Vladimir Ioffe, MD

PSA screening in prostate cancer: The controversy continues"

We strongly believe, based on our studies of 2396 prostate biopsies (performed due to elevated PSA, abnormal digital rectal examination [DRE], or both) done in 2010-2012, 2018, and 2019, that an annual prostate cancer (PCa) screening should be offered to all men 55 years and older, and especially in high-risk men (African-American [AA] men, those with a family history of prostate cancer, and healthy men 70 years and older).

Our recent study, “A Trend Toward Aggressive Prostate Cancer” (

. 2020;22(3):102-109), showed that after the United States Preventive Services Task Force (USPSTF) recommended against PCa screening, there was trend of increasing prostate cancer diagnoses with higher grades despite a decrease in overall biopsy rates. We found that in 2019, compared to 2010-12, the number of biopsies decreased by 45% while the diagnosis of PCa increased threefold.

Prior to 2012, annual PCa screening reduced PCa mortality by 50%. Since the USPSTF recommended against PSA- and DRE-based PCa screening, 50% of primary care physicians do not offer PCa screening.

The American Cancer Society reported 161,360 new cases of PCa in 2017, 164,690 in 2018, 174,650 in 2019, and estimates 191,930 for 2020—an increasing trend. The PCa mortality is also increasing: 26,730 deaths in 2017, 29,430 in 2018, 31,620 in 2019, and an estimated 33,330 in 2020.

Our study identified 3 high-risk groups for increased incidence and grade of PCa: AA men, men with a family history of PCa, and healthy men aged 70 to 80 years old. As the 

 article notes, the PLCO screening study was not only contaminated with screening in the control arm but also only enrolled 4% AA men. In the United States, AA men represent 12% of the population, and in large cities, they represent over 30% of the population. In the major European and UK screening studies, only 1% of patients had African heritage. Therefore, the large PCa screening studies underrepresent AA men.

In 2010, Medicare spent $11.8 billion on PCa care and by 2018 this increased up to $15.3 billion, largely due to the treatment of late-stage disease.

Overdiagnosis and overtreatment is significantly reduced due to improved testing and active surveillance.

, that the USPSTF should reanalyze the long-term data and clearly recommend annual PSA- and DRE-based prostate screening to reduce PCa morbidity, PCa deaths, and the cost of PCa care.

Navin C. Shah, MD, is from Mid-Atlantic Urology Associates, and Vladimir Ioffe, MD, is from 21st Century Oncology, both in Greenbelt, Maryland.

Articles

Drs. Navin C. Shah and Vladimir Ioffe share their insight on the Urology Times September 2020 Cover Story, “PSA Screening in Prostate Cancer—The Controversy Continues.”

Letter to the editor: PSA screening recommendation needs revision amid rising rate of aggressive disease

Although we commend the USPSTF for upgrading the recommendation for PSA- and digital rectal exam-based prostate cancer screening from a “D” to a “C” grade 

 we believe that not enough emphasis is placed on screening high-risk groups for prostate cancer.

Our group of 12 board-certified urologists practicing in the Washington, DC metro region sees a high-risk patient population consisting of 60% African-Americans and 22% men over age 70. We reviewed our patient biopsy data before and after the 2012 USPSTF recommendation against PSA screening. We found that, of 1,194 prostate biopsies, 552 were positive (46%) and 60% were high grade (Gleason score 7-10), even though compared to pre-2012 the prostate biopsies decreased by 30% 

 Our data indicate that the high-risk group consists of African-American men, men with a family history of prostate cancer, and healthy men age 70-80 years old and hence requires prostate cancer screening.

We disagree with the USPSTF regarding the basic statistic on which the recommendations are based. According to the USPSTF statement, 100 men need to be diagnosed with prostate cancer in order to avoid one death from prostate cancer. This statistic is derived from clinical trial data and is not consistent with the actual U.S. cancer statistics provided by the American Cancer Society (ACS). According to the ACS, in 2017 there were 161,360 new cases of prostate cancer and 26,730 deaths due to prostate cancer 

 This means that for 100 men diagnosed with prostate cancer, 16 will die due to prostate cancer. We believe this discrepancy is due to the under-representation of high-risk groups in the clinical trial data upon which the recommendations were based.

"We don’t want to return to the pre-PSA era in which 30% of newly diagnosed prostate cancer cases were metastatic."

A recent analysis of PubMed showed 53 articles that reviewed the clinical value of PSA-based prostate cancer screening found that 75% were in favor of screening 

 Data since the original recommendation against screening in 2012 show increased rates of metastatic disease 

 We don’t want to return to the pre-PSA era in which 30% of newly diagnosed prostate cancer cases were metastatic.

Diagnosis is necessary for proper medical care. All patients with prostate cancer do not undergo surgical or radiation therapy, as some patients are actively observed. In addition, newer technologies like parametric MRI of the prostate gland and genetic testing help to differentiate slow-growing from aggressive prostate cancer. Thus, new clinical tools will guide us in the future treatment of prostate cancer, especially of aggressive tumors.

We strongly believe, as stated in our prior letter published in 

), that PSA-based prostate cancer screening should be made available, especially to African-American men, men with a family history of prostate cancer, and healthy men age 70–80 years old to decrease the morbidity and mortality of prostate cancer. 

"Although we commend the USPSTF for upgrading the recommendation for PSA- and digital rectal exam-based prostate cancer screening from a “D” to a “C” grade (JAMA 2018; 319:1901–13), we believe that not enough emphasis is placed on screening high-risk groups for prostate cancer," write Navin Shah, MD, and Vladimir Ioffe, MD.

Letter: USPSTF recommendation a disservice to high-risk men

 The following letter was sent to the U.S. Preventive Services Task Force (USPSTF) in April 2017 after the USPSTF’s release of an updated draft recommendation on prostate cancer screening. The letter was subsequently sent to 

 discussing urologists’ reaction to the recommendation.

	According to the draft USPSTF statement regarding prostate cancer screening:

	“For men 70 years and older, the draft recommends against PSA-based screening for prostate cancer (D recommendation). The evidence shows that prostate cancer is slow growing, and the 10-year survival rate is quite high. Rates of overdiagnosis are higher in older men, raising the concern that screening may result in more harm than benefit in this age group.”

	We have published three papers in peer-reviewed urology journals focusing on patients 70 years and older. These publications show that men 70 years and older have much higher rates of high-grade (Gleason score 7-10) prostate cancer, higher stages of prostate cancer, and higher prostate cancer-specific morbidity and mortality compared with patients 55-69 years old.

[Quiz]: Baby born with atypical genitalia, XY karyotype

	In 2013, we published, “A comparative analysis of prostate cancer pre-treatment characteristics stratified by age” 

. In our 402 U.S. patients, we found that, compared with patients <70 years old, in patients ≥70 years old:

		69.1% had high Gleason score (7-10) in the presence of a positive DRE 

	In 2016, we published the largest review ever of 5,100 U.S. prostate cancer patients age 70 and older, “Frequency of Gleason score 7 to 10 in 5,100 elderly prostate cancer patients” 

	Based on analysis of 5,100 prostate cancer patients in our practice, we determined that 61% of prostate cancer patients age 70-80, 59% of those age 70-75 years, and 66% of those age 76-80 years have a high-grade prostate cancer. Since biopsy underestimates the grade in Gleason score 6 patients by about 50%, the actual frequency is approximately 80%. In patients with prostate cancer who had an abnormal DRE, 74% had a Gleason score 7-10, approximately 85% when accounting for biopsy undergrading.

	In 2017, we published a review of our patients titled, “Prostate biopsy characteristics: A comparison between pre- and post-USPSTF Prostate Cancer Screening Guidelines of 2012” 

. In this study of 671 U.S. prostate cancer patients, we found that the prostate biopsy rate decreased by 30% post-USPSTF guidelines but the prostate cancer detection rate increased by 33.5%. High-grade Gleason score 7-10 prostate cancer increased by 5.4% post-USPSTF guidelines.

Next: "Since the USPSTF recommendations of 2012, more advanced prostate cancer, metastatic prostate cancer, and prostate cancer-specific deaths have been documented."

	Since the USPSTF recommendations of 2012, more advanced prostate cancer, metastatic prostate cancer, and prostate cancer-specific deaths have been documented. A recent study showed that the incidence of metastatic prostate cancer increased by 72% from 2004 to 2013 

. The 5-year survival rate in metastatic prostate cancer is 28% 

, and the cost of treating metastatic prostate cancer is extremely high. More importantly, patients with metastatic prostate cancer have more pain and a much lower quality of life with certain death. The annual cost of the screening PSA test for prostate cancer is $28.

	In the last 20 years, due to prostate cancer screening, the prostate cancer mortality has been reduced by 50% 

. Additionally, African-Americans have twice the prevalence and twice the death rate due to prostate cancer compared to Caucasians.

Burnout, biopsy, BPH, and more: Post-AUA review

	Diagnosis is necessary for proper medical care. All patients with prostate cancer do not undergo surgical or radiation therapy, as some patients are actively observed. In addition, newer technologies like parametric MRI of the prostate gland helps to differentiate slow-growing from aggressive prostate cancer. Thus, medical research improvements will help us in future investigations and treatment of prostate cancer, especially of aggressive tumors.

	We strongly believe that PSA-based prostate cancer screening should be made available, especially to men 70 years and older to decrease the morbidity and mortality of prostate cancer.

	Navin Shah, MD, and Vladimir Ioffe, MD, Greenbelt, MD

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“We strongly believe that PSA-based prostate cancer screening should be made available, especially to men 70 years and older to decrease the morbidity and mortality of prostate cancer,” write Navin Shah, MD, and Vladimir Ioffe, MD.

Vladimir Ioffe, MD

Articles

Letter to the editor: PSA screening recommendation needs revision amid rising rate of aggressive disease

Letter: USPSTF recommendation a disservice to high-risk men

Dear USPSTF: Don’t discount value of PSA in men 70+