Beyond the Abstract - Trimodality treatment for bladder cancer: Does modern radiotherapy improve the end results? by Mohamed S. Zaghloul, MD

BERKELEY, CA (UroToday.com) - Recent trimodality organ-preservation strategies combine maximal transurethral resection of bladder tumour (TURB), chemotherapy and radiation.

The rationale for performing TURB and radiation is to achieve local tumour control. Application of systemic chemotherapy, most commonly as cisplatin-based regimen, aims at the eradication of micro-metastasis and to act as radio-sensitizers. This role has been established in many diseases and several studies. Cisplatin-based chemotherapy in combination with radiotherapy, following TURB, results in a complete response rate of 50-81%.It is recommended and stressed upon that early cystectomy is performed in individuals who do not achieve a complete response following combination therapy. This will allow about 42-78% of patients to survive with an intact bladder at 3-5 years. A comparable long-term survival rate of 50-60% at 5 years’ follow-up is reported by both multimodality bladder-preserving trials and cystectomy series. Trimodality therapy has the advantage that about half of patients expected to survive with their native bladder intact. However, both therapeutic approaches have never been directly compared. It is worth noting that bladder-preserving multimodality strategy requires very close multidisciplinary co-operation and a high level of patient compliance. Even if a patient has shown a complete response to a multimodality bladder-preserving strategy, the bladder remains a potential source of recurrence, or new tumour appearance. Pathological complete remission at repeat TUR after the initial transurethral resection of the primary tumour, followed by chemotherapy in combination with radiotherapy, was identified as a prognostically important variable. However, even the latter patients are at a life-long risk of developing intravesical tumour recurrences with the need for meticulous surveillance. Despite the absence of such direct randomized trials comparing both modalities, trimodality treatment comprising maximal TURBT followed by different regimens of combined radiochemotherapy achieved comparable results to radical cystectomy in many trials.

With the application of modern radiotherapy, it is possible to safely deliver a high radiation dose, with the sensitizing effect of the concomitant chemotherapeutic agents. These variable regimens of radiochemotherapy were successful in achieving the goal of improved survival rates, with preservation of the native bladder. The clinical target volume (CTV) for irradiating the bladder should encompass the entire outer circumference of the bladder, any extravesical disease spread and any region deemed to be at risk of microscopic disease spread. It has also been extended to include the prostate and prostatic urethra in males or upper vagina in females. The pelvic nodal CTVs extend around external and internal iliac vessels. The external iliac CTV extends anteriorly to include the lateral external iliac nodes. The internal iliac CTV extends laterally to the pelvic sidewall. The contours around the external and internal iliac vessels are joined to create a single volume on each side of the pelvis, including the obturator nodes. The pre-sacral CTV extends anteriorly to the first and second sacral prominence. The planning tumor volume (PTV) margins are 5–10 mm according to the institutional policy of creating CTV–PTV margins. Partial bladder irradiation (bladder tumor with safety margin) may be used as a boost - either through intensity-modulated radiotherapy (IMRT) external beam or via brachytherapy. The partial bladder approach permitted the delivery of a considerably higher dose without increased toxicity. It is estimated that the tolerance of part of the bladder volume is higher than that of the organ as a whole, with tolerance doses estimated at 80 Gy for two-thirds of the bladder compared with 65 Gy for the whole organ.

Radiation uncertainties include set-up errors, patient movement, internal organ movement, and volume changes due to continuous bladder filling (both inter- and intrafraction). The advancement in treatment verification procedures in modern radiotherapy and the use of fiducial markers applied during TUR, reduces set-up errors, while adaptive radiotherapy could decrease the unnecessary irradiation of normal tissues by tracking bladder volume changes. In addition, new radiotherapeutic techniques, such as IMRT and volume-modulated radiotherapy (VMAT), permit dose escalation to the target without increasing the dose to the surrounding normal tissues. The value of this trimodality treatment depends upon the extent and adequacy of TURBT, the use of effective chemotherapeutic agents both as sensitizing and adjuvant agents for radiotherapy, and more importantly, upon the precise technique of irradiation to achieve the desired results. Ensuring target coverage may improve the tumor control probability by ensuring the target receives the intended dose, while reducing dose to critical normal tissues.

Urodynamic tests and quality of life (QoL) studies for long-term survivors treated with trimodality treatment showed that 75% were considered to have bladders with normal function. Furthermore, a questionnaire study revealed that 78.8% were ‘delighted’ or ‘pleased’ in terms of urinary function after trimodality conservative therapy. More than half of men had erections hard enough for intercourse and around 59% were satisfied with their sex life after conservative therapy. Sexual function was reported in 50% of men and 71% of women following bladder preservation. These rates compare favorably with a contemporary questionnaire-based study that reported 13% and 42% potency rate following radical surgery and nerve-sparing cystectomy, respectively.

 

Written by:
Mohamed S. Zaghloul, MD as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.

 

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