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LOCALISED RCC MANAGEMENT(non
surgical)

INTRODUCTION:
• The incidence of renal cell carcinoma (RCC) has increased globally due to advances in
cross-sectional imaging of small renal masses (SRMs).
• SRMs are defined as incidentally image-detected, contrast-enhancing renal tumors less
than or equal to 4 cm in diameter which are usually consistent with stage T1a renal cell
carcinoma
Indolent in nature
Slow growth rates (1–3 mm per year)
low risk of metastasis (1–3%).

• Large renal masses (LRM),
solid localized renal masses >4 cm in size
usually corresponding to T1b and T2 RCC,
can also be followed by AS but with caution
with rapid growth (4–8 mm per year)
A higher risk of M1 metastasis (4–6%)

ACTIVE SURVEILLANCE (AS):
• . Active surveillance is defined as the initial management including the monitoring of renal
tumor size by serial imaging with delayed treatment in case of progression and is now
considered an option in the treatment of localized renal tumors
• AS is not synonymous with “observation” or “watch and wait,”
• It entails a highly individualized follow-up strategy involving serial imaging evaluating the
growth of masses.
• Shared decision-making is an essential component of the process, with the urologist and
patient discussing imaging modality (eg, cross-sectional vs ultrasound) and timing (eg, 3
months vs 6 months) with each imaging result.
• Notably, delayed intervention does not compromise outcomes with this

INDICATIONS FOR AS:
AUA guidelines:
• Patients with renal masses are suspicious of cancer, especially those smaller than 2 cm.
• AS or expectant management should be a priority when the anticipated risk of
intervention or competing risks of death outweigh the potential oncologic benefits of
active treatment.
• When the results of a risk-versus-benefit analysis of the treatment are equivocal and the
patient elects to undergo AS.
• When the oncologic benefits of intervention outweigh the risks of treatment and
competing risks of death, physicians should recommend active treatment.

INDICATIONS :
ASCO Guidelines:
• Absolute indications:
High risk for anesthesia and intervention or life expectancy less than 5 years
• Relative indications:
significant risk of end-stage renal disease (ESRD) if treated, SRM less than 1 cm, or life
expectancy less than 10 years

Contraindications:
• Benign renal masses reliably diagnosed by imaging or biopsy
• Renal masses with irregular borders
• Non-localized renal tumors (i.e., locally, lymphatically, or hematogenously
disseminated)
• When the oncologic benefits of intervention outweigh the risks of treatment and
competing risks of death
• When the patient refuses to be included in AS

Role of Renal Tumour Biopsy before active surveillance:
• Histological characterization of small renal masses by renal tumor biopsy is useful to
select tumors at lower risk of progression based on grade and histotype, which can be
safely managed with AS.
• Pathology can also help to tailor surveillance imaging schedules. In the largest cohort
of biopsy-proven, small, sporadic RCCs followed with AS, a significant difference in
growth and progression among different RCC subtypes was observed.
• Clear-cell RCC small renal masses grew faster than papillary type 1 small renal masses
(0.25 and 0.02 cm/year on average, respectively,)

HOW TO CALCULATE LINEAR
GROWTH RATE?

Multifocal small renal masses and active surveillance:
• It is defined as the presence of more than one tumor, which can be unilateral or bilateral in
SRMs.
• Multifocal SRMs can be synchronic or metachronous and are considered synchronous if
appearing within less than 6 months.
• There is scarce literature about the clinical behavior of these masses,
• Bilateral renal tumors have been observed in 90% of patients with multifocal tumors.
• The most frequent histological RCC variant associated with a multifocality is the papillary
subtype, but any histologic RCC can be multifocal.
• Multifocal renal tumors can be sporadic or associated with genetic syndromes

Focal Ablation
• Focal ablation is a useful approach to treating elderly and extensively
comorbid patients, especially for peripheral SRMs located away from
vital structures.
• The AUA guidelines list focal ablation as an option for any T1a or T1b
renal neoplasm and a recommendation in the setting of comorbidities
conferring high surgical risk.
• Ablation of renal masses is performed by placing probes into lesions.

• This can be achieved laparoscopically or percutaneously.
• Posterior lesions are typically amenable to a percutaneous approach,
whereas anterior neoplasms abutting adjacent organs are typically
approached laparoscopically.
• Ablative techniques:
• radiofrequency ablation,
• microwave ablation, and
• cryoablation

OPTIMAL CANDIDATES
• Small, peripheral neoplasm
• Patient who is a poor surgical candidate who desires treatment
• Patient desiring treatment who refuses surgery
CONTRAINDICATIONS
• Young, healthy patient (long-term oncologic safety is unknown)
• Hilar mass (abutting vessels or collecting system)
• Larger renal mass

• Goal of Ablation: necrosis of the entire SRM and a very thin rim of
adjacent normal renal parenchyma—essentially a negative margin.
• To date however, no randomized prospective trials have compared
ablation modalities or compared ablation to surgery.
• Several retrospective studies have also reported shorter
hospitalization, lower estimated blood loss, and less renal functional
decline after focal ablation compared to partial nephrectomy.

• Based on retrospective studies limited by selection bias and with
shorter follow-up, a meta-analysis found higher recurrence rates with
focal ablation compared to partial nephrectomy.
• Prospective randomized trials comparing partial nephrectomy to
tumor ablation are necessary to accurately compare these two
treatment modalities and better understand the long-term efficacy of
ablation in younger patients.

Cryoablation
• CA or cryotherapy ist he practice of using extreme cold temperature
to treat a varity of pathological conditions
• Now a days cryoprobes use argon gas based probes which rely on
joules Thomson principle .
• Low temperatues can be achieved by the rapid expansion of high
pressure inert gas
• Majority of cryoprobes now employ argon gas-based
systems(cryohit,cryocare, endocare etc)

Mechanism of tissue destruction
• Tissue destruction during CA occurs during the freezing and thawing process
• Rapid freezing in the area closest to the cryoprobe forms ice crystals within the
intracellular space that cause cellular injury through mechanical trauma to the
plasma membranes and organelles
• As the freezing process expands further from the cryoprobe extraclular ice
crystals form leading to the depletion of extracellular water and an osmotic
gradient that cause further intracellular damage through dehydration
• During the thawing process extracellular osmolarity decreases as ice melts
which lead to cellular oedema and further disruption of cell membranes
• In addition to direct cellular injury to blood vessel endothelium during the
freezing process results in platelet activation, vascular thrombosis and tissue
activation

Treatment temperature
• Normal renal parenchyma is typically destroyed at -19.4C
• However, temperature as low as -50 C may be necessary to guarantee
complete cellular death of cancerous tissue because it’s of fibrous
nature
• Therefore preferred target tissue temperature during cryoablation is -
40 C

Freeze thaw cycles
• In vivo animal studies initially demonstrated adequate cell kill in normal
tissue employing single freeze thaw cycle
• However multiple freeze thaw cycles promoted a larger and more
adequate area of liquaefactive necrosis improving cure rates
• Therefore in the treatment of renal malignancies the current
recommendation is to perform double freeze thaw cycle to ensure
complete cellular death(each of 8-10 min)
• Passive thawing relies on ice ball melting without any intervention after
cessation of argon gas through the cryoprobe(time consuming)
• Active thawing –in which helium gas is forced through the cryoprobe
creating a warm effect(joule Thomson effect)

• RFA uses radiofrequency energy to heat tissue to the point of cellular
death
• RFA uses monopolar alternating electric current that is delivered
directly into the target tissue at a frequency of 450-1200 kHz leading
to vibration of ions within the tissue and resulting in molecular
friction and heat production
• Increasing temperature within the target tissue leads to cellular
protein denaturation and cell membrane disintegration
Radiofrequency ablation

Variations in RFA equipment
• RFA can be performed with either a temperature based or impedance
based monitering system
• Temperature based monitering system work by measurement of
tissue temperature at the tip of the electrode and are bsed of
achieving a specified tepmperature for a given period
• Impedance-based systems measure the tissue impedance at the
electrode tip to a predetermined impedance level at which tissue
dissecation/destruction occurs

Single electrode monopolar probe vs
umbrella probe
• Original probe was designed as single electrode monopolar probe
controlled by varying the exposed uninsulated tip- <2cm
• leVaan introduced an insulated monopolar probe with 12 deployable
tines that function as radiofrequency antennas for wider dispersion of
current
• The Christmas tree shaped RTA device (angiodynamics) uses
thermistors embedded in five of the nine electrical tines to modulate
energy based on the temperature of electrode

Dry vs Wet RFA technology
• Dry RFA: as tissue dissecation increases in the target lesion the
charring effect on the tissue leasds to increased temperature and
resistance to AC limiting the ablation zone to <4 cm
• Wet RFA: it delivers a constant saline infusion into the tissue and in
proximity to the probe to lower the tepmeraturer at the probe tip
mitigating the charring effect – allowing for larger zone of ablation

Treatment temperature
• To maximize cellular death without carbonization temperature based
generators are programmed to reach a target temperature of 105 C
and ablation should not be considered successful unless a min 70 C
temperature is reached(tepmerture based system)
• Impedance based system are typically started at 40 to 80 watt and
increased at 10 watt/min to a maximum of 130-200 watt until an
impedance of 200-500 ohms is reached.

Intraoperative monitoring of RFA ablation
• Although possible to visualize the placement of RFA probe using
USG,MRI or CT but no reliable manner to evaltuate the zone of RFA
ablation radiographically
• Successful ablation of a renal lesion is highly dependant on exact
probe placement
• Outcome is dependant on feedback from generator, thermal probes,
presence of gas bubbles within the tumor and absence of contrast
enhancement.

Successful RFA(periabation halo sign)

HIFU(high intensity focussed ultrasound)
• As an acoustic wave is propagated through tissue a portion of energy
is absorbed and converted into heat
• When ultrasound waves are focussed with an appropriately shaped
transducer the temperature at the focal point can exceed the
threshold for cell death
• At sufficiently high intensities(>3500 watt/cm3) cavitiation and
microbubble formation occur that yield extremely high tempertatires
and a mechanically disrupting shockwave effect similar to ESWL
• HIFU employs a transducer that is used for treatment and monitering

Shortcomings of HIFU
• Treatment time is lengthy with a mean duration of 5.5 hours(1.5-9
hours)
• Studies of HIFU in renal masses have shown pathological evidence of
viable tumor at followup
• Purported explanation include poor targeting secondary to
respiratory movement and acoustic interference(acoustic shadowing,
reverbation, and refraction)
• Therefore outcones with renal HIFU have proved inferior to
alternative ablative technologies

Microwave ablation
• Mirowave ablation delivers energy through semiflexible probes that
are inserted directly into the target lesion and functions in a similar
fashion to RFA.
• Microwave energy operates in the 900MHZ to 2.45GHz of the
electromagnetic spectrum
• Microwave energy in this range creates rapid ion oscillation in the
tissue and frictional heat.
• MVA is capable of achieving target temperatures of >60 C with
greater rapidity than RFA

Results:
• Overall, cancer-specific survival significantly differed in the PN versus RN (P < .001), AS
versus TA (P = .03), and AS versus PN (P = .002) groups. There were no significant differences
when TA was compared with PN or RN, with 9-year cancer-specific survival rates of 96.4%
versus 96.3% (PN vs TA, P = .07) and 96.1% versus 96.0% (RN vs TA, P = .14), respectively.
With the exception of cancer-specific survival in AS versus RN groups (P = .29), cancer-
specific survival and OS for all AS comparisons were significantly lower. In addition,
compared with the patients undergoing TA, those in the PN and RN groups had increased
rates of renal, cardiovascular, and thromboembolic adverse events up to 1 year after the
procedure (P < .05 for all comparisons).
Conclusion:
• For T1aN0M0 RCC, TA confers cancer-specific survival and OS similar to those seen with
surgical management, with significantly fewer adverse outcomes at 1 year after the
procedure and similar rates of secondary cancer events compared with surgery

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LOCALISED RCC MANAGEMENT.pptx

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