, I., et al., Retroperitoneal fibrosis: typical and atypical manifestations. Br J Radiol, 2000. 73(866): p. 214-22.

15.    Kardar, A.H., et al., Steroid therapy for idiopathic retroperitoneal fibrosis: dose and duration. J Urol, 2002. 168(2): p. 550-5.

16.    van Bommel, E.F., et al., Long-term renal and patient outcome in idiopathic retroperitoneal fibrosis treated with prednisone. Am J Kidney Dis, 2007. 49(5): p. 615-25.

17.    Fry, A.C., et al., Successful use of steroids and ureteric stents in 24 patients with idiopathic retroperitoneal fibrosis: a retrospective study. Nephron Clin Pract, 2008. 108(3): p. c213-20.

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