Friday's announcement that George is again battling cancer creates a degree of uncertainty for the archdiocese, but church experts say any decisions regarding the cardinal's future at the helm of the local church remain in his hands.
"Nothing is going to be done in terms of governance of the Archdiocese of Chicago that isn't Cardinal George's request and preference," said Rocco Palmo, an authority on the Catholic Church and writer of the blog "Whispers in the Loggia." "I don't think this will hasten anything unless the cardinal wishes otherwise."
The submission of the letter was the first time a Chicago bishop had reached that milestone.
Popes generally don't accept cardinals' resignations when first offered, and George, leader of the Chicago archdiocese for 15 years, said he would be surprised if Pope Benedict XVI immediately agreed to his.
The announcement by the archdiocese that doctors had found cancer cells in George's kidney and liver gave few details on the cardinal's plans, other than to say he would rest at home over the weekend and attend a retreat during the week.
The Rev. Michael Place, chief theologian to George's predecessor, Cardinal Joseph Bernardin, when Bernardin was diagnosed with pancreatic cancer, said George likely alerted the papal delegate to the United States, as well as his auxiliary bishops and family, before making a public announcement about his illness.
Place, former president of the Catholic Health Association, said making that announcement just hours after receiving a diagnosis shows remarkable transparency.
"Facing traumatic news of the return of cancer is difficult for any person," Place said. "The whole experience is challenging. To share the news in a context of faith, while not necessarily easy, is almost a natural thing to do."
George was lauded for his candor while fighting bladder cancer. When Cardinal John Cody died in 1982, most people did not know he had suffered from congestive heart failure for quite some time.
Some think George's openness reflects his lifelong struggle as a survivor of polio — a childhood disease he rarely discusses, but one that has helped shape his ministry.
Bernardin, too, was open about his struggle with cancer. Palmo said that because Bernardin announced that his prognosis was terminal, the Vatican was able to get an early start in its search for a successor to head the Chicago archdiocese. Bernardin led the archdiocese for 14 years; Cody was in place for 17 years before that.
Place noted that much progress has been made in cancer treatments since Bernardin's illness, and said that it's too early to discuss succession or who might handle day-to-day operations if George's health takes a turn for the worse.
He also pointed out that although Bernardin's energy level declined as his cancer progressed, he continued to carry out a number of major duties for more than a year after his diagnosis.
"The presence of cancer cells (in George), while not good news, does not immediately impact the quality of his life," Place said.
According to the statement released Friday, George underwent a "procedure" that showed cancerous cells in his kidney and in a nodule that was removed from his liver.
Medical experts, speaking in general terms based on limited information provided by the archdiocese, said George's cancer most likely is a transitional cell, or urothelial, carcinoma that spread from his bladder to his liver. Another possibility is a primary tumor of the kidney or renal cancer.
Although George canceled at least two appearances this weekend, he still plans to attend an annual retreat in Mundelein this week with bishops from Illinois, Indiana and Wisconsin.
George was installed as archbishop of Chicago, his childhood home, in May 1997, six months after Bernardin's death. He became a cardinal in February 1998, qualifying him to participate in the April 2005 conclave that selected Pope Benedict XVI.
In November 2007, he became the first cardinal elected president of the U.S. Conference of Catholic Bishops.
John Allen, a Vatican analyst and author, said "many bishops in this country think of George as their intellectual leader and had hoped he would keep playing that role for a while."
Allen, who has covered the church for 20 years, said he was saddened by the news about George, an often-controversial church leader.
"George has always been my favorite interview, because whether you agreed with him or not, you were always going to get something smart, provocative and original," he said.
Palmo said that while George has long been seen as the intellectual leader of the American hierarchy, times like this remind everyone that he is first and foremost a spiritual leader.
"At the end of the day, he's looking for prayers. He needs prayers," Palmo said. "That's what kicks in at moments like this."