జర్నల్ ఆఫ్ స్టెమ్ సెల్ రీసెర్చ్ & థెరపీ

నైరూప్య

Results of Organ-Sparring Treatment of Muscle-Invasive Urothelial Carcinoma

Vladimir Startsev

Abstract:

In 2018 newly diagnosed urothelial carcinoma (UC) in Russia were registered in 14,446 cases, including 26% pts in stage III-IV. Thus, for every fourth Russian, UC is first detected in a neglected stage. Due to the Guidelines EAU-2017, cystectomy or alternative therapy with bladder preservation used in the treatment of such patients. Chemotherapy in UC pts (M-VAC, GC and other’s) is accompanied with side effects (myelosuppression, dyspepsia, neuroplegia, etc.) that reduce the patient's QoL and, thus, the effectiveness of therapy.

PURPOSE.  To evaluate the effectiveness of regional (i/arterial) ChTer based on platinum drugs in patients with locally advanced UC.

MATERIALS AND METHODS. We evaluated the results of regional ChTer in 36 patients with UC in stages T3a-4аN0-1M0G2-3 (8 women, 28 males in median age 65,4±4,2 y.o.) in 1998- 2003 гг. Earlier 21 pts received organ-preserving treatment (TURB + neoadjuvant / adjuvant ChTer), with a short clinical effect. All the patients after the catheterization and angiography of the uroperitoneal arteries received courses (from 6 to 36, median 18) of the regional ChTer (cisplatin, 50 mg / m² and adriablastin, 20 mg / m²) and metostrexate (20 mg / m²) + vinblastine (0, 7 mg / m²) intravenously, by the standard MVAC courses. After finishing of ChTer, the main group of pts was observed during 12-60 months (average 28 months) and over the next 10 years they were studied for their overall survival by a prospective study method.

RESULTS. Long-term use of regional ChTer with standard three-week interruptions contributed to partial and complete tumor response in 22 (61.1%) cases. During 24 months after ChTer there were no signs of tumor growth in the bladders of 13 (26.9%) pts. The effect of the treatment was determined by Grade, tumor Stage, the presence of N+ and the previous oncological anamnesis.

In 6 (16.7%) cases, with beam and endoscopic confirmation of the tumor progression, we performed salvage cystectomies. Due to the histological report, in 2 bladders were not any tumor cells, which were regarded as a "medicinal" pathomorphosis.

After 12 months after treatment (16 ChTer courses), 2 patients refused to follow up due to the increase of chronic renal failure: ureterohydronephrosis-II, which required palliative nephrostomy. In first 5 years of follow-up, 10 (27.7%) pts died, among them 6 – with tumor progression. The general toxicity was manifested as moderate myelosuppression (G-I, -II neutropenia and G-II thrombocytopenia). The five-year overall survival (OS) rate was 72.3%, which was consistent with the indicator obtained by foreign researchers. The OS was determined by the tumor Stage of the, the Age and severity of the Concomitant pathology, and the presence of N+.

According to results of follow-up, 9 (25.0%) pts survived 10 years with a functioning bladder. The initial stage of UC in 5 cases was pT3aN0M0G2, in 2 - pT3aN0M0G3, in 1 case – pT3bN1M0G2 and 1 – pT4aN0M0G2. At the beginning of the study, all surviving patients were younger than 65.

CONCLUSIONS:  Regional Chemotherapy was effective in more than 61.1% of UC pT3a-4аN0-1M0G2-3 (complete / partial remission, tumor stabilization). Minimization of side effects was achieved due to selective intra-arterial administration of the drug to the tumor, with a decrease of the medication dose. The life expectancy in 25.0% cases exceeded ten years, which is ahead of the average for pts with locally advanced UC and allows us to confidently talk about the need for further research in this direction.