








































This is an open access article under the terms of a license that permits non-commercial use, provided the original work is properly cited.  
© 2023 The Authors. Société Internationale d'Urologie Journal, published by the Société Internationale d'Urologie, Canada.

SIUJ.ORG SIUJ  •  Volume 4, Number 4  •  July 2023

March 2023 marked the 50th year from the first 
i nt r ave sic a l Bac i l lu s C a l me t te – Guér i n (BCG) 
instillation in a patient with bladder cancer, and this 
was celebrated at the 4th Annual Bladder Cancer 
Forum, held in Kingston, Canada. A major highlight 
of this meeting was a special lecture (https://www.cua.
org/program/16937) by Dr Alvaro Morales in which he 
shared his personal perspectives on the 50 years of BCG 
in bladder cancer with scientists, trainees, and urologists 
from across North America.

BCG immunotherapy remains the gold standard 
treatment for non-muscle invasive bladder cancer 
(NMIBC). This groundbreaking treatment strategy was 
introduced to the treatment of patients with NMIBC 
by Dr Alvaro Morales, a urologist at the Kingston 
General Hospital, Queen’s University. Following the 
initial successes and failures of BCG immunotherapy in 
large, randomized clinical trials across multiple cancer 
types, Alvaro Morales, was enthusiastic about bringing  
this treatment approach for patients with NMIBC in 
early 1970s.

Alvaro was born and raised in Colombia. After 
obtaining his undergraduate medical training from the 
Javeriana University in Bogota, he moved to the United 
States and undertook post-graduate training in surgery 
in Washington DC and Boston. He continued with 
further training in Toronto, Kingston, and Aberdeen, 
and then completed a fellowship at the Laboratory of 
Immunodiagnosis at the National Cancer Institute in 
Bethesda MD. It was during his training in the United 
States that Alvaro became interested in the anti-tumor 
effects of BCG.

In 1972, Alvaro was appointed as a faculty member 
in the Department of Urology at the Kingston General 
Hospital, Queen’s University, by Andrew Bruce. Alvaro’s 
inspiration for bringing BCG to bladder cancer treat-
ment was the 5 principles underlying the anti-tumor  
efficacy of BCG established by Zbar and colleagues 
in the late 1960s[1-3]: (1) limited size of the tumor, (2) 
the ability to mount an immune response to myco-
bacterial antigens, (3) presence of sufficient number of 
viable bacteria in the preparation, (4) contact between 

Dr Alvaro Morales

BCG bacteria and cancer cells, and (5) development of 
immune response against tumor-associated antigens. 
According to Alvaro, each of these 5 features perfectly 
aligned with the desirable local environment present in 
the bladder of intermediate and high-risk patients with 
NMIBC.

BCG was brought to Canada in 1925 by Armand 
Frappier, at the University of Montreal, to conduct 
research on tuberculosis[4]. Alvaro was aware of the 
population-based observational study by Frappier’s 
group in which children receiving BCG vaccine expe-
rienced 50% reduction in leukemia incidence[5]. This 
study prompted Alvaro to access lyophilized BCG from 
the Frappier Institute for a clinical trial that he initi-
ated in 1973 at the Kingston General Hospital, Canada, 
in which 9 patients were enrolled. He developed a BCG 
treatment schedule primarily based on immunological 
principles as well as the initial packaging of the vaccine 
vials by Frappier Institute. These 9 patients did not 
experience recurrence after receiving treatment with 
6 intravesical weekly doses of BCG. Following the first 

Alvaro Morales, Kingston, Canada
Madhuri Koti, D. Robert Siemens
Cancer Research Institute, Queen’s University, Kingston, Canada

Soc Int Urol J. 2023;4(4):341–342 
DOI: 10.48083/AMJG5367

343

GIANTS IN UROLOGY

http://SIUJ.org
https://www.cua.org/program/16937
https://www.cua.org/program/16937


publication by Alvaro Morales on the success of BCG 
immunotherapy in 1976[6], this treatment approach was 
validated in 2 large, randomized trials sponsored by the 
American National Cancer Institute[7], approved by the 
FDA for treatment of carcinoma in situ, and adopted 
by urologists across the world. Of note, Alvaro faced a 
few initial challenges in securing funding to initiate this 
first BCG trial in patients with NMIBC. His application 
to obtain funding support from the Medical Research 
Council of Canada was rejected with feedback that this 
treatment approach is a “throwback to the stone age of 
immunology.” The first BCG trial was later supported 
by the Cancer Institute of New York. This success was 
followed by additional funding from the Ontario Cancer 
Treatment and Research Foundation for the subsequent 
remarkably efficacious trial on patients with carcinoma 
in situ, for which no other treatment besides cystectomy 
was then available[6].

Donald Lamm with investigators from the South 
West Oncology Group, further developed the 3-week 
maintenance schedule that was added to the initially 
established induction schedule of 6 weekly doses[8]. 
After close to 5 decades of continuous success, BCG 
remains to be matched or surpassed by any novel ther-
apeutic. In a recent publication, in addition to high-
lighting the major milestones in improving response 
to BCG, Alvaro shared the letter written to him by the 
daughter of Professor Camille Guérin, thanking him for 
developing this treatment for bladder cancer after she 
had received 24 instillations for her own treatment of 
NMIBC[9].

In 1982, Alvaro Morales became the head of the 
department of urology and continued in this position 
until 1997. He served as the president of the Canadian 
Urologica l Association in 1993–1994. Following 
retirement from clinical practice Alvaro established 
the Center for Applied Urologic Research at Queen’s 
University in 2004.

For his seminal contributions in the field of urology, 
he received several awards including the CUA Lifetime 
Achievement award in 1999, Yamanouchi (renamed the 
Mostafa Elhilali) award from the Société Internationale 
d’Urologie (2002), the William B Coley medal from the 

Cancer Research Institute of New York (1992), the Hugh 
Hampton Young award of the AUA and the Colombian 
Order of Merit. In 2011, Alvaro Morales was appointed 
to the Order of Canada, the highest accolade for 
Canadians who make extraordinary contributions to the 
nation. Eventually he developed other related interests 
that included endocrinological aspects of male aging 
and the effect of androgens in prostate cancer. Alvaro 
has published over 340 papers and 2 books on his areas 
of interest. Alvaro’s peers and colleagues describe him 
as a humble leader and a role model for several of his 
trainees and surgeon scientists. Undoubtedly, this Giant 
in Urology has made one of the most significant contri-
butions in the treatment of patients with bladder cancer.

References

1. Zbar B, Tanaka T. Immunotherapy of cancer: regression of tumors 
af ter intralesional injection of living Mycobacterium bovis. 
Science.1971;172:271–273. doi:10.1126/science.172.3980.271

2. Bast RC, Jr, Zbar B, Borsos T, Rapp HJ. BCG and cancer (first 
of two parts). N Engl J Med.1974; 290:1413-1420. doi:10.1056/
NEJM197406202902506.

3. Bast RC, Jr, Zbar B, Borsos T, Rapp HJ. BCG and cancer. N Engl J 
Med.1974;290:1458–1469, doi:10.1056/NEJM197406272902605.

4. Frappier A, Guy R. The use of BCG. Can Med Assoc J.1949;61:18–24.

5. Davignon L, Robillard P, Lemonde P, Frappier A. B.C.G. vaccination 
and leukemia mor t alit y. Lan cet.19 70 ; 2: 6 3 8 . doi:10.1016 /
s0140-6736(70)91402-9.

6. Morales A , Eidinger D, Bruce AW. Intracavit ar y B acillus 
Calmette-Guerin in the treatment of superficial bladder tumors. J 
Urol.1976;116:180–183. doi:10.1016/s0022-5347(17)58737-6.

7. Lamm DL, Thor DE, Harris SC, Reyna JA, Stogdill VD, Radwin HM. 
Bacillus Calmette-Guerin immunotherapy of superficial bladder cancer. 
J Urol. 124:38–40. doi:10.1016/s0022-5347(17)55282-9.

8. Lamm DL. Optimal BCG treatment of superficial bladder cancer 
as defined by American trials. Eur Urol.1992;21 (Suppl 2):12–16, 
doi:10.1159/000474915.

9. Lamm DL, Morales A A. BCG success stor y: from prevention 
o f t u b e r c ulo sis t o o p t im al blad der c an c er t r e a t m e n t . 
Vaccine.2021;39:7308–7318. doi:10.1016/j.vaccine.2021.08.026.

344 SIUJ  •  Volume 4, Number 4  •  July 2023 SIUJ.ORG

GIANTS IN UROLOGY

http://SIUJ.org

