Renal Cell Carcinoma The New Frontier (To boldly go... ) Sean A. Pierre, MD, RCPSC (Urology)

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1 The New Frontier (To boldly go... ) Sean A. Pierre, MD, RCPSC (Urology) QUEENSWAY CARLETON HOSPITAL DIVISION OF UROLOGY NEPEAN, ON, CANADA

2 Disclosures None

3 Objectives Advances in the field of Renal Cell Carcinoma Intro/Review Challenges Timeline of Change Diagnosis Management Surgical Management Medical

4 Objectives Advances in the field of Renal Cell Carcinoma Intro/Review Challenges Timeline of Change Diagnosis Management Surgical Management Medical What does this mean for Urology Nurses?

5 What does this mean for Urology Nurses? Overall Goals Understand the thinking that goes into a treatment option Understand the pros and cons Understand the potential challenges Help in identifying and managing challenges

6 Quick Intro/Review Most common primary tumour of kidney 6 th most common solid malignancy Diagnoses/year Deaths/year

7 Lack of Symptoms Late Diagnosis Location of tumour Difficult to Access Difficult to biopsy Difficult to remove Challenges

8 Challenges Radiation-resistant tumour Chemotherapy resistant tumour

9 Few controllable risk factors Smoking Benign kidney tumours can mimic appearance of renal cell carcinoma Site of metastasis for some common tumours Breast, Melanoma Challenges

10 Where did we start? Where are we now? Where are we going? Timeline of Change

11 Timeline of Change Where did we start? Where are we now? Where are we going? How did we get from there to here?

12 Where did we start? Where are we now? Where are we going? Timeline of Change How did we get from there to here? How are we trying to get to where we want to be?

13 Objectives Timeline of Change Diagnosis Management Surgical Management Medical

14 Objectives Timeline of Change Diagnosis Management Surgical Management Medical What does this mean for Urology Nurses?

15 Star Trek Timeline of Change Star Trek Enterprise Official Theme Song Intro (3rd & 4th Season Intro) (1).mp4

16 Diagnosis Where did we start? Symptoms Imaging

17 Diagnosis Where did we start? Symptoms Flank Mass Flank Pain Gross Hematuria Paraneoplastic syndromes: anemia etc. From metastases: bony pain, weight loss

18 Diagnosis Where did we start? Symptoms Challenges/Limitations Mass had to be fairly large or have already metastasized Meant that you were late and cure was unlikely

19 Diagnosis Where did we start? Imaging: Intravenous Pyelogram/Urogram

20 Diagnosis Where did we start? Imaging: Intravenous Pyelogram/Urogram Didn t really image renal TISSUE Looked for distorsion in renal collecting system Mass had to be fairly large or be in a particular location Meant that you were late and cure was unlikely

21 Diagnosis Where did we start? Imaging: Intravenous Pyelogram/Urogram

22 Diagnosis Where are we now? Symptoms Improved Imaging Biopsy

23 Diagnosis Where are we now? Symptoms? Who needs Symptoms? Often Asymptomatic Smaller tumour at diagnosis Increased chance of cure

24 Diagnosis Where are we now? Imaging MUCH improved Smaller tumour at diagnosis More accurate assessment of local extent of disease More accurate assessment of metastases

25 Biopsy Renal Cell Carcinoma Diagnosis Where are we now? Rules out benign tumour Rules out metastatic tumour

26 Diagnosis Where are we now? How did we get here? Screening Computers Staining

27 Diagnosis Where are we now? Screening Checking ASYMPTOMATIC individuals Microhematuria Syndromes vhl, Tuberous Sclerosis, Hereditary Non-Polyposis Colon Cancer Family History Diagnosis BEFORE symptoms Smaller tumour at diagnosis Higher chance of cure

28 Diagnosis Where are we now? Screening: Limits Checking everyone is EXPENSIVE Lots of Negative tests Better in the REALLY High Risk patients

29 Diagnosis Where are we now? Imaging Computers allowed for improvements in acquiring and processing complex information

30 Diagnosis Where are we now? Imaging Computers allowed for improvements in acquiring and processing complex information Ultrasound CT Abdomen and Pelvis MRI Abdomen

31 Diagnosis Where are we now? Imaging Ultrasound CT MRI

32 Diagnosis Where are we now? Imaging: Limits No Pathology Can t tell... Benign vs. Malignant Primary Kidney Tumour vs. Metastasis Low Grade vs. High Grade Slow growing vs. Fast Growing

33 Diagnosis Where are we now? Imaging: Limits Cannot detect Micrometastases Small-volume spread of disease outside the kidney Horse may already be out of the barn

34 Biopsy Renal Cell Carcinoma Diagnosis Where are we now? Pathology specimen patient and lesion-specific information Usually done in combination with imaging increased specimen yield

35 Diagnosis Where are we now? Biopsy: Limits Can be difficult to Access lesion Fear of Post-Biopsy Complications Non-Diagnostic Rate Getting better and better Fear of Seeding the biopsy tract Myth but still difficult to dispel Cannot detect Micrometastases

36 Diagnosis Where are we going? Goals Accurate diagnosis of malignant disease Better screening Detection of Micrometastases Improved Imaging Improved Biopsies Genetics

37 Diagnosis Where are we going? Improved Imaging Goal: Allow differentiation between different lesions without the need for biopsy

38 Diagnosis Where are we going? Improved Imaging Goal: Allow differentiation between different lesions without the need for biopsy Optical Coherence Tomography

39 Diagnosis Where are we going? Improved Imaging: Optical Coherence Tomography Acquisition of information from scattering of infrared light passed through tissue to determine different tissue types Similar idea to CT (=computed tomography) which uses scattering of x-rays rather than light Can be combined with endoscopy and microscopy

40 Diagnosis Where are we going? Improved Imaging: Optical Coherence Tomography Barwari et al, AUA 2014

41 Diagnosis Where are we going? Improved Imaging: Optical Coherence Tomography

42 Diagnosis Where are we going? Improved Imaging: Optical Coherence Tomography Advantages Pathologic information without need for biopsy

43 Diagnosis Where are we going? Improved Imaging: Optical Coherence Tomography Challenges/Limitations Experimental Expensive No information on metastases or micrometastases

44 Diagnosis Where are we going? Improved Biopsy Goal: Allow more reliable differentiation between different types of lesions on the biopsy specimen Benign vs. Malignant Primary vs. Secondary

45 Diagnosis Where are we going? Improved Biopsy Goal: Allow more reliable differentiation between different types of lesions on the biopsy specimen Stains Preparation of tissue with chemicals which interact with microscopic components of the tissue More reliable lesion identification Decreased Non- Diagnostic Rate Less tissue required for diagnosis

46 Diagnosis Where are we going? Improved Biopsy: Stains

47 Diagnosis Where are we going? Improved Biopsy: Stains Advantages More reliable lesion identification Decreased Non-Diagnostic Rate Less tissue required for diagnosis

48 Diagnosis Where are we going? Improved Biopsy Challenges/Limitations Still have to Biopsy Anterior location of tumour can still be a challenge Central location of tumour can still be a challenge No information on metastases or micrometastases

49 Diagnosis Where are we going? Genetics Goal: Identify those individuals who will likely develop tumours and screen them Allows for early treatment higher chance of cure

50 Diagnosis Where are we going? Genetics Goal: Identify those individuals who will likely develop tumours and screen them Allows for early treatment higher chance of cure Genes involved (to date) vhl: von Hippel Lindau gene (syndrome of same name) TS: Tuberous Sclerosis gene (syndrome of same name) HNPCC: Hereditary Non-Polyposis Colon Cancer p53: Common tumour suppressor gene

51 Diagnosis Where are we going? Genetics Advantages Allows for early treatment higher chance of cure

52 Diagnosis Where are we going? Genetics Challenges/Limitations Not everyone with the gene will definitely develop tumour (unlike BRCA) Insurance coverage more difficult for these individuals even in the absence of disease No practical prophylactic therapy (still need kidney tissue to live)

53 Mx (Surgical) Where did we start?

54 Mx (Surgical) Where did we start? Open Radical Nephrectomy Entire kidney and adrenal gland (sometimes with part of abdominal/flank wall) removed Lots of different surgical approaches Flank (most common now) Subcostal (looks like open cholecystectomy scar) Midline (old school) Dorsal Lumbotomy (paediatrics)

55 Mx (Surgical) Where did we start? Open Radical Nephrectomy

56 Mx (Surgical) Where did we start? Open Radical Nephrectomy Advantages Excellent Cure Rate (if lesion diagnosed early enough) Great exposure Assessment of Other Organs Predictable complications

57 Mx (Surgical) Where did we start? Open Radical Nephrectomy Challenges/Limitations Large Incision Pain Delay of Return to Function Renal Insufficiency Complications of large operation (pneumonia, DVT, PE, etc.)

58 Mx (Surgical) Where are we now? Laparoscopic Radical Nephrectomy Open Partial Nephrectomy Laparoscopic Partial Nephrectomy Thermal Ablative Techniques Robot-assisted Laparoscopic Partial Nephrectomy

59 Mx (Surgical) Where are we now? Laparoscopic Radical Nephrectomy Goal: Removal of entire kidney using relatively small incisions

60 Mx (Surgical) Where are we now? Laparoscopic Radical Nephrectomy

61 Mx (Surgical) Where are we now? Laparoscopic Radical Nephrectomy Advantages Smaller incisions Decreased pain Faster recovery Adrenal gland usually left in situ

62 Mx (Surgical) Where are we now? Laparoscopic Radical Nephrectomy Challenges/Limitations Still losing the entire kidney Renal Insufficiency Technically challenging More challenging the larger the lesion Still an OR Still risk to other organs (minimal but real)

63 Mx (Surgical) Where are we now? Open Partial Nephrectomy Goal: Only remove the tumour (and small amount of normal surrounding tissue)

64 Mx (Surgical) Where are we now? Open Partial Nephrectomy

65 Mx (Surgical) Where are we now? Open Partial Nephrectomy Advantages Leave behind healthy functioning kidney tissue Decrease Renal Insufficiency Same cancer control rate as with Open Radical Nephrectomy IF no tumour left behind Can often do with fairly large tumours Can often do with fairly central tumours

66 Mx (Surgical) Where are we now? Open Partial Nephrectomy Challenges/Limitations Still Open Surgery large incision, pain, delay return to function Can be technically challenging Higher risk of peri-op/post-op bleeding Some limit to size of lesion that can be treated Some limit to degree to which a central lesion can be treated Possibility of leaving some tumour behind = Positive Margin

67 Mx (Surgical) Where are we now? Laparoscopic Partial Nephrectomy Goal: Removal of just the tumour (with some surrouding normal tissue) using small incisions

68 Mx (Surgical) Where are we now? Laparoscopic Partial Nephrectomy

69 Mx (Surgical) Where are we now? Laparoscopic Partial Nephrectomy Advantages Leave behind healthy functioning kidney tissue Decrease Renal Insufficiency Same cancer control rate as with Open Radical Nephrectomy Decreased Pain Decreased time to Return to Function

70 Mx (Surgical) Where are we now? Laparoscopic Partial Nephrectomy Challenges/Limitations Very technically challenging More challenging the larger the lesion More challenging the more central the lesion Controlling bleeding very challenging Still a Major OR Still risk to other organs (minimal but real) Possibility of leaving some tumour behind = Positive Margin

71 Mx (Surgical) Where are we now? Thermal Ablative Techniques Goal: Place needles into tumour and either heat or freeze tumour kill tumour cells Freeze = Cryoablation Heat = Radiofrequency Ablation Done percutaneously with local anesthetic and/or conscious sedation Facilitated by Improved Imaging (ultrasound, CT)

72 Mx (Surgical) Where are we now? Thermal Ablative Techniques

73 Mx (Surgical) Where are we now? Thermal Ablative Techniques Advantages Leave behind healthy functioning kidney tissue Decrease Renal Insufficiency Often done as outpatient i.e. No OR Decreased Pain Decreased time to Return to Function Minimal risk to other organs

74 Mx (Surgical) Where are we now? Thermal Ablative Technique Challenges/Limitations Technically challenging Cancer control INFERIOR to other techniques Possibility of leaving some tumour behind = Positive Margin More challenging the larger the lesion More challenging the more central the lesion More challenging the more anterior the lesion

75 Mx (Surgical) Where are we now? Robot-Assisted Laparoscopic Partial Nephrectomy Goal: Removal of just the tumour (with some surrouding normal tissue) using small incisions and robotic instrument control

76 Mx (Surgical) Where are we now? Robot-Assisted Laparoscopic Partial Nephrectomy

77 Mx (Surgical) Where are we now? Robot-assisted Laparoscopic Partial Nephrectomy Advantages Leave behind healthy functioning kidney tissue Decrease Renal Insufficiency Same cancer control rate as with Open Radical Nephrectomy Decreased Pain Decreased time to Return to Function

78 Mx (Surgical) Where are we now? Robot-assisted Laparoscopic Partial Nephrectomy Advantages Leave behind healthy functioning kidney tissue Decrease Renal Insufficiency Same cancer control rate as with Open Radical Nephrectomy Decreased Pain Decreased time to Return to Function Similar to Laparoscopic Partial Nephrectomy

79 Mx (Surgical) Where are we now? Robot-Assisted Laparoscopic Partial Nephrectomy Challenges/Limitations Somewhat technically challenging More challenging the larger the lesion More challenging the more central the lesion Controlling bleeding very challenging Still an OR Still risk to other organs (minimal but real) Possibility of leaving some tumour behind = Positive Margin

80 Mx (Surgical) Where are we now? Robot-Assisted Laparoscopic Partial Nephrectomy Challenges/Limitations EXPENSIVE!!!

81 Mx (Surgical) Where are we now? Laparoscopic Radical Nephrectomy Open Partial Nephrectomy Laparoscopic Partial Nephrectomy Thermal Ablative Techniques Robot-assisted Laparoscopic Partial Nephrectomy

82 Mx (Surgical) Where are we going? Goals Decrease the Technical Challenges Decrease amount of Normal tissue removed Decrease the pain/function/risk of other organ injury Decrease the Positive Margin rate How? Image-guided Partial Nephrectomy Radiosurgery

83 Mx (Surgical) Where are we going? Image-guided Partial Nephrectomy Goal: The use of real-time imaging during surgery to facilitate efficient removal of a tumour minimizing the removal of normal tissue Can be done via Open, Laparoscopic or Robotassisted Laparoscopic approaches more common with the last two

84 Mx (Surgical) Where are we going? Image-guided Partial Nephrectomy

85 Mx (Surgical) Where are we going? Image-guided Partial Nephrectomy Advantages Decrease some Technical Challenges Leave behind even more healthy functioning kidney tissue Decrease Renal Insufficiency Better able to address Larger lesions Better able to address more Central lesions Decrease the Positive Margin Rate Same cancer control rate as with Open Radical Nephrectomy

86 Mx (Surgical) Where are we going? Image-guided Partial Nephrectomy Challenges/Limitations STILL technically challenging Still an OR Still risk to other organs (minimal but real) EXPENSIVE

87 Mx (Surgical) Where are we going? Radiosurgery Goal: Deliver high dose of radiation to tumours with high precision No actual cutting Usually Robot-assisted/guided

88 Mx (Surgical) Where are we going? Radiosurgery

89 Mx (Surgical) Where are we going? Radiosurgery Advantages Leave behind even more healthy functioning kidney tissue Decrease Renal Insufficiency No actual cutting no issues with blood loss Decreased effects on nearby organs

90 Mx (Surgical) Where are we going? Radiosurgery Challenges/Issues More challenging to address Larger lesions Inferior cancer control rate compared to other options Possibility of leaving some tumour behind = Positive Margin Better for treatment of metastases rather than isolated primary lesions

91 Mx (Medical) Where did we start? Not much Most chemotherapy and radiation therapy options ineffective initially Immunotherapy IL1 and Interferon-ᵞ IV Administration Poorly tolerated Minimal increase in survival

92 Mx (Medical) Where are we now? Targeted therapy Specific molecules/receptors more essential to the tumour than normal cells in terms of growth and metastastic spread TK: Tyrosine Kinase VEGF receptor: Vascular Endothelial Growth Factor receptor mtor: Mammalian target of Rapamycin

93 Mx (Medical) Where are we now? Targeted therapy Hutson et al, Jan 2011

94 Mx (Medical) Where are we now? Targeted therapy Advantages Decreased side effects Decrease tumour growth and induce tumour shrinkage can make an inoperable tumour into an operable tumour Many are ORAL, not IV administration patient can be home

95 Mx (Medical) Where are we now? Targeted therapy Challenges/Issues Still not usually a cure Still have side effects Unclear as to whether truly decreases mortality

96 Mx (Medical) Where are we going? Goals Decrease side effects by targeting JUST the tumour cells and no other cells Prevention in higher risk populations Cure rather than control Genetic targets Vaccines

97 Mx (Medical) Where are we going? Genetic targets Genes involved (to date) vhl: von Hippel Lindau gene (syndrome of same name) TS: Tuberous Sclerosis gene (syndrome of same name) HNPCC: Hereditary Non-Polyposis Colon Cancer p53: Common tumour suppressor gene

98 Mx (Medical) Where are we going? Genetic targets Challenges./Limitations VERY early stages of development

99 Mx (Medical) Where are we going? Vaccines More accurate to say Immune System Stimulation Increase patient own body s immune response to tumours Usually by activating host immune cells in the lab with cancer cells then giving the host immune cells back to patient

100 Mx (Medical) Where are we going? Vaccines Challenges/Limitation VERY early stages of development

101 What does this mean for Urology Nurses? Overall Goals Understand the thinking that goes into a treatment option Understand the pros and cons Understand the potential challenges Help in identifying and managing challenges

102 Summary Advances in Diagnosis, Surgery and Medical therapy of Renal Cell Carcinoma Improved patient outcomes Decreased mortality for some Still a long way to go

103 Thank You!

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